Cancer April 2008

EDITOR SPEAKS
Vol. 6 Editor-in-Chief Sectional Editor Issue 3 April - June 2008 Dr. Vinay Aggarwal Dr. Arun Kumar Goel Editorial Board Dr. Ashok Grover Dr. Hariharan Dr. Sharda Jain Dr. Rajiv Gupta Dr. Deepak Pande Dr. Vineet Jain Dr. B.K. Gupta Dr. Atul Jain Photographer Design and Layout Dr. Madhumita Puri Dr. Parkash Gera Dr. S. Arul Rhaj Dr. Yogesh Jhamb Dr. Neeraj Jain Mr. S.K. Singhal Mr. Atul Gandotra Mr. Mukesh Kapoor Ms. Tabassum This issue of Medi-Focus is dedicated to oncology for two reasons. First and foremost is the rising importance of oncology as a super specialty. The second is related to the fact that the upcoming Pushpanjali Crosslay Hospital will have cancer care as one of the important super specialty disciplines with services that are the best in the country and at par with international standards. The rising importance of oncology as a super specialty can be highlighted through many statistics. Overall, the burden of cancer is rising rapidly in India and large parts of the world. Reasons for this are only partially understood. However, there are many preventable causes including tobacco use, infections (viral infections e.g. hepatitis B, human papilloma virus etc.), dietary and lifestyle factors. Globally, cancer incidence is nearly 10 million new cases per year. The same figure for India is somewhere between 8 lakh and 1 million cases per year. The prevalence of the disease is nearly three times the incidence. Cancer is a disease with a high mortality ratio (nearly 55 to 60% of cancer patients die of disease). In addition, the disease is a big social and financial burden on patients and their families. Thus, sustained efforts are required to counter the preventable factors in cancer causation. What has caused a dramatic change in mindset is the increasing success in the curative treatment of cancer. This has been achieved by improved understanding of the disease through research. Treatment based on this understanding has become more aggressive in many situations with integration of multiple modalities of treatment eg, surgery, drug therapy (chemotherapy, hormonal therapy, immunotherapy etc) and radiation therapy. A combination of modalities has led to synergistic outcomes. Currently, cure rates may be as high as 90% for most stage I cancers, while cure can be achieved in many stage IV cancers through aggressive treatment eg, curative treatment of metastatic disease in liver, lungs etc. On the other hand, organ and function conservation has been achieved by the present improved understanding of the pattern of spread and combination of modalities. Outcomes like breast conservation, sphincter conservation, laryngeal conservation, limb salvage are all leading examples of this approach. Another important visible trend at present is the development of therapeutic approaches that minimize the morbidity related to cancer therapy. This has happened in all the three fields of cancer care. In surgery, major advances in plastic and reconstructive surgery have allowed major surgical resections with excellent cosmetic and functional reconstructions, and the limits of reconstruction are progressively being pushed further. In medical oncology, development of hematopoietic growth factors has mitigated the risk of life threatening neutropenia to a large extent and has allowed administration of chemotherapy without dose reduction or delays. At the same time, development of targeted drugs has led to the availability of medicines that often have minimal or no myelotoxicity. Similarly, in the field of radiation therapy, the development of modern radiotherapy equipments and techniques (3D conformal radiation, intensity modulated radiation, image guided radiation) has allowed administration of radiation while progressively minimizing normal tissue exposure. This has further led a reduction of the long term side effects of radiation while maintaining or improving cure rates. Sadly, the glaring lacuna is the gross shortage of high quality cancer care facilities and manpower in the country. USA has nearly 4000 radiotherapy installations today while India has about 300 radiation facilities for a country that is nearly five times more populous. Further, nearly half the 300 installations have technology that is practically outdated today. Pushpanjali Crosslay Hospital has taken a big step in this direction with the establishment of a super specialty center of cancer care called the “Galaxy Cancer Institute”. The center will be equipped with latest radiotherapy facilities and will have the services of the largest team of senior cancer professionals in the whole of northern India. Further, the ultramodern diagnostic facilities (64 slice CT scan, MRI scan, gamma camera, PETCT scan, frozen section, etc) and high end operation theatre and ICU services completes the picture of a world class comprehensive cancer care center. I urge you to benefit from the academic treat that has been brought together in this issue. Your response and feedback is welcome.

CONTENTS
1. Brachytherapy: past, present and future 2. Challenges in setting up a cancer center 3. CML - a success story in oncology 4. Modern radiation techniques: IMrt and Igrt 5. History of medical oncology 6. Surgical oncology and role of plastic surgeon 7. Idiopathic perforation of gall bladder 8. Acute pancreatitis: imaging. 5 10 13 18 21 25 27 29

9. Medical News 32 Physical therapy for the Family Clinician 10. Pushpanjali Healthcare Events and Initiatives 11. Subscribers Feedback 12. guidelines for submission of Manuscripts
• Owned, Edited, Printed and Published by Dr. Vinay Aggarwal for and on behalf of Pushpanjali Medical Publications Pvt. Ltd., A-14, Pushpanjali, Vikas Marg Extn., Delhi-110092 Printed at Kumar Offset Printer, 381, Patparganj Industrial Area, Delhi - 110 092 All disputes to be settled in Delhi Courts only.

34 37 39

• •

All rights reserved. • No responsibility is taken for returning unsolicited manuscripts unless a self-addressed stamped envelope is enclosed. • Views expressed in articles in Pushpanjali Medi-Focus do not necessarily reflect those of the editorial board.

Dr. Arun Kumar Goel
3 Vol. 6, Issue 3 April - June 2008

CONSULTANT CHAIRMAN Dr. Vinay Aggarwal MEDICAL DIRECTOR Dr. gaurav Aggarwal PHYSICIAN Dr. Parkash gera Dr. Navin Atal Dr. Amit Chabbra

RESIDENCE

CHAMBER

LIST Of CONSULTANTS MOBILE DAY/TIMING

E-MAIL ADDRESS

22374612 22374612 22375440, 22371284 42408075 3240604

22371818 22371818 22075641 22140637 22411236 22414049-22453724 22582002 659014833 22432218 22582002 22507728 22094892 22548796, 22519888 22545000 22545000 95121-2652347 95120 2630365

9811050403 9899550403 9810000944 9810115132 9871701699 9810121609 9811008306 9312644808 9810183236 9810089120 9810262229 9818088114 9810281671 9811168281 9810061958 9810366571 9810121098 9818372811 9810060565 9811703004 9810025926 9810038879 9312010421 9811073613 9810244149 93112070380 9810110405 9811441064 9810272563 9811120545 9810249015 9810166989 9810108614 9811351486 9313926194 9312876694 9810064554 9811047047

11.30 am -1.00 pm (Daily) 8.00 pm - 9.00 pm (Daily) 9.00 pm - 11.00 pm (Daily) 4.00 pm - 5.30 pm (Daily) 11.00 am - 1230 pm (Daily) 8.00 am - 9.00 am (Daily) 10.00 am - 12.00 noon (tue, Wed, Fri) 7.00 pm - 8.00 pm (Mon, Fri) 1.00 pm - 2.00 pm (Daily) 9.00 am - 11.00 am (Mon, thur, Sat) 6.00 am - 8.00 am (tue, Wed, thus, Sat) 11.30 am - 1.30 pm (Daily) On Call 11.30 am - 1.00 pm (Daily) 10.00 am - 12.00 noon (Daily) 10.00 am-12.00 noon (Daily) 4.00 pm - 6.00 pm (Mon to Fri) 1.00 pm - 2.00 pm (Sat) 6.00 pm - 8.00 pm (Daily) 9.30 am - 12.30 pm (tue, thu, Sat) 10.30 am - 12.00 noon (Daily) 9.30 am - 12.30 pm (Mon, Wed, Fri) 5.00 pm - 6.00 pm (Daily) On Call 6.00 pm - 8.00 pm (Daily) On Call (tue, thu, Fri, Sun) On Call (Mon, Wed) On Call (Sat) 12.00 noon - 1.30 pm (Daily) 8.30 pm - 9.30 pm (Daily) 4.00 pm - 6.00 pm (Daily) On Call On Call On call 10.00 am- 1.00 pm (Daily, except Wed) 4.00 pm - 7.00 pm (Wed) On Call 1.00 pm - 2.00 pm (Mon, thu)

[email protected] [email protected]

[email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]

PHYSICIAN-CHEST SPL. Dr. Ashok grover 22541854 PHYSICIAN & NON INASIVE CARDIOLOGIST Dr. Mukesh Ajmera 22374502 GYNAECOLOGIST Dr. Sharda Jain Dr. Kanika gupta Dr. Bakul Arora Dr. Anita Jain Dr. rekha Sarin Dr. Meenakshi SURGEON Dr. Yogesh Jhamb Dr. Sameer Paruthi CHILD SPECIALIST Dr. Deepak Pande Dr. Vineet Jain Dr. S.K.Mittal 22238838-22238847 22149718, 22169718 22750757, 22750551 95120-4112881, 2640397 65261328 22378281 22243742, 42182025 95120-4112881, 2640397

CHILD PHYSIOTHERAPIST Dr. Deepika Mittal 22153892 PAEDIATRIC SURGEON Dr. Anurag Krishna 24112687, 24114887 ORTHOPAEDIC SURGEON Dr. B.K.Malik Dr. girish Chhabra 95120-2628200, 2625200 Dr. P.K.Dhar 22244801 Dr. Ashish Sao Dr. r.K.Sachdeva 22162135 Dr. Daulat Singh 22120442 Dr. Alok Sharma ANAESTHETIST Dr. rajesh Dhall Dr. Swaraj garg Dr. rakesh Atray ENT SURGEON Dr. Atul Jain Dr. Anurag Jain 22167122 22543003 22152245, 22157745 22376205 22720901

[email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]

GASTROENTEROLOGIST Dr. Neeraj Jain 22371024 ONCOLOGIST Dr. M.Nandi Dr. Dinesh Singh ONCO SURGEON Dr. Umang Mittal EYE SPECIALIST Dr. L.D. Sota Dr. P. C. Bhatia URO-SURGEON Dr. C.M.goel 95121-2668149 26016636 26515263, 26863998 95120-2630717

4 Vol. 6, Issue 3 April - June 2008

CONSULTANT PATHOLOGIST Dr. Vandana Arora Dr. Archana Sood MICROBIOLOGIST Dr. Narinder Saini RADIOLOGIST Dr. Mukesh Koshal Dr. Laveena Ajmera NEUROLOGIST Dr. B.K.gupta Dr. Nirmala Lahoti NEURO SURGEON Dr. raj Kumar Dr. J. Kumar Dr. Sanjeev gupta NEPHROLOGIST Dr. Neeru Aggarwal PSYCHIATRIST Dr. raman Jeet Jaswal Dr. Amitabh Saha Dr. r.K.Srivastava

RESIDENCE 22246806 22096401 22376289 22546704 22371675, 22371033 22540271, 22526601

CHAMBER 22381445 30946399

MOBILE 9811009938 9312319887 9810252127 9810062179 9810076408 9811084263 9810061981

DAY/TIMING 9.00 am - 4.00 pm (Daily) On Call 8.00 am - 9.00 am (Daily) 12.00 noon - 1.30 pm (Daily) On Call On Call On Call

E-MAIL ADDrESSS [email protected]

[email protected] [email protected]

[email protected] [email protected]

95120-2724591 22526533

9868399665 95120-2780736 26140058 9871650111 9910240919 9811415489 22094879 22097417, 22093186 22592073, 22169732 22091758 22161397 22541842 22147652 22510904 22412008 22372728 22540624 22112343 9868814326 9810321662

9810273684 9810955753 9810266275 9810526533 9818796611 9818294190 9891192777 9818796611 9818294190 9810292498 22513835 9810003628 9810033525 9891063467 9810033882 9313759050 9811106203 9810073795 9811744426 9811151154 9910081484 9810123067 9810067539 9811022434 9313100602 9810130292 9810049714 9811047912 9811319070 9810197049 9811137098 9312504480 9811305435 9810395657 9811112688 9871803070 9312224659

On Call On Call 1.00 pm - 2.00 pm (Mon to Fri) 9.00 am to 10.00 am (Sat) On Call 07.00pm-8.00pm(Mon) On Call 6.00 pm - 8.00 pm (Fri) 06.00pm-07.00pm(Mon) On Call 6.00 pm - 8.00 pm (Mon - Sat.) 11.00am-1.00pm (thur) 10.00 am - 2.00 pm (Daily) 5.00 pm - 8.00 pm [email protected]





PSYCHOSEXUAL DISORDERS Dr. (Col.) V.K. Wadia 55469686 PSYCHOLOGIST Dr. Amitabh Saha Dr. r.K. Srivastava CARDIOLOGIST Dr. Dhirendra Singhania

[email protected] [email protected] [email protected] [email protected] [email protected] [email protected]

ENDOCRINOLOGIST Dr. I.P.S Kochar (Paediatric) DENTIST Dr. geeta Paul/ /Dr. rahul Paul HOMOEOPATHIC PHYSICIAN Dr. M.M. Aggarwal 22434770 PLASTIC SURGEON Dr. Manoj Bansal Dr. r.K. Sandhir SKIN SPECIALIST Dr. ritu gupta Dr. V.K. Upadhyaya DIETICIAN Mrs. Archna gupta CHEST SURGEON Dr. r.C. Jain RHEUMATOLOGIST Dr. Anish Aggarwal 22155057 95120-2458588 22152084 26803436, 26808035 95120-2753546

12.00 am - 1.00 pm (Mon, tue) [email protected] 11.00 am - 1.00 pm (tue, Wed, Fri, Sat) On Call 10.00 am -11.00 am (Mon - Fri) On call 10.00 am - 12.00 pm (Daily) On call 4.00 pm - 7.00 pm (Fri) On Call On Call On Call On Call On Call On Call On Call [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]

COURTESY CONSULTANTS Dr. Poonam gupta 22095708 Dr. S.P. Singh 22152036 Dr. Jyoti Aggarwal 22238871 Dr. Deepak Lahoti Dr. Madhu Ahuja 22516733 Dr. Deepak Sarin 65901485 fAMILY PHYSICIANS Dr. V.K.Malhotra Dr. Ajay Aggarwal Dr. Ajay Arora Dr. Vipin Jain Dr. K.B. Bhatia Dr. Hari Haran Dr. Atul Aggarwal Dr. D.r. rai Dr. V.P. S. Chawla Dr. Sangeeta gupta Dr. Ashwani goyal Dr. A.K. Jain Dr. rakesh gupta D. Saroj Parkash 22157127 22156672 22372065 22372727 22549804 22459608 22155979



[email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]

5 Vol. 6, Issue 3 April - June 2008

EMPANELLED ORGANISATIONS 1 2 3 4 5 6 7 8 9 10 11
9.00 am - 11.00 am (Daily) [email protected]

Paramount Healthcare Pvt. Ltd. Vipul Medcorp Pvt. Ltd. Park Mediclaim Construction Corp. Ltd. E-Meditek SolutionsLtd genins India Ltd. United Healthcre Pvt.Ltd. Heritage Healthcare Family Health Plan raksha tPA East West Assist BSES Alankit Pvt. Ltd Medi Assist India Ltd. Med Save India Pvt. Ltd. MD India Healthcare Services (P) Ltd. ttK Healthcare Health India Star Health Allied Insurance Co. Lt. Mother Dairy Micromatic Machine tools Pvt. Ltd Bharat Heavy Electricals Ltd.(BHEL Central Electronic Limited good Health Plan Ltd. Focus Healthcare Safeway Mediclaim Services Pvt. Ltd. Maruti Udyog Ltd National Projects Construction Corporation Ltd Medicare Services Club Medicare tPAServices Pvt. Ltd rothshield Health (tPA) Servces Ltd. Sri gokulam Health Services tPA(P) Ltd Parekh Healthcare Apollo DKV Health Insurance Paramount Healthcare Management P Hygiecare CHM Pvt. Ltd. Mecon Limited National textiles Corporation Ltd. National Building Construction Corporation Ltd. (NBCC) Dabur & Excelcia Foods E-Medlife Arankari Placement Services Pvt. Ltd National Industrial Development Corporation Ltd Hospital Services Consultancy Corporation (India) Ltd. NEFFD Conoritum For Educational Communication M/S Venus Medicare Services Met Life India Universal Medi-Aid Services Ltd

