Managing the Peritoneal Surface Component of Gastrointestinal Cancer; Part 1. Patterns of Dissemination and Treatment Options

January 1, 2004
Paul H. Sugarbaker, MD, FACS

Oncology, ONCOLOGY Vol 18 No 1, Volume 18, Issue 1

Until recently, peritoneal carcinomatosis was a universally fatalmanifestation of gastrointestinal cancer. However, two innovations intreatment have improved outcome for these patients. The new surgicalinterventions are collectively referred to as peritonectomy procedures.During these procedures, all visible cancer is removed in an attempt toleave the patient with only microscopic residual disease. Perioperativeintraperitoneal chemotherapy, the second innovation, is employed toeradicate small-volume residual disease. The intraperitoneal chemotherapyis administered in the operating room with moderate hyperthermiaand is referred to as heated intraoperative intraperitoneal chemotherapy.If tolerated, additional intraperitoneal chemotherapy canbe administered during the first 5 postoperative days. The use of thesecombined treatments, ie, cytoreductive surgery and intraperitoneal chemotherapy,improves survival, optimizes quality of life, and maximallypreserves function. Part 1 of this two-part article describes the naturalhistory of gastrointestinal cancer with carcinomatosis, the patterns ofdissemination within the peritoneal cavity, and the benefits and limitationsof peritoneal chemotherapy. Peritonectomy procedures are also definedand described. Part 2, to be published next month in this journal,discusses the mechanics of delivering perioperative intraperitoneal chemotherapyand the clinical assessments used to select patients who willbenefit from combined treatment. The results of combined treatment asthey vary in mucinous and nonmucinous tumors are also discussed.

ABSTRACT: Until recently, peritoneal carcinomatosis was a universally fatal manifestation of gastrointestinal cancer. However, two innovations in treatment have improved outcome for these patients. The new surgical interventions are collectively referred to as peritonectomy procedures. During these procedures, all visible cancer is removed in an attempt to leave the patient with only microscopic residual disease. Perioperative intraperitoneal chemotherapy, the second innovation, is employed to eradicate small-volume residual disease. The intraperitoneal chemotherapy is administered in the operating room with moderate hyperthermia and is referred to as heated intraoperative intraperitoneal chemotherapy. If tolerated, additional intraperitoneal chemotherapy can be administered during the first 5 postoperative days. The use of these combined treatments, ie, cytoreductive surgery and intraperitoneal chemotherapy, improves survival, optimizes quality of life, and maximally preserves function. Part 1 of this two-part article describes the natural history of gastrointestinal cancer with carcinomatosis, the patterns of dissemination within the peritoneal cavity, and the benefits and limitations of peritoneal chemotherapy. Peritonectomy procedures are also defined and described. Part 2, to be published next month in this journal, discusses the mechanics of delivering perioperative intraperitoneal chemotherapy and the clinical assessments used to select patients who will benefit from combined treatment. The results of combined treatment as they vary in mucinous and nonmucinous tumors are also discussed.

The quality of care directed toward patients with gastrointestinal cancer has a profound effect on survival.[1] Nevertheless, the treatments that have evolved over the past several decades have become increasingly complex. Currently, the use of radiotherapy and systemic chemotherapy combined with surgery continues to improve survival, optimize quality of life, and maximally preserve function. Surgical procedures also continue to evolve toward new standards of care.[2] Undoubtedly, the increasing complexity of the management of gastrointestinal cancer has improved patient care.

A better understanding of the natural progression of surgically treated gastrointestinal cancer has also evolved over the past several decades. The emphasis in clinical research on "anatomic sites of surgical treatment failure" has provided oncologists with a target for radiation and chemotherapeutic clinical investigations. One aspect of surgical treatment failure in gastrointestinal cancer that presents itself as a prominent need for better understanding and concentrated research activities is peritoneal surface dissemination. Until recently, peritoneal carcinomatosis was a universally fatal manifestation of gastrointestinal cancer.

Treatment Innovations

TABLE 1


Evolution of Treatments for Peritoneal Carcinomatosis From Gastrointestinal Cancer

Despite the grim outlook for patients with this disease, laboratory and clinical research efforts have continued (Table 1).[3-17] Recent success with a curative approach stems from two treatment innovations-one surgical and the second chemotherapeutic- specifically developed for the management of peritoneal carcinomatosis. The new surgical interventions are collectively referred to as peritonectomy procedures.[3] Using highvoltage electrosurgery and a thorough knowledge of the distribution patterns of peritoneal carcinomatosis, the surgeon resects the lining of the abdomen and pelvis at all sites with visible evidence of cancerous implants. 

The second innovation, perioperative intraperitoneal chemotherapy, is employed to eradicate small-volume residual disease. This intraperitoneal chemotherapy must be an integral part of the surgery for peritoneal carcinomatosis, because the perioperative timing of intraperitoneal drug administration is crucial for success.[ 18] In a majority of peritoneal surface malignancy treatment centers, the intraperitoneal chemotherapy is administered in the operating room with moderate hyperthermia[19]; this treatment is referred to as heated intraoperative intraperitoneal chemotherapy. Additional chemotherapy may be used as an abdominal lavage for the first 5 postoperative days, and such treatment is referred to as early postoperative intraperitoneal chemotherapy.

