Commentary (Petrelli): Managing the Peritoneal Surface Component of Gastrointestinal Cancer

Dr. Paul H. Sugarbaker hasspent most of his surgical oncologycareer researching andtreating patients with peritoneal surfacemalignancies. His participationin the treatment of 385 patients withappendiceal malignancy over a 15-year period is probably the largestsuch experience ever reported.[1] Dr. Sugarbaker has demonstrated that inpatients with peritoneal carcinomatosisfrom gastrointestinal malignancies,the best treatment results are associatedwith mucinous epithelial malignancyof the appendix.Intracoelomic CancerDissemination
Dr. Sugarbaker's research has ledhim to describe the profound impactthat intraperitoneal fluid has on thepatterns of cancerous disseminationwithin the peritoneal cavity.[2] Basedon observations collected from hisexperience in reoperative surgical procedures, he has described and contrastedthree important mechanismsof intracoelomic cancer dissemination.These patterns include (1) gastrointestinalcancer implantation, which occursin a random fashion immediatelyadjacent to the primary neoplasm thathas penetrated the serosal surface;(2) the development of ascitic fluid ormucus by cancers that subsequentlycause the characteristic redistributedpattern of implants; and (3) intraperitonealcancer dissemination caused bysurgical dissection, which is referredto as tumor cell entrapment.Surgeon's Skill
Early in my career, I was severelycritical of Dr. Sugarbaker's reportsabout the management of peritonealsurface malignancies. This criticismwas based on the fact that his datawere not reproducible by otherinvestigators. However, I am nowconvinced that this criticism was unwarranted.A surgeon treating patientswith peritoneal surface gastrointestinalcancer must master the technical skillsrequired for the completion of peritonectomy,and Dr. Sugarbaker has emphasizedthat this procedure is necessary toremove all visible cancer in an attemptto leave the patient with only microscopicresidual disease. I believe that the inabilityto reproduce Dr. Sugarbaker'sresults has been in some part due to thefailure to perform a complete peritonectomy.This meticulous procedure mustbe mastered to achieve the same resultsas Dr. Sugarbaker.Just mastering the technical aspectsis not enough. Surgeons must also understandthe dissemination patterns ofgastrointestinal cancer spread to peritonealsurfaces in order to develop successfultreatment programs. As Dr.Sugarbaker states in part 1 of his article,unless all sites are inspected and allfoci of cancerous implants removed,"patients will be left with gross diseaseand a poor long-term outcome." Understandingthe natural history has provento be helpful in understanding thepotential deadly nature of peritonealcarcinomatosis. Unfortunately, peritonealcarcinomatosis does not equatewith a good quality of dying[3]; largeand small bowel obstruction with associatedbowel perforation does not leadto an easy death.Multidisciplinary Approach
Although in the past the diagnosisof peritoneal carcinomatosis from intra-abdominal gastrointestinal tumorscarried a fatal prognosis, recent reportshave differed.[4,5] These reportshave demonstrated that the treatment of peritoneal carcinomatosis is a particulararea in oncology whereprogress needs to continue.It is sometimes difficult for readersto distinguish between the standardof care and investigationaltreatments. One major advance stemmingfrom Dr. Sugarbaker's experienceis that the standard of care forthe treatment of peritoneal surfacemalignancies must involve a multidisciplinaryteam approach. Withoutquestion, this is best illustrated by avisit to Dr. Sugarbaker's multidisciplinaryunit at the Washington CancerInstitute in Washington, DC. Overthe years, he has assembled a team ofenterostomal therapists, social workers,nutritionists, surgical and medicaloncologists, and other paramedicalpersonnel who make his program asuccess. A multidisciplinary team approachis mandatory for any institutionthat wants to initiate a treatmentprogram for patients with peritonealsurface malignancies.Areas for Further Research
Although there is increasing evidencedocumenting some degree ofefficacy for such treatment,[4,5] severalissues still need to be addressed.Areas in which there are a wide rangeof research opportunities include(1) the efficacy and safety of open vsclosed peritoneal chemotherapy perfusion,(2) the proper choice of chemotherapeuticoptions and perfusiontechniques, (3) in intraperitoneal hyperthermicperfusion, the amount ofheat necessary for optimal cell killand acceptable morbidity and mortality,(4) simpler and less costly perfusionapparatus, (5) quantitative prognosticindicators that will allow proper selectionof patients for therapy (this hascome a long way, as described by Dr.Sugarbaker), and (6) better definitionof the role of additional systemic therapyin combination with intraperitonealchemotherapy.Dr. Sugarbaker notes that severalauthors have tested the combinationof cytoreductive surgery and hyperthermicintraperitoneal intraoperativechemotherapy. However, readers mustbe aware that there are considerabledifferences between series regarding both tumor-related issues (such as tumorhistology and tumor stage at laparotomy)and technical features (asdescribed above). It is this heterogeneityamong series and the absence ofwell-designed phase III randomizedtrials that make many investigatorspessimistic about this approach to peritonealcarcinomatosis.Another area that sometimes frustratesefforts to interpret the literatureconcerning peritoneal surface malignanciesis the issue of quality of life.Recent results by McQuellon and associatesfrom the ComprehensiveCancer Center of Wake Forest University[5] demonstrated long-termsurvival with good quality of life forselected patients with peritoneal carcinomatosisafter cytoreductive surgeryand intraperitoneal hyperthermicchemotherapy. Such results are importantif we are to make progress inthis area of cancer research.Conclusions
In my opinion, this review by Dr.Sugarbaker is outstanding and shouldbe mandatory reading for physiciansinvolved in the treatment of patientswith peritoneal carcinomatosis. Witha multidisciplinary team approach andqualified surgeons, more programswill become available across the UnitedStates. Such an effort has beenundertaken in Delaware, where a collaborationbetween the Tunnell CancerCenter at Beebe Hospital and theHelen F. Graham Cancer Center atChristiana Care has resulted in multidisciplinaryteams and a program forthe treatment of peritoneal surfacemalignancies.Nevertheless, a definitive assessmentof the management value of cytoreductivesurgery and intraperitoneal chemotherapywill be possible only if thetechnique is standardized and phase IIIclinical trials are undertaken.

Disclosures:

The author has no significantfinancial interest or other relationshipwith the manufacturers of any products or providersof any service mentioned in this article.

References:

1.

Sugarbaker PH, Chang D: Results of treatmentof 385 patients with peritoneal surfacespread of appendiceal malignancy. Ann SurgOncol 6:727-731, 1999.

2.

Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity andconcepts supporting an ordered pathophysiology,in Sugarbaker PH (ed): Peritoneal Carcinomatosis:Principles of Management, pp 79-100. Boston, Kluwer, 1996.

3.

Jones T: I want to live!, in Erdrich L,Kenison K (eds): The Best American Short Stories 1993, pp 127-145. New York, HoughtonMifflin Co, 1993.

4.

Pilati P, Mocellin S, Rossi CR, et al:Cytoreductive surgery combined with hyperthermicintraperitoneal intraoperative chemotherapy 10:508-513, 2003.

5.

McQuellon R, Loggie BW, Lehman AB,et al: Long-term survivorship and quality oflife after cytoreductive surgery plus intraperitonealhyperthermic chemotherapy for peritonealcarcinomatosis. Ann Surg Oncol 10:155-162, 2003.for peritoneal carcinomatosis arisingfrom colon adenocarcinoma. Ann Surg Oncol