LIST Of CONSULTANTS
CONSULTANT PHONE NO PHYSICIAN Dr. ruby Bansal r) 2614076 M) 9891376756 Dr. Amit Chabbra r) 3240604 M) 9871701699 GYNAECOLOGIST Dr. rachna Pandey M) 9891237891 CHILD SPECIALIST Dr. (Mrs.) VP Dobhal M) 9811161590 SURGEON Dr. Vijay S. Pandey r) 95120-2628254 M) 9818492809 ENDOCRINOLOGIST Dr. S.K. Wangnoo r) 22618242 22621357 M) 9810113922 CARDIOLOGIST Dr. Dhirender Singhania M) 9871650111 DAY / TIMINGS E-MAIL ADDRESS

12 13 14

11.00 am - 1.00 pm (Daily)

[email protected]

15 16 17 18 19 20 21 22 23 24 25 26

5.00 pm - 7.00 pm (tue, thurs, Sat)

[email protected]

9.00 pm - 10.00 am (Daily)

[email protected]

11.00 am - 1.00 pm (Mon, thur)

[email protected]

7.00 pm - 9.00 pm (Mon, Wed)

[email protected]

27 28 29

8.00 pm - 9.00 pm (Mon, Sat)

[email protected]

30 31 32 33

ORTHOPAEDIC SURGEON Dr. Ashish Sao 6.30 pm - 8.30 pm M) 9312010421 (Mon, Wed, Fri) DERMATOLOGIST Dr. ritu gupta r) 22371114 M) 9891063467 ENT Dr. Saket Aggarwal M) 9811231599 PHYSIOTHERAPIST Dr. Md. Majid Khan M) 9873207660 Dr. Mehreen Khan M) 9899295475 Dr. Sonika Saraswat M) 9899649920 HOMOEOPATHIC Dr. Priya Kapor M) 9312770969

[email protected]

34 35 36

7.30 pm - 9.00 pm (Wed, Fri)

[email protected]

37 38 39 40 41 42 43

11.00 am - 1.00 pm (Mon, thurs)

[email protected]

8.30 am - 8.30 pm (Daily) 8.30 am - 8.30 pm (Daily) 8.30 am - 2.00 pm (Daily)

[email protected]

[email protected]

44 45 46 47 48

10.00 am - 12.00 noon (Daily)

[email protected]

6 Vol. 6, Issue 3 April - June 2008

Brachytherapy: Past, Present and Future
Arun Kumar Rathi and Vikash Kumar

the word brachytherapy is derived from the greek word “brachios” meaning short and refers to the therapeutic use of encapsulated radionuclides within or close to a tumor. Henri Becquerel discovered natural radioactivity in 1896 when he found that Uranium produced a black spot on photographic plates that had not been exposed to sunlight. two years Brachytherapy derived later, Marie and Pierre from greek word “braCurie working in chios” meaning short. Becquerel’s laboratory • In 1901 Pierre Curie extracted Polonium first suggested inserfrom a ton of Uranium tion of small radium ore and later in the tube into a tumor at the St. Louis Hospisame year, extracted tal in Paris. radium. In 1901, • Several isotopes are Pierre Curie suggested used; gold-198, ioto Danlos at St. Louis dine-125, phosphoHospital in Paris that a rus-32. small radium tube be • Development of inserted into a tumor man-made isotopes thus heralding the birth and after-loading techniques reduced of brachytherapy.1 In the early twentieth hazards. century, major brachytherapy work was done at the Curie Institute in Paris and at Memorial Hospital in New York. Dr. robert Abbe, the chief surgeon at St. Lukes Hospital of New York, placed tubes into tumor beds after resection, and later inserted removable radium sources thus introducing the after-loading technique as early as 1905. Dr. William Myers at Ohio State University developed several radioisotopes, including gold-198, Cobalt-60, Iodine-125, and Phosphorus-32 for clinical brachytherapy. these were implanted surgically by Drs. Arthur James (surgeon) and Ulrich Henschke (radiation oncologist). the discovery of man-made radioisotopes and remote afterloading techniques has reduced radiation exposure hazards. Newer imaging modalities (PEt scan, Ct scan, magnetic resonance imaging, transrectal ultrasound) and sophisticated computerized treatment planning has helped to achieve increased positional accuracy and superior, optimized dose distribution. Finally, while brachytherapy was initially used only for treatment of cancer, it has now been found to be useful in non-malignant diseases (for example, in the prevention of vascular restenosis) as well. It is clear that brachytherapy is the optimum way of delivering conformal radiotherapy tailored to the shape of the tumor while sparing surrounding normal tissues. Some of the diseases now treated with brachy7 Vol. 6, Issue 3 April - June 2008
radiation exposure

therapy include prostate cancer, cervical cancer, endometrial cancer, head and neck cancer and coronary artery disease. Brachytherapy has been proven to be very effective and safe, providing a good alternative to surgical removal of the prostate, breast, and cervix, while reducing the risk of certain long-term side effects.2, 3 Brachytherapy can be split into five mai types:4

Better positional accuracy and superior optimization of dose delivery achievable due to modern • imaging modalities • computerized treatment planning systems. Malignant diseases treated with brachytherapy include: • cancers of the prostate, cervix and endometrium, head & neck, • Very superficial tumours like ocular cancers. Non-cancerous disease treated with brachytherapy are those due to vascular stenoses, like CAD.

• Mould brachytherapy: Superficial tumors can be treated using sealed sources placed close to the skin. Dosimetry s ften erio p formed with refertypes of Brachytherapy ence to the Man1. Mould Brachytherachester system; py: Used for superfia rule-based apcial tumors. 2. Strontium Plaque: proach designed Used for very superfito ensure that the cial tumors. dose to all parts of 3. Interstitial Brachytherthe target volume apy: Used for brachyis within 10% of therapy within tissues the prescription and on tumor beds. dose. 4. Intracavitary Brachytherapy: Used for • Surface Appliplacing sources incator is usually side preexisting body called Strontium cavities. plaque therapy 5. Intravascular Brachyand is used for therapy: Source placed inside vesvery superfisels for treatment of stecial lesions less noses and re-stenoses than 1mm thick. the beta (electron) particles produced from Strontium’s radioactive decay have a very shallow penetration. As the electrons only penetrate a few mm of air, radiation protection issues are slightly less but very different from other radiation sources.

Arun Kumar Rathi Associate Professor Dept. of Radiotherapy Maulana Azad Medical College and Lok Nayak Hospital New Delhi Vikash Kumar Senior Resident Dept. of Radiotherapy Maulana Azad Medical College and Lok Nayak Hospital New Delhi

• Interstitial brachytherapy. Here the sources are inserted into tissue. the first treatments of this kind used needles containing radium226, arranged according to the Manchester system, but modern methods tend to use Iridium-192 wire. Iridium wire can be arranged either using the Manchester or

the Paris system; the latter was designed specifically to take advantage of the new nuclide. • Intracavitary brachytherapy places the sources inside a preexisting body cavity. the most common applications of this method are gynecological in nature, although it can also be performed on the nasopharynx. • Intravascular brachytherapy places a catheter with the sources inside the vasculature. the most common application of this method is the treatment of coronary in-stent re-stenosis, although the therapy has also been investigated for use in the treatment of peripheral vasculature stenoses. Remote and Manual After-loading Machines After-loading machines perform brachytherapy treatments. Manual After-loading Machines: In the early days of brachytherapy (1920), the only way to place the radioactive material into the hollow tubes or hollow body cavities was for someone to carry the source up to the patient’s bedside (room or operating theater) in a safe, take it out and place it inside the hollow destination. By necessity, the staff member (usually the doctor) undertaking this received some radiation dose. this was manual loading. In cases such as cervix Manual Loading: Earliest way brachytherapy where a Heyman of placing radioactive source. Maximum radiation exposure capsule was used, radiation to staff. exposure from manual loading could be appreciable as all Manual remote after-loading: Metal tubes are placed initially. the sources had to be placed Source placed manually later individually while the patient in a single step. Exposure was anaesthetized on the to staff less than manual operating bed. It was not long loading. before the doctors who were Remote after-loading: Source exposed reasoned that their introduced inside small tubes exposure could be lessened by by machine that is operated placing metal tubes first, and remotely. Although exposure then placing the radioactive to staff reduced to minimum, sources inside metal tubes at very careful planning required a later time. the metal tubes to avoid errors. Machines are allowed the development of costly. standard sizing and strength sources so that source numbers could be calculated first, and then prepared to facilitate a single step procedure to manually after load. Manual after-loading machines could not be activated from outside the room, as the source had to be manually inserted. the source would have been prepared as a source train and inserted in a theater or ward. Remote After-loading Machines: Although manual after-loading reduced exposures, the guiding principle of radiation protection is to keep exposures as low as reasonably achievable (ALArA) given prevailing economic, political and societal factors. the move to reduce exposures even Advantages of Remote over Manual further led to the introduction • No radiation exposure in of remote after-loading. this patient transit technique relies on the use of • No exposure to theater or hollow tubes which are connected ward staff to a safe containing a small radioactive source welded to a wire that is driven out by a stepping motor to predetermined positions to deliver radiation dose. A plan is produced that describes the patterns of the stepping motor (distance and dwell time). the nurse or therapeutic radiographer that administers can leave the room (located either in theatre or ward) and start the treatment 8 Vol. 6, Issue 3 April - June 2008

outside. Empty catheters are placed into the patient and the ‘live’ source is entered at a later date. After this the check has been performed the source leaves its secure safe and the treatment begins. the development of the remote after-loading machines is a benefit to the many radiation safety issues surrounding manual after-loading machines, but they are expensive and more prone to error. LDR brachytherapy
LDR BRACHYTHERAPY

Low dose rate (LDr) involves Permanent seed Implants: implanting radioactive material radioactive seeds and can be implanted temporarily introduced and left within or permanently. the body. radiation travels • Permanent seed implants: few millimeters and the commonly used for prostate source decays slowly over cancer, radioactive seeds are time. Commonly used for cancer of the prostate. left in tissue. the radioactive seeds are about the size of Temporary seed loadings: a grain of rice, and give off Source placed inside radiation that travels only a catheters or needles and few millimeters to kill nearby kept in the body to be cancer cells. With permanent removed after brief period. Commonly used for implants the radioactivity gynecological cancers. of the seeds decays with time while the actual seeds permanently stay within the treatment area. • temporary seed loadings: sources are placed in catheters, needles, or other appliances for a brief period of time and then removed (gynecological cancers). LDr brachytherapy with a Figure 1. Interstitial implant in machine works in a similar way. carcinoma breast Another variant is the sources being in the form of active and inactive balls which are again, driven into the patient using a machine. HDR brachytherapy High Dose rate (HDr) treatment dose of 20cgy/min brachytherapy is a common or more delivered by sources brachytherapy method referring within catheters as per the to the treatment dose of 20cgy Manchester or Paris system. per minutes or above (ICrU Machines are used to introduce the source into the 38). Applicators in the form of catheters for preset time to catheters are arranged, usually deliver the calculated dose. according to the Manchester Advantage is minimal or Paris system on, or in the exposure to staff and patient. A high dose rate source treatment time is much (often iridium 192, Ir-192) is quicker. then driven along the catheters on the end of a wire by a machine while the patient is isolated in a room. the source dwells in a preplanned position for a preset time before stepping forward along the catheter and repeating, to build up the required dose distribution. the advantage of this treatment over implanting radioactive sources directly is that there is lower staff exposure and the source can be more active due to low staff exposure, thus Figure 2. HDR Brachytherapy making treatment times quicker.
after-loading system

HDR braachytherapy:

Newer Techniques in Brachytherapy
Mammosite Mammosite® is the name of a special catheter designed for ease of delivery of high-doserate radiation to the breast after lumpectomy for tumour less than 3cm size and no lymphnode involvement. the treatment allows for radiation to be placed in the area of the lumpectomy, and only a limited area of the
Mamosite • Special catheter for HDr radiation to breast after lumpectomy (<3 cms) and no auxiliary lymph node metastasis. • Only tumor area of breast is irradiated twice a day for 5 days. • Useful for small tumors.

diagnosed, metastatic and recurrent brain tumors by delivering radiation from within the tumor resection cavity.7 the gliaSite balloon catheter is implanted within the tumor cavity at the time of resection surgery. Following a simple treatment planning protocol, the balloon is infused with Iotrex® radiotherapy Solution, an organically bound 125I liquid radiation source that delivers a highly conformal dose of radiation to the target area. Optimal delivery • Delivers radiation from within the tumor resection cavity • Maximizes the dose of radiation to target area • Conformal, spherically uniform dose of radiation delivered directly to areas most likely for recurrence • radiation treatment completed within 3 to 7 days Intraoperative (IORT) using system radiotherapy the Intrabeam
IORT with Intrabeam Intrabeam system is an excellent solution for APBI and intra operative boosting in breast cancer. A single high dose delivery possible without concerns

Figure 3. Mammosite® radiation system

total breast receives radiation. the treatment is administered twice a day for five days, and then the catheter is easily removed. radiation is delivered to the area surrounding the excised tumor and not to the entire breast. the treatment is much shorter than traditional external beam radiation to the entire breast, but fewer women qualify for
Gliasite RTS Delivers site specific internal rt to brain. Minimizes rt exposure to healthy areas. Designed to be placed inside the tumour resected cavity and deliver high dose of rt for 3 to 7 days. Involves placement of a balloon in the tumor resection cavity and later the liquid rt source is infused into it by machine. Highly conformal delivery is achieved. dose

this type of treatment. the use of mammosite for ductal carcinomas is preferred to lobular type carcinomas.5 GliaSite Working in conjunction with leading neurosurgeons and radiation oncologists, Cytyc Surgical Products has developed a patented cancer treatment device, the gliaSite radiation therapy System (rtS), which is designed to deliver site-specific internal radiation therapy and minimize radiation exposure to healthy brain tissue.

