cancer april 2008

Vol. 6, Issue 3 April - June 20083

Vol. 6 Issue 3 April - June 2008

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EDITOR SPEAKS

Editor-in-Chief Dr. Vinay Aggarwal

SectionalEditor Dr. Arun Kumar Goel

EditorialBoard

Dr. Ashok Grover

Dr. Hariharan Dr. Madhumita Puri Dr. Sharda Jain Dr. Parkash Gera Dr. Rajiv Gupta Dr. S. Arul Rhaj Dr. Deepak Pande Dr. Yogesh Jhamb Dr. Vineet Jain Dr. Neeraj Jain Dr. B.K. Gupta Mr. S.K. Singhal Dr. Atul Jain Mr. Atul Gandotra

Photographer Mr. Mukesh Kapoor

DesignandLayout Ms.Tabassum

CONTENTS

1. Brachytherapy:past,presentandfuture 5

2. Challengesinsettingupacancercenter 10

3. CML-asuccessstoryinoncology 13

4. Modernradiationtechniques:IMrt 18 andIgrt

5. Historyofmedicaloncology 21

6. Surgicaloncologyandroleof 25 plasticsurgeon

7. Idiopathicperforationofgallbladder 27

8. Acutepancreatitis:imaging. 29

9. MedicalNews 32 PhysicaltherapyfortheFamilyClinician

10. PushpanjaliHealthcareEvents 34 andInitiatives

11. SubscribersFeedback 37

12. guidelinesforsubmissionof 39Manuscripts

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, PET-CT 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.

Dr. Arun Kumar Goel


LIST Of CONSULTANTSCONSULTANT RESIDENCE CHAMBER MOBILE DAY/TIMING E-MAIL ADDRESS

CHAIRMANDr.VinayAggarwal 22374612 22371818 9811050403 [email protected]

MEDICAL DIRECTORDr.gauravAggarwal 22374612 22371818 9899550403 [email protected]

PHYSICIANDr.Parkashgera 22375440,22371284 22075641 9810000944 11.30am-1.00pm(Daily)Dr.NavinAtal 42408075 22140637 9810115132 8.00pm-9.00pm(Daily) [email protected] 3240604 9871701699 9.00pm-11.00pm(Daily) [email protected]

PHYSICIAN-CHEST SPL.Dr.Ashokgrover 22541854 22411236 9810121609 4.00pm-5.30pm(Daily) [email protected]

PHYSICIAN & NON INASIVECARDIOLOGISTDr.MukeshAjmera 22374502 9811008306 11.00am-1230pm(Daily) [email protected]

GYNAECOLOGISTDr.ShardaJain 22238838-22238847 22414049-22453724 9312644808 8.00am-9.00am(Daily) [email protected] 22149718,22169718 9810183236 10.00am-12.00noon(tue,Wed,Fri)Dr.BakulArora 22750757,22750551 9810089120 7.00pm-8.00pm(Mon,Fri) [email protected] 95120-4112881,2640397 22582002 9810262229 1.00pm-2.00pm(Daily) [email protected] 65261328 659014833 9818088114 9.00am-11.00am(Mon,thur,Sat) [email protected] 9810281671 6.00am-8.00am(tue,Wed,thus,Sat) [email protected]

SURGEONDr.YogeshJhamb 22378281 9811168281 11.30am-1.30pm(Daily) [email protected] 9810061958 OnCall [email protected]

CHILD SPECIALISTDr.DeepakPande 22243742,42182025 22432218 9810366571 11.30am-1.00pm(Daily) [email protected] 95120-4112881,2640397 22582002 9810121098 10.00am-12.00noon(Daily) [email protected] 9818372811 10.00am-12.00noon(Daily)

CHILD PHYSIOTHERAPIST Dr.DeepikaMittal 22153892 4.00pm-6.00pm(MontoFri)

PAEDIATRIC SURGEONDr.AnuragKrishna 24112687,24114887 9810060565 1.00pm-2.00pm(Sat) [email protected]

ORTHOPAEDIC SURGEONDr.B.K.Malik 9811703004 6.00pm-8.00pm(Daily) [email protected] 95120-2628200,2625200 22507728 9810025926 9.30am-12.30pm(tue,thu,Sat) [email protected] 22244801 9810038879 10.30am-12.00noon(Daily) [email protected] 9312010421 9.30am-12.30pm(Mon,Wed,Fri) [email protected] 22162135 22094892 9811073613 5.00pm-6.00pm(Daily) [email protected] 22120442 9810244149 OnCall [email protected] 93112070380 6.00pm-8.00pm(Daily) [email protected]

ANAESTHETISTDr.rajeshDhall 22167122 9810110405 OnCall(tue,thu,Fri,Sun) [email protected] 22543003 22548796,22519888 9811441064 OnCall(Mon,Wed) [email protected] 22152245,22157745 9810272563 OnCall(Sat) [email protected]

ENT SURGEONDr.AtulJain 22376205 22545000 9811120545 12.00noon-1.30pm(Daily) [email protected] 22720901 9810249015 8.30pm-9.30pm(Daily) [email protected]

GASTROENTEROLOGISTDr.NeerajJain 22371024 22545000 9810166989 4.00pm-6.00pm(Daily) [email protected]

ONCOLOGISTDr.M.Nandi 9810108614 OnCall [email protected] 9811351486 OnCall [email protected]

ONCO SURGEON Dr.UmangMittal 95121-2668149 95121-2652347 9313926194 Oncall [email protected]

EYE SPECIALISTDr.L.D.Sota 26016636 9312876694 10.00am-1.00pm(Daily,exceptWed) [email protected] 4.00pm-7.00pm(Wed)Dr.P.C.Bhatia 26515263,26863998 9810064554 OnCall [email protected]

URO-SURGEONDr.C.M.goel 95120-2630717 951202630365 9811047047 1.00pm-2.00pm(Mon,thu) [email protected]


CONSULTANT RESIDENCE CHAMBER MOBILE DAY/TIMING E-MAILADDrESSSPATHOLOGISTDr.VandanaArora 22246806 9811009938 9.00am-4.00pm(Daily) [email protected] 22096401 9312319887 OnCall

MICROBIOLOGISTDr.NarinderSaini 22376289 22381445 9810252127 8.00am-9.00am(Daily) [email protected]

RADIOLOGISTDr.MukeshKoshal 22546704 9810062179 12.00noon-1.30pm(Daily) [email protected] 9810076408 OnCall

NEUROLOGISTDr.B.K.gupta 22371675,22371033 9811084263 OnCall [email protected] 22540271,22526601 30946399 9810061981 OnCall [email protected]

NEURO SURGEONDr.rajKumarDr.J.Kumar 9810273684 OnCallDr.Sanjeevgupta 9868399665 9810955753 OnCall

NEPHROLOGISTDr.NeeruAggarwal 95120-2724591 95120-2780736 9810266275 1.00pm-2.00pm(MontoFri) [email protected] 9.00amto10.00am(Sat)

PSYCHIATRISTDr.ramanJeetJaswal 22526533 9810526533 OnCallDr.AmitabhSaha 9818796611 07.00pm-8.00pm(Mon) Dr.r.K.Srivastava 9818294190 OnCall

PSYCHOSEXUAL DISORDERSDr.(Col.)V.K.Wadia 55469686 26140058 9891192777 6.00pm-8.00pm(Fri) [email protected]

PSYCHOLOGISTDr.AmitabhSaha 9818796611 06.00pm-07.00pm(Mon) [email protected] 9818294190 OnCall [email protected]

CARDIOLOGISTDr.DhirendraSinghania 9871650111 6.00pm-8.00pm(Mon-Sat.) [email protected]

ENDOCRINOLOGISTDr.I.P.SKochar(Paediatric) 9910240919 11.00am-1.00pm(thur) [email protected]//Dr.rahulPaul 9811415489 9810292498 10.00am-2.00pm(Daily) [email protected] 5.00pm-8.00pmHOMOEOPATHIC PHYSICIANDr.M.M.Aggarwal 22434770 22094879 22513835

PLASTIC SURGEONDr.ManojBansal 22155057 22097417,22093186 9810003628 12.00am-1.00pm(Mon,tue) [email protected] 11.00am-1.00pm(tue,Wed,Fri,Sat)

Dr.r.K.Sandhir 95120-2458588 22592073,22169732 9810033525 OnCall [email protected]

SKIN SPECIALISTDr.ritugupta 9891063467 10.00am-11.00am(Mon-Fri) [email protected] 22152084 22091758 9810033882 Oncall [email protected]

DIETICIANMrs.Archnagupta 9313759050 10.00am-12.00pm(Daily) [email protected]

CHEST SURGEONDr.r.C.Jain 26803436,26808035 9811106203 Oncall [email protected]

RHEUMATOLOGISTDr.AnishAggarwal 95120-2753546 9810073795 4.00pm-7.00pm(Fri) [email protected]

COURTESY CONSULTANTSDr.Poonamgupta 22095708 22161397 9811744426 [email protected] 22152036 9811151154 [email protected] 22238871 9910081484 [email protected] Dr.DeepakLahoti 9810123067 [email protected] 22516733 22541842 9810067539Dr.DeepakSarin 65901485 22147652 9811022434 [email protected]

fAMILY PHYSICIANSDr.V.K.Malhotra 22157127 9313100602 OnCallDr.AjayAggarwal 9810130292 OnCall [email protected] 22156672 22510904 9810049714 OnCall [email protected] 22372065 22412008 9811047912 OnCall [email protected] 22372727 22372728 9811319070 OnCall [email protected] 22549804 22540624 9810197049 OnCall [email protected] 22459608 9811137098 [email protected] 9312504480 [email protected] 9811305435 [email protected] 9810395657Dr.Ashwanigoyal 22112343 9811112688 [email protected] 9871803070Dr.rakeshgupta 22155979 9868814326 9312224659 [email protected] 9810321662 OnCall


EMPANELLED ORGANISATIONS

1 ParamountHealthcarePvt.Ltd.

2 VipulMedcorpPvt.Ltd.

3 ParkMediclaimConstructionCorp.Ltd.

4 E-MeditekSolutionsLtd

5 geninsIndiaLtd.

6 UnitedHealthcrePvt.Ltd.

7 HeritageHealthcare

8 FamilyHealthPlan

9 rakshatPA

10 EastWestAssist

11 BSES

12 AlankitPvt.Ltd

13 MediAssistIndiaLtd.

14 MedSaveIndiaPvt.Ltd.

15 MDIndiaHealthcareServices(P)Ltd.

16 ttKHealthcare

17 HealthIndia

18 StarHealthAlliedInsuranceCo.Lt.

19 MotherDairy

20 MicromaticMachinetoolsPvt.Ltd

21 BharatHeavyElectricalsLtd.(BHEL

22 CentralElectronicLimited

23 goodHealthPlanLtd.

24 FocusHealthcare

25 SafewayMediclaimServicesPvt.Ltd.

26 MarutiUdyogLtd

27 NationalProjectsConstruction

CorporationLtd

28 MedicareServicesClub

29 MedicaretPAServicesPvt.Ltd

30 rothshieldHealth(tPA)ServcesLtd.

31 SrigokulamHealthServicestPA(P)Ltd

32 ParekhHealthcare

33 ApolloDKVHealthInsurance

34 ParamountHealthcareManagementP

35 HygiecareCHMPvt.Ltd.

36 MeconLimited

37 NationaltextilesCorporationLtd.

38 NationalBuildingConstruction

CorporationLtd.(NBCC)

39 Dabur&ExcelciaFoods

40 E-Medlife

41 ArankariPlacementServicesPvt.Ltd

42 NationalIndustrialDevelopmentCorporationLtd

43 HospitalServicesConsultancyCorporation(India)Ltd.

44 NEFFD

45 ConoritumForEducationalCommunication

46 M/SVenusMedicareServices

47 MetLifeIndia

48 UniversalMedi-AidServicesLtd

LIST Of CONSULTANTS

CONSULTANT DAY / TIMINGS E-MAIL ADDRESSPHONE NO

PHYSICIANDr.rubyBansal 9.00am-11.00am [email protected]) 2614076 (Daily)M) 9891376756Dr.AmitChabbrar) 3240604 11.00am-1.00pm [email protected]) 9871701699 (Daily)

GYNAECOLOGISTDr.rachnaPandey 5.00pm-7.00pm [email protected]) 9891237891 (tue,thurs,Sat)

CHILD SPECIALISTDr.(Mrs.)VPDobhal 9.00pm-10.00am [email protected]) 9811161590 (Daily)

SURGEONDr.VijayS.Pandey 11.00am-1.00pm [email protected]) 95120-2628254 (Mon,thur)M) 9818492809

ENDOCRINOLOGISTDr.S.K.Wangnoo 7.00pm-9.00pm [email protected]) 22618242 (Mon,Wed) 22621357M) 9810113922

CARDIOLOGISTDr.Dhirender 8.00pm-9.00pm [email protected] Singhania (Mon,Sat)M) 9871650111

ORTHOPAEDIC SURGEONDr.AshishSao 6.30pm-8.30pm [email protected]) 9312010421 (Mon,Wed,Fri)

DERMATOLOGISTDr.ritugupta 7.30pm-9.00pm [email protected]) 22371114 (Wed,Fri)M) 9891063467 ENTDr.SaketAggarwal 11.00am-1.00pm [email protected]) 9811231599 (Mon,thurs)

PHYSIOTHERAPISTDr.Md.MajidKhan 8.30am-8.30pm [email protected]) 9873207660 (Daily)Dr.MehreenKhan 8.30am-8.30pmM) 9899295475 (Daily)Dr.SonikaSaraswat 8.30am-2.00pm [email protected]) 9899649920 (Daily)

HOMOEOPATHIC

Dr.PriyaKapor 10.00am-12.00noon [email protected]

M)9312770969 (Daily)


Brachytherapy: Past, Present and Future

Arun Kumar Rathi and Vikash Kumar

the word brachytherapy is derived from thegreek word “brachios” meaning short andrefers to the therapeutic use of encapsulatedradionuclideswithinorclosetoatumor.HenriBecquerel discovered natural radioactivity in1896 when he found that Uranium produceda black spot on photographic plates that hadnot been exposed tosunlight. two yearslater,MarieandPierreCurie working inBecquerel’s laboratoryextracted PoloniumfromatonofUraniumore and later in thesame year, extractedradium. In 1901,PierreCuriesuggestedtoDanlos at St. LouisHospitalinParisthatasmall radium tube beinserted into a tumorthusheraldingthebirthofbrachytherapy.1

In the early twentiethcentury, majorbrachytherapy workwas done at the Curie Institute in Paris andatMemorialHospital inNewYork.Dr.robertAbbe,thechiefsurgeonatSt.LukesHospitalofNewYork, placed tubes into tumor beds afterresection,andlaterinsertedremovableradiumsources thus introducing the after-loadingtechniqueasearlyas1905.Dr.WilliamMyersat Ohio State University developed severalradioisotopes, including gold-198, Cobalt-60,Iodine-125, and Phosphorus-32 for clinicalbrachytherapy.thesewereimplantedsurgicallyby Drs. Arthur James (surgeon) and UlrichHenschke(radiationoncologist).thediscoveryof man-made radioisotopes and remote after-loading techniques has reduced radiationexposure hazards. Newer imaging modalities(PEtscan,Ctscan,magneticresonanceimaging,transrectal ultrasound) and sophisticatedcomputerized treatment planning has helpedto achieve increased positional accuracy andsuperior, optimized dose distribution. Finally,whilebrachytherapywasinitiallyusedonlyfortreatmentofcancer,ithasnowbeenfoundtobeusefulinnon-malignantdiseases(forexample,inthepreventionofvascularrestenosis)aswell.It is clear that brachytherapy is the optimumway of delivering conformal radiotherapytailoredtotheshapeofthetumorwhilesparingsurroundingnormaltissues.

Someofthediseasesnowtreatedwithbrachy-

therapy includeprostatecancer,cer-vical cancer, endo-metrialcancer,headandneckcancerandcoronary arterydis-ease.Brachytherapyhas been proven tobe very effectiveand safe, providingagoodalternativetosurgical removal oftheprostate, breast,and cervix, whilereducing theriskofcertain long-termsideeffects.2,3

Brachytherapy canbesplitintofivemaitypes:4

•Mould brachy-therapy: Superficial tumors can be treatedusingsealedsourcesplacedclosetotheskin.Dosimetryisoftenper-formedwithrefer-ence to theMan-chester system;a rule-based ap-proach designedtoensurethatthedosetoallpartsofthetargetvolumeis within 10% ofthe prescriptiondose.

• Surface Appli-cator is usuallycalled Strontium plaque therapyand is used forvery superfi-cial lesions lessthan 1mm thick.the beta (elec-tron) particlesproduced from Strontium’s radioactive de-cayhaveaveryshallowpenetration.Astheelectronsonlypenetrateafewmmofair,ra-diationprotectionissuesareslightlylessbutverydifferentfromotherradiationsources.

