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

February 1, 2004

No American surgeon has thesame breadth of experiencewith extensive peritoneal resectionas Dr. Paul Sugarbaker. Moreover,only a few clinicians worldwidehave the same level of experiencewith intraperitoneal chemotherapy fora variety of intraperitoneal cancers,particularly after peritoneal resection.[1] The value of these therapiesis unquestionable in patients with lowgradetumors confined to the peritonealcavity. A number of patientstreated in this fashion show no evidenceof recurrent disease a decadeor more posttreatment.

No American surgeon has thesame breadth of experiencewith extensive peritoneal resectionas Dr. Paul Sugarbaker. Moreover,only a few clinicians worldwidehave the same level of experiencewith intraperitoneal chemotherapy fora variety of intraperitoneal cancers,particularly after peritoneal resection.[1] The value of these therapiesis unquestionable in patients with lowgradetumors confined to the peritonealcavity. A number of patientstreated in this fashion show no evidenceof recurrent disease a decadeor more posttreatment.On the other hand, many of thesetumors progress slowly, with a proportionof untreated patients surviving 3,5, or more years. Although 60% ofresected patients survive 5 years, theirtumors may still recur and lead to death10 or more years later. The terminalphase of this disease tends to be prolongedand for the patient, miserable.Invasive Progression
Pseudomyxomas adhere to peritonealsurfaces in their early stages butbecome invasive as they progress.Notching of the liver surface seen oncomputed tomography predicts progressionto cancer with invasive capability.Minute peritoneal metastases arenot uncommonly found in patientswith gastric, gallbladder, pancreatic,and colonic cancers. When such metastasesare confined to the immediatearea of the primary cancer,localized peritoneal resection combinedwith radical resection of theprimary cancer followed by intraperitonealchemotherapy may become arational approach for patients withgallbladder and colon cancers.[1]However, minute tumor seedlings inthe pelvis, at the base of the smallbowel, along the mesenteric border ofthe bowel, or under the diaphragm suggestmore widespread dissemination forwhich the risk-benefit ratio of aggressivetherapy must be considered.Treatment Strategies
Extensive peritoneal resection is atedious and meticulous procedure,sped up somewhat by selective use ofelectroevaporation or argon laser destruction.Resection of the entire peritonealsurface often takes 18 hours toperform, whereas localized resectioncan be performed more expeditiouslywith low mortality and morbidityrates. Postoperatively, shifts in fluidfrom the raw peritoneal surfaces resemblethose associated with extensiveburns and require continuousmonitoring for fluid replacement.We prefer that the initial lavage ofthe peritoneal cavity be performedwith hypotonic solutions to lyse freefloatingtumor and red blood cells andfacilitate removal of clots and debrisby prompt suction evacuation beforeclosing the abdomen. Peritoneal lavageage and intraperitoneal thermochemotherapycan then proceed using 2 L ofintraperitonenal fluid to ensure thatall recesses of the peritoneal cavityare exposed to the solution. Postchemotherapyflushes of the peritoneumshould continue until thedrainage is clear.Complications and Exceptions
While chemical peritonitis is notan uncommon complication of intraperitonealchemotherapy,[2] pancreatitiscan also occur.[3] Pancreatitisdevelops more commonly when theperitoneal surface over the pancreashas been removed as part of the peritonealresection of the lesser peritonealsac; it is not seen after radical D2gastrectomy, during which this liningis routinely removed, suggesting thatthe intraperitoneal chemotherapy isthe precipitating factor.Dr. Sugarbaker recommends thatreconstruction of the gastrointestinaltract be deferred until after the intraoperativeintraperitoneal chemotherapyhas been completed, althoughothers have suggested that this is unnecessary.[1,4] If anastomosis isdelayed until after intraperitoneal chemotherapyhas been completed, wewould suggest that the ends of thebowel be trimmed a few millimetersto remove anastomotic mucosa thathas been exposed to the drugs, becausemany antineoplastic agents delaywound healing.Re-exploration of patients whohave received intraperitoneal chemotherapyoften reveals a glistening, well-defined capsule[5] containing a sac thatis smaller than the original peritonealcavity. If the tumor recurs, it is usuallyfound in areas that were once the wallsof the peritoneal cavity but are now behindthe wall of this fibrous sac.Dr. Sugarbaker indicates that thereare 13 peritoneal cavity areas but onlylists 12. The 13th is the lesser peritonealsac. He also describes the techniquefor control of peritonealmetastases of colon cancer, but thetables refer to gastric cancer. Intraperitonealchemotherapy for gastriccancer must be accompanied by a wideD2 resection because peritoneal andlymphatic metastases are frequentlyassociated with this primary.[6] Unfortunately,we still do not have optimalagents for management of gastriccancer. Thus, except in cases of serosa-invading but peritoneum-negativegastric cancer, intraperitoneal treatmentremains experimental.[7-9]Conclusions
Peritoneal resection, with or withoutintraperitoneal chemotherapy, isan accepted treatment for pseudomyxoma peritonei. Dr. Sugarbakermakes a strong argument for its use inselected colon cancer patients, providedthat an R-O surgical resectioncan be performed. For other gastrointestinalcancers, the potential benefitsof surgery and intraperitonealchemotherapy remain unproven andshould only be used when following apeer-reviewed protocol under theguidance and auspices of an institutionalreview board.Dr. Sugarbaker is to be commendedfor his continuing research into themanagement of the peritoneal disseminationof cancer.

Disclosures:

The author has nosignificant financial interest or other relationshipwith the manufacturers of any productsor providers of any service mentioned in thisarticle.

References:

1.

Glehen O, Osinsky D, Cotte E, et al: Intraperitonealchemohyperthermia using aclosed abdominal procedure and cytoreductivesurgery for the treatment of peritoneal carcinomatosis:Morbidity and mortality analysis of216 consecutive procedures. Ann Surg Oncol10:863-869, 2003.

2.

Arbuck SG, Douglass HO Jr, Trave F,et al: A phase II trial of 5-fluorouracil andhigh-dose leucovorin in gastric carcinoma and a phase I trial of intraperitoneal 5-fluorouraciland leucovorin. NCI Monogr 5:203-205,1987.

3.

Esquivel J, Vidal-Jove J, Steves MA,et al: Morbidity and mortality of cytoreductivesurgery and intraperitoneal chemotherapy.Surgery 113:631-636, 1993.

4.

Homazoe R, Maeta M, Kaibara N: Intraperitonealthermochemotherapy for preventionof peritoneal recurrence for gastric cancer.Cancer 73:2048-2052, 1994.

5.

Markman M, Cleary S, Howell SB, et al:Complications of extensive adhesion formationafter intraperitoneal chemotherapy. SurgGynecol Obstet 162:445-448, 1986.

6.

Douglass HO Jr, Nava HR, Smith JL, etal: Intraperitoneal surgical adjuvant chemotherapyfor gastric cancer. Reg Cancer Treat8:13-19, 1995.

7.

Yu W, Whang I, Suh I, et al: Prospectiverandomized trial of early postoperative intraperitonealchemotherapy as an adjuvant to resectablegastric cancer. Ann Surg 228:347-354,1998.

8.

Kim JY, Bae HS: A controlled clinicalstudy of serosa-invasive gastric carcinoma patientswho underwent surgery plus intraperitonealhyperthermo-chemo-perfusion (IHCP).Gastric Cancer 4:27-33, 2001.

9.

Kunisaki C, Shimada H, Nomura M, etal: Lack of efficacy of prophylactic continuoushyperthemic peritoneal perfusion on subsequentperitoneal recurrence and survival inpatients with advanced gastric cancer. Surgery131:521-528, 2002.