Intraoperative radiotherapy of geographic miss of the (IOrt) with low-energy X-rays boost target volume. (30-50 KV) is an innovative As a preliminary boost of technique that can be used 20 gy, it reduces the time for EBrt by 1.5 weeks for both for accelerated partial breast cancer. breast irradiation (APBI) and Used for delivery of single intraoperative boosting in high dose rt to resected patients affected by breast cancer. tumor area immediately on Immediately after tumor resection resection of brain tumors. the tumor bed can be treated radiation is emitted from within the central area of with low-distance X-rays by a the cavity to spread radially. single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBrt), the purpose of IOrt is to cover the tumor bed safely. the intraoperatively delivered dose after tumor resection is 20 gy prescribed to the applicator surface. EBrt is delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18MV photons. IOrt with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients.8 As a preliminary boost it has the advantage of reducing the EBrt course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. the treatment is well
Figure 5. INTRABEAM® System

Designed to be placed inside the tumor resection cavity, the gliaSite rtS delivers radiation with Iotrex® radiotherapy Solution, a proprietary 125I radiation source placed inside a balloon catheter. targeted tissue receives a high dose of radiation, while exposure to healthy tissue is minimized. treatment is administered for 3 to 7 days.6 the liaSite adiation g r therapy System (rtS) is designed for the treatment of newly 9 Vol. 6, Issue 3 April - June 2008

Figure 4. Gliasite® Radiation

tolerated and does not cause greater damage than the expected late reaction in normal tissue. the INtrABEAM® system delivers single, high doses of precisely controlled radiation directly into the cavity of a resected brain tumor. Performed immediately after a confirming biopsy, use of the INtrABEAM® system conveniently combines diagnosis and treatment into one patient visit. With the INtrABEAM® System, X-rays are generated by forming With the INtrABEAM® System, X-rays are generated by forming and focusing an electron beam in an electron accelerator. the beam travels down an evacuated needle, hits a thin gold target and X-rays are emitted from the needle tip in a spherically symmetric pattern with precise control of the depth of penetration. the tumor or tumor cavity is irradiated directly during the tumor resection. Endovascular therapy restenosis is the major limitation to a full expansion of all revascularization procedures. Elastic coil, unfavorable remodeling and a proliferative response to injury are the more importune mechanisms to restenosis. Ionizing radiation based on the inhibitory effect on cellular proliferation has been widely used in the treatment of numerous neoplastic and non neoplastic conditions. gamma intracoronary radiation therapy after coronary angioplasty is given by using a wire 0.018 and 0.014 inches in diameter and 30 mm active length with 192 Iridium into the closed channel polyethylene catheter. A dose of 25 gy and 20 gy to the diameter of the reference artery is given. there is a great expectation regarding the efficacy and safety of vascular brachytherapy to increasing the use of endovascular recanalization procedures.

References 1. Available from: http://www.americanbrachytherapy.org/ aboutBrachytherapy 2. Merrick gS, Butler WM, Wallner KE, galbreath rW, Adamovich E (2005). “Monotherapeutic brachytherapy for clinically organ-confined prostate cancer”. West Virginia Medical Journal 101 (4): 168-171. 3. Mazeron JJ, Noel g, Simon JM, racadot S, Jauffret E (2003). “Brachytherapy in head and neck cancers”. Cancer radiotherapy 7 (1): 62-72. 4. Available from: http://en.wikipedia.org/wiki/Brachytherapy 5. Partial-Breast Irradiation therapy With MammoSite Appears to Offer Similar results as Whole-Breast Irradiation therapy F. Vicini and others American Society of Clinical Oncology Annual Meeting, June 2006, Abstract 529 6. tatter, et al. An inflatable balloon catheter and liquid 125I radiation source (gliaSite radiation therapy System) for treatment of recurrent malignant glioma: multicenter safety and feasibility trial. J. Neurosurgery. 2003; 99: 297-303. 7. Halligan, et al. Operation and permanent low activity 125I brachytherapy for recurrent high grade astocytomas. Int J rad Onc Biol Phys. 1996; 35:541-547. 8. the tArgIt trial: targeted intraoperative radiation therapy versus conventional postoperative whole-breast radiotherapy after breast-conserving surgery for the management of early-stage invasive breast cancer (a trial update). the American Journal of Surgery, Volume 194, Issue 4, Pages 507 - 510 D. Holmes, M. Baum, D. Joseph. mechanical heart valves. J Am Coll Cardiol 1999;33:1637– 41.

11 Vol. 6, Issue 3 April - June 2008

Challenges in Setting Up a Cancer Center
Dinesh Singh and Arun Kumar Goel
It is a Herculean task to set up a cancer centre. the challenges are manifold because it requires integration of many different specialties both in the medical and non-medical fields. I have undertaken this exercise twice, first to set up the Dharamshila Cancer Hospital and then the galaxy Cancer Institute at the Pushpanjali Crosslay Hospital. Each time the experience presented different and interesting challenges. As the essential first step, meticulous planning on the drawing board, initially for the macro aspects and subsequently to delve deep into the micro details is required. Statutory, legal and radiological regulatory requirements should be known, adhered to and integrated to the local building laws and by-laws, fire safety requirements, etc. Integration of different civic, electric, mechanical, biomedical branches and of the technical team with these agencies is a very different kind of job that has to be undertaken early in the project, otherwise delays are inevitable. Any lack of coordination between any of these agencies heightens the delay. Knowledge of the line-up of different components of the projSetting up a Cancer center ect in a sequence of time and space • technical intricacies needs to be done • Multiple complex integrations in advance by each • Best equipment selection department to gain • Multi-modality team apmaximum mileage. proach It is a strategy such • Architectural & structural details as this that ensures timely completion. • Construction & installa
tion

results in the best delivery of cancer care to the patient. this has also to be considered from the drawing board through the implementation of the project. By best cancer care I understand both medical care and in-house experience of receiving that medical care. the end result should be world class anti-cancer services with our Indian traditional love and care. Conceptualization of comprehensive care involves integration of all concerned modalities from planning stage because each specialty involves very different requirements. Each specialty is undergoing rapid transformation, modification and up-gradation. there are rapid changes in utilization of or integration of different diagnostic and therapeutic modalities. For example, management of a cancer patient starts with an early and accurate diagnosis, both anatomical and pathological, and etiological where applicable. this is followed by its further characterizations or sub classification for diagnostic as well as therapeutic purposes. A complete staging work up and a concerted treatment strategy are the next steps. Many situations have overlapping treatment solutions involving different modalities. A good treatment center is one in which all specialties work in cohesion and not in competition with each other so that patient care remains as the supreme motto. Practicing global standard protocols for management of this disease with the Providing the best to palatest technology tients and care-providers • Best of medical faciliand personalized ties, in-house comfort, care provides empathy the best chance • Making anti-cancer of cure. By this treatment least traum e t h o d o l o g y matic with a positive the same qualapproach • World Class Cancer ity of care can Care in a homely envibe provided may ronment be received in the best centers of the world with the added advantage of it being in the home environment and at an affordable cost. For an example, Igrt (Image guided radiotherapy) at a reputed center in USA costs approximately 70,000.00 US Dollars or INr 28 lacs exclusive of the cost of travel, stay and local transport, local expenses etc. the same treatment could be made available in less than 2 lacs INr. Patient and caregivers should be given complete

Dinesh Singh Consultant Radiation Oncologist Pushpanjali Crosslay Hospital Delhi Arun Kumar Goel Senior Consultant Surgical Oncologist Pushpanjali Crosslay Hospital Delhi

Selection of world • Commissioning of services class equipments needs to be done judiciously and by meticulously evaluating the merits and demerits of the equipments in relation to the requirements of the patient population served, kind of malignancies encountered, availability of other facilities in the area and its vicinity. Oncology requires multi-modality management. Each cancer patient requires services of many specialties, viz, radiation, surgical, medical oncology, radiology, pathology, microbiology, social welfare department and support groups and many more. Interdepartmental functioning that works to keeping all the desired specialties within the physical reach of the patient and caregiver in a manner that is convenient to all 12

Vol. 6, Issue 3 April - June 2008

information about different protocols for treatment so that they can select treatment modality in overlapping situations. Such situations are not very uncommon eg, cancer of uterine cervix, early stage cancer of larynx to name a few. Providing a world class cancer treatment center to the society is very satisfying work. It gives an opportunity to serve the society in two ways, one it creates job opportunities for technical and non technical persons and secondly, it provides treatment to patients near their homes. Cancer treatment is a lengthy process that puts a lot of social, economical psychological pressure on both the patient and the entire family. It is associated with a lot of ups and downs. Providing a soothing, homely environment both in ambience and behavior of the staff while providing anticancer treatment is highly important because it acts as a soothing balm for the patient and the care givers. We are very satisfied with the current project – the galaxy Cancer Institute; we have been able to integrate various modalities of cancer treatment, ie, Surgical Oncology, radiation Oncology, Medical Oncology, gynecological Oncology at one place on a single dedicated Oncology floor. the advantage is that patients will get advice from all specialists then and there in the best coordinated manner. OPD and IPD services are on the same floor thus the admitted patients will be continuously attended by senior doctors throughout the day. Adequate junior staff is going to be present round-the-clock to carry out patient care very compassionately. Equipments World class latest equipment, which is not present even in many centers in USA and Europe, e.g., 120 leaves, Dynamic Multi-leaf Collimators, On Board Imaging with Kilo voltage Cone Beam Ct, Image guided radiotherapy (Igrt), respiratory gating, 30 Channel Micro-selectron brachytherapy are some of them. All these and other equipments are able to deliver radiotherapy very precisely to the accuracy of 1-2 mm. Its advantage is that we can spare normal surrounding tissues from being exposed to radiation. the end result is that a greater dose of radiation can be given very safely with minimal side effects. this facilitates dose escalation and ultimately enhanced cure rates. Dynamic Tumor Tracking: Location of a tumor in relation to external skin markings is not always satisfactory. the tumor can move between treatment fractions (intra-fraction movement)

and during treatment fraction Inter-fractional and Intradelivery (inter-fraction). Using fractional movement is a Igrt, we use daily KV scanning factor that necessitates ad(Cone Beam Ct available on dition of extra margin beboard the linear accelerator) to yond the target volume. In create three-dimensional images conventional radiation, it that pinpoint the exact position of amounts to adding 3–5 cm the tumor. In the past, we had to of normal tissue all around compensate for tumor movements the target volume in all by planning the radiation field three dimensions. the vollarger than the tumor volume thus ume thus added is significant leading to increase in exposing a significant volume of morbidity and limiting dose healthy tissue to radiation. With to be delivered. the Varian Igrt, there are two robotically controlled “arms” to capture Ct, fluoroscopic and x-ray images on a daily basis, thus we can pinpoint the exact position of the cancer just prior to treatment. this increased precision allows for higher doses of radiation with fewer side effects. Brachytherapy High Dose Rate Brachytherapy is among the high end treatment modalities. Brachytherapy is a method of treating cancer in which sealed radioactive sources are inserted either directly into the tumor or in its vicinity. In this method, radiation is from within the tumor or very close to it. By this method very high doses of radiation can be given very safely to a select group of tumors, examples being carcinoma of uterine cervix, head and neck cancers (lip, buccal mucosa, tongue, tonsil) esophageal cancer, malignant brain tumors, soft tissue carcinomas, to name a few. At the galaxy Cancer Institute, a 30-channel HDR Brachytherapy from Nucletron, Holland has been installed, which again is a first for northern India. We are confident that with the ingredients of world class equipments, renowned doctors, technical and non technical staff with national and international training, coordinated effort among the different departments within oncology, within the hospital and between different hospitals along with a lot of Empathy will ensure that our patients will receive the best of care and cure at the Galaxy Cancer Institute, Pushpanjali Crosslay Hospital.

World class medical equipment

great environment for treatment and care

galaxy Cancer Institute @ Pushpanjali Crosslay Hospital

Large dedicated team with empathy

13 Vol. 6, Issue 3 April - June 2008

CML - A Success Story in Oncology
AK Vaid
Chronic myelogenous leukemia (CML), a clonal myeloproliferative disorder, results from the neoplastic transformation of the primitive hematopoietic stem cell. the hallmark of CML is the presence of a balanced translocation between the long arms of chromosomes 9 and 22, t (9; 22) (q34; q11), known as the Philadelphia (Ph) chromosome. Despite the constant Ph chromosome– related molecular Discovery of the Philadelevents in CML, phia chromosome, the hallmark of CML, 40 years ago the disease is has changed the clinical heterogeneous in course, therapy and prognoits presentation sis of CML. and clinical the availability of effective course. therapy, first with interAfter the initial feron-a and Bone Marrow transplant and more redescriptions of cently oral imatinib MesylCML more than ate has changed the natural 150 years ago, history and prognosis of the little meaningful disease. progress was made in its treatment for more than a century. radiation therapy and busulfan contributed more towards improving quality of life than to prolonging survival. But since the discovery of the Ph chromosome over 40 years ago, the clinical course, therapy, and prognosis of patients with CML have changed significantly. the availability of effective therapy, first with interferon-a (IFN-a) and bone marrow transplantation and more recently with imatinib mesylate (StI571, glivec), has changed the natural history of the disease and, in some instances, the prognostic significance of certain clinical variables. Understanding of the pathogenesis of the disease began with the discovery of the Philadelphia (Ph) chromosome followed by appreciation of its molecular the molecular counterpart counterpart, the of the Philadelphia chromoBCR-ABL fusion some is the abnormal BCr_ gene. recognition ABL fusion gene. of the tyrosine the pathogenesis of CML kinase (tK) activ- lies with the abnormal tyity of the Bcr-Abl rosine kinase activity of the proteins led to BCr-ABL encoded proteins the discovery of a CML is characterized by a new series of com- biphasic (at times triphasic) pounds targeted course: Chronic, Acceleragainst BCR-ABL– ated and Blastic. encoded proteins, Symptoms include fatigue, which inhibited night sweats, weight loss the tK activity, and symptoms attributable to splenomegally, like left thus aborting the upper quadrant abdominal signals control- discomfort, early satiety or ling the leukemic anorexia. phenotype. One 15 Vol. 6, Issue 3 April - June 2008 of the tK inhibitors, imatinib mesylate (IM), was found to have a high and relatively specific biochemical activity and an acceptable pharmacokinetic and toxicity profile, and was thus rapidly introduced into clinical practice. this resulted in a revolutionary step in the management of CML and a paradigm shift in the management of cancer in general.

Figure 2. HDR Brachytherapy after-loading system

AK Vaid Senior Consultant Medical Oncologist Artemis Health Institute New Delhi

the natural history of CML is characterized by a biphasic (and sometimes triphasic) course. the disease is diagnosed in the Chronic phase: Lasts for a chronic phase median duration of 35 – 65 (CP) in over months, busalphan or hy80% of patients. droxyurea does not change this. the presenting Accelerated phase: 2/3rd characteristics in of chronic phase patients’ CP are variable. progress to this poorly deUp to 40% of fined phase lasting for a mepatients may be dian of 1 – 2 years. a s y m p t o m a t i c Blastic phase: Almost all at the time of patients eventually progress diagnosis with to this phase where there are the disease being > 20% blasts in the blood or marrow. Nearly 50% of discovered during them have a myeloid transa routine medical formation, 25% lymphoid e x a m i n a t i o n . and in 25% blasts are unWhen symptoms identifiable. are present, they the median survival is include fatigue, about 3 – 9 months and it is night sweats, ultimately fatal. Prognosis is relatively better with lymweight loss, or phoid blast crisis. manifestations of