• Interstitial brachytherapy.Herethesourcesare insertedinto tissue.thefirst treatmentsofthiskindusedneedlescontainingradium-226, arranged according to the Manchestersystem, but modern methods tend to useIridium-192 wire. Iridium wire can bearranged either using the Manchester or

Arun Kumar RathiAssociate ProfessorDept. of Radiotherapy MaulanaAzadMedicalCollegeandLokNayakHospitalNewDelhi

Vikash KumarSenior ResidentDept. of Radiotherapy MaulanaAzadMedicalCollegeandLokNayakHospitalNewDelhi

Brachytherapyderivedfromgreekword“bra-chios”meaningshort.• In1901PierreCuriefirstsuggestedinser-tionofsmallradiumtubeintoatumorattheSt.LouisHospi-talinParis.

• Severalisotopesareused; gold-198, io-dine-125, phospho-rus-32.

• Development ofman-made isotopesand after-loadingtechniques reducedradiation exposurehazards.

Betterpositionalaccuracyandsuperioroptimizationof dose delivery achiev-ableduetomodern• imagingmodalities• computerized treat-ment planning sys-tems.

Malignant diseases treat-ed with brachytherapyinclude:• cancersoftheprostate,cervix and endometri-um,head&neck,

• Very superficial tu-mourslikeocularcan-cers.

Non-cancerous diseasetreatedwithbrachythera-pyarethoseduetovascu-larstenoses,likeCAD.

typesofBrachytherapy1. Mould Brachythera-

py: Used for superfi-cialtumors.

2. Strontium Plaque:Usedforverysuperfi-cialtumors.

3.InterstitialBrachyther-apy:Usedforbrachy-therapywithintissuesandontumorbeds.

4. Intracavitary Brachy-therapy: Used forplacing sources in-sidepreexistingbodycavities.

5. Intravascular Brachy-therapy:

Sourceplacedinsideves-sels for treatment of ste-nosesandre-stenoses


theParissystem;the latterwasdesignedspecifically to takeadvantageofthenewnuclide.

• Intracavitary brachytherapyplacesthesourcesinsideapre-existingbodycavity.themostcommonapplicationsof thismethodare gynecological innature, although it canalsobeperformedonthenasopharynx.

• Intravascular brachytherapy places a catheter with thesourcesinsidethevasculature.themostcommonapplicationofthismethodisthetreatmentofcoronaryin-stentre-stenosis,althoughthetherapyhasalsobeeninvestigatedforuseinthetreatmentofperipheralvasculaturestenoses.

Remote and Manual After-loading Machines

After-loadingmachinesperformbrachytherapytreatments.

Manual After-loading Machines: In the early days ofbrachytherapy (1920), the only way to place the radioactivematerialintothehollowtubesorhollowbodycavitieswasforsomeone tocarry thesourceup to thepatient’sbedside (roomoroperatingtheater)inasafe,takeitoutandplaceitinsidethehollowdestination.Bynecessity,thestaffmember(usuallythedoctor)undertakingthisreceivedsomeradiationdose.thiswasmanual loading.

In cases such as cervixbrachytherapywhereaHeymancapsule was used, radiationexposure frommanual loadingcould be appreciable as allthe sources had to be placedindividually while the patientwas anaesthetized on theoperating bed. It was not longbefore the doctors who wereexposed reasoned that theirexposure couldbe lessenedbyplacing metal tubes first, andthen placing the radioactivesources inside metal tubes ata later time. the metal tubesallowed the development ofstandard sizing and strengthsourcessothatsourcenumberscouldbecalculatedfirst,andthenpreparedtofacilitateasinglestepproceduretomanuallyafterload.

Manual after-loading machines could not be activated fromoutsidetheroom,asthesourcehadtobemanuallyinserted.thesourcewouldhavebeenpreparedasasourcetrainandinsertedinatheaterorward.

Remote After-loading Machines:Althoughmanualafter-loadingreducedexposures,theguidingprincipleofradiationprotectionistokeepexposuresaslowasreasonablyachievable(ALArA)given prevailing economic,political and societal factors.themove to reduce exposures evenfurther led to the introductionof remote after-loading. thistechnique relies on the use ofhollowtubeswhichareconnectedto a safe containing a smallradioactivesourceweldedtoawirethatisdrivenoutbyasteppingmotortopredeterminedpositionstodeliverradiationdose.Aplanisproducedthatdescribesthepatterns of the steppingmotor (distance anddwell time).thenurseortherapeuticradiographerthatadministerscanleavetheroom(locatedeitherintheatreorward)andstartthetreatment

outside.Emptycathetersareplacedintothepatientandthe‘live’source isenteredata laterdate.After this thecheckhasbeenperformed the source leaves its secure safe and the treatmentbegins.thedevelopmentoftheremoteafter-loadingmachinesisabenefittothemanyradiationsafetyissuessurroundingmanualafter-loadingmachines,buttheyareexpensiveandmorepronetoerror.

LDR brachytherapy

Low dose rate (LDr) involvesimplanting radioactive materialandcanbeimplantedtemporarilyorpermanently.• Permanent seed implants: commonly used for prostatecancer, radioactive seeds areleft in tissue. the radioactiveseeds are about the size ofa grain of rice, and give offradiation that travels only afewmillimeters tokillnearbycancer cells. With permanentimplants the radioactivityof the seeds decays withtime while the actual seedspermanently stay within thetreatmentarea.

• temporary seed loadings:sourcesareplacedincatheters,needles, or other appliancesforabriefperiodof timeandthen removed (gynecologicalcancers).

LDr brachytherapy with amachineworksinasimilarway.Another variant is the sourcesbeingintheformofactiveandinactiveballswhichareagain,drivenintothepatientusingamachine.

HDR brachytherapy

High Dose rate (HDr)brachytherapy is a commonbrachytherapymethodreferringto the treatment dose of 20cgyper minutes or above (ICrU38). Applicators in the form ofcatheters are arranged, usuallyaccording to the Manchesteror Paris system on, or in thepatient.Ahighdoseratesource(often iridium 192, Ir-192) isthendriven along the catheters

ontheendofawirebyamachinewhilethepatientis isolated in a room.the source dwellsinapreplannedpositionforapresettimebeforesteppingforwardalongthecatheterand repeating, to build up the requireddose distribution. the advantage of thistreatment over implanting radioactivesourcesdirectlyisthatthereislowerstaffexposure and the source can be moreactive due to low staff exposure, thusmakingtreatmenttimesquicker.

Manual Loading:Earliestwayof placing radioactive source.Maximum radiation exposuretostaff.

Manual remote after-loading:Metaltubesareplacedinitially.Source placed manually laterin a single step. Exposureto staff less than manualloading.

Remote after-loading: Sourceintroduced inside small tubesby machine that is operatedremotely. Although exposureto staff reduced tominimum,verycarefulplanningrequiredto avoid errors.Machines arecostly.

Advantages of Remote over Manual•No radiation exposure inpatienttransit

•No exposure to theater orwardstaff

LDR BRACHYTHERAPY

Permanent seed Implants: radioactive seedsintroduced and left withinthe body. radiation travelsfew millimeters and thesource decays slowly overtime. Commonly used forcanceroftheprostate.

Temporary seed loadings: Source placed insidecatheters or needles andkept in the body to beremoved after brief period.Commonly used forgynecologicalcancers.

Figure 1. Interstitial implant in carcinoma breast

HDR braachytherapy:treatmentdoseof20cgy/minormoredeliveredbysourceswithin catheters as per theManchesterorParissystem.

Machines are used tointroducethesourceintothecatheters for preset time todeliverthecalculateddose.

Advantage is minimalexposure to staff andtreatment time is muchquicker.

Figure 2. HDR Brachytherapy after-loading system


Figure3.Mammosite®radiationsystem

Newer Techniques in Brachytherapy

MammositeMammosite® is the name of aspecial catheter designed forease of delivery of high-dose-rateradiationtothebreastafterlumpectomy for tumour lessthan3cmsizeandnolymphnodeinvolvement. the treatmentallowsforradiationtobeplacedin theareaof the lumpectomy,and only a limited area of the

total breast receivesradiation.thetreatmentis administered twicea day for five days,and then the catheteris easily removed.radiation is deliveredto theareasurroundingthe excised tumor andnot to theentirebreast.the treatment is muchshorter than traditionalexternalbeamradiationto theentirebreast,butfewerwomenqualifyfor

thistypeoftreatment.theuseofmammositeforductalcarcinomasis preferred to lobular typecarcinomas.5

GliaSiteWorking in conjunction withleading neurosurgeons andradiation oncologists, CytycSurgicalProductshasdevelopedapatentedcancertreatmentdevice,the gliaSite radiation therapySystem (rtS),which isdesignedto deliver site-specific internalradiation therapy and minimizeradiation exposure to healthybraintissue.

Designed to be placed inside the tumor resection cavity, thegliaSite rtS delivers radiation with Iotrex® radiotherapySolution, a proprietary 125I radiation source placed inside a

balloon catheter.targeted tissuereceives a high doseof radiation, whileexposure to healthytissue is minimized.treatment isadministered for3 to7days.6

thegliaSiteradiationtherapySystem(rtS)is designed for thetreatment of newly

diagnosed,metastaticandrecurrentbraintumorsbydeliveringradiationfromwithinthetumorresectioncavity.7thegliaSiteballoon catheter is implanted within the tumor cavity at thetimeofresectionsurgery.Followingasimpletreatmentplanningprotocol, the balloon is infused with Iotrex® radiotherapySolution,anorganicallybound125Iliquidradiationsourcethatdeliversahighlyconformaldoseofradiationtothetargetarea.

Optimal delivery

• Deliversradiationfromwithinthetumorresectioncavity

• Maximizesthedoseofradiationtotargetarea

• Conformal,sphericallyuniformdoseofradiationdelivereddirectlytoareasmostlikelyforrecurrence

• radiation treatmentcompletedwithin3to7days

Intraoperative radiotherapy (IORT) using the Intrabeam system

Intraoperative radiotherapy(IOrt) with low-energy X-rays(30-50 KV) is an innovativetechnique that can be usedboth for accelerated partialbreast irradiation (APBI) andintraoperative boosting inpatientsaffectedbybreastcancer.Immediatelyaftertumorresectionthe tumor bed can be treatedwith low-distance X-rays by asingle high dose.Whereas oftena geographic miss in coveringtheboost targetoccurswithexternalbeamboost radiotherapy(EBrt),thepurposeofIOrtistocoverthetumorbedsafely.

theintraoperativelydelivereddoseaftertumorresectionis20gyprescribedtotheapplicatorsurface.EBrtisdeliveredwithastandardtwo-tangential-fieldtechniqueusinglinearacceleratorswith 6- or 18-MV photons.IOrt withthe Intrabeamsystem is afeasible methodtodeliverasinglehigh radiationdose to breastcancer patients.8

As a preliminaryboost it has theadvantage ofreducing theEBrt course by1.5 weeks, andasAPBI itmightbe a promisingtool for patientswithalowriskofrecurrence. thetreatment iswell

Mamosite•Special catheter for HDrradiation to breast afterlumpectomy(<3cms)andno auxiliary lymph nodemetastasis.

•Onlytumorareaofbreastis irradiated twice a dayfor5days.

•Usefulforsmalltumors.

Gliasite RTS

Deliverssitespecificinternalrt to brain. Minimizes rtexposuretohealthyareas.

Designedtobeplacedinsidethe tumour resected cavityanddeliverhighdoseofrtfor3to7days.

Involves placement ofa balloon in the tumorresectioncavityandlatertheliquidrt source is infusedintoitbymachine.

Highly conformal dosedeliveryisachieved.

Figure 4. Gliasite® Radiation

IORT with Intrabeam

Intrabeam system is anexcellent solution for APBIandintraoperativeboostinginbreastcancer.

Asinglehighdosedeliverypossible without concernsof geographic miss of theboosttargetvolume.

As a preliminary boost of20 gy, it reduces the timefor EBrt by 1.5 weeks forbreastcancer.

Used for delivery of singlehigh dose rt to resectedtumor area immediately onresection of brain tumors.radiation is emitted fromwithin the central area ofthecavitytospreadradially.

Figure 5. INTRABEAM® System


toleratedanddoesnotcausegreaterdamagethantheexpectedlatereactioninnormaltissue.

theINtrABEAM®systemdeliverssingle,highdosesofpreciselycontrolledradiationdirectlyintothecavityofaresectedbraintumor.Performedimmediatelyafteraconfirmingbiopsy,useoftheINtrABEAM®systemconvenientlycombinesdiagnosisandtreatmentintoonepatientvisit.

With the INtrABEAM® System, X-rays are generated byforming

WiththeINtrABEAM®System,X-raysaregeneratedbyformingand focusinganelectronbeam inanelectronaccelerator.thebeamtravelsdownanevacuatedneedle,hitsathingoldtargetandX-raysareemittedfromtheneedletipinasphericallysymmetricpattern with precise control of the depth of penetration. thetumor or tumor cavity is irradiated directly during the tumorresection.

Endovascular therapy

restenosis is the major limitation to a full expansion ofall revascularization procedures. Elastic coil, unfavorableremodelingandaproliferativeresponseto injuryarethemoreimportunemechanisms to restenosis. Ionizing radiation basedon the inhibitory effect on cellular proliferation has beenwidelyused in the treatmentofnumerousneoplasticandnonneoplastic conditions.gamma intracoronary radiation therapyafter coronary angioplasty is given by using awire 0.018 and0.014 inches in diameter and 30 mm active length with 192Iridiumintotheclosedchannelpolyethylenecatheter.Adoseof25gyand20gytothediameterofthereferencearteryisgiven.thereisagreatexpectationregardingtheefficacyandsafetyofvascular brachytherapy to increasing the use of endovascularrecanalizationprocedures.

References 1. Available from: http://www.americanbrachytherapy.org/

aboutBrachytherapy2. Merrick gS, Butler WM, Wallner KE, galbreath rW,

AdamovichE(2005).“Monotherapeuticbrachytherapyforclinically organ-confined prostate cancer”. West VirginiaMedicalJournal101(4):168-171.

3. Mazeron JJ, Noel g, Simon JM, racadot S, Jauffret E(2003).“Brachytherapyinheadandneckcancers”.Cancerradiotherapy7(1):62-72.

4. Availablefrom:http://en.wikipedia.org/wiki/Brachytherapy5. Partial-Breast Irradiation therapy With MammoSite

AppearstoOfferSimilarresultsasWhole-BreastIrradiationtherapyF.ViciniandothersAmericanSocietyofClinicalOncologyAnnualMeeting,June2006,Abstract529

6. tatter, et al.An inflatableballooncatheter and liquid 125Iradiation source (gliaSite radiation therapy System) fortreatmentofrecurrentmalignantglioma:multicentersafetyandfeasibilitytrial.J.Neurosurgery.2003;99:297-303.

7. Halligan, et al.Operationandpermanent lowactivity 125Ibrachytherapy for recurrenthighgradeastocytomas. Int JradOncBiolPhys.1996;35:541-547.

8. the tArgIt trial: targeted intraoperative radiationtherapy versus conventional postoperative whole-breastradiotherapy after breast-conserving surgery for themanagement of early-stage invasive breast cancer (a trialupdate). the American Journal of Surgery, Volume 194,Issue4,Pages507-510D.Holmes,M.Baum,D.Joseph.

mechanicalheartvalves.JAmCollCardiol1999;33:1637–41.


Dinesh SinghConsultant Radiation OncologistPushpanjali Crosslay HospitalDelhi

Arun Kumar Goel Senior ConsultantSurgical OncologistPushpanjali Crosslay HospitalDelhi

Challenges in Setting Up a Cancer Center

Dinesh Singh and Arun Kumar Goel

ItisaHerculeantasktosetupacancercentre.thechallengesaremanifoldbecauseitrequiresintegrationofmanydifferentspecialtiesbothinthemedicalandnon-medicalfields.

Ihaveundertakenthisexercisetwice,firsttosetup theDharamshilaCancerHospital and thenthegalaxyCancer Institute at thePushpanjaliCrosslay Hospital. Each time the experiencepresenteddifferentandinterestingchallenges.

Astheessentialfirststep,meticulous planning on the drawing board, initially for the macroaspectsandsubsequentlytodelvedeepintothemicro details is required. Statutory, legal andradiological regulatory requirements shouldbe known, adhered to and integrated to thelocal building laws and by-laws, fire safetyrequirements,etc.

Integrationofdifferentcivic,electric,mechani-cal, biomedical branches and of the technicalteamwiththeseagenciesisaverydifferentkindofjobthathastobeundertakenearlyintheproj-ect, otherwise delays are inevitable. Any lackofcoordinationbetweenanyof theseagenciesheightensthedelay.Knowledgeoftheline-upofdifferent compo-nents of the proj-ect in a sequenceof time and spaceneeds to be doneinadvancebyeachdepartmenttogainmaximummileage.Itisastrategysuchasthisthatensurestimelycompletion.