splenomegaly such as left upper quadrant abdominal discomfort, early satiety, or anorexia. When treated with conventional chemotherapy (ie, busulfan, hydroxyurea), the median survival in CP is 35 to 65 months. this survival is no different from what has been reported for untreated patients or patients treated with radiotherapy.Approximately two-thirds of patients go through an intermediate phase known as accelerated phase (AP) before progressing to the blastic phase. AP is a poorly defined stage. Interferon-α based therapy there is no universally accepted can increase the survival at definition for this phase of the 10 years to 78%, if complete eradication of Ph chromodisease. the median survival some occurs. for patients in AP is 1 to 2 years. With bone marrow transMost patients eventually progress plants 78% 3-year survival to a blastic phase unless the has been reported. Majority disease can be eliminated or of them are Ph negative. suppressed effectively before Allogenic SCT is the only reaching this stage. Blastic phase treatment with potential is characterized by the presence of for cure, but 40% patients ≥30% of blasts in the peripheral are usually eligible for this blood or bone marrow or by treatment. It is most effecthe presence of extramedullary tive when done in chronic blastic disease. the World Health phase. Organization recently proposed 20% patients relapse after a change in the criteria to ≥ 20% allogenic transplant. Many blasts. the blastic transformation of them respond to DLI. is of myeloid lineage in nearly 50% of patients, lymphoid in 25%, and undifferentiated in 25%. the blastic phase is usually fatal, with a median survival of 3 to 9 months. Patients with lymphoid blastic phase have a somewhat better complete remission rate after induction chemotherapy (30%–50%) and a longer median survival (9 months) compared with patients with myeloid or undifferentiated lineages (complete remission rate, 10%–20%; median survival, 3 months). the natural history of the disease may Problems of allogenic SCT be affected by effective therapy that leads to the elimination of Mortality 20% – 40% related matched donors the Ph chromosome. the median found only for 30% of CML survival for all patients treated patients. with Interferon-α–based therapy is gVHD is a problem with un65 to 90 months, and patients who related matched donors. achieve a complete eradication of Molecular matched UrD the Ph positive clone have a survival transplants may reduce probability of 78% at 10 years. Bone gVHD marrow transplantation offers the possibility of cure to a fraction of patients who have CML, and 3-year survival probabilities of 78% recently have been reported. there is, however, less information regarding the long-term follow up of patients treated with bone marrow transplantation. Currently, allogeneic SCt is the only treatment with known curative potential in CML, but it is an option for only about 40% of the patients with this disease. Longterm survival rates associated with human leukocyte antigen (HLA)-matched related-donor transplants range from 50%– 75% in patients with chronic-phase CML. Survival rates after transplantation during the accelerated phase are approximately 50% lower, and 5-year survival rates are <20% for patients who receive transplants during blast crisis. Approximately 75%–90% of patients are in complete hematological remission following transplantation test negative for residual leukemia as measured by reverse transcriptase polymerase chain reaction (rt-PCr) amplification of BCr-ABL transcripts. the significance of the presence of rt-PCr amplified transcripts following SCt is somewhat controversial, but this finding may augur a clinical relapse. the risk for relapse after allogeneic transplant in CML 16 Vol. 6, Issue 3 April - June 2008

is about 20%. Many patients who relapse respond to donor leukocyte infusions (so-called adoptive immunotherapy). SCt additionally carries a significant risk of treatment-related morbidity and mortality. the probability of SCt-related death has been reported to range from 20%–40%. A related HLAmatched donor can be found for fewer than 30% of CML patients. transplants from unrelated or non HLA-matched donors have higher mortality risks. Use of an allograft from an HLA-matched unrelated donor (UrD) can be considered if the patient does not have an HLA-identical sibling, but this option has historically been limited by donor availability and by greater toxicity (due mainly to the effects of graft-vs.-host disease [gVHD]) than with related-donor transplants. However, recent reports suggest that results with UrD molecularly matched transplants in selected younger patients can approach those achieved with relateddonor transplants.

Chemotherapy in CML
the alkylating agent busulphan, introduced in the 1950s, was shown to reduce elevated white blood cell counts and diseaserelated signs and symptoms in a majority of patients with CML. However, this agent causes serious adverse effects, including myelosuppression as well as pulmonary, hepatic, and cardiac fibrosis. Hydroxyurea (HU) demonstrated a more rapid onset of action and better side-effect Chemotherapy profile than busulphan. However, hydroxyurea monotherapy also Busulphan, Hydroxyurea, does not produce cytogenetic HHt, Ara-C. remission or significantly delay • Hydroxyurea is the prethe onset of accelerated-phase or ferred drug because of its rapid onset of action blast-crisis CML, and its effects are and better side effect primarily palliative. Adverse effects profile. associated with HU therapy include nausea and other gastrointestinal • It does not increase survival nor produces cytoreactions, myelosuppression, skin genetic remission. atrophy, and drug fever. Long-term • Occasionally potentially therapy can produce a lichenoid serious side effects ocdermopathy, lower-extremity cur. ulcers, cutaneous squamous cell carcinoma, gangrene of the toes, vasculitis, and life-threatening pulmonary reactions. the plant alkaloid homoharringtonine (HHT) has been shown to have efficacy in treating CML both as monotherapy and when administered with Ara-C. However, at high doses and with short infusion schedules, HHt has been associated with serious cardiovascular complications, such as hypotension and arrhythmias. Imatinib mesilate (Glivec) is the first in a new class of cancer drugs, the signal transduction inhibitors, rationally designed to competitively inhibit BCr-ABL tyrosine kinase activity. By blocking specific signals in cells expressing the BCr-ABL protein, imatinib reduces the uncontrolled cellular proliferation of white blood cells that is a characteristic feature of the disease. Imatinib has changed the current approach to the management of CML. A complete cytogenetic response is achieved in 50% to 60% of patients treated with imatinib after failing IFN-a therapy and in 75% to 90% of those treated with imatinib as their first line of therapy. With such an effective therapy, the prognostic significance of some clinical variables previously associated with outcome is changing. Due to the short-term follow-up at this time and the good overall results, few variables have been identified to have an impact on survival, and most of the data is mostly applicable to response and progression to AP or blastic phase. the estimated overall survival of patients who receive imatinib as initial therapy is 89% at 60 months. Patients who had

a complete cytogenetic response or in whom levels of BCr-ABL transcripts had fallen dramatically had a significantly lower risk of disease progression than did patients without a complete cytogenetic response.

Imatinib mesilate: A competitive inhibitor of BCr_ABL tyrosine kinase activity. • Complete cytogenetic response of 75% - 90% on first line use, 50% - 60% in INF failed patients. • 5 year survival - 89% • Side effects are minimal and drug removal due to toxicity is parctically never required. • response monitored by rt-PCr for BCr_ABL in marrow. Q-PCr estimation in peripheral blood may turn out to be the method of choice in future.

there are considerable efforts being made internationally to standardize the methodology and reporting of PCr technologies; these efforts are crucial if molecular response is to become the common currency to assess drug therapy. In the near future, it may be that the ideal way to monitor CML patients will be a combination of PCr for BCr-ABL and, kinase-domain mutation monitoring using only peripheral blood samples. It is currently recommended that imatinib therapy be continued indefinitely if the patient is benefiting. Anecdotal reports suggest that the discontinuation of imatinib, even in patients with undetectable levels of BCrABL transcripts, results in relapse. Although it is not known why imatinib is not able to eradicate the malignant clone, potential mechanisms include drug efflux, and amplification or mutation of the BCr-ABL gene. It is also possible that imatinib cannot completely inhibit BCr-ABL kinase activity; low levels of activity would allow cells to survive but not proliferate. As an alternative, the malignant clone could persist through mechanisms that are independent of the BCrABL kinase. Initial studies of two new inhibitors of the BCrABL kinase that are more potent than imatinib — dasatinib and nilotinib-showed high response rates in patients who had had a relapse during imatinib therapy. Despite their potency, these inhibitors cannot eradicate all CML cells in vitro. the range of options for the Imatinib with its excellent management of CML has now ability to control disease widened considerably with the and tolerability has lead to a introduction of imatinib. With imatinib now established as the rethinking as to how to incorporate it in patients who first-line pharmacotherapy for are potential candidates for newly diagnosed CML, a key SCt with HLA matched sibconsideration is how to incorporate ling donors. it into the treatment of patients who are candidates for stem cell • For the present, the approach is to continue transplant. One approach is to imatinib in responders administer imatinib initially to all who are poor risk for patients with a new diagnosis of SCt. CML while they are being evaluated • Young good risk patient for a transplant. Younger patients with mortality risk of < 10% - 15% from SCt who have incomplete cytogenetic who have a matched responses to first-line imatinib sibling donor should be therapy and have suitable donors taken up for SCt. may be considered for stem cell • this group of patients transplantation. For inadequately who are responders responding patients without and have potential donors have to be closely donors, an increase in the imatinib monitored with regular dose, with or without the addition assesment of disease of other agents (e.g., IFN, Ara-C), status. the assesscan be considered. the choices ment strategies are not are less clear for patients who standardized yet, but 3 respond adequately to imatinib monthly assessment of and have HLA-matched donors. BCr_ABL in peripheral blood by FISH or Q-PCr the 10%–15% of patients at low risk for death from transplantation if cytogenetically negative seems reasonable. (ie, young patients with sibling donors) could be considered for Patients on hydroxyurea and / or INF-α should be immediate SCt. transplantation among higher-risk patients might switched over to imatinib. be reserved for those who show signs of disease progression on imatinib. However, until long-term survival data are available for imatinib-treated patients, decision making regarding transplant candidates with CML, particularly newly diagnosed cases, will present a challenge. Patients with potential transplant donors who are receiving imatinib should be monitored closely. While the exact monitoring schedule is unclear, an approach that 17

Imatinib is a well tolerated drug and devoid of any serious organ specific toxicities. the most frequently reported adverse effects of imatinib in clinical studies include nausea, vomiting, edema (fluid retention), muscle cramps, skin rash, diarrhea, heartburn, and headache. Cytopenia, particularly neutropenia nd hrombocytopenia, a t has been reported in all studies, with a higher incidence in people in blast crisis and the accelerated phase compared with those in chronic phase. In clinical studies, 1% of people in the chronic phase were withdrawn because of adverse events, 2% in the accelerated phase and 5% in the blastcrisis phase. In patients who achieve a complete cytogenetic response, realtime polymerase chain reaction (rt-PCr) is the most sensitive way to continue to monitor their disease and to predict relapse and imatinib resistance. A proportion of patients test negative for BCr-ABL by rt-PCr; however, patients still may have a significant number of leukemic cells remaining despite being rt-PCr negative. the long-term significance of becoming PCr negative on imatinib is not yet known, but evidence so far suggests that these patients will have a good chance of longterm progression-free survival. It seems that the achievement of a major molecular response increasingly will be an important arbiter in directing treatment strategy. Among other things, since Q-PCr on peripheral blood is becoming such an important measure of response, this raises the issue of whether clinicians should continue to do bone marrow assessments on CML patients or whether peripheral blood testing would be sufficient.

Mechanism of action of BCR-ABL and of Its Inhibition by Imatinib. Panel A shows the BCr-ABL oncoprotein with a molecule of adenosine triphosphate (AtP) in the kinase pocket. the substrate is activated by the phosphorylation of one of its tyrosine residues. It can then activate other downstream effector molecules. When imatinib occupies the kinase pocket (Panel B), the action of BCr-ABL is inhibited, preventing phosphorylation of its substrate. ADP denotes adenosine diphosphate.

Vol. 6, Issue 3 April - June 2008

includes annual bone marrow sampling (to screen for secondary cytogenetic abnormalities) and 3 monthly assessments of disease burden (e.g., peripheral blood fluorescence in situ hybridization for BCr-ABL or quantitative PCr if cytogenetically negative) seems a reasonable minimum. In such patients, the lack of an MCr or loss of a hematologic or chromosomal response should be considered grounds for proceeding to alternative therapies like stem cell transplant or a second generation tyrosine kinase inhibitor like dasatinib. there is another issue whether patients who are currently receiving hydroxyurea or IFN-based treatments be switched to treatment with imatinib? the available evidence suggests a strong rationale for making such a recommendation, particularly for hydroxyurea treated and IFN-non responsive patients. Achievement of a complete cytogenetic remission (CCr) is associated with 5- to 10-year survival rates of approximately 50%– 80% and has been a consistent early marker of survival prolongation in Current recommendation is CML patients treated with IFN-based to continue therapy indefiregimens. this clearly indicates nitely as relapses do comthat patients who do not achieve monly occur with disconand maintain CCrs with IFN-based tinuation. therapy should be considered as Dasatinib and nilotinib are candidates for imatinib treatment. newer inhibitors of BCr_ Imatinib therapy has so far surpassed all other non transplant therapeutic options for CML and should be incorporated into all patients’ treatment regimens once the presence and diagnosis of Ph positive CML are confirmed.
ABL tyrosine kinase used for patients who relapse on imatinib. Despite high response rates, relapses on discontinuing therapy indicate these drugs cannot completely eradicate the Ph positive clone.

References 1. goldman J. Management of chronic myeloid leukemia. Semin Hematol 2003;40:1-103. 2. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330-1340. 3. Holyoake tL. recent advances in the molecular and cellular biology of chronic myeloid leukaemia: lessons to be learned from the laboratory. Br J Haematol. 2001;113:11-23. 4. Druker BJ, tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl-tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561-566. 5. Druker BJ, talpaz M, resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCr-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031-1037. 6. Savage Dg, Antman KH. Imatinib mesylate: a new oral targeted therapy. N Engl J Med. 2002; 346:683-693. 7. Peggs K, Mackinnon S. Imatinib mesylate: the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med. 2003;348:1048-1050. 8. Stone rM. Optimizing treatment of chronic myeloid leukemia: a rational approach. Oncologist 2004;9:259-270. 9. Hehlmann r, Berger U, Hochhaus A. Chronic myeloid leukemia: a model for oncology. Ann Hematol. 2005; 84:487497. 10. http://bloodjournal.hematologylibrary.org/cgi/reprint/ blood-2006-02-005686v1.pdf 11. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645-652. 12. Brian J. Druker. Five-Year Follow-up of Patients receiving Imatinib for Chronic Myeloid Leukemia. N Engl J Med 2006; 355:2408-17.

18 Vol. 6, Issue 3 April - June 2008

Modern Radiation Techniques: IMRT and IGRT
GK Rath and DN Sharma
radiation therapy (rt) is one of the three principal modalities of cancer treatment. the goal of rt has always been to confine the radiation dose to tumor-bearing tissues and avoid irradiation of normal tissues and structures. this maximizes tumor control rates and reduces the risk of radiation-induced normal tissue damage1. Advances in modern radiation technology have been focused on delivering the therapeutic dose of radiation in highly conformal fashion. the advent of linear accelerator, Ct scan and computerized treatment planning systems have resulted into the three dimensional conformal rt (3D-Crt). IMrt (intensity modulated radiation therapy) and Igrt (image guided radiation therapy) are the refined variants of 3D-Crt. IMRT: IMrt is the delivery of radiation to the patient via fields that have non-uniLinear accelerator, Ct scan form radiation flu- and computerized treatment ence. IMrt differs planning systems have led from other forms of to the development of three dimensional conformal raradiotherapy in a diotherapy and its more number of impor- advanced versions i.e. IMrt tant areas includ- and Igrt. ing localization of targets and normal tissues, treatment planning, optimization, delivery and treatment verification1. It employs radiation beams with non-uniform intensity which when added together within a patient can produce a dose distribution with a concave IMRT (intensity modulated RT) employs radiation shape. radiotherapy beams with non-uniform planning studies intensity have confirmed the dosimetric advantages of IMrt over conventional or conformal techniques, and recently some studies evaluating its clinical impact have been published2. these have mostly been reports of single-centre experience and some Head & Neck cancer is Phase I/II clinical an ideal model for IMrt. studies that have re- Parotid gland sparing and ported high levels of dose escalation are the usual reasons for using tumor control and/or IMrt. a reduction in normal 20 Vol. 6, Issue 3 April - June 2008 tissue radiation toxicity. IMrt is rapidly becoming part of the standard treatment of patients with prostate and head and neck cancer, particularly in centers in the USA. Published data pertaining to clinical indications of this therapy for head and neck, central nervous system, and lung tumors is now widely available. thoracic and abdominal the main indica- tumors may move up to 3.0 cms due to respiratory tions in head and movements. neck cancer are Igrt makes it possible to parotid gland spar- take tumor motion into acing and dose esca- count during radiation treatment planning and delivery lation to tumors close to organs at risk. For central nervous system tumors, IMrt has been used to reduce normal tissue radiation by more conformal dose distributions. to date, the majority of reports concern patients treated in the context of clinical trials, and for most tumor types longer term follow up of treated patients will be required to confirm the clinical benefits of IMrt. the head and neck region can be readily immobilized, and accurate assessment of set up uncertainties can be Igrt based treatment protomade. this makes cols have been used in management of prostate cancer, head and neck cancer cervix, lung cancer, cancer an ideal head & neck cancer, pancremodel for IMrt atic cancer et. because the tight dose gradients that can be achieved with IMrt can be used to avoid OAr located close to the PtV. Parotid sparing IMrt requires the mean dose to the spared gland to be less than 24–26 gy. this has raised concern about a potential risk of tumor recurrence in the spared area. IGRT: Organ motion is very crucial to radiation therapy planning to avoid overdosing to normal tissues and under dosing to tumor tissue3. thoracic and abdominal tumors may move up to 3.0 cm due to respiratory movements. Various strategies have been used to reduce this uncertainty in treatment planning. One of these is image guided radiotherapy (Igrt). Igrt or Ig-IMrt refers to use of newly emerging radiation planning, patient set up, and delivery procedures that integrate cutting edge image based tumor definition methods, patient