Selection of world class equipmentsneeds to be donejudiciously andby meticulously evaluating the merits anddemerits of the equipments in relation to therequirementsof thepatientpopulationserved,kindofmalignancies encountered, availabilityofotherfacilitiesintheareaanditsvicinity.

Oncologyrequiresmulti-modality management.Each cancerpatient requires services ofmanyspecialties, viz, radiation, surgical, medicaloncology, radiology, pathology, microbiology,socialwelfare department and support groupsandmanymore.Interdepartmentalfunctioningthatworkstokeepingallthedesiredspecialtieswithin the physical reach of the patient andcaregiverinamannerthatisconvenienttoall

resultsinthebestdeliveryofcancercaretothepatient.thishasalsotobeconsideredfromthedrawing board through the implementation ofthe project. By best cancer care I understandboth medical care and in-house experienceof receiving thatmedical care.the end resultshouldbeworld class anti-cancer services with our Indian traditional love and care.

Conceptualization of comprehensive careinvolvesintegrationofallconcernedmodalitiesfrom planning stage because each specialtyinvolves very different requirements. Eachspecialty is undergoing rapid transformation,modification and up-gradation. there arerapidchangesinutilizationoforintegrationofdifferentdiagnosticandtherapeuticmodalities.For example,management of a cancer patientstartswithanearlyandaccuratediagnosis,bothanatomical and pathological, and etiologicalwhere applicable. this is followed by itsfurther characterizations or sub classificationfordiagnosticaswellas therapeuticpurposes.A complete staging work up and a concertedtreatment strategy are the next steps. Manysituationshaveoverlappingtreatmentsolutionsinvolving different modalities. A goodtreatmentcenterisoneinwhichallspecialtiesworkincohesion and not in competition witheachother so thatpatient care remains as thesuprememotto.

Practicing global standard protocols for man-agement of thisdiseasewith thelatesttechnologyandpersonalizedcare providesthe best chanceof cure. By thism e t h o d o l o g ythe same qual-ity of care canbeprovidedmaybe received inthe best centersof theworldwiththe added advantage of it being in the home environment andatanaffordable cost.Foranexample, Igrt (Imageguided radiotherapy)ata reputed center in USA costs approximately70,000.00USDollarsor INr28 lacsexclusiveofthecostoftravel,stayandlocaltransport,lo-calexpensesetc.thesametreatmentcouldbemadeavailableinlessthan2lacsINr.

Patientandcaregiversshouldbegivencomplete

Setting up a Cancer center

• technicalintricacies• Multiple complex inte-grations

• Bestequipmentselection• Multi-modality team ap-proach

• Architectural&structur-aldetails

• Construction & installa-tion

• Commissioning of ser-vices

Providing the best to pa-tients and care-providers• Best of medical facili-

ties, in-house comfort,empathy

• Making anti-cancertreatment least trau-matic with a positiveapproach

• World Class CancerCare in a homely envi-ronment


informationaboutdifferentprotocolsfortreatmentsothattheycan select treatmentmodality in overlapping situations. Suchsituationsarenotveryuncommoneg,cancerofuterinecervix,earlystagecanceroflarynxtonameafew.

Providingaworldclasscancertreatmentcentertothesocietyisverysatisfyingwork.Itgivesanopportunitytoservethesocietyintwoways,oneitcreates jobopportunities for technicalandnon technical persons and secondly, it provides treatment topatientsneartheirhomes.

Cancer treatment isa lengthyprocess thatputsa lotofsocial,economical psychological pressure on both the patient andtheentire family. It isassociatedwitha lotofupsanddowns.Providing a soothing, homely environment both in ambienceandbehaviorof thestaffwhileprovidinganticancer treatmentishighly important because it acts as a soothingbalm for thepatientandthecaregivers.

Weareverysatisfiedwiththecurrentproject–thegalaxyCancerInstitute;wehavebeenable to integrate variousmodalities ofcancer treatment, ie, Surgical Oncology, radiation Oncology,Medical Oncology, gynecological Oncology at one place on asinglededicated Oncology floor.theadvantageisthatpatientswill get advice from all specialists then and there in the bestcoordinatedmanner.OPD and IPD services are on the same floor thustheadmittedpatientswillbecontinuouslyattendedby seniordoctors throughout theday.Adequate junior staff isgoingtobepresentround-the-clocktocarryoutpatientcareverycompassionately.

Equipments

Worldclasslatestequipment,whichisnotpresenteveninmanycentersinUSAandEurope,e.g.,120leaves,DynamicMulti-leafCollimators, On Board Imaging with Kilo voltage Cone BeamCt,Imageguidedradiotherapy(Igrt),respiratorygating,30ChannelMicro-selectronbrachytherapyaresomeofthem.

Alltheseandotherequipmentsareabletodeliverradiotherapyverypreciselytotheaccuracyof1-2mm.Itsadvantageisthatwecansparenormalsurroundingtissuesfrombeingexposedtoradiation.theendresultisthatagreaterdoseofradiationcanbegivenverysafelywithminimalsideeffects.thisfacilitatesdoseescalationandultimatelyenhancedcurerates.

Dynamic Tumor Tracking: Location of a tumor in relation toexternalskinmarkingsisnotalwayssatisfactory.thetumorcanmove between treatment fractions (intra-fraction movement)

and during treatment fractiondelivery (inter-fraction). UsingIgrt, we use daily KV scanning(Cone Beam Ct available onboard the linear accelerator) tocreate three-dimensional imagesthatpinpointtheexactpositionofthetumor.Inthepast,wehadtocompensatefortumormovementsby planning the radiation fieldlargerthanthetumorvolumethusexposing a significant volume ofhealthy tissue to radiation. Withthe Varian Igrt, there are tworobotically controlled “arms” tocaptureCt,fluoroscopicandx-rayimagesonadailybasis,thuswecanpinpointtheexactpositionof thecancer justprior to treatment. this increasedprecisionallowsforhigherdosesofradiationwithfewersideeffects.

Brachytherapy

High Dose Rate Brachytherapyisamongthehighendtreatmentmodalities. Brachytherapy is a method of treating cancer inwhich sealed radioactive sources are inserted either directlyintothetumororinitsvicinity.Inthismethod,radiationisfromwithinthetumororveryclosetoit.Bythismethodveryhighdosesofradiationcanbegivenverysafelytoaselectgroupoftumors,examplesbeingcarcinomaofuterinecervix,headandneck cancers (lip, buccal mucosa, tongue, tonsil) esophagealcancer,malignantbraintumors,softtissuecarcinomas,tonameafew.

AtthegalaxyCancerInstitute,a30-channel HDR Brachytherapy fromNucletron, Holland has been installed,which again is afirstfornorthernIndia.

We are confident that with the ingredients of world classequipments, renowned doctors, technical and non technicalstaff with national and international training, coordinatedeffortamongthedifferentdepartmentswithinoncology,withinthe hospital and between different hospitals along with a lotofEmpathywill ensure that ourpatientswill receive thebest of care and cure at the Galaxy Cancer Institute, Pushpanjali Crosslay Hospital.

Inter-fractional and Intra-fractional movement is afactor that necessitates ad-dition of extra margin be-yond the target volume. Inconventional radiation, itamounts to adding 3–5 cmof normal tissue all aroundthe target volume in allthree dimensions. the vol-ume thus added is signifi-cant leading to increase inmorbidityandlimitingdosetobedelivered.

Worldclassmedicalequipment

galaxyCancerInstitute@

PushpanjaliCrosslayHospital

greatenvironmentfortreatmentandcare

Largededicatedteamwithempathy


AK VaidSenior Consultant Medical OncologistArtemis Health InstituteNew Delhi

CML - A Success Story in Oncology

AK Vaid

Chronic myelogenous leukemia (CML), aclonalmyeloproliferativedisorder,resultsfromthe neoplastic transformation of the primitivehematopoieticstemcell.thehallmarkofCMLis the presence of a balanced translocationbetweenthelongarmsofchromosomes9and22,t(9;22)(q34;q11),knownasthePhiladelphia(Ph) chromosome. Despite the constant Phc h r om o s om e –related molecularevents in CML,the disease isheterogeneous inits presentationand clinicalcourse.

After the initialdescriptions ofCML more than150 years ago,little meaningfulprogresswasmadein its treatmentformorethanacentury.radiationtherapyandbusulfan contributedmore towards improvingqualityof life thantoprolongingsurvival.ButsincethediscoveryofthePhchromosomeover40years ago, the clinical course, therapy, andprognosis of patientswithCMLhave changedsignificantly.the availability of effective ther-apy, first with interferon-a (IFN-a) and bonemarrowtransplantationandmorerecentlywithimatinibmesylate(StI571,glivec),haschangedthenaturalhistoryofthediseaseand,insomeinstances,theprognosticsignificanceofcertainclinicalvariables.Understandingofthepatho-genesisofthediseasebeganwiththediscoveryofthePhiladelphia(Ph)chromosomefollowedby appreciationof its molecularcounterpart, theBCR-ABL fusiongene. recognitionof the tyrosinekinase (tK) activ-ity of the Bcr-Ablproteins led tothediscoveryofanewseriesofcom-pounds targetedagainst BCR-ABL–encoded proteins,which inhibitedthe tK activity,thus aborting thesignals control-ling the leukemicphenotype. One

of the tK inhibitors, imatinib mesylate (IM),wasfoundtohaveahighandrelativelyspecificbiochemical activity and an acceptable phar-macokineticandtoxicityprofile,andwasthusrapidly introduced into clinical practice. thisresultedinarevolutionarystepinthemanage-mentofCMLandaparadigmshiftintheman-agementofcanceringeneral.

thenaturalhistoryofCMLischaracterizedbya biphasic (and sometimes triphasic) course.the disease isdiagnosed in thechronic phase(CP) in over80% of patients.the presentingcharacteristics inCP are variable.Up to 40% ofpatients may bea s ymp t oma t i cat the time ofdiagnosis withthe disease beingdiscoveredduringaroutinemedicale x am i n a t i o n .When symptomsare present, theyinclude fatigue,night sweats,weight loss, ormanifestations of

Discovery of the Philadel-phiachromosome, thehall-mark of CML, 40 years agohas changed the clinicalcourse,therapyandprogno-sisofCML.

the availability of effectivetherapy, first with inter-feron-a and Bone Marrowtransplant and more re-cently oral imatinibMesyl-atehaschangedthenaturalhistoryandprognosisofthedisease.

the molecular counterpartofthePhiladelphiachromo-someistheabnormalBCr_ABLfusiongene.

the pathogenesis of CMLlies with the abnormal ty-rosinekinaseactivityoftheBCr-ABLencodedproteins

CML is characterized by abiphasic(attimestriphasic)course: Chronic, Acceler-atedandBlastic.

Symptoms include fatigue,night sweats, weight lossand symptoms attributableto splenomegally, like leftupper quadrant abdominaldiscomfort, early satiety oranorexia.

Figure 2. HDR Brachytherapy after-loading system

Chronic phase: Lasts for amediandurationof35–65months, busalphan or hy-droxyurea does not changethis.

Accelerated phase: 2/3rdof chronic phase patients’progress to this poorly de-finedphaselastingforame-dianof1–2years.

Blastic phase: Almost allpatientseventuallyprogresstothisphasewherethereare> 20% blasts in the bloodor marrow. Nearly 50% ofthemhaveamyeloid trans-formation, 25% lymphoidand in 25% blasts are un-identifiable.

the median survival isabout3–9monthsanditisultimatelyfatal.Prognosisisrelatively better with lym-phoidblastcrisis.


splenomegalysuchasleftupperquadrantabdominaldiscomfort,early satiety, or anorexia. When treated with conventionalchemotherapy(ie,busulfan,hydroxyurea),themediansurvivalinCPis35to65months.thissurvivalisnodifferentfromwhathasbeenreportedforuntreatedpatientsorpatientstreatedwithradiotherapy.Approximately two-thirds of patients go throughanintermediatephaseknownasacceleratedphase(AP)beforeprogressing to the blastic phase.AP is a poorly defined stage.there is no universally accepteddefinition for this phase of thedisease. the median survivalforpatients inAPis1to2years.Mostpatientseventuallyprogressto a blastic phase unless thedisease can be eliminated orsuppressed effectively beforereaching this stage. Blastic phaseischaracterizedbythepresenceof≥30% of blasts in the peripheralblood or bone marrow or bythe presence of extramedullaryblasticdisease.theWorldHealthOrganization recently proposedachangeinthecriteriato≥20%blasts.theblastic transformationis of myeloid lineage in nearly50%ofpatients,lymphoidin25%,andundifferentiatedin25%.theblasticphaseisusuallyfatal,withamediansurvivalof3to9months.Patientswithlymphoidblasticphasehave a somewhatbetter complete remission rateafterinductionchemotherapy(30%–50%)andalongermediansurvival (9 months) compared with patients with myeloid orundifferentiated lineages (complete remission rate, 10%–20%;median survival, 3 months). thenaturalhistoryof thediseasemaybe affected by effective therapythat leads to the elimination ofthe Ph chromosome. the mediansurvival for all patients treatedwith Interferon-α–based therapy is65to90months,andpatientswhoachieve a complete eradication ofthePhpositiveclonehaveasurvivalprobabilityof78%at10years.Bonemarrow transplantation offers thepossibility of cure to a fraction ofpatientswhohaveCML,and3-yearsurvivalprobabilitiesof78%recentlyhavebeenreported.thereis,however,lessinformationregardingthelong-termfollowupofpatientstreatedwithbonemarrow transplantation. Currently, allogeneic SCt is the onlytreatmentwith known curative potential in CML, but it is anoptionforonlyabout40%ofthepatientswiththisdisease.Long-term survival rates associated with human leukocyte antigen(HLA)-matched related-donor transplants range from 50%–75% in patientswith chronic-phase CML. Survival rates aftertransplantationduringtheacceleratedphaseareapproximately50%lower,and5-yearsurvivalratesare<20%forpatientswhoreceivetransplantsduringblastcrisis.Approximately75%–90%of patients are in complete hematological remission followingtransplantationtestnegativeforresidualleukemiaasmeasuredby reverse transcriptase polymerase chain reaction (rt-PCr)amplification of BCr-ABL transcripts. the significance of thepresence of rt-PCr amplified transcripts following SCt issomewhat controversial, but this findingmay augur a clinicalrelapse.theriskforrelapseafterallogeneictransplantinCML

is about 20%. Many patients who relapse respond to donorleukocyte infusions (so-called adoptive immunotherapy).SCt additionally carries a significant risk of treatment-relatedmorbidity andmortality. the probability of SCt-related deathhas been reported to range from 20%–40%. A related HLA-matcheddonorcanbefoundforfewerthan30%ofCMLpatients.transplants fromunrelated or nonHLA-matched donors havehighermortalityrisks.UseofanallograftfromanHLA-matchedunrelateddonor(UrD)canbeconsideredifthepatientdoesnothaveanHLA-identical sibling,but thisoptionhashistoricallybeenlimitedbydonoravailabilityandbygreater toxicity (duemainlytotheeffectsofgraft-vs.-hostdisease[gVHD])thanwithrelated-donortransplants.However,recentreportssuggest thatresultswithUrDmolecularlymatched transplants in selectedyounger patients can approach those achieved with related-donortransplants.

Chemotherapy in CML

thealkylating agentbusulphan, introduced in the1950s,wasshowntoreduceelevatedwhitebloodcellcountsanddisease-relatedsignsandsymptomsinamajorityofpatientswithCML.However, this agent causes serious adverse effects, includingmyelosuppression as well as pulmonary, hepatic, and cardiacfibrosis. Hydroxyurea (HU) demonstrated a more rapid onsetof action and better side-effectprofile thanbusulphan.However,hydroxyurea monotherapy alsodoes not produce cytogeneticremission or significantly delaythe onset of accelerated-phase orblast-crisisCML,anditseffectsareprimarilypalliative.AdverseeffectsassociatedwithHUtherapyincludenausea and other gastrointestinalreactions,myelosuppression, skinatrophy,anddrugfever.Long-termtherapy can produce a lichenoiddermopathy, lower-extremityulcers, cutaneous squamous cellcarcinoma, gangrene of the toes,vasculitis,andlife-threateningpulmonaryreactions.

theplantalkaloidhomoharringtonine (HHT)hasbeenshownto have efficacy in treating CML both as monotherapy andwhen administered with Ara-C. However, at high doses andwith short infusion schedules,HHthas been associatedwithseriouscardiovascularcomplications,suchashypotensionandarrhythmias.