GK Rath Chief Dr Br Ambedkar Institute - rotary Cancer Hospital DN Sharma Assistant Professor Department of Radiation Oncology All India Institute of Medical Sciences New Delhi

positioning devices and radiation delivery guidance tools. In Igrt uncertainties about tumor position in daily treatment are resolved by acquiring volumetric images on the treatment machine. Igrt makes it possible to take tumor motion into account during radiation treatment planning and delivery. Use of MrI, PEt, PEt–Ct based planning enhances the tumor localization leading to accurate image registration. Ct scanners capable of 4D imaging can sort out images according to phase of respiration. Various methods are used during the treatment delivery process itself. Megavoltage radiation based images have been used for treatment verification in two dimensions. Igrt applications in use include cone based Ct systems (CBCt), gating, cyber knife and 4D PEt. Igrt protocols have been evaluated in cancer cervix and use of serial MrI coupled with repeat IMrt planning to account for tumor regression during treatment can lead to significantly lower dose to bladder and rectum. Igrt has been studied for dose escalation in cancer of pancreas with increased local control rate. Lung cancer has been studied using MVCt based tomotherapy and a decrease in tumor volume of 2.3% per day has been documented4. Igrt has also been studied in prostate cancer, cancer esophagus, head and neck cancers. there are still many limitations with current Igrt systems. these systems are still evolving and no one strategy of image guidance is appropriate for all clinical situations. the added cost also needs to be balanced to the likely benefit expected. It needs to be stressed that inappropriate use of these highly conformal techniques may lead to unsuitable margin reduction. Long term consequences and particularly the

debate about likelihood of second malignancies will only be resolved by a long-term follow up. All these innovations in image guidance theoretically lead to better geometric and dosimetric benefits. It promises a new chapter in dose escalation combined with a reduction in treatment morbidities. the facilities of IMrt and Igrt are gaining popularity in India as well. though these facilities are available in limited centers; many centers are fast making effortsto procure these facilities. References 1. Nutting C. Editorial. Intensity-modulated radiotherapy (IMrt): the most important advance in radiotherapy since the linear accelerator? British Journal of radiology (2003) 76, 673. 2. guerrero Urbano Mt and Nutting CM. Clinical use of intensity-modulated radiotherapy: Part I. British Journal of radiology (2004) 77, 88-96. 3. Hematology/oncology clinics of North America: Modern radiation 4. Kupelian P, ramsey C, Meeks S, Willoughby t, Forbes A, Wagner t, Langen K. Serial megavoltage Ct imaging during external beam radiotherapy for non–small-cell lung cancer: Observations on tumor regression during treatment. International Journal of radiation Oncology, Biology, Physics. 63 (4) 1024 – 1028.

21 Vol. 6, Issue 3 April - June 2008

History of Medical Oncology
Shyam Aggarwal
Origin of the word Cancer the origin of the word cancer is credited to the greek physician Hippocrates (460-370 BC)1, considered the “Father of Medicine.” Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In greek these words refer to a crab, most likely applied to the disease Era of cancer because the fingerchemotherapy like spreading projections from 1940 – 1950: the beginning a cancer called to • role of Nitrogen Musmind the shape of tard, the first alkylating a crab. agent, in treatment of I: Cancer chemotherapy 1940–1950
lymphoma described. • Aminopterin and subsequently Methotrexate was first used in 1948 to induce remission in ALL. • roy Hertz and Min ghiu Li used methotexate to cure choriocarcinoma in 1958. the first solid cancer to be cured by chemotherapy. • Joseph Burchenal with the help of 2 pharmaceutical chemists at Memorial Sloan-Kettering discoverd 6-MP, a highly active anti-leukemia drug. • Eli Lily natural products group discovered the anti cancer effects of Vinca alkaloids (Vincristine) • National Cancer Chemotherapy Service Centre at the NCI was created in 1955 by the United States Congress. the NCCSC developed the methodologies and crucial tools for chemo-therapeutic development.

discovered by Lucy Wills, when she was working in India in 19374. It seemed to stimulate the proliferation of acute lymphoblastic leukemia (ALL) cells when administered to children with this cancer. Sidney Farber5 from Harvard demonstrated that aminopterin, a compound related to the vitamin folic acid, produced remission in acute leukemia in children. Aminopterin blocked a critical chemical reaction needed for DNA replication. that drug was the predecessor of methotrexate, a commonly used cancer treatment drug today. When administered to children with ALL in 1948, these agents became the first drugs to induce remission in children with ALL. remissions were brief, but the principle was clear - antifolates could suppress proliferation of malignant cells, and could thereby re-establish normal bone-marrow function. remarkably, a decade later at the National Cancer Institute, Min Chiu Li6 and roy Hertz discovered that the same methotrexate treatment alone could cure choriocarcinoma (1958), a germ-cell malignancy that originates in trophoblastic cells of the placenta. this was the first solid tumor to be cured by chemotherapy. 6-MP and vinca alkaloids: Joseph Burchenal, at Memorial Sloan-Kettering Cancer Center in New York, with Farber’s help, started his own methotrexate study and found the same effects. He then decided to try and develop antimetabolites in the same way as Farber, by making small changes in a metabolite needed by a cell to divide. With the help of george Hitchings and gertrude Elion, two pharmaceutical chemists, many purine analogues were tested, culminating in the discovery of 6-mercaptopurine (6-MP), which was subsequently shown to be a highly active antileukemic drug. the Eli Lilly natural products group found that alkaloids of the Madagascar periwinkle (Vinca rosea), originally discovered in a screen for anti-diabetic drugs, blocked proliferation of tumor cells. the antitumor effect of the vinca alkaloids (eg, vincristine) was later shown to be due to their ability to inhibit microtubule polymerization, and therefore cell division. the United States Congress created a National Cancer Chemotherapy Service Center (NCCSC) at the NCI in 1955 in response to early successes. this was the first centralized program to promote drug discovery for cancer - the NCCSC developed the methodologies and crucial tools (like cell lines and animal models) for chemotherapeutic development.

The Beginning: During World War II, naval personnel who were exposed to mustard gas2 as a result of a military action, on Autopsy observations had revealed profound lymphoid and myeloid suppression. thus, beginnings of the modern era of cancer chemotherapy can be traced directly to the discovery of nitrogen mustard, a chemical warfare agent, as an effective treatment for cancer. Louis S goodman and Alfred gilman reasoned that this agent could be used to treat lymphoma, since lymphoma is a tumor of lymphoid cells. this agent served as the model for a long series of similar but more effective agents (called “alkylating” agents) that killed rapidly proliferating cancer cells by damaging their DNA3,4.
Shyam Aggarwal Senior Consultant Medical Oncologist Sir ganga ram Hospital New Delhi

1950-1960 Antifolates: Folic acid (citrovorum factor), a vitamin crucial for DNA metabolism, had been 23

Vol. 6, Issue 3 April - June 2008

1960-1970

Combination chemotherapy: In 1965, a major break-through in cancer therapy occurred. James Holland, Emil Freireich, and Emil Frei hypothesized that cancer chemotherapy should follow the strategy of antibiotic therapy for tuberculosis with combinations of drugs, each with a different mechanism of action. Cancer cells could conceivably mutate to become resistant to a single agent, but by using different drugs concurrently it would be more difficult for the tumor to develop resistance to the combination. Holland, Freireich, and Frei simultaneously administered methotrexate (an antifolate), vincristine (a Vinca alkaloid), 6-mercaptopurine (6-MP) and prednisone — together referred to as the POMP regimen — and induced long-term remissions in children with acute lymphoblastic leukaemia (ALL). Using randomized clinical studies by St Jude Children’s research Hospital, the Medical research Council in the UK (UKALL protocols) and german Berlin-Frankfurt-Münster clinical trials group (ALL-BFM protocols), ALL in children has become largely a curable disease. this approach was extended to the lymphomas in 1963 by Vincent t DeVita and george Canellos at the NCI, who ultimately proved in the late 1960s that nitrogen mustard, vincristine, procarbazine and prednisone — known as the MOPP regimen — could cure patients with Hodgkin’s and non-Hodgkin’s lymphoma. Currently, nearly all successful cancer chemotherapy regimens use this paradigm of multiple drugs given simultaneously. II: Adjuvant therapy Chemotherapy drugs were most effective when used in patients with tumors of smaller volume. the use of chemotherapy after surgery to destroy the few remaining cancer cells in the body is called adjuvant therapy. Adjuvant therapy was tested first in breast cancer and found to be effective. It was later used in colon cancer, cancer of the testis, and others. Emil Frei first demonstrated this effect - high doses of methotrexate prevented recurrence of osteosarcoma following surgical removal of the primary tumor. 5-fluorouracil, an inhibitor of DNA synthesis, was later shown to improve survival when used as an adjuvant to surgery in treating patients with colon cancer. Similarly, the landmark trials of Bernard Fisher, chair of the National Surgical Adjuvant Breast and Bowel Project, and of gianni Bonadonna7, working in the Istituto Nazionale tumori di Milano, Italy, proved that adjuvant chemotherapy after complete surgical resection of breast tumors significantly extended survival — particularly in more advanced cancer. III: Drug discovery In 1956, C gordon Zubrod, took over the Division of Cancer treatment of the NCI and guided development of new drugs. 24 Vol. 6, Issue 3 April - June 2008

• In 1965 for the first time Holland, Freireich and Frei applied the principle of combination chemotherapy in the management of cancer in the same lines of antibiotic combinations. • they used the POMP regimen to achieve long term remissions in ALL. • With subsequent developments of the UKALL and BFM protocols ALL in children became a curable disease. • the late 1960’s also saw the development of the MOPP regimen by Vincent t DeVita and george Canellos for treatment of lymphomas. • Emil Frei was the first to demonstrate the effect of adjuvant chemotherapy in preventing relapse after surgery for osteosarcoma. • this drastically changed the prognosis of breast and colon cancers in the subsequent years.

Zubrod had a particular interest in natural products, and established a broad program for collecting and testing plant and marine sources, a controversial program that led to the discovery of taxanes (in 1964) and camptothecins (in 1966). Both classes of drug were isolated and characterized by the laboratory of Monroe Wall at the research triangle Institute.

The taxanes: Paclitaxel (taxol) was a novel antimitotic agent that promoted microtubule assembly. this agent proved difficult to synthesize and could only be obtained from the bark of the Pacific Yew tree8, which forced the NCI into the costly business of harvesting substantial quantities of yew trees from public lands. After 4 years of clinical testing in solid tumors, it was found in 1987 (23 years after its initial discovery) • Paclitaxel from the bark to be effective in ovarian cancer of Pacific Yew tree was discovered way back in therapy.
1964, but its clinical utility in ovarian cancer was The camptothecins: Another drug established 23 years later class originating from the NCI was in 1987 only. the camptothecins. Camptothecin, • Camptothecin, an inderived from a Chinese ornamental hibitor of topoisimerase 1, was extracted for the tree, inhibits topoisomerase I, Chinese ornamental tree an enzyme that allows DNA in 1966. However it took unwinding. Despite showing 30 more years in 1996 to promise in preclinical studies, the have a stable analogue of the drug, namely Iragent had little antitumor activity rinotecan for the use in in early clinical trials, and dosing cancers of the colon, lung was limited by kidney toxicity: and ovary. its lactone ring is unstable at neutral pH, so while in the acidic environment of the kidneys it becomes active, damaging the renal tubules. In 1996 a more stable analogue, irinotecan, won Food and Drug Administration (FDA) approval for the treatment of colon cancer. Now, this agent is being used to treat lung and ovarian cancers.

• Paclitaxel from the bark of Pacific Yew tree was discovered way back in 1964, but its clinical utility in ovarian cancer was established 23 years later in 1987 only. • Camptothecin, an inhibitor of topoisimerase 1, was extracted for the Chinese ornamental tree in 1966. However it took 30 more years in 1996 to have a stable analogue of the drug, namely Irrinotecan for the use in cancers of the colon, lung and ovary.

Platinum-based agents: Cisplatin, a platinum-based compound, was discovered by a Michigan State University researcher, Barnett rosenberg, working under an NCI contract. this was yet another serendipitous discovery: rosenberg had initially wanted to explore the possible effects of an electric field on the growth of bacteria. He observed that the bacteria unexpectedly ceased to divide when placed in an electric field. And that the cause was an experimental artifact - the inhibition of bacterial division was

• the period 1970 to 1990 saw the development of various anti-cancer drugs that had established medical oncology as a strong force in the treatment of cancers. • Cisplatin that had practically changed the scenario of chemotherapy for solid cancers, was discovered accidentally. • Other important anti cancer drugs discovered during this period include, carboplatin, nitrosoureas, Fludarabine, topoisomerase II inhibitors (anthracyclines and epipodophyllotoxins)

pinpointed to an electrolysis product of the platinum electrode rather than the electrical field. this accidental discovery, however, soon initiated a series of investigations. Studies on the effects of platinum compounds on cell division culminated in the synthesis of cisplatin. this drug was pivotal in the cure of testicular cancer. Subsequently, Eve Wiltshaw and others at the Institute of Cancer research in the United Kingdom extended the clinical usefulness of the platinum compounds with their development of carboplatin, a cisplatin derivative with broad antitumor activity and comparatively less nephrotoxicity. Nitrosoureas: A second group, with an NCI contract, led by John Montgomery at the Southern research Institute, synthesized nitrosoureas, an alkylating agent which cross-links DNA. Fludarabine-phosphate, a purine analogue has become a mainstay in treatment of patients with chronic lymphocytic leukemia. 1970 to 1990 Anthracyclines and epipodophyllotoxins: Many other molecules were developed, including anthracyclines and epipodophyllotoxins — both of which inhibited the action of topoisomerase II, an enzyme crucial for DNA synthesis. IV: Supportive care during chemotherapy Clinical investigators realized that the ability to manage these toxicities was crucial to the success of cancer chemotherapy as patients receiving these agents experienced severe side-effects that limited the doses which could be administered limiting in the process the beneficial effects. Many chemotherapeutic agents cause profound suppression of the bone marrow. this is reversible, but takes time to recover. Support with platelet and red-cell transfusions as well as broad-spectrum antibiotics in case of infection during this period is crucial to allow the patient to recover. Most of these agents caused very severe nausea (termed chemotherapy-induced nausea and vomiting) which, while not directly causing patient deaths, was unbearable at higher doses. the development of new drugs to prevent nausea (the prototype of which was ondansetron) was of great practical use. the design of indwelling intravenous catheters (eg, Hickman lines, PICC lines, subclavian chemo-ports) allowed safe administration of chemotherapy as well as supportive therapy. V: Bone Marrow Transplantation With the successes of combination chemotherapy and the discovery of many new agents, there was a feeling at this time that all cancers could be treated, if only one could administer the correct combination of drugs, at the correct doses and at the correct intervals. the important contribution during this period was the discovery of a means that allowed the administration of previously lethal doses of chemotherapy. the patient’s bone marrow was first harvested, the chemotherapy administered, and the harvested marrow then returned to patient a few days later. this approach, termed autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, including those with advanced breast cancer, however, rigorous studies have failed to confirm this benefit is no longer widely used for solid tumors. the proven curative benefits of high doses of chemotherapy af25 Vol. 6, Issue 3 April - June 2008

forded by autologous bone marrow rescue are limited to Hodgkin’s disease patients who had failed therapy with conventional combination chemotherapy. However, autologous transplantation continues to be used as a component of therapy for a number of hematologic malignancies. VI: Cancer Treatments: Biologic Therapy the understanding of the biology of cancer cells has led to the development of biologic agents that mimic some of the natural signals that the body uses to regulate Biologic Therapy growth. this cancer treatment, called biological response modifier 1. Interferons (BrM) therapy, biologic therapy, 2. Interleukins 3. Hormonal therapy biotherapy, or immunotherapy, 4. targeted therapy has proven effective for several • tyrosine Kinase Inhibitors cancers through the clinical trial • Monoclonal Antibodprocess. Some of these biologic ies agents, occurring naturally in • radio labelled Monoclonal antibodies the body, can now be produced • toxin labelled Monoin the laboratory. Examples are clonal antibodies interferons, interleukins, and other cytokines. these agents are given to patients to imitate or influence the natural immune response either by directly altering the cancer cell growth or acting indirectly to help healthy cells control the cancer. One of the most exciting applications of biologic therapy has come from identifying certain tumor targets, called antigens, and aiming an antibody at these targets. this method was first used to localize tumors in the body for diagnosis and more recently has been used to attack cancer cells. Scientists are also studying vaccines that would boost the body’s immune response to cancer cells and thereby prevent cancer from developing. Hormonal therapy: the hormonal contribution to several categories of breast cancer subtypes was recognized during this time, leading to the development of pharmacological modulators (eg, of oestrogen) such as tamoxifen. For post menopausal women, aromatase inhibitors are better than tamoxifen. Targeted therapy: Molecular and genetic approaches to understanding cell biology uncovered entirely new signaling networks that regulate cellular activities such as proliferation and survival. Many of these networks were found to be radically altered in cancer cells, and these alterations had a genetic basis caused by a chance somatic mutation. Tyrosine kinase inhibitors: the classic example of targeted development is imatinib mesylate (gleevec), a small molecule which inhibits a signaling molecule kinase. the genetic abnormality causing chronic myelogenous leukemia (CML) has been known for a long time to be a chromosomal translocation creating an abnormal fusion protein, kinase BCr-ABL, which signals aberrantly, leading to uncontrolled proliferation of the leukemia cells. Imatinib precisely inhibits this kinase. Brian Druker9, working in Oregon Health Science University, had extensively researched the abnormal enzyme kinase in CML. He reasoned that precisely inhibiting this kinase with a drug would control the disease and have little effect on normal cells. Druker collaborated with Novartis chemist Nick Lydon, who developed several candidate inhibitors. From these, imatinib was found to

have the most promise in laboratory experiments. First Druker and then other groups worldwide demonstrated that when this small molecule is used to treat patients with chronic-phase CML, 90% achieve complete hematological remission. It is hoped that molecular targeting of similar defects in other cancers will have the same effect. Monoclonal antibodies: Another branch in targeted therapy is the increasing use of monoclonal antibodies in cancer therapy. . Monoclonal antibodies (or proteins) bind to tumor-associated cell surface antigens and destroy tumor cells through a variety of methods. Although monoclonal antibodies (immune proteins which can be selected to precisely bind to almost any target) have been around for decades, they were derived from mice and did not function particularly well when administered to humans, causing allergic reactions and being rapidly removed from circulation. “Humanization” of these antibodies (genetically transforming them to be as similar to a human antibody as possible) has allowed the creation of a new family of highly effective humanized monoclonal antibodies. rituximab, a drug used to treat lymphomas, is a prime example. Liposomal therapy: Liposomal therapy is a new technique that uses chemotherapy drugs that have been packaged inside liposomes (synthetic fat globules). this liposome, or fatty coating, helps them penetrate the cancer cells more selectively and decreases possible side effects (such as hair loss, nausea, and vomiting). Examples of liposomal medications are Doxil (the encapsulated form of doxorubicin) and Daunoxome (the encapsulated form of daunorubicin).

References 1. Abeloff: Clinical Oncology, 3rd ed. Churchill Livingston, 2004. pp 408-413. 2. gilman A. the initial clinical trial of nitrogen mustard. Am J Surg 1963;105:574-8. 3. goodman LS, Wintrobe MM, Dameshek W, goodman MJ, gilman A and McLennan Mt. Nitrogen mustard therapy. Use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia, and certain allied and miscellaneous disorders. J Am Med Assoc 1946; 105:475-476. reprinted in JAMA 1984; 251:2255-61. 4. h t t p : / / e n . w i k i p e d i a . o rg / w i k i / H i s t o r y _ o f _ c a n c e r _ chemotherapy 5. Farber S, Diamond LK, Mercer rD, Sylvester rF, Wolff JA. temporary remissions in acute leukemia in children produced by folic antagonist, 4-aminopteroylglutamic acid (aminopterin). N Engl J Med 1948;238:787–793. 6. Li MC, Hertz r, Bergenstal DM. therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Engl J Med 1958; 259:66–74. 7. Bonadonna g, Brusamolino E, Valagussa P, rossi A, Brugnatelli L, Brambilla C, De Lena M, tancini g, Bajetta E, Musumeci r, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 1976;294:405-10. 8. http://www.botgard.ucla.edu/html/botanytextbooks/ economicbotany/taxus/index.html 9. http://www.hhmi.org/research/investigators/druker_bio. html

26 Vol. 6, Issue 3 April - June 2008

Surgical Oncology and Role of Plastic Surgeon
Manoj Bansal
Significant advances have occurred in the management of advanced cancers in the past two decades. Apart from improving the survival rates, the current therapy emphasizes the preservation or restoration of form and function, thereby improving the quality of life for patients. towards achieving this end, the reconstructive surgeon has made great contributions. Aided by greater understanding of skin perfusion and with the development of new microvascular flaps, reconstructive plastic surgery has redefined the management of malignancies, which has led to the acceptance of a team approach in the treatment of cancers. the Plastic surgeon is an important member of the team, right from treatment planning, to execution and follow up. the role of reconstructive surgery is important in the management of most of the solid tumors except intracranial and intra-abdominal tumors. the head and neck malignancies are the most common the world over and the reconstructive needs are both aesthetic as well as functional. Further, the aggressive management of soft tissue sarcomas and other tumors of thoracoabdominal wall leave huge defects. rapid advancements in the treatment of tumors of breast has shifted the focus from radical mastectomy to breast conserving surgery, and the increased incidence of early onset coupled with greater demand of fulfillment of aesthetic needs has made the role of plastic surgeon all the more important. Evolution of Reconstructive Surgery: During the early period of evolution of plastic surgery, there were limited options available and so primary reconstruction was difficult, unreliable and time consuming. With the development of forehead, deltopectoral and pectoralis major myocutaneous flaps, primary reconstruction of big defects became possible but required at least two stages of surgery. the flaps were limited in size and their reach was limited. With the advent of micro-vascular free flaps, reconstruction was possible in a single stage with matching composite tissue. Head and Neck Reconstruction: Head and neck cancer is one of the leading causes of cancer related deaths and disfigurement especially in Indian subcontinent. Although there has been significant progress in the management of head and neck cancers such as introduction of organ-sparing strategies using concurrent chemo-radiotherapy and biological modulation of cancer with epidermal growth factor pathway interruption, none of the strategies has come 27 Vol. 6, Issue 3 April - June 2008 close to the contribution made by reconstructive surgery. reconstructive surgery has improved the respectability of advanced head and neck cancers leading to an improved quality of life. Largely, current reconstructive techniques can offer predictable results in the restoration of the form and function and are fast approaching the ultimate reconstructive goal of ‘replacing like with like’. Pedicled versus free flaps in head and neck reconstruction: the replacement of the traditional concept of ‘reconstructive elevator’ with the concept of the ‘reconstructive ladder’ has led to the provision of an option of the most appropriate technique of reconstruction as the initial procedure. For many years, pedicled flaps like pectoralis major myocutaneous flap have been the workhorse of head and neck reconstructive surgeons. However, these flaps have some limitations like: 1. Limited reach because of which there are more chances of distal flap necrosis and wound gape due to tension by the downward pull of the flap. 2. Bulk and pliability of the tissue in the flap may not always suit the defect to be reconstructed. 3. Difficulty in contouring the flap to the defect in different planes than that of the pedicled flap. Although all these drawbacks can be overcome by the use of free flaps, the technique is not frequently adapted because of various reasons. Surgical expertise, time factor and questionable benefit in advanced cases with poor prognosis are some of the arguments against the wide use of free flaps. Free flaps are also associated with some drawbacks like the need for vigorous monitoring and re-exploration if required. Oral Cancers Surgery is the mainstay for the treatment of oral cancers. Functional and aesthetic outcomes of surgical resections can be made more acceptable by immediate reconstruction using local and distant flaps. tongue can be reconstructed after hemi- or even total glossectomy using pectoralis major flap (pedicled) or radial artery forearm flap (free flap). radial forearm flap can be used even as sensate flap for tongue. Likewise other defects of buccal mucosa, hard palate or floor of mouth can be reconstructed using various flaps to give good functional result.

Manoj Bansal Senior Consultant Plastic Surgeon Pushpanjali Medical Centre Delhi

Mandibular Reconstruction the reconstructive needs and choice of flap depends on the site of defect and the dentate status of the patient. A lateral defect distal to the premolar teeth, especially in edentulous patient can be reconstructed using pedicled flaps like pectoralis major myocutaneous flap and trapezius flap. However, lateral defects in dentate patients and anterior mandibular defects require skeletal reconstruction. Fibula osseous or osteocutaneous flaps have become the favored methyod in centres across the world. Breast Reconstruction the incidence of breast cancer is on the rise and the age at which it occurs is on the decline. this means there are more breast cancer patients who are of a younger age group. With the increasing awareness of self image, these patients prefer immediate breast reconstruction after surgery. Such reconstruction should aim at resulting in an aesthetic outcome that matches the patients’ expectations and without interfering in the oncologic treatment. Autologous tissue, implants or both are used for reconstruction. It can be done immediately, ie, at the time of mastectomy or in a delayed fashion, which depends on various factors. Immediate reconstruction It is ideal for patients with early disease (stage I or II). Advantages 1. Decreases psychological trauma 2. reduced cost 3. Less morbidity 4. Better survival 5. Better aesthetic result Disadvantages Potential for delay of adjuvant therapy if postoperative complications occur. Relative contraindications 1. Advanced breast cancers stage III or more. 2. requirement of postoperative radiation. 3. Medical o-morbidities uch s evere besity, ardiopulmonary c s a s o c disease and diabetes.

Delayed reconstruction It is usually performed several months after the mastectomy. Advantages 1. Fewer complications as compared with immediate reconstruction. 2. Final pathology results of the breast cancer are available. therefore more informed decision regarding reconstruction in the context of the entire treatment regimen could be made. Disadvantages 1. Prolongs overall treatment of patient 2. radiation changes may compromise the skin envelop, thus resulting in a poorer final aesthetic outcome. 3. technically more challenging. 4. requires at least two stages and therefore is less cost effective. Methods of breast reconstruction 1. Direct implant placement without tissue expansion - usually not possible due to availability of limited amount of skin cover. 2. tissue expansion followed by permanent implant placement - most common. 3. Autologous tissue reconstruction using pedicled flaps - Latissimus dorsi flap, transverse rectus Abdominis myocutaneous flap (trAM flap) 4. Free flaps - Free trAM flap • Deep inferior epigastric artery perforator flap • Superficial inferior epigastric artery perforator flap • Superior gluteal artery perforator flap • Inferior gluteal artery perforator flap • transverse upper gracilis flap In summary, the role of reconstructive plastic surgeon should be consistently viewed as an integral part of the team looking after cancer patients. References 1. Kiyonori Harii. the role of plastic surgery in surgical therapy for cancer patients. Jpn. J. Clin. Oncol.1990; 20: 4857

28 Vol. 6, Issue 3 April - June 2008

Idiopathic Perforation of Gall Bladder
A Case Report
AK Mittal
gall bladder perforation is an infrequent but fatal disease. It is usually a complication of acute cholecystitis with or without stone and rarely reported in association with trauma neoplasm chemotherapy or vascular disease. Idiopathic perforation of gall bladder without any demonstrable cause is worthy of reporting. History A healthy male aged 40 years presented in the Shivam Surgical and Maternity Centre, Karkardooma, New Delhi in Emergency with severe pain in abdomen with occasional vomiting. He had a history of high-grade fever of 104°F. there was no history of trauma or of drug abuse of long duration. the patient went from one hospital to another receiving symptomatic treatment on an outpatient basis. Examination On clinical examination, he was found to have generalized pain in abdomen with mild distension. Vitals were maintained with temperature at 99°F. tachycardia and generalized tenderness all over abdomen was also reported. Investigations tLC 11900, P91 L4 e4 m4, blood urea 95, creatine 2 mg, Na 135, k 3.2, s. amylase 62.2, l.f. normal, and ultrasound showed free fluid in peritoneal cavity with gall bladder edema with sludge. Ultrasound guided fluid aspiration revealed purulent greenish color. A plain x-ray abdomen erect did not show any gas under diaphragm. Diagnosis Keeping in mind that the diagnosis could be perforated appendix or small bowel sealed perforation, high risk consent was taken and exploratory laprotomy done with right mid paramedian incision. Operative findings were that the small bowel and appendix were normal, bilious colored fluid about 500 ml was sucked out keeping in mind that it could be sealed duodenal perforation. Upper abdomen was explored but duodenum was found to be normal. there was a small perforation in the gallbladder showing bile leak. Cholecystectomy was done and the abdomen was closed after thorough peritoneal wash with a drain in. Postoperative recovery was good and uneventful. gall bladder was thick, edematous with small gangrenous patch with a perforation, cut gallbladder showed small sludge without any stone. Patient improved well, his renal function returned to normal in 48 hours. the biopsy report was Acute cholecystitis with glandularis proliferans. Discussion Perforation of gall bladder is reported 3 to 10% of 29 Vol. 6, Issue 3 April - June 2008 cases and is usually associated with presence of stone in gall bladder. Mortality is 12 to 16%. It is believed that initial inflammation is chemically induced and thereafter followed by secondary infection mostly E.coli and streptococcus faecalis. In rare cases, cholecystitis may occur without stone. this may be because of infection else where in body leading to mucosal inflammation, ischemia, necrosis and finally perforation. In 1934, Neimmer presented his classic description of gall bladder perforation and mentioned that non obstructive cholecystitis is unlikely to become perforated. Intense inflammation with virulent infection and existence of immunocompromised state leads to thrombosis of blood vessels and transluminal necrosis and perforation. gall bladder perforation without any apparent cause is supposed to be rare and presents a difficult problem for diagnosis and management. It is often misdiagnosed as acute appendicitis and at times as sealed duodenal perforation. the younger patient in an immunocompromised patient has a higher incidence of perforation. Peritonitis due to gall bladder perforation is associated with high mortality as quoted by Essen high (39.1%). the reason for this could be that acalculous chocystitis is associated with severe infection and delay in diagnosis. My patient, a young male, suffered high grade fever for one day with pain in abdomen. He went from one hospital to another hospital in search of treatment. He was diagnosed when we aspirated ultrasound guided purulent greenish fluid, and decided to explore further, keeping in mind that it may be a perforation of the small bowel or a perforated appendix. It was per operative diagnosis that gall bladder was found perforated with the abdomen full of greenish fluid. Delay in surgical intervention is a major reason for high mortality and morbidity. In case of this patient, who was toxic with renal impairment, we operated upon after high risk consent. Post operative recovery was good as we gave good coverage of antibiotic therapy. the patient was discharged on the sixth day. References
1. tsai CJ, Wu CS. risk factors for perforation of gallbladder. A combined hospital study in a Chinese population. Scand J gastroenterol 1991;26:1027-34. 2. Simmons tC, Miller C, Weaver r. Spontaneous gall bladder perforation. Am Surg, 1989 May;55(5):311-3. 3. Croley gg. gangrenous cholecystitis: Five

AK Mittal Laparoscopic Surgeon and Urologist Shivam Surgical and Maternity Centre New Delhi

patients with intestinal obstruction. Am Surg. 1992 May;58(5):284-92. 4. Babb rr. Acute acalculous cholecystitis: A review. J Clin gastroenterol 1992; 15: 238-41.