Imatinib mesilate (Glivec) isthefirstinanewclassofcancerdrugs, the signal transduction inhibitors, rationally designedto competitively inhibit BCr-ABL tyrosine kinase activity.By blocking specific signals in cells expressing the BCr-ABLprotein,imatinibreducestheuncontrolledcellularproliferationofwhitebloodcellsthatisacharacteristicfeatureofthedisease.ImatinibhaschangedthecurrentapproachtothemanagementofCML.Acompletecytogeneticresponseisachievedin50%to60%ofpatientstreatedwithimatinibafterfailingIFN-atherapyandin75%to90%ofthosetreatedwithimatinibastheirfirstlineof therapy.With suchaneffective therapy, theprognosticsignificance of some clinical variables previously associatedwith outcome is changing.Due to the short-term follow-up atthistimeandthegoodoverallresults,fewvariableshavebeenidentifiedtohaveanimpactonsurvival,andmostofthedataismostlyapplicabletoresponseandprogressiontoAPorblasticphase. the estimated overall survival of patientswho receiveimatinibasinitialtherapyis89% at 60 months.Patientswhohad

Interferon-α based therapycan increase thesurvivalat10yearsto78%,ifcompleteeradication of Ph chromo-someoccurs.

With bone marrow trans-plants 78% 3-year survivalhasbeenreported.MajorityofthemarePhnegative.

Allogenic SCT is the onlytreatment with potentialfor cure, but 40% patientsare usually eligible for thistreatment. It is most effec-tive when done in chronicphase.

20% patients relapse afterallogenic transplant. ManyofthemrespondtoDLI.

Problems of allogenic SCT

Mortality20%–40%related matched donorsfoundonlyfor30%ofCMLpatients.

gVHDisaproblemwithun-relatedmatcheddonors.

Molecular matched UrDtransplants may reducegVHD

Chemotherapy

Busulphan,Hydroxyurea,HHt,Ara-C.• Hydroxyureaisthepre-

ferred drug because ofitsrapidonsetofactionand better side effectprofile.

• Itdoesnotincreasesur-vivalnorproducescyto-geneticremission.

• Occasionallypotentiallyserious side effects oc-cur.


a complete cytogenetic responseor in whom levels of BCr-ABLtranscriptshadfallendramaticallyhad a significantly lower riskof disease progression than didpatients without a completecytogeneticresponse.

Imatinib is a well tolerated drugand devoid of any serious organspecific toxicities. the mostfrequentlyreportedadverseeffectsof imatinib in clinical studiesinclude nausea, vomiting, edema(fluid retention), muscle cramps,skinrash,diarrhea,heartburn,andheadache. Cytopenia, particularlyneutropeniaandthrombocytopenia,has been reported in all studies,withahigher incidence inpeoplein blast crisis and the acceleratedphase compared with those inchronic phase. In clinical studies,1%ofpeopleinthechronicphasewerewithdrawnbecauseofadverseevents,2%intheacceleratedphaseand5%intheblast-crisisphase.

Inpatientswhoachieveacompletecytogeneticresponse,real-timepolymerasechainreaction (rt-PCr) is themostsensitivewaytocontinuetomonitortheirdiseaseandtopredictrelapseand imatinib resistance.Aproportionofpatients testnegativefor BCr-ABL by rt-PCr; however, patients still may have asignificant number of leukemic cells remaining despite beingrt-PCrnegative.the long-termsignificanceofbecomingPCrnegative on imatinib is not yet known, but evidence so farsuggests that these patients will have a good chance of long-termprogression-freesurvival.Itseemsthattheachievementofamajormolecular response increasinglywill be an importantarbiter in directing treatment strategy. Among other things,sinceQ-PCronperipheralbloodisbecomingsuchanimportantmeasureofresponse,thisraisestheissueofwhethercliniciansshould continue to do bone marrow assessments on CMLpatientsorwhetherperipheralbloodtestingwouldbesufficient.

there are considerable efforts being made internationally tostandardizethemethodologyandreportingofPCrtechnologies;theseeffortsarecrucialifmolecularresponseistobecomethecommoncurrencytoassessdrugtherapy.Inthenearfuture,itmay be that the idealway tomonitorCMLpatientswill be acombinationofPCrforBCr-ABLand,kinase-domainmutationmonitoringusingonlyperipheralbloodsamples.

Itiscurrentlyrecommendedthatimatinibtherapybecontinuedindefinitelyifthepatientisbenefiting.Anecdotalreportssuggestthat the discontinuation of imatinib, even in patients withundetectable levels of BCrABL transcripts, results in relapse.Althoughitisnotknownwhyimatinibisnotabletoeradicatethemalignantclone,potentialmechanismsincludedrugefflux,andamplificationormutationof theBCr-ABLgene. It is alsopossible that imatinib cannot completely inhibit BCr-ABLkinaseactivity;lowlevelsofactivitywouldallowcellstosurvivebutnotproliferate.Asanalternative,themalignantclonecouldpersist throughmechanisms that are independentof theBCr-ABL kinase. Initial studies of two new inhibitors of the BCr-ABLkinasethataremorepotentthanimatinib—dasatinibandnilotinib-showedhigh response rates inpatientswhohadhada relapseduring imatinib therapy.Despite theirpotency, theseinhibitorscannoteradicateallCMLcellsinvitro.

the range of options for themanagement of CML has nowwidened considerably with theintroduction of imatinib. Withimatinib now established as thefirst-line pharmacotherapy fornewly diagnosed CML, a keyconsiderationishowtoincorporateit into the treatment of patientswho are candidates for stem celltransplant. One approach is toadministerimatinibinitiallytoallpatients with a new diagnosis ofCMLwhiletheyarebeingevaluatedfora transplant.Youngerpatientswhohave incomplete cytogeneticresponses to first-line imatinibtherapyandhavesuitabledonorsmay be considered for stem celltransplantation. For inadequatelyresponding patients withoutdonors,anincreaseintheimatinibdose,withorwithouttheadditionof other agents (e.g., IFN,Ara-C),can be considered. the choicesare less clear for patients whorespond adequately to imatiniband have HLA-matched donors.the 10%–15% of patients at lowriskfordeathfromtransplantation(ie, young patients with siblingdonors) could be considered forimmediate SCt. transplantationamong higher-risk patientsmightbe reserved for those who showsigns of disease progression on

imatinib.However,untillong-termsurvivaldataareavailableforimatinib-treatedpatients,decisionmakingregardingtransplantcandidateswithCML,particularlynewlydiagnosedcases,willpresent a challenge. Patients with potential transplant donorswhoarereceivingimatinibshouldbemonitoredclosely.Whilethe exact monitoring schedule is unclear, an approach that

Imatinib mesilate: AcompetitiveinhibitorofBCr_ABLtyrosinekinase

activity.

• Complete cytogeneticresponse of 75% - 90%on first line use, 50%-60% in INF failedpa-tients.

• 5yearsurvival-89%• Sideeffectsareminimal

and drug removal duetotoxicityisparcticallyneverrequired.

• responsemonitored byrt-PCrforBCr_ABLinmarrow. Q-PCr estima-tioninperipheralbloodmay turn out to be themethodofchoiceinfu-ture.

Mechanism of action of BCR-ABL and of Its Inhibition by Imatinib.PanelAshowstheBCr-ABLoncoproteinwithamoleculeofadenosinetriphosphate(AtP)inthekinasepocket.thesubstrateisactivatedbythephosphorylationofoneofitstyrosineresidues.Itcanthenactivateotherdownstreameffectormolecules.Whenimatiniboccupiestheki-nasepocket(PanelB),theactionofBCr-ABLisinhibited,preventingphosphorylationofitssubstrate.ADPdenotesadenosinediphosphate.

Imatinib with its excellentability to control diseaseandtolerabilityhasleadtoarethinking as to how to in-corporateitinpatientswhoare potential candidates forSCtwithHLAmatchedsib-lingdonors.

• For thepresent, theap-proach is to continueimatinib in responderswho are poor risk forSCt.

• Younggoodriskpatientwithmortalityriskof<10% - 15% from SCtwho have a matchedsiblingdonorshouldbetakenupforSCt.

• this group of patientswho are respondersand have potential do-nors have to be closelymonitored with regularassesment of diseasestatus. the assess-ment strategies are notstandardized yet, but 3monthly assessment ofBCr_ABL inperipheralbloodbyFISHorQ-PCrif cytogenetically nega-tiveseemsreasonable.

Patients on hydroxyureaand / or INF-α should beswitchedovertoimatinib.


References 1. goldman J. Management of chronic myeloid leukemia.

SeminHematol2003;40:1-103.2. Sawyers CL. Chronic myeloid leukemia. N Engl J Med.

1999;340:1330-1340.3. HolyoaketL.recentadvancesinthemolecularandcellular

biologyofchronicmyeloidleukaemia:lessonstobelearnedfromthelaboratory.BrJHaematol.2001;113:11-23.

4. Druker BJ, tamura S, Buchdunger E, et al. Effects of aselectiveinhibitoroftheAbl-tyrosinekinaseonthegrowthofBcr-Ablpositivecells.NatMed.1996;2:561-566.

5. DrukerBJ,talpazM,restaDJ,etal.EfficacyandsafetyofaspecificinhibitoroftheBCr-ABLtyrosinekinaseinchronicmyeloidleukemia.NEnglJMed.2001;344:1031-1037.

6. Savage Dg, Antman KH. Imatinib mesylate: a new oraltargetedtherapy.NEnglJMed.2002;346:683-693.

7. Peggs K, Mackinnon S. Imatinib mesylate: the new goldstandardfortreatmentofchronicmyeloidleukemia.NEnglJMed.2003;348:1048-1050.

8. Stone rM. Optimizing treatment of chronic myeloidleukemia:arationalapproach.Oncologist2004;9:259-270.

9. Hehlmann r, Berger U, Hochhaus A. Chronic myeloidleukemia:amodelforoncology.AnnHematol.2005;84:487-497.

10.http://bloodjournal.hematologylibrary.org/cgi/reprint/blood-2006-02-005686v1.pdf

11.KantarjianH,SawyersC,HochhausA,etal.Hematologicandcytogeneticresponsestoimatinibmesylateinchronicmyelogenousleukemia.NEnglJMed.2002;346:645-652.

12.Brian J.Druker. Five-Year Follow-up of PatientsreceivingImatinib for Chronic Myeloid Leukemia. N Engl J Med2006;355:2408-17.

includesannualbonemarrowsampling(toscreenforsecondarycytogeneticabnormalities)and3monthlyassessmentsofdiseaseburden(e.g.,peripheralbloodfluorescenceinsituhybridizationfor BCr-ABL or quantitative PCr if cytogenetically negative)seemsa reasonableminimum. Insuchpatients, the lackofanMCrorlossofahematologicorchromosomalresponseshouldbe considered grounds for proceeding to alternative therapieslikestemcelltransplantorasecondgenerationtyrosinekinaseinhibitorlikedasatinib.

there is another issue whether patients who are currentlyreceiving hydroxyurea or IFN-based treatments be switchedto treatmentwith imatinib?the available evidence suggests astrongrationaleformakingsucharecommendation,particularlyfor hydroxyurea treated and IFN-non responsive patients.Achievement of a complete cytogenetic remission (CCr) isassociatedwith5-to10-yearsurvivalratesofapproximately50%–80%andhasbeenaconsistentearlymarker of survival prolongation inCMLpatientstreatedwithIFN-basedregimens. this clearly indicatesthat patients who do not achieveandmaintainCCrswith IFN-basedtherapy should be considered ascandidatesforimatinibtreatment.

Imatinib therapy has so farsurpassed all other non transplanttherapeutic options for CML andshould be incorporated into allpatients’ treatment regimens oncethe presence and diagnosis of PhpositiveCMLareconfirmed.

Current recommendation isto continue therapy indefi-nitely as relapses do com-monly occur with discon-tinuation.

Dasatinib and nilotinib arenewer inhibitors of BCr_ABL tyrosine kinase usedforpatientswho relapseonimatinib.

Despitehighresponserates,relapses on discontinuingtherapyindicatethesedrugscannotcompletelyeradicatethePhpositiveclone.


GK RathChiefDrBrAmbedkarInstitute-rotaryCancerHospital

DN SharmaAssistant Professor Department of Radiation OncologyAllIndiaInstituteofMedicalSciencesNewDelhi

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

ratesandreducestheriskofradiation-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

treatmentplanningsystemshaveresulted into

thethreedimensionalconformalrt(3D-Crt).

IMrt (intensity modulated radiation therapy)

andIgrt(imageguidedradiationtherapy)are

therefinedvariantsof3D-Crt.

IMRT: IMrtis thedeliveryofradiationto the

patient via fields

thathavenon-uni-

formradiationflu-

ence.IMrtdiffers

fromotherformsof

radiotherapy in a

number of impor-

tant areas includ-

ing localization of

targetsandnormal

tissues,treatmentplanning,optimization,deliv-

eryandtreatmentverification1.Itemploysradi-

ationbeamswithnon-uniformintensitywhich

whenaddedtogetherwithinapatientcanpro-

duceadosedistribu-

tion with a concave

shape. radiotherapy

planning studies

have confirmed the

dosimetricadvantag-

esofIMrtovercon-

ventionalorconformaltechniques,andrecently

somestudiesevaluatingitsclinicalimpacthave

been published2. these have mostly been re-

portsofsingle-centre

experienceandsome

Phase I/II clinical

studies that have re-

portedhigh levels of

tumor control and/or

areductioninnormal

tissueradiationtoxicity.IMrtisrapidlybecom-

ing part of the standard treatment of patients

with prostate and head and neck cancer, par-

ticularlyincentersintheUSA.Publisheddata

pertainingtoclinicalindicationsofthistherapy

forheadandneck,centralnervoussystem,and

lungtumorsisnow

widely available.

the main indica-

tions in head and

neck cancer are

parotidglandspar-

inganddoseesca-

lation to tumors

close to organs at

risk.Forcentralnervoussystemtumors, IMrt

hasbeenusedtoreducenormaltissueradiation

bymoreconformaldosedistributions.todate,

themajorityofreportsconcernpatientstreated

in the context of clinical trials, and for most

tumor types longer term follow up of treated

patientswillberequiredtoconfirmtheclinical

benefitsofIMrt.theheadandneckregioncan

be readily immobilized, and accurate assess-

mentofsetupun-

certainties can be

made.thismakes

head and neck

cancer an ideal

model for IMrt

because the tight

dosegradientsthatcanbeachievedwithIMrt

canbeusedtoavoidOArlocatedclosetothe

PtV. Parotid sparing IMrt requires themean

dosetothesparedglandtobelessthan24–26

gy. this has raised concern about a potential

riskoftumorrecurrenceinthesparedarea.

IGRT:Organmotionisverycrucialtoradiation

therapyplanningtoavoidoverdosingtonormal

tissues and under dosing to tumor tissue3.

thoracic and abdominal tumors may move

up to 3.0 cm due to respiratory movements.

Variousstrategieshavebeenusedtoreducethis

uncertaintyintreatmentplanning.Oneofthese

is image guided radiotherapy (Igrt). Igrt

or Ig-IMrt refers to use of newly emerging

radiationplanning,patientsetup,anddelivery

procedures that integrate cutting edge image

based tumor definition methods, patient

Igrtbasedtreatmentproto-colshavebeenusedinman-agement of prostate cancer,cancer cervix, lung cancer,head&neckcancer,pancre-aticcanceret.

thoracic and abdominaltumors may move up to3.0 cms due to respiratorymovements.

Igrt makes it possible totake tumormotion into ac-countduringradiationtreat-mentplanninganddelivery

Head & Neck cancer isanidealmodelforIMrt.Parotidglandsparinganddose escalation are theusual reasons for usingIMrt.

IMRT (intensity modulat-ed RT) employs radiation beams with non-uniform intensity

Linear accelerator, Ct scanandcomputerizedtreatmentplanning systems have ledtothedevelopmentofthreedimensional conformal ra-diotherapy and its moreadvancedversionsi.e.IMrtandIgrt.


positioning devices and radiation delivery guidance tools. In

Igrt uncertainties about tumor position in daily treatment

areresolvedbyacquiringvolumetric imageson the treatment

machine. Igrt makes it possible to take tumor motion into

account during radiation treatment planning and delivery.

UseofMrI,PEt,PEt–Ctbasedplanningenhancesthetumor

localizationleadingtoaccurateimageregistration.Ctscanners

capableof4Dimagingcansortoutimagesaccordingtophase

ofrespiration.Variousmethodsareusedduringthetreatment

delivery process itself. Megavoltage radiation based images

havebeenused for treatment verification in twodimensions.