Acute Pancreatitis: Imaging
Parveen Gulati and Shailender Chaturvedi
Acute pancreatitis is an acute inflammatory condition of the pancreas. Diagnosis of acute pancreatitis is usually made clinically. radiology has four major roles in patients with acute pancreatitis. 1. Contributing to the diagnosis where clinical findings are equivocal. 2. Staging of the severity of the inflammatory process. 3. Detection of the cause and complication. 4. Interventional treatment of the complications. Conventional abdominal radiograph and barium studies are occasionally useful in diagnosing acute pancreatitis and in detecting late complications [abscess, stricture, fistulas]. these, however, have no role in early evaluation of the severity, which is crucial for management. Ultrasound is usually indicated early in patients with acute pancreatitis to look for the presence of gallstone/CBD stones. Pancreatic enlargement, necrosis, abscess and fluid collection can also be seen on ultrasound examination, but visualization is often impaired because of overlying bowel gas, making the detection of intra-pancreatic abnormality and retroperitoneal collections, difficult. Imaging procedures are usually not relied upon as most cases of acute pancreatitis are diagnosed clinically. However, often the history and presentation of the patient may not be straight forward, and a reliable imaging modality is needed to establish the diagnosis. • In patients with mild pancreatitis, Ct adds little as the disease process in such cases usually regresses spontaneously and recovery is complete.
Parveen Gulati Director Imaging Pushpanjali Crosslay Hospital Clinical Diagnostic Centre M r Centre - green Park, New Delhi Shailender Chaturvedi Consultant Radiologist M r Centre - green Park New Delhi

and has now become indispensable and integral part of new classification system. • the extent of pancreatic inflammation on early scanning correlates well with subsequent fluid replacement requirement and pseudo cyst development. Acute edematous or interstitial pancreatitis is seen as diffuse or focal swelling of the pancreas with or without obliteration of peripancreatic fat planes and with or without peripancreatic fluid collection or phlegmon formation. When the fluid becomes loculated and shows welldefined enhancing wall it is called pseudocyst, which can be seen anywhere in the abdomen or even in the chest or the thigh, however most commonly seen in lesser sac and left anterior pararenal spaces. Hemorrhage is seen as hyperdense area on plain Ct images. Pancreatitis is graded in five distinct groups from A to E, which fairly correlates with the severity of the disease, clinical follow up findings, morbidity and mortality. Bolus enhanced CT has shown overall accuracy of 87% with a sensitivity of 100% for detection of severe pancreatic necrosis, which falls to sensitivity of 50% if only minimal necrosis is there. Most patient with severe pancreatitis exhibit one or several pancreatic fluid collections (grade D and E) on the initial Ct study. Pancreatic necrosis is seen as area of nonenhancement on IV bolus contrast enhanced Ct scan. Pancreatic necrosis can be differentiated from abscess as abscesses are more homogeneous and show well defined enhancing walls. the extent of pancreatic necrosis is quantified into <30%, 30-50% & >50% of the pancreatic gland. the accuracy of CT for assessing the presence and extent of pancreatic parenchymal injury depends on several factors, with the most important being the quality of the study. Intravenous contrast material is essential, particularly in patients with severe pancreatitis1 to enable visualization of pancreas and differentiation of the gland from heterogeneous collection or fluid and peripancreatic inflammatory tissue. Pancreatic necrosis is seen as area of nonenhancement. Smaller area of fluid collection

• In patients who do not improve within 24 to 36 hours Ct is warranted. • In patients with uncertain diagnosis or suspected severe pancreatitis, Ct is of great help to look for extent of necrosis, haemorrhage, collections, pseudo cyst formation and other complications. Ct with bolus IV contrast enhancement exactly depicts and quantifies the pancreatic injury 31

Vol. 6, Issue 3 April - June 2008

within pancreatic parenchyma sometimes mimics necrosis and should not be mistaken. Ct scan done early within 12 hours may not show necrosis well, as it develops after 24-48 hours only. Ct does not help and is not used to assess the extent of retropancreatic fat necrosis. In practice, all heterogeneous areas of peripancreatic collections are considered areas of fat necrosis unless proved otherwise. Infective complications of the pancreatitis are uncommon but life threatening. Overall incidence of pancreatic abscess is 4%, which increases with severity of the attack and can be as high as 50-70% in a fatal case of necrotizing pancreatitis. Pancreatic abscess is different from infected necrosis as it has more defined focal pus collection with definite enhancing walls; infected necrosis, on the other hand, is a diffuse inflammation in the pancreas and peripancreatic region with less defined walls. Pancreatic abscess seldom occurs before five weeks of symptoms by which time the symptoms of acute pancreatitis have already subsided. Pulmonary and renal insufficiency is also relatively uncommon in patients with abscess formation. A variety of Ct findings help diagnose the abscess. Most diagnostic Ct findings lie in demonstration of gas in pancreatic or peripancreatic region, which is produced by gas forming bacteria. the gas however, can arise from fistulous communication with bowel loop also. If gas is not present and if the patient has high persistent fever and high leucocyte count, Ct guided aspiration of the collection is strongly recommended. Pancreatic abscess usually requires surgical debridement. Ct guided percutaneous drainage however may play an initial role. Fluid collection and pseudocyst formation can occur within or adjacent to the pancreas. Pseudocysts are the collection of necrotic tissue, old blood and pancreatic secretions. these secretions are rich in proteolytic enzymes and become loculate in lesser sac or may extend along retroperitoneal tissue planes in any direction. Pseudocysts have been reported in the mediastinum, neck and even in the groin. they can also be present intramurally in bowel loops leading to obstruction. A mature pseudocyst has a well defined wall of granulation tissue and fibrosed tissue. Both Ct and USg have been reported to be good in following up the phlegmon and pseudocyst. In most of the cases pseudocyst resolves within 4 weeks. Pseudocysts that persist beyond six weeks need to be drained. Percutaneous catheter drainage can also be performed which is associated with lesser morbidity and mortality and a cure rate of above 70%. Some of the collection communicate with the pancreatic duct. If pancreatic duct–fluid communication is demonstrated by ErCP and there is no ductal obstruction between papilla and its communication, then the percutaneous drainage is usually successful. If the downstream duct is partially obstructed or if an isolated fistula to the upstream pancreatic duct is subsequently recognized, distal pancreatectomy will usually be necessary. While inserting the catheter, traversing the adjacent organ should be avoided. Vascular involvement by pancreatitis is not uncommon. Major peripancreatic and intrapancreatic arteries and veins may be eroded or thrombosed by the direct effect of pancreatic enzymes. this can lead to hemorrhage due to vascular erosion, rupture of varices or leakage from arterial pseudoaneurysm. Contrast enhanced Ct, Doppler and angiography help identify the vascular complications. 32 Vol. 6, Issue 3 April - June 2008

gastro-intestinal involvement by pancreatitis is frequent. gastrointestinal tract can be involved by direct extension of the inflammatory process from the contiguous pancreas resulting in perforation, necrosis or edema of the wall of the stomach or bowel. It can also be secondarily involved by dissection of the pancreatic enzymes through mesenteric attachments or by thrombosis or stenosis of mesenteric arteries and veins resulting in ischemia, necrosis or perforation. Major venous thrombosis can be readily picked by bolus contrast enhanced Ct seen as hypodense filling defect. the ischemic bowel can also be diagnosed on bolus contrast enhanced Ct which appear as thick walled edematous long segment of bowel loop with reduced enhancement of the wall, relatively increased enhancement of the mucosal and serosal lining and obliteration of the surrounding fat planes. Biliary duct involvement: Edema in the head of the pancreas caused by acute pancreatitis can cause transient compression of the CBD. the CBD may be directly involved in acute necrotizing pancreatitis leading to stenosis or destruction. In such cases surgical or non operative drainage is necessary to avoid secondary biliary cirrhosis. Biliary duct ischemia can be detected by USg, Ct or Direct cholangiography using ErCP or PtC. Role of MRI: recent advancements in MrI technology with development of parallel imaging and superb breath hold scans have made MrI an excellent tool to evaluate the pancreas. A big advantage is lack of radiation, superb soft tissue contrast delineation of pancreatico billiary ductal anatomy and demonstration of vascular complications without giving contrast. MrI can detect the presence and extent of necrosis and peripancreatic fluid collections and is superior to Ct in the detection of mild acute pancreatitis. the sensitivity and specificity of CECt and MrI has been found to be almost same. MrI is superior to Ct in demonstrating the underlying etiologies, such as choledocholithiasis or pancreatic divisum. the major limitation of MrI is in evaluation of very sick patients on life support. To summarise, contrast enhanced Ct presently is the imaging modality of choice to help stage the severity of inflammatory process, direct pancreatic necrosis and depict local complications However MrI is fast replacing the CECt in number of these patients. Ct severity index has shown to be an excellent correlation between the development of local complication and the incidence of mortality. Non-surgical intervention can be performed under USg and Ct guidance with reduced mortality and morbidity as compared to the surgical intervention. At present, contrast enhanced Ct has become an integral part and almost indispensable in assessing the initial injury and thus to help in proper management of the patient.

References 1. Balthazar EJ. Acute Pancreatitis: Assessment of Severity with Clinical and Ct Evaluation. radiology 2002;223:603.

Medical News Physical Therapy for the Family Clinician
“Physical therapists are an integral part of inpatient and outpatient treatment of neurological and musculoskeletal injuries and disabilities, “write Scott E. rand, MD, from the Conroe Medical Education Foundation in Conroe, texas, and colleagues. “they also can assist with an augment the care of patients with cardiac, pulmonary, and developmental disorders. Family physicians should have some understanding of the various treatments and modalities used by physical therapists.” Although existing guidelines recommend physical therapy as part of the treatment regimen for musculoskeletal conditions, these lack specific recommendations regarding which exercises and adjunct modalities should be used. to decrease pain and increase mobility and flexibility, physical therapists use specific techniques and modalities. In patients with low back pain, some studies suggest that having physical therapists instruct patients on how to perform specific exercises may improve outcomes. Evidence of efficacy is variable for most modalities, and there is a death of randomized controlled trials to support their use. Because any given clinical condition may benefit from use of several different modalities, treatment decisions for an individual patient should be based on the expertise of the therapist, availability of the equipment, and goals set by the attending clinician. When prescribing physical therapy, the clinician should specify the diagnosis (using proper coding to allow for accurate insurance billing and reimbursement); type, frequency, and duration of the prescribed therapy; specific protocols or treatments that the clinician wants the therapist to use; therapeutic goals; and safety precautions, such as joint range-of-motion limitations, weight-bearing limitations, and illnesses that affect participation in therapy). For a therapist to perform the requested services, clinician signature and date are required. Frequently used modalities of physical therapy include ultrasound, phonophoresis, iontophoresis, electrical stimulation, and lowlevel laser therapy. In ultrasound therapy, high-frequency sound waves are used to warm superficial soft tissues or with the intention of facilitating tissue healing at the cellular level. Ultrasound may be useful for tendon injuries or for short-term pain relief of muscle strain or spasm, but it should not be used near malignant tumors, nerve tissue in a patient who has recently had a laminectomy, 34 Vol. 6, Issue 3 April - June 2008 joint replacements, permanent pacemakers, thrombophlebitis, eyes reproductive organs, areas of acute inflammation, epiphyseal plates, or over breast implants. For Olympic athletes, exemption is needed for use of ultrasound. Phonophoresis refers to use of ultrasound to deliver therapeutic medications to subcutaneous tissues. this modality may be useful for inflammatory conditions including tendonitis, arthritis, and bursitis, and contraindications are the same as for ultrasound. During iontophoresis, an electric current helps deliver ionically charged substances through the skin to reach deeper tissues. therefore, it may be indicated for calcific tendinopathy, inflammatory conditions, or hyperhidrosis. Contraindications to use of iontophoresis include allergy or sensitivity to the substance being applied, open wounds, or impaired sensation. Iontophoresis also should not be used in the immediate vicinity of metallic implants, wires, or staples. Electrical stimulation causes a therapeutic effect by generating an action potential in nerve tissue, thereby causing a muscle contraction or change in sensory input. Electronic muscle stimulation may be useful for muscle spasm or contusion, whereas transcutaneous electrical nerve stimulation may help relieve neuropathic pain. Electrical stimulation is contraindicated in patients with cardiac pacemakers, known cardiac arrhythmias, or thrombophlebitis or thrombosis. It should not be used at all on the abdomen or pelvis of pregnant patients, and it should be used only with caution in patients with cardiac disease, malignant tumors, open wounds, or in those with impaired sensation, cognitive function, or communication ability. Low-level laser therapy acts via absorption of photon radiation, thereby affecting cellular oxidative metabolism and reducing concentrations of prostaglandin E2. this modality may be effective for minor musculoskeletal pain, carpal tunnel syndrome, osteoarthritis, or rheumatoid arthritis. However, it should be used with caution in patients with malignant tumors or in those being treated with anticoagulants, corticosteroids, or immunosuppressants, and it should not be used on the uterus of pregnant patients. Patients and therapists should use safety goggles to limit eye exposure to therapeutic wavelengths. Specific clinical recommendations are as follows: • Supervised therapeutic exercise improves outcomes in patients who have osteoarthritis or claudication of the knee (level of evidence, B). Compared with home exercise has been

Study Report

shown to improve walking speed and distance. • Compared with usual care, iontophoresis is associated with improved outcomes in patients with myositis ossificans (level of evidence, B). • In patients with osteoarthritis and rheumatoid arthritis, low-level laser therapy has been demonstrated to offer limited benefit (level of evidence, B). this modality has been associated with symptomatic benefit in the treatment of several inflammatory conditions, without known adverse effects. Better standardization should help define the role of this modality. “the frequency and duration of physical therapy treatments will vary based on the patient’s condition,” the study authors conclude. “Acute muscle strains often benefit from daily treatment over a short period, whereas chronic injuries are usually addressed less frequently over an extended period…it is important for the physical therapist to document the patient’s progress so that the physician can modify the care plan, if needed.” Clinical Context: For patients with neurologic and musculoskeletal injuries and disabilities, physical therapy is a cornerstone of management. In addition, physical therapy can be useful in the treatment of patients with cardiac, pulmonary, and developmental conditions. therefore, it is useful for family practitioners and primary care providers to be familiar with available modalities of physical therapy and treatment regimens, and indications and contraindications for their use. treatment decisions for an individual patient should be based on the expertise of the therapist, availability of needed equipment, and goals set by the attending clinician. the present review describes recommended use of various modalities of physical therapy and necessary components of a physical therapy prescription. Study Highlights • the physical therapy prescription should include diagnosis (with proper coding for accurate insurance billing and reimbursement); type, frequency, and duration of the prescribed therapy; preferred protocols or treatments; therapeutic goals; and safety precautions (eg. Joint rangeof-motion and weight-bearing limitations, and concurrent illnesses). For a therapist to perform the requested services, clinician signature and date are required. Frequency and duration of physical therapy treatments vary based on the patient’s condition. Acute muscle strains may benefit from a short period of daily treatment, whereas less frequent treatment during a longer period is appropriate for chronic injuries. the physical therapist should document the patient’s progress so that the clinician can modify the care plan as needed. In ultrasound therapy, high-frequency sound waves warm superficial soft tissues or promote tissue healing at the cellular level. Ultrasound may be useful for tendon injuries or for shortterm pain relief of muscle strain or spasm. It should not be used near malignant tumors, nerve tissue in a patient who has recently had a laminectomy, joint replacements, permanent pacemakers, thrombophlebitis, eyes, reproductive organs, areas of acute inflammation, epiphyseal plates, or over breast implants. Exemption is needed for use of ultrasound in Olympic athletes. Phonophoresis, or ultrasound used to deliver therapeutic medications to subcutaneous tissues, may be useful for inflammatory conditions (eg, tendonitis, arthritis, and bursitis). Contraindications are the same as for ultrasound. 35 Vol. 6, Issue 3 April - June 2008