Igrt applications in use include cone based Ct systems

(CBCt),gating,cyberknifeand4DPEt. Igrtprotocolshave

beenevaluatedincancercervixanduseofserialMrIcoupled

with repeat IMrt planning to account for tumor regression

duringtreatmentcanleadtosignificantlylowerdosetobladder

andrectum.Igrthasbeenstudiedfordoseescalationincancer

ofpancreaswithincreasedlocalcontrolrate.Lungcancerhas

beenstudiedusingMVCtbasedtomotherapyandadecrease

intumorvolumeof2.3%perdayhasbeendocumented4.Igrt

has also been studied in prostate cancer, cancer esophagus,

headandneckcancers.there are stillmany limitationswith

currentIgrtsystems.thesesystemsarestillevolvingandno

one strategy of image guidance is appropriate for all clinical

situations.theaddedcostalsoneedstobebalancedtothelikely

benefitexpected.Itneedstobestressedthatinappropriateuse

of these highly conformal techniquesmay lead to unsuitable

marginreduction.Longtermconsequencesandparticularlythe

debate about likelihood of secondmalignancies will only be

resolvedbyalong-termfollowup.Alltheseinnovationsinimage

guidancetheoreticallyleadtobettergeometricanddosimetric

benefits.Itpromisesanewchapterindoseescalationcombined

withareductionintreatmentmorbidities.

thefacilitiesofIMrtandIgrtaregainingpopularityinIndia

aswell.thoughthesefacilitiesareavailableinlimitedcenters;

manycentersarefastmakingeffortstoprocurethesefacilities.

References

1. Nutting C. Editorial. Intensity-modulated radiotherapy

(IMrt):themostimportantadvanceinradiotherapysince

the linearaccelerator?British Journalofradiology (2003)

76,673.

2. guerrero Urbano Mt and Nutting CM. Clinical use of

intensity-modulatedradiotherapy:PartI.BritishJournalof

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

duringexternalbeamradiotherapyfornon–small-celllung

cancer:Observationsontumorregressionduringtreatment.

International Journal of radiation Oncology, Biology,

Physics.63(4)1024–1028.


Shyam AggarwalSenior Consultant Medical OncologistSirgangaramHospitalNewDelhi

History of Medical Oncology

Shyam Aggarwal

Origin of the word Cancer

theoriginofthewordcanceriscreditedtothegreek physician Hippocrates (460-370 BC)1,consideredthe“FatherofMedicine.”Hippocratesused the terms carcinos and carcinoma todescribe non-ulcer forming and ulcer-formingtumors. In greek these words refer to a crab,mostlikelyappliedto the diseasebecausethefinger-like spreadingprojections froma cancer called tomindtheshapeofacrab.

I: Cancer chemotherapy

1940–1950

The Beginning:DuringWorldWarII,navalpersonnelwhowereexposedtomustardgas2asaresultofamilitaryaction,onAutopsyobservations hadrevealed profoundlymphoidandmy-eloid suppression.thus, beginningsof themodern eraof cancer chemo-therapy can betraced directlyto the discoveryof nitrogen mus-tard, a chemicalwarfare agent, asan effective treat-ment for cancer.Louis S goodmanandAlfredgilmanreasonedthatthisagentcouldbeusedtotreatlymphoma,sincelymphomaisatumoroflym-phoidcells.thisagentservedasthemodelforalongseriesofsimilarbutmoreeffectiveagents(called “alkylating” agents) that killed rapidlyproliferating cancer cells by damaging theirDNA3,4.

1950-1960

Antifolates: Folic acid (citrovorum factor), avitamincrucialforDNAmetabolism,hadbeen

discoveredbyLucyWills,whenshewasworkingin India in 19374. It seemed to stimulate theproliferation of acute lymphoblastic leukemia(ALL)cellswhenadministeredtochildrenwiththiscancer.

SidneyFarber5fromHarvarddemonstratedthataminopterin,acompoundrelatedtothevitaminfolic acid, produced remission in acute leuke-miainchildren.AminopterinblockedacriticalchemicalreactionneededforDNAreplication.that drug was the predecessor of methotrex-ate, a commonly used cancer treatment drugtoday.WhenadministeredtochildrenwithALLin1948,theseagentsbecamethefirstdrugstoinduceremissioninchildrenwithALL.remis-sions were brief, but the principle was clear- antifolates could suppress proliferation ofmalignantcells,andcouldtherebyre-establishnormal bone-marrow function. remarkably, adecade later at the National Cancer Institute,MinChiuLi6androyHertzdiscoveredthatthesamemethotrexate treatmentalonecouldcurechoriocarcinoma(1958),agerm-cellmalignan-cy that originates in trophoblastic cells of theplacenta. thiswas the first solid tumor to becuredbychemotherapy.

6-MP and vinca alkaloids: Joseph Burchenal,at Memorial Sloan-Kettering Cancer Centerin New York, with Farber’s help, started hisown methotrexate study and found the sameeffects.Hethendecidedtotryanddevelopanti-metabolitesinthesamewayasFarber,bymakingsmallchangesinametaboliteneededbyacelltodivide.WiththehelpofgeorgeHitchingsandgertrude Elion, two pharmaceutical chemists,manypurineanaloguesweretested,culminatingin the discovery of 6-mercaptopurine (6-MP),whichwassubsequentlyshowntobeahighlyactiveantileukemicdrug.

the Eli Lilly natural products group foundthat alkaloids of the Madagascar periwinkle(Vinca rosea),originallydiscoveredinascreenfor anti-diabetic drugs, blocked proliferationof tumor cells. the antitumor effect of thevinca alkaloids (eg, vincristine) was latershown to be due to their ability to inhibitmicrotubulepolymerization,andthereforecelldivision.theUnitedStatesCongresscreatedaNationalCancerChemotherapyServiceCenter(NCCSC) at the NCI in 1955 in response toearly successes. thiswas the first centralizedprogram topromotedrugdiscovery for cancer-theNCCSCdevelopedthemethodologiesandcrucialtools(likecelllinesandanimalmodels)forchemotherapeuticdevelopment.

Era of cancer chemotherapy

1940 – 1950: the begin-ning

• role of Nitrogen Mus-tard, the first alkylatingagent, in treatment oflymphomadescribed.

• Aminopterin and sub-sequently Methotrexatewasfirstusedin1948toinduceremissioninALL.

• royHertzandMinghiuLi used methotexate tocure choriocarcinoma in1958.thefirstsolidcan-certobecuredbychemo-therapy.

• Joseph Burchenal withthe help of 2 pharma-ceutical chemists atMe-morial Sloan-Ketteringdiscoverd6-MP, ahighlyactive anti-leukemiadrug.

• Eli Lily natural productsgroupdiscoveredtheanticancereffectsofVincaal-kaloids(Vincristine)

• National Cancer Chemo-therapy Service CentreattheNCIwascreatedin1955bytheUnitedStatesCongress. the NCCSCdeveloped the method-ologies and crucial toolsfor chemo-therapeuticdevelopment.


1960-1970

Combination chemotherapy: In1965, a major break-through incancer therapy occurred. JamesHolland,EmilFreireich,andEmilFrei hypothesized that cancerchemotherapy should follow thestrategy of antibiotic therapy fortuberculosis with combinationsof drugs, each with a differentmechanism of action. Cancercells could conceivably mutateto become resistant to a singleagent,butbyusingdifferentdrugsconcurrently it would be moredifficult for the tumor to developresistance to the combination.Holland, Freireich, and Freisimultaneously administeredmethotrexate (an antifolate),vincristine (a Vinca alkaloid),6-mercaptopurine (6-MP) andprednisone — together referredto as the POMP regimen — andinduced long-term remissions inchildrenwithacutelymphoblasticleukaemia (ALL). Usingrandomizedclinical studiesbyStJudeChildren’sresearchHospital,the Medical research Council intheUK(UKALLprotocols)andgermanBerlin-Frankfurt-Münsterclinical trialsgroup(ALL-BFMprotocols),ALLinchildrenhasbecomelargelyacurabledisease.

thisapproachwasextendedtothelymphomasin1963byVincenttDeVitaandgeorgeCanellosattheNCI,whoultimatelyprovedinthelate1960sthatnitrogenmustard,vincristine,procarbazineand prednisone — known as the MOPP regimen — couldcure patients with Hodgkin’s and non-Hodgkin’s lymphoma.Currently,nearlyallsuccessfulcancerchemotherapyregimensusethisparadigmofmultipledrugsgivensimultaneously.

II: Adjuvant therapy

Chemotherapydrugsweremosteffectivewhenusedinpatientswithtumorsofsmallervolume.theuseofchemotherapyaftersurgery to destroy the few remaining cancer cells in the bodyis called adjuvant therapy. Adjuvant therapy was tested firstinbreastcancerandfoundtobeeffective. Itwaslaterusedincolon cancer, cancer of the testis, and others. Emil Frei firstdemonstratedthiseffect-highdosesofmethotrexatepreventedrecurrence of osteosarcoma following surgical removal of theprimary tumor. 5-fluorouracil, an inhibitor of DNA synthesis,waslatershowntoimprovesurvivalwhenusedasanadjuvanttosurgeryintreatingpatientswithcoloncancer.Similarly,thelandmarktrialsofBernardFisher,chairoftheNationalSurgicalAdjuvantBreastandBowelProject,andofgianniBonadonna7,workingintheIstitutoNazionaletumoridiMilano,Italy,provedthatadjuvantchemotherapyaftercompletesurgicalresectionofbreasttumorssignificantlyextendedsurvival—particularlyinmoreadvancedcancer.

III: Drug discovery

In 1956, C gordon Zubrod, took over the Division of Cancertreatment of the NCI and guided development of new drugs.

Zubrodhadaparticularinterestinnaturalproducts, andestablishedabroadprogramforcollectingandtestingplantandmarine sources,acontroversialprogramthatledtothediscoveryoftaxanes(in1964)andcamptothecins(in1966).Bothclassesofdrugwere isolatedandcharacterized by the laboratoryof Monroe Wall at the researchtriangleInstitute.

The taxanes: Paclitaxel (taxol)wasanovelantimitoticagentthatpromoted microtubule assembly.this agent proved difficult tosynthesize and could only beobtainedfromthebarkofthePacificYewtree8,whichforcedtheNCIintothecostlybusinessofharvestingsubstantialquantitiesofyewtreesfrompubliclands.After4yearsofclinicaltestinginsolidtumors,itwasfoundin1987(23yearsafteritsinitialdiscovery)to be effective in ovarian cancertherapy.

The camptothecins: Another drugclassoriginatingfromtheNCIwasthe camptothecins. Camptothecin,derivedfromaChineseornamentaltree, inhibits topoisomerase I,an enzyme that allows DNAunwinding. Despite showingpromise inpreclinicalstudies, theagent had little antitumor activityin early clinical trials, anddosingwas limited by kidney toxicity:its lactone ring is unstable atneutralpH, sowhile in theacidicenvironment of the kidneys it becomes active, damaging therenaltubules.In1996amorestableanalogue, irinotecan,wonFoodandDrugAdministration(FDA)approvalforthetreatmentofcoloncancer.Now,thisagentisbeingusedtotreatlungandovariancancers.

Platinum-based agents:Cisplatin,a platinum-based compound,was discovered by a MichiganState University researcher,Barnettrosenberg,workingunderan NCI contract. this was yetanother serendipitous discovery:rosenberg had initially wantedto explore the possible effects ofan electric field on the growthof bacteria. He observed that thebacteria unexpectedly ceased todividewhenplaced inanelectricfield. And that the cause wasan experimental artifact - theinhibitionofbacterialdivisionwas

• In1965forthefirsttimeHolland, Freireich andFreiappliedtheprincipleof combination chemo-therapy in the manage-ment of cancer in thesame lines of antibioticcombinations.

• they used the POMPregimen to achieve longtermremissionsinALL.

• With subsequent devel-opments of the UKALLand BFM protocols ALLinchildrenbecameacur-abledisease.

• the late 1960’s also sawthe development of theMOPP regimen by Vin-centtDeVitaandgeorgeCanellosfortreatmentoflymphomas.

• EmilFreiwasthefirsttodemonstratetheeffectofadjuvant chemotherapyin preventing relapse af-ter surgery for osteosar-coma.

• this drastically changedthe prognosis of breastandcoloncancers in thesubsequentyears.

• Paclitaxel from the barkof Pacific Yew tree wasdiscovered way back in1964,butitsclinicalutil-ityinovariancancerwasestablished23yearslaterin1987only.

• Camptothecin, an in-hibitor of topoisimerase1, was extracted for theChinese ornamental treein1966.Howeverittook30moreyearsin1996tohave a stable analogueof the drug, namely Ir-rinotecan for the use incancersofthecolon,lungandovary.

• Paclitaxel from the barkof Pacific Yew tree wasdiscovered way back in1964,butitsclinicalutil-ityinovariancancerwasestablished23yearslaterin1987only.

• Camptothecin, an in-hibitor of topoisimerase1, was extracted for theChinese ornamental treein1966.Howeverittook30moreyearsin1996tohave a stable analogueof the drug, namely Ir-rinotecan for the use incancersofthecolon,lungandovary.

• theperiod1970to1990saw the development ofvariousanti-cancerdrugsthathadestablishedmed-icaloncologyasastrongforce in the treatment ofcancers.

• Cisplatin that had prac-tically changed the sce-nario of chemotherapyfor solid cancers, wasdiscoveredaccidentally.

• Other important anticancer drugs discoveredduring this period in-clude, carboplatin, ni-trosoureas, Fludarabine,topoisomerase II inhibi-tors (anthracyclines andepipodophyllotoxins)


pinpointedtoanelectrolysisproductoftheplatinumelectroderather than the electrical field. this accidental discovery,however,sooninitiatedaseriesofinvestigations.

Studiesontheeffectsofplatinumcompoundsoncelldivisionculminatedinthesynthesisofcisplatin.thisdrugwaspivotalinthecureoftesticularcancer.Subsequently,EveWiltshawandothersattheInstituteofCancerresearchintheUnitedKingdomextended the clinical usefulness of the platinum compoundswiththeirdevelopmentofcarboplatin,acisplatinderivativewithbroadantitumoractivityandcomparativelylessnephrotoxicity.

Nitrosoureas: Asecondgroup,withanNCIcontract,ledbyJohnMontgomery at the Southern research Institute, synthesizednitrosoureas, an alkylating agent which cross-links DNA.Fludarabine-phosphate,apurineanaloguehasbecomeamainstayintreatmentofpatientswithchroniclymphocyticleukemia.

1970 to 1990

Anthracyclines and epipodophyllotoxins: Many othermolecules were developed, including anthracyclines andepipodophyllotoxins— both of which inhibited the action oftopoisomeraseII,anenzymecrucialforDNAsynthesis.

IV: Supportive care during chemotherapy

Clinical investigators realized that the ability tomanage thesetoxicitieswascrucialtothesuccessofcancerchemotherapyaspatients receiving these agents experienced severe side-effectsthat limited the doses which could be administered limitingin the process the beneficial effects. Many chemotherapeuticagentscauseprofoundsuppressionofthebonemarrow.thisisreversible,buttakestimetorecover.Supportwithplateletandred-celltransfusionsaswellasbroad-spectrumantibioticsincaseofinfectionduringthisperiodiscrucialtoallowthepatienttorecover.Mostoftheseagentscausedveryseverenausea(termedchemotherapy-inducednauseaandvomiting)which,whilenotdirectlycausingpatientdeaths,wasunbearableathigherdoses.thedevelopmentofnewdrugstopreventnausea(theprototypeof which was ondansetron) was of great practical use. thedesignof indwelling intravenouscatheters (eg,Hickman lines,PICClines,subclavianchemo-ports)allowedsafeadministrationofchemotherapyaswellassupportivetherapy.

V: Bone Marrow Transplantation

With the successes of combination chemotherapy and thediscoveryofmanynewagents,therewasafeelingatthistimethatall cancerscouldbe treated, ifonlyonecouldadministerthecorrectcombinationofdrugs,atthecorrectdosesandatthecorrectintervals.theimportantcontributionduringthisperiodwas thediscovery of ameans that allowed the administrationofpreviouslylethaldosesofchemotherapy.thepatient’sbonemarrowwasfirstharvested,thechemotherapyadministered,andtheharvestedmarrowthenreturnedtopatientafewdayslater.thisapproach,termedautologousbonemarrowtransplantation,wasinitiallythoughttobeofbenefittoawidegroupofpatients,includingthosewithadvancedbreastcancer,however,rigorousstudieshave failed to confirm thisbenefit isno longerwidelyusedforsolidtumors.

theprovencurativebenefitsofhigh doses of chemotherapy af-

fordedbyautologousbonemarrowrescuearelimitedtoHodg-kin’sdiseasepatientswhohadfailedtherapywithconventionalcombination chemotherapy. However, autologous transplanta-tioncontinuestobeusedasacomponentoftherapyforanum-berofhematologicmalignancies.

VI: Cancer Treatments: Biologic Therapy

theunderstandingofthebiologyofcancercellshasledtothedevelopmentofbiologicagentsthatmimicsomeofthenaturalsignalsthatthebodyusestoregulategrowth. this cancer treatment,calledbiologicalresponsemodifier(BrM) therapy, biologic therapy,biotherapy, or immunotherapy,has proven effective for severalcancers through the clinical trialprocess. Some of these biologicagents, occurring naturally inthe body, can now be producedin the laboratory. Examples areinterferons, interleukins, andother cytokines.these agents aregiven to patients to imitate or influence the natural immuneresponse either by directly altering the cancer cell growth oractingindirectlytohelphealthycellscontrolthecancer.