•

•

• •

•

•

• •

•

• •

•

•

During iontophoresis, electric current delivers ionically charged substances through the skin to deeper tissues. It may be indicated for calcific tendinopathy, inflammatory conditions, or hyperhidrosis, and is contraindicated for allergy or sensitivity to the applied substance, open wounds, or impaired sensation. It should not be used near metallic implants, wires, or staples. Electrical stimulation generates an action potential in nerve tissue, which causes a muscle contraction or change in sensory input. Contraindications are cardiac pacemakers, cardiac arrhythmias, thrombophlebitis, thrombosis, and abdominal or pelvic use in pregnancy. It should be used only with caution in patients with cardiac disease, malignancy, open wounds, or in those with impaired sensation, cognition, or communication. Electronic muscle stimulation may relieve muscle spasm or contusion; transcutaneous electrical nerve stimulation may help neuropathic pain. Low-level laser therapy acts via absorption of photon radiation, affecting cellular oxidative metabolism and reducing concentrations of prostaglandin E2. It may be effective for minor musculoskeletal pain, carpal tunnel syndrome, osteoarthritis, or rheumatoid arthritis. Low-level laser therapy should be used with caution in patients with malignant tumors or in those being treated with anticoagulants, corticosteroids, or immunosuppressants. It should not be used over the uterus of pregnant patients. Safety goggles are needed to limit eye exposure to therapeutic wavelengths. Supervised therapeutic exercise improves outcomes for osteoarthritis or claudication of the knee. Supervised therapeutic vs home exercise has been shown to improve walking speed and distance. Iontophoresis vs usual care improves outcomes in patients with myositis ossificans. In osteoarthritis and rheumatoid arthritis, low-level laser therapy has been shown to provide limited benefit, without known adverse effects. Better standardization should be helpful. A physical therapy prescription should include diagnosis; type, frequency, and duration of the prescribed therapy; specific protocols or treatments that the clinician wants the therapist to use; therapeutic goals; and safety precautions. For a therapist to perform the requested services, clinician signature and date are required. Supervised therapeutic exercise improves outcomes in patients who have osteoarthritis or claudication of the knee. Compared with usual care, iontophoresis is associated with improved outcomes in patients with myositis ossificans. In patients with osteoarthritis and rheumatoid arthritis, lowlevel laser therapy has been demonstrated to offer limited benefit. Level of evidence for all of these recommendations is grade B.

•

•

Target Audience: this article is intended for primary care clinicians, physiatrists, physical therapist, neurologists, orthopedists, rheumatogists, and other specialists who care for patients with musculoskeletal and other conditions requiring physical therapy. goal: the goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care. Source: Barclay L. Physical therapy modalities helpful for the Family clinician to know. Accessed: http://www.medscape.com/ viewarticle/567325. Various treatments and modalities that a family clinician should know and include in physical therapy orders are reviewed in an article published in the December 1 issue of the American Family Physician.

• •

Pushpanjali Health Care Events and Initiatives
Welcome!
Pushpanjali Healthcare is proud to welcome young Dr. gaurav Aggarwal who on completing his MD in Medicine has taken over as Medical Director of Pushpanjali Medical Centre Heart & trauma Hospital. team Pushpanjali wishes the new Medical Director great success in his new role assignment.

Dr. Anish Aggarwal making his presentation

Lecture on Multi disciplinary Approach to Pain Management
Pushpanjali Crosslay Hospital and IMA East Delhi branch organized a lecture on “Multi disciplinary Approach to Pain Management” by Dr. Arvinder Singh, Director, Diagnostic and Interventional Pain Management and rehabilitation, New York, USA.

of the same were put across by Dr. Aggarwal, inviting lots of questions and interaction among the audience. the lecture was sponsored by Sanofi Aventis.

Sunday May 11th, 2008 was fixed for the religious Anushthan of Pushpanjali Crosslay Hospital.
Dr. PD garg and Atul gandotra were assigned the responsibility of organizing the event. this included working on the list of invitees, designing invitations, delegating work related to the dais, PA system, media, tent, catering etc. the planning and action under the overall leadership of Dr. Vinay Aggarwal started six weeks before the D-Day. Every member of Crosslay not only happily accepted their assigned roles but worked with diligence and initiative. the execution of the event was typical of a programmed conveyor belt, despite a heavy shower and thunderstorm the night before. A team of learned pujaris from Brindaban started a Yagna in the premises of PCH from 9 in the morning under the overall responsibility of Mr. Kaushik, who worked with total devotion

Dr. Arvinder delivering his talk

the lecture was attended by over 100 practicing physicians from across East Delhi and adjoining areas. Dr. M Abbass, President, IMA and Dr. SN Mishra, Secretary-general, IMA were also present.

Guest Lecture on “The Enigma of Spondyloarthro-pathies”
Carrying on with the legacy of CME, yet another guest lecture for medical practitioners was organized on 20th April, 2008 at IMA EDB Bhawan. Eminent and well known rheumatologist Dr. Anish Aggarwal discussed “the Enigma of Spondyloarthropathies” and other rheumatic conditions with a very interested audience. In a very lucid manner the attributes of rheumatism besides management approach 36 Vol. 6, Issue 3 April - June 2008

Vaasthu anushthan puja being performed

and dedication. the Yagna concluded in the presence of Didi Maa Sadhavi r i t a m b h a r a , Shri rajnath Singh Ji, PCH leadership and family members at 11.30 am on the day of the inauguration. Dr. Vinay Aggarwal escort Shri Ashok Singhal Ji to the dais In the meantime, invitees arrived at the main pandal in large numbers with each one being received at the entrance and personally greeted. Over

Shri Indresh Kumar and other distinguished guests appreciated the initiative and courage of the entire team for undertaking such a gigantic challenge of putting up a healthcare facility that is not only timely but also a boon to community. Each one of them wished PCH great success and wanted PCH to become a role model among healthcare facilities across the world. the function was followed by Preeti Bhoj. Despite the day being hot and humid, everyone thoroughly enjoyed the afternoon. Smiles of satisfaction was there to be seen on the face of every team member and the leadership for putting up a fine show as a well-knit team.

first Dr Lucy Oommen Award
St. Stephen’s Hospital conferred the First Dr. Lucy Oommen Award for excellence in Mother and Child Care for 2008 to Dr. Sharda Jain in recognition of her distinguished service in the area of women’s health. Dr. Sharda Jain has worked at length in areas of social upliftment and public education on issues like female feticide. Dr. Sharda Jain in her moment of glory It is a matter of great pride and honor that Dr. Jain was thus felicitated.

Dr. Vijay Agarwal Executive Director Pushpanjali Crosslay Hospital addressing the audience

1700 guests besides Pushpanjali Healthcare team and their respective families attended the function. Dr. Vijay Agarwal briefed the dignitaries on the dias, media and guests on salient features of PCH and the same was lauded by one and all. Didi Maa Sadhavi ritambhara blessed PCH and the leadership while Shri rajnath Singh (Chief guest), Dr. ramesh Pokhryial,

Ist Inter Hospital Nursing Quiz Contest
the 1st Inter Hospital Nursing Quiz Contest held on May 7 (Preliminary round) and May 14 (grand Finale) was a runaway success. the Quiz Contest involved over 10 top corporate hospitals of NCr with over 60 participants. Cecily Babu of Artemes Hospital gave a tough fight in the finals to other four finalists and won the championship that was commemorated with a beautiful rotating trophy and a cash award of rs. 10,000. Congratulations to Cecily! Now – PCH Nurses have a big challenge to bring back the rotating trophy in 2009 to the home ground!

Didi Maa Sadhvi Ritambhraa Dr. Vinay Aggarwal and Shri Rajnath Singh on the dais

Ancy receives trophy for winning nurses quiz from Akhil Jain

37 Vol. 6, Issue 3 April - June 2008

20th June 2008 - Dyspepsia – An approach to management A Lecture by Dr. Dinesh Sinhal & Dr. Pankaj Tyagi Chaired by : Dr. Neeraj Jain
A guest Lecture by Dr. Dinesh Singal and Dr. Pankaj tyagi was organized on 20 June, 2008 at the Indian Medical Association, East Delhi Branch under the aegis of the continuing Medical Education Programme. Dr. Neeraj Jain, Sr. Consultant in the department of gastroenterology at Pushpanjali Medical Centre and Pushpanjali Crosslay Hospital chaired the session. Dr. Dinesh Singal and Dr. Pankaj tyagi spoke on the topic “Dyspepsia – An approach to management”. Over 75 medical professional from East Delhi attended the lecture.

26th July 2008
Spreading the message of “Living Beautifully”, A lecture session by Dr Dinesh Bhargava was organized by Shri Krishn Medical & research Centre under the leadership of Dr Harihan at Mayur Vihar Phase – 1. Over 100 ladies of all age groups attended the session which was highly interactive and aroused lot of interest among participants regarding benefits from Aesthetic Surgery as it facilitates living beautifully both physically and mentally.
Chairperson Dr. Neeraj Jain sharing his experiences

An interactive session followed the lecture, where the queries and doubts of the audience regarding this issue were answered. the event was sponsored by Sun Pharma.

1st July 2008 A “Red Letter Day” for Pushpanjali Healthcare
Dr Vinay Aggarwal, our ever ebullient and vibrant leader was honored with Dr B C roy Award on Ist July, 2008 by Dr Pratibha Patil, President of India at a glittering function at rashtrapati Bhawan, New Delhi.

Dr. Dinesh Bhargava addressing the delegates

Health is certainly more valuable than money, because it is by health that money is procured; but thousands and millions are of small avail to alleviate the tortures of the gout, to repair the broken organs of sense, or resuscitate the powers of digestion. Poverty is, indeed, an evil from which we naturally fly ; but let us not run from one enemy to another, nor take shelter in the arms of sickness. Johnson

38 Vol. 6, Issue 3 April - June 2008

Guidelines for Submission of Manuscripts

You are invited to contribute your articles, case reports, clinical experiences and any other relevant material which is for the benefit of clinical community at large. the articles/ contribution should be sent to: The Editor in-Chief Dr. Vinay Aggarwal & The Editor Dr Ashok Grover PUSHPANJALI MEDICAL PUBLICAtIONS PVt. LtD. A-14, Pushpanjali, Vikas Marg Extn. Delhi – 110092 E-mail : [email protected] [email protected] Manuscripts can be submitted by e-mail, but it is mandatory that photographs (if any) should be submitted in glossy paper by post. to maintain the uniformity the articles, authors should follow the following pattern: All Manuscripts submitted to Medi-Focus should not have been published in any form in any other publication, and become the property of the publishers. All manuscripts must be accompanied by the following written statement signed by all the authors. “the undersigned author (s) certify (ies) that the article is original, is not under consideration by any other journal, and has not been previously published. All copyright ownership of the manuscript entitled (title of article) is hereby transferred to the publishers of Medi-focus.” Articles will be edited for style and grammar. technical jargon is to be kept to a minimum. American spellings are used in the Journal.

Structured Abstract. Should be a factual condensation of the entire work with objective, methods, results, conclusions and should be in one para. the abstract should state the purposes of the study or investigation, basic procedures (selection of study subjects or laboratory animal; Observational and analytical methods), main findings (giving specific data and their statistical significance, if possible), and the principal conclusion. It should emphasize new and important aspects of the study or observations. Clinical Briefs must not exceed 1000 words with one figure and 5-8 references. text. Authors must consider and follow the format : Introduction, Material and Methods, results, Discussion, and Conclusion (if necessary). the matter must be written in a manner which is easy to understand, and should be restricted to the topic discussed. Do not use vertical lines or underlining in the text. Acknowledgments should be placed as the last element of the text before references. Abbreviate measurements (cm, ml). Abbreviations should be used sparingly and must be preceded by the full form initially. references. In citing other work, only references consulted in the original should be included. If it is against citation by others this should also be stated. Use the Sequential numbering system. Arrange the reference list in the sequence in which the references are first cited. In the text, references cited should be superscripted and should appear on top of the line after the punctuation. responsibility for the accuracy and completeness of references lies with the author. references should not exceed 15-20 in number. the Journal follows the Vancouver system of references. references should be numbered and listed consecutively in the order in which they are first cited in the text. tables should be identified in the text by superior Arabic numerals. the full list of references at the end of the paper should include : names and initials of all authors (unless more than 6, when only the first 3 are given followed by et al); the title of the paper; the journal title abbreviated according to the style of Index Medicus; year of publication; volume number; first and last page numbers. references of books should

Preparation of Manuscripts
Format. the manuscript must not exceed 1012 pages typed in double space (including 1520 references). Number all pages in sequence, beginning with the title page. Submit a copy of all elements arranged as follows: title Page. this should contain the title of the manuscript (5-6 words title) the names of all authors, and their affiliations, a short title (not more than 20 letters to be used as running head) and at the bottom of the page, institution where the work has been carried out, and the address for all correspondence and reprints, including Fax, Phone and E-mail. 41 Vol. 6, Issue 3 April - June 2008

give the book title, place of publication, publisher and year; those of multiple authorship should also include the chapter title, first and last page numbers, and names and initials of editors. 1. Mehta MN, Mehta JN. Serum lipids and ABO blood groups in cord blood of neonates. Indian J Pediatr 1984; 51 : 30-43. 2. Smith gDL. Chronic Ear Disease. Edinburgh; Churchill Livingstone, 1980 : 78-81. 3. Malhotra KC. Medicogenetic problems of Indian tribes. In Verma IC, ed. Medical genetics in India. Vol. 2., Pondicherry; Auroma Enterprises, 1978; 51-55. Papers accepted but not yet published should be included in the references followed by “In press”. those in preparation, personal communications and unpublished observations should be referred to as such in the text only. For more detailed information about the Vancouver system, authors should consult “Uniform requirements for manuscripts submitted to biomedical journals’ (Br Med J. 1982; 284 : 1766-70). Legends. A descriptive legend must accompany each illustration and must define all abbreviations used therein. Illustrations and graphs. Submit glossy black and white photographs. the cost reproduction of colour photographs will be borne entirely by the author. Number all illustrations with Arabic numericals (1, 2).

tables. these must be self-explanatory. the data must be clearly organized and should supplement and not duplicate the text. Explanatory matter should be given as footnotes. Statistical analyses used must be appropriate. Each table must have a title and should be numbered with Arabic numericals (1, 2).

Manuscript Submission Checklist
1. three copies of manuscript in hard copy 2. Name and address correspondence. of author responsible for

3. Structured Abstract (150-200 words) & 3-5 key words. 4. references, cited consecutively in the text. 5. three glossy prints for illustrations. 6. Documentation of permission to reuse any previously published material. 7. Covering letter, including statement of originality and signifying approval of final copy by all authors. 8. Upon final acceptance of the manuscript, a CD disk in MS Word should be submitted. the disk should be labeled with the title of article, file name and version used and must contain the final revised manuscript material.

42 Vol. 6, Issue 3 April - June 2008