One of themost exciting applications of biologic therapy hascomefromidentifyingcertaintumortargets,calledantigens,andaiminganantibodyatthesetargets.thismethodwasfirstusedtolocalizetumorsinthebodyfordiagnosisandmorerecentlyhasbeenusedtoattackcancercells.Scientistsarealsostudyingvaccinesthatwouldboostthebody’simmuneresponsetocancercellsandtherebypreventcancerfromdeveloping.

Hormonal therapy: the hormonal contribution to severalcategoriesofbreastcancersubtypeswasrecognizedduringthistime,leadingtothedevelopmentofpharmacologicalmodulators(eg,ofoestrogen)suchastamoxifen.Forpostmenopausalwomen,aromataseinhibitorsarebetterthantamoxifen.

Targeted therapy: Molecular and genetic approaches tounderstanding cell biology uncovered entirely new signalingnetworks that regulate cellular activities such as proliferationandsurvival.Manyofthesenetworkswerefoundtoberadicallyalteredincancercells,andthesealterationshadageneticbasiscausedbyachancesomaticmutation.

Tyrosine kinase inhibitors: the classic example of targeteddevelopment is imatinibmesylate (gleevec), a smallmoleculewhich inhibits a signaling molecule kinase. the geneticabnormalitycausingchronicmyelogenousleukemia(CML)hasbeenknownforalongtimetobeachromosomaltranslocationcreating an abnormal fusion protein, kinase BCr-ABL, whichsignals aberrantly, leading to uncontrolled proliferation of theleukemia cells. Imatinib precisely inhibits this kinase. BrianDruker9, working in Oregon Health Science University, hadextensivelyresearchedtheabnormalenzymekinaseinCML.Hereasonedthatpreciselyinhibitingthiskinasewithadrugwouldcontrolthediseaseandhavelittleeffectonnormalcells.DrukercollaboratedwithNovartischemistNickLydon,whodevelopedseveralcandidateinhibitors.Fromthese,imatinibwasfoundto

Biologic Therapy

1.Interferons2.Interleukins3.Hormonaltherapy4.targetedtherapy• tyrosineKinaseInhib-itors

• Monoclonal Antibod-ies

• radio labelled Mono-clonalantibodies

• toxin labelled Mono-clonalantibodies


havethemostpromise in laboratoryexperiments.FirstDrukerandthenothergroupsworldwidedemonstratedthatwhenthissmallmoleculeisusedtotreatpatientswithchronic-phaseCML,90%achievecompletehematologicalremission.Itishopedthatmoleculartargetingofsimilardefectsinothercancerswillhavethesameeffect.

Monoclonal antibodies: Anotherbranch in targeted therapy istheincreasinguseofmonoclonalantibodiesincancertherapy..Monoclonalantibodies(orproteins)bindtotumor-associatedcellsurfaceantigensanddestroytumorcellsthroughavarietyofmethods.Althoughmonoclonalantibodies(immuneproteinswhich can be selected to precisely bind to almost any target)have been around for decades, they were derived from miceand did not function particularly well when administered tohumans, causingallergic reactions andbeing rapidly removedfromcirculation.“Humanization”oftheseantibodies(geneticallytransforming them to be as similar to a human antibody aspossible) has allowed the creation of a new family of highlyeffectivehumanizedmonoclonalantibodies.rituximab,adrugusedtotreatlymphomas,isaprimeexample.

Liposomal therapy: Liposomal therapy is a new techniquethatuseschemotherapydrugs thathavebeenpackaged insideliposomes (synthetic fat globules). this liposome, or fattycoating,helpsthempenetratethecancercellsmoreselectivelyand decreases possible side effects (such as hair loss, nausea,and vomiting). Examples of liposomal medications are Doxil(the encapsulated form of doxorubicin) and Daunoxome (theencapsulatedformofdaunorubicin).

References 1. Abeloff: Clinical Oncology, 3rd ed. Churchill Livingston,

2004.pp408-413.

2. gilmanA.theinitialclinicaltrialofnitrogenmustard.AmJSurg1963;105:574-8.

3. goodmanLS,WintrobeMM,DameshekW,goodmanMJ,gilmanA andMcLennanMt.Nitrogenmustard therapy.Useofmethyl-bis (beta-chloroethyl) aminehydrochlorideand tris (beta-chloroethyl) amine hydrochloride forHodgkin’sdisease, lymphosarcoma, leukemia,andcertainalliedandmiscellaneousdisorders.JAmMedAssoc1946;105:475-476.reprintedinJAMA1984;251:2255-61.

4. ht tp : / /en.wikipedia .org /wiki /History_of_cancer_chemotherapy

5. Farber S, Diamond LK, Mercer rD, Sylvester rF, WolffJA. temporary remissions in acute leukemia in childrenproducedbyfolicantagonist,4-aminopteroylglutamicacid(aminopterin).NEnglJMed1948;238:787–793.

6. LiMC,Hertzr,BergenstalDM.therapyofchoriocarcinomaandrelatedtrophoblastictumorswithfolicacidandpurineantagonists.NEnglJMed1958;259:66–74.

7. Bonadonna g, Brusamolino E, Valagussa P, rossi A,BrugnatelliL,BrambillaC,DeLenaM,tancinig,BajettaE,Musumecir,VeronesiU.Combinationchemotherapyasanadjuvanttreatmentinoperablebreastcancer.NEnglJMed1976;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


Manoj Bansal Senior ConsultantPlastic SurgeonPushpanjaliMedicalCentreDelhi

Surgical Oncology and Role of Plastic Surgeon

Manoj Bansal

Significant advances have occurred in themanagement of advanced cancers in thepast two decades. Apart from improving thesurvival rates, thecurrent therapyemphasizesthe preservation or restoration of form andfunction, thereby improving the quality oflife for patients. towards achieving this end,the reconstructive surgeon has made greatcontributions.Aidedby greaterunderstandingofskinperfusionandwiththedevelopmentofnewmicrovascularflaps,reconstructiveplasticsurgery has redefined the management ofmalignancies,whichhasledtotheacceptanceofateamapproachinthetreatmentofcancers.the Plastic surgeon is an important memberof the team, right from treatmentplanning, toexecutionandfollowup.

theroleofreconstructivesurgeryisimportantinthemanagementofmostofthesolidtumorsexceptintracranialandintra-abdominaltumors.theheadandneckmalignanciesare themostcommontheworldoverandthereconstructiveneedsarebothaestheticaswellas functional.Further,theaggressivemanagementofsofttissuesarcomasandothertumorsofthoracoabdominalwallleavehugedefects.rapidadvancementsinthe treatment of tumors of breast has shiftedthe focus from radical mastectomy to breastconservingsurgery,andtheincreasedincidenceofearlyonsetcoupledwithgreaterdemandoffulfillmentofaestheticneedshasmadetheroleofplasticsurgeonallthemoreimportant.

Evolution of Reconstructive Surgery: Duringtheearlyperiodofevolutionofplasticsurgery,there were limited options available and soprimaryreconstructionwasdifficult,unreliableandtimeconsuming.Withthedevelopmentofforehead, deltopectoral and pectoralis majormyocutaneous flaps, primary reconstructionof big defects became possible but requiredat least two stages of surgery. the flaps werelimited in size and their reach was limited.With the advent of micro-vascular free flaps,reconstruction was possible in a single stagewithmatchingcompositetissue.

Head and Neck Reconstruction: Headandneckcancer is one of the leading causes of cancerrelated deaths and disfigurement especiallyin Indian subcontinent. Although there hasbeen significant progress in the managementofheadandneckcancerssuchasintroductionof organ-sparing strategies using concurrentchemo-radiotherapyandbiologicalmodulationofcancerwithepidermalgrowthfactorpathwayinterruption, none of the strategies has come

closetothecontributionmadebyreconstructivesurgery.

reconstructive surgery has improved therespectability of advanced head and neckcancers leading toan improvedqualityof life.Largely, current reconstructive techniques canofferpredictableresultsintherestorationoftheformandfunctionandarefastapproachingtheultimate reconstructive goal of ‘replacing likewithlike’.

Pedicled versus free flaps in head and neck reconstruction: the replacement of thetraditional concept of ‘reconstructive elevator’with theconceptof the ‘reconstructive ladder’hasledtotheprovisionofanoptionofthemostappropriate techniqueof reconstructionas theinitialprocedure.

For many years, pedicled flaps like pectoralismajor myocutaneous flap have been theworkhorse of head and neck reconstructivesurgeons. However, these flaps have somelimitationslike:1. Limited reach because of which there aremore chances of distal flap necrosis andwoundgapeduetotensionbythedownwardpulloftheflap.

2. Bulk and pliability of the tissue in theflap may not always suit the defect to bereconstructed.

3. Difficultyincontouringtheflaptothedefectindifferentplanesthanthatofthepedicledflap.

Althoughallthesedrawbackscanbeovercomeby the use of free flaps, the technique is notfrequentlyadaptedbecauseofvariousreasons.Surgicalexpertise,timefactorandquestionablebenefit inadvancedcaseswithpoorprognosisare some of the arguments against the wideuseof free flaps.Free flapsarealsoassociatedwithsomedrawbacksliketheneedforvigorousmonitoringandre-explorationifrequired.

Oral Cancers

Surgeryisthemainstayforthetreatmentoforalcancers. Functional and aesthetic outcomes ofsurgicalresectionscanbemademoreacceptableby immediate reconstruction using local anddistantflaps.tonguecanbereconstructedafterhemi-oreventotalglossectomyusingpectoralismajor flap (pedicled) or radial artery forearmflap(freeflap).radialforearmflapcanbeusedevenassensateflapfortongue.Likewiseotherdefectsofbuccalmucosa,hardpalateorfloorofmouthcanbereconstructedusingvariousflapstogivegoodfunctionalresult.


References 1. Kiyonori Harii. the role of plastic surgery in surgical

therapyforcancerpatients.Jpn.J.Clin.Oncol.1990;20:48-57

Mandibular Reconstruction

thereconstructiveneedsandchoiceofflapdependsonthesiteofdefectandthedentatestatusof thepatient.Alateraldefectdistal to the premolar teeth, especially in edentulous patientcanbereconstructedusingpedicledflapslikepectoralismajormyocutaneousflapandtrapeziusflap.However,lateraldefectsin dentate patients and anterior mandibular defects requireskeletalreconstruction.Fibulaosseousorosteocutaneousflapshavebecomethefavoredmethyodincentresacrosstheworld.

Breast Reconstruction

theincidenceofbreastcancerisontheriseandtheageatwhichitoccursisonthedecline.thismeanstherearemorebreastcancerpatientswho are of a younger age group.With the increasingawarenessofselfimage,thesepatientspreferimmediatebreastreconstruction after surgery. Such reconstruction should aimatresulting inanaestheticoutcomethatmatchesthepatients’expectationsandwithoutinterferingintheoncologictreatment.Autologoustissue,implantsorbothareusedforreconstruction.Itcanbedoneimmediately,ie,atthetimeofmastectomyorinadelayedfashion,whichdependsonvariousfactors.

Immediate reconstructionItisidealforpatientswithearlydisease(stageIorII).

Advantages 1.Decreasespsychologicaltrauma2.reducedcost3.Lessmorbidity4.Bettersurvival5.Betteraestheticresult

Disadvantages

Potential for delay of adjuvant therapy if postoperativecomplicationsoccur.

Relative contraindications1.AdvancedbreastcancersstageIIIormore.2.requirementofpostoperativeradiation.3.Medicalco-morbiditiessuchassevereobesity,cardiopulmonarydiseaseanddiabetes.

Delayed reconstructionItisusuallyperformedseveralmonthsafterthemastectomy.

Advantages1. Fewer complications as compared with immediatereconstruction.

2. Final pathology results of the breast cancer are available.thereforemoreinformeddecisionregardingreconstructioninthecontextoftheentiretreatmentregimencouldbemade.

Disadvantages1. Prolongsoveralltreatmentofpatient2. radiationchangesmaycompromisetheskinenvelop,

thusresultinginapoorerfinalaestheticoutcome.3. technicallymorechallenging.4. requiresatleasttwostagesandthereforeislesscost

effective.

Methods of breast reconstruction1. Directimplantplacementwithouttissueexpansion-usuallynot possible due to availability of limited amount of skincover.

2. tissueexpansionfollowedbypermanentimplantplacement-mostcommon.

3. Autologous tissue reconstruction using pedicled flaps- Latissimus dorsi flap, transverse rectus Abdominismyocutaneousflap(trAMflap)

4. Freeflaps-FreetrAMflap• Deepinferiorepigastricarteryperforatorflap• Superficialinferiorepigastricarteryperforatorflap• Superiorglutealarteryperforatorflap• Inferiorglutealarteryperforatorflap• transverseuppergracilisflap

Insummary,theroleofreconstructiveplasticsurgeonshouldbeconsistentlyviewedasanintegralpartoftheteamlookingaftercancerpatients.


AK Mittal Laparoscopic Surgeon and UrologistShivamSurgicalandMaternityCentreNewDelhi

Idiopathic Perforation of Gall BladderA Case Report

AK Mittal

gall bladder perforation is an infrequent butfatal disease. It is usually a complication ofacute cholecystitis with or without stone andrarely reported in association with traumaneoplasm chemotherapy or vascular disease.Idiopathic perforation of gall bladder withoutanydemonstrablecauseisworthyofreporting.

History

A healthy male aged 40 years presented inthe Shivam Surgical and Maternity Centre,Karkardooma, New Delhi in Emergency withsevere pain in abdomen with occasionalvomiting.Hehadahistoryofhigh-gradefeverof104°F.therewasnohistoryoftraumaorofdrugabuseoflongduration.thepatientwentfromonehospital toanotherreceivingsymptomatictreatmentonanoutpatientbasis.

Examination

On clinical examination, he was found tohave generalized pain in abdomen withmild distension. Vitals were maintainedwith temperature at 99°F. tachycardia andgeneralized tenderness all over abdomen wasalsoreported.

Investigations

tLC 11900, P91 L4 e4 m4, blood urea 95,creatine2mg,Na135, k 3.2, s. amylase62.2,l.f. normal, and ultrasound showed free fluidin peritoneal cavity with gall bladder edemawithsludge.Ultrasoundguidedfluidaspirationrevealedpurulentgreenishcolor.Aplainx-rayabdomen erect did not show any gas underdiaphragm.

Diagnosis

Keeping in mind that the diagnosis could beperforated appendix or small bowel sealedperforation, high risk consent was taken andexploratory laprotomy done with right midparamedian incision. Operative findingswere that the smallbowel andappendixwerenormal,biliouscoloredfluidabout500mlwassucked out keeping in mind that it could besealed duodenal perforation. Upper abdomenwas explored but duodenumwas found to benormal. there was a small perforation in thegallbladdershowingbileleak.Cholecystectomywas done and the abdomen was closed afterthorough peritoneal wash with a drain in.Postoperativerecoverywasgoodanduneventful.gall bladderwas thick, edematouswith smallgangrenous patch with a perforation, cutgallbladder showed small sludge without anystone.Patientimprovedwell,hisrenalfunctionreturned to normal in 48 hours. the biopsyreportwasAcutecholecystitiswithglandularisproliferans.

Discussion Perforationofgallbladderisreported3to10%of

casesandisusuallyassociatedwithpresenceofstoneingallbladder.Mortalityis12to16%.Itisbelievedthatinitialinflammationischemicallyinduced and thereafter followed by secondaryinfection mostly E.coli and streptococcusfaecalis. In rare cases, cholecystitis mayoccur without stone. this may be because ofinfectionelsewhereinbodyleadingtomucosalinflammation, ischemia, necrosis and finallyperforation.

In 1934, Neimmer presented his classicdescription of gall bladder perforation andmentioned that non obstructive cholecystitisis unlikely to become perforated. Intenseinflammation with virulent infection andexistence of immunocompromised stateleads to thrombosis of blood vessels andtransluminal necrosis and perforation. gallbladderperforationwithoutanyapparentcauseis supposed tobe rareandpresentsadifficultproblem for diagnosis and management. It isoften misdiagnosed as acute appendicitis andat times as sealed duodenal perforation. theyounger patient in an immunocompromisedpatient has a higher incidence of perforation.Peritonitis due to gall bladder perforation isassociated with high mortality as quoted byEssenhigh (39.1%).the reason for this couldbethatacalculouschocystitisisassociatedwithsevereinfectionanddelayindiagnosis.

Mypatient,ayoungmale,sufferedhighgradefever for one day with pain in abdomen. Hewent fromonehospital to anotherhospital insearchoftreatment.Hewasdiagnosedwhenweaspiratedultrasoundguidedpurulentgreenishfluid,anddecidedtoexplorefurther,keepinginmindthat itmaybeaperforationof thesmallbowel or a perforated appendix. It was peroperativediagnosisthatgallbladderwasfoundperforated with the abdomen full of greenishfluid.Delayinsurgical interventionisamajorreason for high mortality and morbidity. Incaseof thispatient,whowas toxicwith renalimpairment,we operated upon after high riskconsent.Postoperativerecoverywasgoodaswegave good coverage of antibiotic therapy. thepatientwasdischargedonthesixthday.

References 1. tsai CJ, Wu CS. risk factors for perforation

of gallbladder.A combinedhospital study ina Chinese population. Scand J gastroenterol1991;26:1027-34.

2. SimmonstC,MillerC,Weaverr.Spontaneousgall bladder perforation. Am Surg, 1989May;55(5):311-3.

3. Croleygg.gangrenous cholecystitis: Fivepatientswithintestinalobstruction.AmSurg.1992May;58(5):284-92.

4. Babbrr.Acuteacalculouscholecystitis:Areview.JClingastroenterol1992;15:238-41.


Parveen Gulati Director Imaging PushpanjaliCrosslayHospitalClinicalDiagnosticCentreMrCentre-greenPark,NewDelhi

Shailender ChaturvediConsultant Radiologist MrCentre-greenParkNewDelhi

Acute Pancreatitis: Imaging

Parveen Gulati and Shailender Chaturvedi

Acute pancreatitis is an acute inflammatorycondition of the pancreas. Diagnosis ofacute pancreatitis is usually made clinically.radiologyhasfourmajorrolesinpatientswithacutepancreatitis.

1. Contributingtothediagnosiswhereclinicalfindingsareequivocal.

2. Stagingoftheseverityoftheinflammatoryprocess.

3. Detectionofthecauseandcomplication.4. Interventional treatment of thecomplications.

Conventional abdominal radiograph and barium studies are occasionally useful indiagnosing acute pancreatitis and indetectinglatecomplications [abscess, stricture, fistulas].these, however, have no role in earlyevaluationof theseverity,which iscrucial formanagement.

Ultrasound is usually indicated early inpatientswithacutepancreatitistolookforthepresence of gallstone/CBD stones. Pancreaticenlargement, necrosis, abscess and fluidcollection can also be seen on ultrasoundexamination,butvisualizationisoftenimpairedbecause of overlying bowel gas, making thedetection of intra-pancreatic abnormality andretroperitonealcollections,difficult.

Imaging proceduresareusuallynotrelieduponasmostcasesofacutepancreatitisarediagnosedclinically. However, often the history andpresentationofthepatientmaynotbestraightforward, and a reliable imaging modality isneededtoestablishthediagnosis.• In patients with mild pancreatitis, Ctadds little as the disease process in suchcases usually regresses spontaneously andrecoveryiscomplete.

• Inpatientswhodonotimprovewithin24to36hoursCtiswarranted.

• In patients with uncertain diagnosis orsuspected severe pancreatitis, Ct is ofgreat help to look for extent of necrosis,haemorrhage, collections, pseudo cystformation and other complications. CtwithbolusIVcontrastenhancementexactlydepictsandquantifiesthepancreaticinjury

and has now become indispensable andintegralpartofnewclassificationsystem.

• the extent of pancreatic inflammationon early scanning correlates well withsubsequent fluid replacement requirementandpseudocystdevelopment.

Acute edematous or interstitial pancreatitis isseenasdiffuseorfocalswellingofthepancreaswith or without obliteration of peripancreaticfat planes andwith orwithout peripancreaticfluidcollectionorphlegmon formation.Whenthe fluid becomes loculated and shows well-definedenhancingwallitiscalledpseudocyst,which can be seen anywhere in the abdomenoreveninthechestorthethigh,howevermostcommonly seen in lesser sac and left anteriorpararenal spaces. Hemorrhage is seen ashyperdenseareaonplainCtimages.Pancreatitisis graded in five distinct groups fromA to E,whichfairlycorrelateswiththeseverityofthedisease, clinical followup findings,morbidityandmortality.

Bolus enhanced CThasshownoverallaccuracyof87%withasensitivityof100%fordetectionof severe pancreatic necrosis, which falls tosensitivity of 50% if onlyminimal necrosis isthere. Most patient with severe pancreatitisexhibitoneorseveralpancreaticfluidcollections(gradeDandE)ontheinitialCtstudy.

Pancreatic necrosis is seen as area of non-enhancementonIVboluscontrastenhancedCtscan. Pancreaticnecrosis canbedifferentiatedfromabscessasabscessesaremorehomogeneousand show well defined enhancing walls. theextent of pancreatic necrosis is quantifiedinto<30%,30-50%&>50%of thepancreaticgland.

theaccuracy of CTforassessingthepresenceandextentofpancreaticparenchymalinjurydependson several factors, with the most importantbeing the quality of the study. Intravenouscontrast material is essential, particularly inpatients with severe pancreatitis1 to enablevisualization of pancreas and differentiationof the gland from heterogeneous collection orfluid and peripancreatic inflammatory tissue.Pancreatic necrosis is seen as area of non-enhancement. Smaller area of fluid collection


withinpancreaticparenchymasometimesmimicsnecrosisandshould not bemistaken. Ct scan done early within 12 hoursmay not show necrosis well, as it develops after 24-48 hoursonly.Ctdoesnothelpand isnotused to assess the extentofretropancreaticfatnecrosis.Inpractice,allheterogeneousareasofperipancreaticcollectionsareconsideredareasoffatnecrosisunlessprovedotherwise.

Infectivecomplicationsofthepancreatitisareuncommonbutlifethreatening.Overallincidenceofpancreaticabscessis4%,whichincreaseswithseverityoftheattackandcanbeashighas50-70%ina fatalcaseofnecrotizingpancreatitis.Pancreaticabscess isdifferentfrominfectednecrosisasithasmoredefinedfocalpuscollectionwith definite enhancingwalls; infectednecrosis, onthe other hand, is a diffuse inflammation in the pancreas andperipancreaticregionwithlessdefinedwalls.Pancreaticabscessseldomoccursbeforefiveweeksofsymptomsbywhichtimethesymptomsofacutepancreatitishavealreadysubsided.Pulmonaryandrenalinsufficiencyisalsorelativelyuncommoninpatientswithabscessformation.AvarietyofCtfindingshelpdiagnosetheabscess.MostdiagnosticCtfindingslieindemonstrationofgasinpancreaticorperipancreaticregion,whichisproducedbygasformingbacteria.thegashowever,canarisefromfistulouscommunicationwithbowelloopalso.Ifgasisnotpresentandifthepatienthashighpersistent feverandhighleucocytecount,Ctguidedaspirationofthecollectionisstronglyrecommended.Pancreatic abscess usually requires surgical debridement. Ctguidedpercutaneousdrainagehowevermayplayaninitialrole.

Fluidcollectionandpseudocyst formationcanoccurwithinoradjacenttothepancreas.Pseudocystsarethecollectionofnecrotictissue,oldbloodandpancreaticsecretions.thesesecretionsarerichinproteolyticenzymesandbecomeloculateinlessersacormayextendalongretroperitonealtissueplanesinanydirection.Pseudocystshavebeenreported in themediastinum,neckandeven in the groin. they can also be present intramurally inbowelloopsleadingtoobstruction.Amaturepseudocysthasawelldefinedwallofgranulationtissueandfibrosedtissue.BothCt and USg have been reported to be good in following upthephlegmonandpseudocyst.Inmostofthecasespseudocystresolves within 4 weeks. Pseudocysts that persist beyond sixweeksneed to bedrained. Percutaneous catheter drainage canalsobeperformedwhichisassociatedwithlessermorbidityandmortalityandacurerateofabove70%.Someofthecollectioncommunicatewiththepancreaticduct.Ifpancreaticduct–fluidcommunicationisdemonstratedbyErCPandthereisnoductalobstruction between papilla and its communication, then thepercutaneousdrainageisusuallysuccessful.

If thedownstreamduct ispartiallyobstructedor ifan isolatedfistulatotheupstreampancreaticductissubsequentlyrecognized,distalpancreatectomywillusuallybenecessary.Whileinsertingthecatheter,traversingtheadjacentorganshouldbeavoided.

Vascular involvement bypancreatitis is not uncommon.Majorperipancreatic and intrapancreatic arteries and veins may beerodedorthrombosedbythedirecteffectofpancreaticenzymes.this can lead to hemorrhage due to vascular erosion, ruptureof varices or leakage from arterial pseudoaneurysm. ContrastenhancedCt,Dopplerandangiographyhelpidentifythevascularcomplications.

gastro-intestinal involvement by pancreatitis is frequent.

gastrointestinaltractcanbeinvolvedbydirectextensionofthe

inflammatoryprocessfromthecontiguouspancreasresultingin

perforation,necrosisoredemaofthewallofthestomachorbowel.

Itcanalsobesecondarilyinvolvedbydissectionofthepancreatic

enzymes throughmesenteric attachments or by thrombosis or

stenosisofmesentericarteriesandveinsresulting in ischemia,

necrosisorperforation.Majorvenousthrombosiscanbereadily

pickedbyboluscontrastenhancedCtseenashypodensefilling

defect. the ischemic bowel can also be diagnosed on bolus

contrastenhancedCtwhichappearasthickwallededematous

long segment of bowel loopwith reduced enhancement of the

wall, relatively increased enhancement of the mucosal and

serosalliningandobliterationofthesurroundingfatplanes.

Biliary duct involvement: Edema in the head of the pancreas

causedbyacutepancreatitiscancausetransientcompressionof

theCBD.theCBDmaybedirectlyinvolvedinacutenecrotizing

pancreatitis leading to stenosis or destruction. In such cases

surgicalornonoperativedrainageisnecessarytoavoidsecondary

biliarycirrhosis.BiliaryductischemiacanbedetectedbyUSg,

CtorDirectcholangiographyusingErCPorPtC.

Role of MRI: recent advancements in MrI technology with

developmentofparallel imagingandsuperbbreathholdscans

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

specificityofCECtandMrIhasbeenfoundtobealmostsame.

MrIissuperiortoCtindemonstratingtheunderlyingetiologies,

such as choledocholithiasis or pancreatic divisum. the major

limitation ofMrI is in evaluation of very sickpatients on life

support.

To summarise, contrast enhancedCtpresently is the imaging

modality of choice to help stage the severity of inflammatory

process,directpancreaticnecrosisanddepictlocalcomplications

However MrI is fast replacing the CECt in number of these

patients. Ct severity index has shown to be an excellent

correlationbetweenthedevelopmentoflocalcomplicationand

the incidence of mortality. Non-surgical intervention can be

performedunderUSgandCtguidancewithreducedmortality

and morbidity as compared to the surgical intervention. At

present,contrastenhancedCthasbecomeanintegralpartand

almostindispensableinassessingtheinitial injuryandthusto

helpinpropermanagementofthepatient.

References 1. Balthazar EJ. Acute Pancreatitis: Assessment of

Severity with Clinical and Ct Evaluation. radiology2002;223:603.


“Physical therapists are an integral partof inpatient and outpatient treatment ofneurological andmusculoskeletal injuries anddisabilities, “write Scott E. rand, MD, fromthe Conroe Medical Education Foundation inConroe,texas, andcolleagues. “theyalsocanassist with an augment the care of patientswith cardiac, pulmonary, and developmentaldisorders.Familyphysiciansshouldhavesomeunderstanding of the various treatments andmodalitiesusedbyphysicaltherapists.”

Although existing guidelines recommendphysical therapy as part of the treatmentregimen for musculoskeletal conditions, theselackspecificrecommendationsregardingwhichexercises and adjunct modalities should beused.

to decrease pain and increase mobility andflexibility, physical therapists use specifictechniquesandmodalities.Inpatientswithlowback pain, some studies suggest that havingphysical therapists instruct patients on howto perform specific exercises may improveoutcomes. Evidence of efficacy is variablefor most modalities, and there is a death ofrandomized controlled trials to support theiruse.

Because any given clinical condition maybenefitfromuseofseveraldifferentmodalities,treatment decisions for an individual patientshouldbebasedontheexpertiseofthetherapist,availabilityof theequipment,andgoalssetbytheattendingclinician.

When prescribing physical therapy, theclinician should specify the diagnosis (usingproper coding to allow for accurate insurancebilling and reimbursement); type, frequency,anddurationoftheprescribedtherapy;specificprotocolsortreatmentsthattheclinicianwantsthetherapisttouse;therapeuticgoals;andsafetyprecautions, such as joint range-of-motionlimitations, weight-bearing limitations, andillnesses that affect participation in therapy).Foratherapisttoperformtherequestedservices,cliniciansignatureanddatearerequired.

Frequently used modalities of physicaltherapy include ultrasound, phonophoresis,iontophoresis, electrical stimulation, and low-levellasertherapy.

In ultrasound therapy, high-frequency soundwavesareusedtowarmsuperficialsofttissuesorwiththeintentionoffacilitatingtissuehealingatthecellularlevel.Ultrasoundmaybeusefulfortendoninjuriesorforshort-termpainreliefofmusclestrainorspasm,butitshouldnotbeusednearmalignant tumors,nerve tissue inapatient who has recently had a laminectomy,

joint replacements, permanent pacemakers,thrombophlebitis, eyes reproductive organs,areasofacuteinflammation,epiphysealplates,or over breast implants. ForOlympic athletes,exemptionisneededforuseofultrasound.

Phonophoresis refers to use of ultrasound todelivertherapeuticmedicationstosubcutaneoustissues. this modality may be useful forinflammatory conditions including tendonitis,arthritis,andbursitis,andcontraindicationsarethesameasforultrasound.

Duringiontophoresis,anelectriccurrenthelpsdeliver ionically charged substances throughthe skin to reach deeper tissues. therefore,it may be indicated for calcific tendinopathy,inflammatory conditions, or hyperhidrosis.Contraindications to use of iontophoresisinclude allergy or sensitivity to the substancebeing applied, open wounds, or impairedsensation.Iontophoresisalsoshouldnotbeusedintheimmediatevicinityofmetallicimplants,wires,orstaples.

Electrical stimulation causes a therapeuticeffectbygeneratinganactionpotentialinnervetissue, thereby causing a muscle contractionor change in sensory input.Electronicmusclestimulationmaybeusefulformusclespasmorcontusion, whereas transcutaneous electricalnervestimulationmayhelprelieveneuropathicpain. Electrical stimulation is contraindicatedin patients with cardiac pacemakers, knowncardiac arrhythmias, or thrombophlebitis orthrombosis.Itshouldnotbeusedatallontheabdomenorpelvisofpregnantpatients,anditshould be used only with caution in patientswith cardiac disease, malignant tumors, openwounds, or in thosewith impaired sensation,cognitivefunction,orcommunicationability.

Low-level laser therapy acts via absorptionof photon radiation, thereby affectingcellular oxidative metabolism and reducingconcentrations of prostaglandin E2. thismodality may be effective for minormusculoskeletalpain,carpaltunnelsyndrome,osteoarthritis,orrheumatoidarthritis.However,it should be used with caution in patientswith malignant tumors or in those beingtreatedwithanticoagulants, corticosteroids,orimmunosuppressants,anditshouldnotbeusedontheuterusofpregnantpatients.Patientsandtherapistsshouldusesafetygogglestolimiteyeexposuretotherapeuticwavelengths.

Specific clinical recommendations are asfollows:• Supervised therapeutic exercise improves

outcomesinpatientswhohaveosteoarthritisorclaudicationoftheknee(levelofevidence,B).Comparedwithhomeexercisehasbeen

Study Report

Medical NewsPhysical Therapy for the Family Clinician


showntoimprovewalkingspeedanddistance.• Comparedwithusualcare,iontophoresisisassociatedwith

improved outcomes in patients with myositis ossificans(levelofevidence,B).

• In patients with osteoarthritis and rheumatoid arthritis,low-level laser therapy has been demonstrated to offerlimited benefit (level of evidence, B). this modality hasbeenassociatedwith symptomaticbenefit in the treatmentofseveralinflammatoryconditions,withoutknownadverseeffects.Betterstandardizationshouldhelpdefinetheroleofthismodality.

“thefrequencyanddurationofphysicaltherapytreatmentswillvarybasedonthepatient’scondition,”thestudyauthorsconclude.“Acute muscle strains often benefit from daily treatment overa shortperiod,whereas chronic injuries areusually addressedlessfrequentlyoveranextendedperiod…itisimportantforthephysicaltherapisttodocumentthepatient’sprogresssothatthephysiciancanmodifythecareplan,ifneeded.”

Clinical Context: Forpatientswithneurologicandmusculoskeletalinjuries and disabilities, physical therapy is a cornerstone ofmanagement.Inaddition,physicaltherapycanbeusefulinthetreatmentofpatientswithcardiac,pulmonary,anddevelopmentalconditions. therefore, it is useful for family practitioners andprimarycareproviders tobe familiarwithavailablemodalitiesofphysicaltherapyandtreatmentregimens,andindicationsandcontraindicationsfortheiruse.

treatmentdecisionsforanindividualpatientshouldbebasedontheexpertiseofthetherapist,availabilityofneededequipment,and goals set by the attending clinician. the present reviewdescribes recommended use of various modalities of physicaltherapy and necessary components of a physical therapyprescription.

Study Highlights

• thephysicaltherapyprescriptionshouldincludediagnosis(with proper coding for accurate insurance billing andreimbursement); type, frequency, and duration of theprescribed therapy; preferred protocols or treatments;therapeuticgoals;andsafetyprecautions (eg. Joint range-of-motionandweight-bearing limitations,andconcurrentillnesses).

• Foratherapisttoperformtherequestedservices,cliniciansignatureanddatearerequired.

• Frequencyanddurationofphysicaltherapytreatmentsvarybasedonthepatient’scondition.Acutemusclestrainsmaybenefitfromashortperiodofdailytreatment,whereaslessfrequenttreatmentduringalongerperiodisappropriateforchronicinjuries.

• the physical therapist should document the patient’sprogresssothatthecliniciancanmodifythecareplanasneeded.

• Inultrasoundtherapy,high-frequencysoundwaveswarmsuperficial soft tissues or promote tissue healing at thecellularlevel.

• Ultrasoundmaybeusefulfortendoninjuriesorforshort-termpainreliefofmusclestrainorspasm.Itshouldnotbeusednearmalignanttumors,nervetissueinapatientwhohasrecentlyhadalaminectomy,jointreplacements,permanentpacemakers, thrombophlebitis, eyes, reproductive organs,areas of acute inflammation, epiphyseal plates, or overbreastimplants.

• Exemption is needed for use of ultrasound in Olympicathletes.

• Phonophoresis, or ultrasoundused todeliver therapeuticmedications to subcutaneous tissues, may be useful forinflammatory conditions (eg, tendonitis, arthritis, andbursitis).Contraindicationsarethesameasforultrasound.

• During iontophoresis, electric current delivers ionicallycharged substances through the skin todeeper tissues. Itmaybe indicated for calcific tendinopathy, inflammatoryconditions, or hyperhidrosis, and is contraindicated forallergyorsensitivitytotheappliedsubstance,openwounds,orimpairedsensation.Itshouldnotbeusednearmetallicimplants,wires,orstaples.

• Electricalstimulationgeneratesanactionpotentialinnervetissue, which causes a muscle contraction or change insensory input. Contraindications are cardiac pacemakers,cardiac arrhythmias, thrombophlebitis, thrombosis,and abdominal or pelvic use in pregnancy. It should beused onlywith caution in patients with cardiac disease,malignancy, open wounds, or in those with impairedsensation,cognition,orcommunication.

• Electronicmusclestimulationmayrelievemusclespasmorcontusion;transcutaneouselectricalnervestimulationmayhelpneuropathicpain.

• Low-level laser therapy acts via absorption of photonradiation, affecting cellular oxidative metabolism andreducing concentrations of prostaglandin E2. It may beeffective for minor musculoskeletal pain, carpal tunnelsyndrome,osteoarthritis,orrheumatoidarthritis.

• Low-level laser therapy should be used with caution inpatientswithmalignanttumorsorinthosebeingtreatedwithanticoagulants,corticosteroids,orimmunosuppressants.Itshould not be used over the uterus of pregnant patients.Safety goggles are needed to limit eye exposure totherapeuticwavelengths.

• Supervised therapeutic exercise improves outcomes forosteoarthritis or claudication of the knee. Supervisedtherapeuticvshomeexercisehasbeenshownto improvewalkingspeedanddistance.

• Iontophoresisvsusualcareimprovesoutcomesinpatientswithmyositisossificans.

• In osteoarthritis and rheumatoid arthritis, low-level lasertherapyhasbeenshowntoprovidelimitedbenefit,withoutknown adverse effects. Better standardization should behelpful.

• Aphysicaltherapyprescriptionshouldincludediagnosis;type, frequency, and duration of the prescribed therapy;specificprotocolsortreatmentsthattheclinicianwantsthetherapisttouse;therapeuticgoals;andsafetyprecautions.Foratherapisttoperformtherequestedservices,cliniciansignatureanddatearerequired.

• Supervised therapeutic exercise improves outcomes inpatientswhohaveosteoarthritisorclaudicationoftheknee.Comparedwithusualcare,iontophoresisisassociatedwithimprovedoutcomesinpatientswithmyositisossificans.Inpatientswithosteoarthritisandrheumatoidarthritis,low-levellasertherapyhasbeendemonstratedtoofferlimitedbenefit.LevelofevidenceforalloftheserecommendationsisgradeB.

Target Audience: this article is intended for primary careclinicians, physiatrists, physical therapist, neurologists,orthopedists, rheumatogists, andother specialistswhocare forpatients with musculoskeletal and other conditions requiringphysicaltherapy.

goal: the goal of this activity is to provide medical news toprimary care clinicians and other healthcare professionals inordertoenhancepatientcare.

Source: Barclay L. Physical therapymodalities helpful for theFamilycliniciantoknow.Accessed:http://www.medscape.com/viewarticle/567325. Various treatments and modalities that afamily clinician should know and include in physical therapyordersare reviewed inanarticlepublished in theDecember1issueoftheAmerican Family Physician.


Pushpanjali Health Care Events and Initiatives

Dr. Arvinder delivering his talk

Dr. Anish Aggarwal making his presentation

Welcome!PushpanjaliHealthcareis

proud towelcomeyoung

Dr.gauravAggarwalwho

on completing his MD

in Medicine has taken

over asMedical Director

ofPushpanjaliMedicalCentreHeart&trauma

Hospital. team Pushpanjali wishes the new

MedicalDirectorgreatsuccess inhisnewrole

assignment.

Lecture onMulti disciplinary Approach to Pain ManagementPushpanjali 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,NewYork,USA.

thelecturewasattendedbyover100practicing

physiciansfromacrossEastDelhiandadjoining

areas. Dr. M Abbass, President, IMA and Dr.

SNMishra, Secretary-general, IMAwere also

present.

Guest Lecture on“The Enigma of Spondyloarthro-pathies”Carrying on with the legacy of CME, yet

anotherguest lecture formedicalpractitioners

was organized on 20th April, 2008 at IMA

EDB Bhawan. Eminent and well known

rheumatologist Dr. AnishAggarwal discussed

“the Enigma of Spondyloarthropathies” and

otherrheumaticconditionswithaveryinterested

audience.Inaverylucidmannertheattributes

ofrheumatismbesidesmanagementapproach

of the samewere put across byDr.Aggarwal,

invitinglotsofquestionsandinteractionamong

theaudience.

thelecturewassponsoredbySanofiAventis.

Sunday May 11th, 2008 was fixed for the religious Anushthan of Pushpanjali Crosslay Hospital.Dr.PDgarg andAtulgandotrawere assigned

the responsibility of organizing the event.

this includedworking on the list of invitees,

designing invitations, delegating work related

to the dais, PA system, media, tent, catering

etc.theplanningandactionundertheoverall

leadership of Dr. Vinay Aggarwal started six

weeksbeforetheD-Day.

Every member of Crosslay not only happily

accepted their assigned rolesbutworkedwith

diligence and initiative. the execution of the

event was typical of a programmed conveyor

belt,despiteaheavyshowerandthunderstorm

thenightbefore.

A team of learned pujaris from Brindaban

startedaYagnainthepremisesofPCHfrom9in

themorningundertheoverallresponsibilityof

Mr.Kaushik,whoworkedwithtotaldevotion

Vaasthu anushthan puja being performed


and dedication.

the Yagna con-

cluded in the

presenceofDidi

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.

Inthemeantime,

inviteesarrivedatthemainpandalinlargenumberswitheach

onebeingreceivedattheentranceandpersonallygreeted.Over

1700guestsbesidesPushpanjaliHealthcareteamandtheirre-

spectivefamiliesattendedthefunction.

Dr.VijayAgarwalbriefedthedignitariesonthedias,mediaand

guestsonsalientfeaturesofPCHandthesamewaslaudedby

oneandall.

DidiMaaSadhaviritambharablessedPCHandtheleadership

whileShrirajnathSingh(Chiefguest),Dr.rameshPokhryial,

ShriIndreshKumarandotherdistinguishedguestsappreciated

the initiative and courage of the entire team for undertaking

suchagiganticchallengeofputtingupahealthcarefacilitythat

isnotonly timelybutalsoaboon tocommunity.Eachoneof

themwishedPCHgreatsuccessandwantedPCHtobecomea

rolemodelamonghealthcarefacilitiesacrosstheworld.

thefunctionwasfollowedbyPreetiBhoj.Despitethedaybe-

inghotandhumid,everyonethoroughlyenjoyedtheafternoon.

Smilesofsatisfactionwastheretobeseenonthefaceofevery

teammemberandtheleadershipforputtingupafineshowas

awell-knitteam.

first Dr Lucy Oommen AwardSt. 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

intheareaofwomen’s

health.Dr.ShardaJain

has worked at length

in areas of social

upliftmentandpublic

education on issues

likefemalefeticide.

It is amatter of great pride and honor thatDr. Jainwas thus

felicitated.

Ist Inter Hospital Nursing Quiz Contestthe 1st Inter Hospital Nursing Quiz Contest held on May 7

(Preliminaryround)andMay14(grandFinale)wasarunaway

success. the Quiz Contest involved over 10 top corporate

hospitalsofNCrwithover60participants.

CecilyBabuofArtemesHospitalgaveatoughfightinthefinals

to other four finalists and won the championship that was

commemorated with a beautiful rotating trophy and a cash

awardofrs.10,000.CongratulationstoCecily!

Now–PCHNurseshaveabigchallengetobringbacktherotating

trophyin2009tothehomeground!

Ancy receives trophy for winning nurses quiz from Akhil Jain

Dr. Sharda Jain in her moment of glory

Dr. Vinay Aggarwal escort Shri Ashok Singhal Ji to the dais

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

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


20th June 2008 - Dyspepsia – An approach to management A Lecture by Dr. Dinesh Sinhal & Dr. Pankaj TyagiChaired by : Dr. Neeraj JainAguestLecturebyDr.DineshSingalandDr.Pankajtyagiwasorganizedon20June,2008attheIndianMedicalAssociation,EastDelhiBranchundertheaegisofthecontinuingMedical

EducationProgramme.

Dr.NeerajJain,Sr.Consultantinthedepartmentofgastroenter-ology atPushpanjaliMedicalCentre andPushpanjaliCrosslayHospitalchairedthesession.Dr.DineshSingalandDr.Pankajtyagispokeonthetopic“Dyspepsia–Anapproachtomanage-ment”.Over75medicalprofessionalfromEastDelhiattendedthelecture.

An interactivesession followed the lecture,where thequeriesanddoubtsoftheaudienceregardingthisissuewereanswered.

theeventwassponsoredbySunPharma.

1st July 2008

A “Red Letter Day” for Pushpanjali Healthcare

DrVinayAggarwal, our ever ebullient andvibrant leaderwashonoredwithDrBCroyAwardonIstJuly,2008byDrPratibhaPatil, President of India at a glittering function at rashtrapatiBhawan,NewDelhi.

26th July 2008Spreadingthemessageof“LivingBeautifully”,AlecturesessionbyDrDineshBhargavawasorganizedbyShriKrishnMedical&researchCentreunder the leadershipofDrHarihanatMayurViharPhase–1.Over100ladiesofallagegroupsattendedthesessionwhichwashighlyinteractiveandarousedlotofinterestamongparticipantsregardingbenefitsfromAestheticSurgeryas

itfacilitateslivingbeautifullybothphysicallyandmentally.

Chairperson Dr. Neeraj Jain sharing his experiences

Dr. Dinesh Bhargava addressing the delegates

Healthiscertainlymorevaluablethanmoney,becauseitisbyhealththatmoneyis

procured;butthousandsandmillionsareofsmallavailtoalleviatethetorturesof

thegout,torepairthebrokenorgansofsense,orresuscitatethepowersofdigestion.

Povertyis,indeed,anevilfromwhichwenaturallyfly;butletusnotrunfromone

enemytoanother,nortakeshelterinthearmsofsickness.

Johnson


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You are invited to contribute your articles,case reports, clinical experiences and anyotherrelevantmaterialwhichisforthebenefitof clinical community at large. the articles/contributionshouldbesent to:

The Editor in-ChiefDr. Vinay Aggarwal

&

The EditorDr Ashok Grover

PUSHPANJALIMEDICALPUBLICAtIONSPVt.LtD.

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All Manuscripts submitted to Medi-Focusshould not have been published in any formin any other publication, and become theproperty of the publishers. All manuscriptsmustbeaccompaniedbythefollowingwrittenstatement signed by all the authors. “theundersigned author (s) certify (ies) that thearticle is original, is not under considerationby any other journal, and has not beenpreviouslypublished.Allcopyrightownershipof the manuscript entitled (title of article)is hereby transferred to the publishers ofMedi-focus.”

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Structured Abstract. Should be a factualcondensationoftheentireworkwithobjective,methods, results, conclusions and shouldbe in one para. the abstract should statethe purposes of the study or investigation,basic procedures (selection of study subjectsor laboratory animal; Observational andanalytical methods), main findings (givingspecific data and their statistical significance,if possible), and the principal conclusion. Itshould emphasize new and important aspectsof thestudyorobservations.

Clinical Briefs must not exceed 1000 wordswithone figureand5-8references.

text. Authors must consider and follow theformat : Introduction, Material and Methods,results, Discussion, and Conclusion (ifnecessary). the matter must be written in amanner which is easy to understand, andshould be restricted to the topic discussed.Donotusevertical linesorunderlining inthetext.

Acknowledgmentsshouldbeplacedasthelastelementof the textbeforereferences.

Abbreviate measurements (cm, ml).Abbreviations should be used sparingly andmustbeprecededby the full forminitially.

references. In citing other work, onlyreferences consulted in theoriginal shouldbeincluded.Ifitisagainstcitationbyothersthisshouldalsobestated.

Use the Sequential numbering system.Arrange the reference list in the sequence inwhich the references are first cited. In thetext, references cited should be superscriptedandshouldappearon topof the lineafter thepunctuation. responsibility for the accuracyand completeness of references lies with theauthor.

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the Journal follows the Vancouver system ofreferences. references should be numberedandlistedconsecutivelyintheorderinwhichthey are first cited in the text. tables shouldbe identified in the text by superior Arabicnumerals.thefulllistofreferencesattheendofthepapershouldinclude:namesandinitialsofallauthors (unlessmore than6,whenonlythe first 3 are given followed by et al); thetitleof thepaper; the journal title abbreviatedaccording to the style of IndexMedicus; yearof publication; volume number; first and lastpage numbers. references of books should


give the book title, place of publication, publisher and year;those of multiple authorship should also include the chaptertitle, first and last page numbers, and names and initials ofeditors.

1. Mehta MN, Mehta JN. Serum lipids and ABO bloodgroups in cord blood of neonates. Indian J Pediatr 1984;51 :30-43.

2. Smith gDL. Chronic Ear Disease. Edinburgh; ChurchillLivingstone,1980 :78-81.

3. Malhotra KC. Medicogenetic problems of Indian tribes.In Verma IC, ed. Medical genetics in India. Vol. 2.,Pondicherry;AuromaEnterprises,1978;51-55.

Papers accepted but not yet published should be included inthe references followed by “In press”. those in preparation,personal communications and unpublished observationsshouldbereferred toassuch in the textonly.

For more detailed information about the Vancouversystem, authors should consult “Uniform requirements formanuscripts submitted to biomedical journals’ (Br MedJ.1982;284 :1766-70).

Legends.Adescriptivelegendmustaccompanyeachillustrationandmustdefineallabbreviationsusedtherein.

Illustrations and graphs. Submit glossy black and whitephotographs.thecostreproductionofcolourphotographswillbe borne entirely by the author.Number all illustrationswithArabicnumericals (1,2).

tables. these must be self-explanatory. the data must beclearly organized and should supplement and not duplicatethe text. Explanatory matter should be given as footnotes.Statisticalanalysesusedmustbeappropriate.Eachtablemusthave a title and should be numberedwithArabic numericals(1,2).

Manuscript Submission Checklist

1. threecopiesofmanuscript inhardcopy

2. Name and address of author responsible forcorrespondence.

3. StructuredAbstract (150-200words)&3-5keywords.

4. references,citedconsecutively in the text.

5. threeglossyprints for illustrations.

6. Documentation of permission to reuse any previouslypublishedmaterial.

7. Covering letter, including statement of originality andsignifyingapprovalof finalcopybyallauthors.

8. Uponfinalacceptanceofthemanuscript,aCDdiskinMSWord should be submitted. the disk should be labeledwith the title of article, file name and version used andmustcontain the final revisedmanuscriptmaterial.

cancer april 2008

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