Because these combined treatment modalities have been employed in large numbers of patients, selection factors associated with improved longterm survival and acceptable morbidity and mortality have been established. The purpose of this article is to present the management plans and updated results of the combined treatment-ie, cytoreductive surgery with peritonectomy procedures plus perioperative intraperitoneal chemotherapy- in patients with peritoneal carcinomatosis from gastrointestinal cancer.

Natural History Studies

Surgeons, especially those involved in reoperative surgery for gastrointestinal cancer, have repeatedly observed the intracoelomic dissemination of cancer. Nevertheless, little was done to clarify the impact of peritoneal seeding on survival until a report by Chu and colleagues was published.[20] These investigators studied 100 patients with nongynecologic malignancy who had biopsyproven peritoneal carcinomatosis. Themean survival of 45 colorectal cancer patients was 8.5 months; of 20 pancreatic cancer patients, 2.4 months; and of 6 gastric cancer patients, 2.2 months. The presence or absence of ascites was an important prognostic variable in all these patients.

In 2000, Sadeghi and coworkers reported on 370 patients with peritoneal carcinomatosis from nongynecologic malignancies who were enrolled in a European prospective multicenter trial (Evolution of Peritoneal Carcinomatosis 1 [EVOCAPE 1]).[21] These patients had the benefit of fluorouracil (5-FU)-based systemic chemotherapy, but the results were remarkably similar to those reported by Chu a decade earlier. The mean survival of 118 patients with carcinomatosis from colorectal cancer was 6.9 months; of 58 patients with pancreatic cancer, 2.9 months; and of 125 patients with gastric cancer, 6.5 months.

In 2002, Jayne and colleagues from Singapore used a database of 3,019 colorectal cancer patients to identify 349 (13%) with peritoneal carcinomatosis.[22] Of special interest were the 125 patients (58%) who had synchronous primary colorectal cancer and peritoneal implants. The median survival of those patients was only 7 months. The authors reported that survival was adversely affected by the extent of peritoneal carcinomatosis and the stage of the primary cancer.

These survival statistics as they relate to the natural history of peritoneal surface dissemination demonstrate the aggressive behavior of gastrointestinal cancer with carcinomatosis. These studies also show that peritoneal carcinomatosis can occur along with lymph node and liver metastases or as isolated peritoneal surface dissemination. In the Sadeghi et al study, 91 of the 118 colorectal cancer patients (77%) had no liver or lung metastases at the time that carcinomatosis was diagnosed.[21] In the Jayne et al study, 80% of the carcinomatosis patients in the synchronous group had no liver or systemic metastases.[22]

These natural history studies have proven to be helpful in understandingthe lethal nature of peritoneal carcinomatosis. However, the full impact of the profound deterioration of quality of life that accompanies disease progression has not been adequately communicated. Intestinal obstruction, bowel perforation with fistula formation, and nutritional deprivation cause immeasurable prolonged suffering in this group of patients. One of the most agonizing cancer deaths occurs from the progression of peritoneal carcinomatosis.[23]

Pathobiology of Peritoneal Dissemination of Cancer

Although metastases through lymphatic channels to local lymph nodes and through the portal blood to the liver have been intensively studied, the dissemination of cancer cells on peritoneal surfaces has received less attention. In 1931, Sampson may have been the first to describe this type of cancer dissemination in humans.[24] He observed that cancer cells escaped from primary ovarian cancer into the free peritoneal cavity, that they adhered to the mesothelial surface, that invasion occurred, and that a visible cancer nodule became apparent. He also distinguished cancer dissemination by implantation (spread) within the coelomic space from dissemination by way of lymphatic channels (metastases).

Sampson described the "life history of peritoneal carcinomatosis implants" as follows: (1) escape of the cancer cells from the primary ovarian tumor into the free peritoneal cavity; (2) migration of these cells to their site of implantation; (3) reaction of the peritoneal surface injured by the cancer cells so that fixation of the cancer in fibrin and organization of this fibrin occurred; and (4) progression of the cancerous implant at that site.

An important concept in tumor biology that has great relevance to the understanding of carcinomatosis derives from the studies of Weiss.[25] He described the phenomenon of "metastatic inefficiency," recognizing that the bloodstream may "teem with cancer cells" and yet no metastases may develop. In other words, eventhough the portal vasculature of the liver may receive innumerable cells from a primary malignancy on a daily basis, less than half of gastrointestinal cancer patients will develop liver metastases. Thus, hematogenous dissemination of gastrointestinal cancer is rightfully characterized as metastatically inefficient.

In contrast, cancer cells disseminate with great efficiency within the peritoneal cavity. A profound example of the metastatic efficiency of intraperitoneal cancer cells was reported by Kodera and colleagues.[26] They observed no long-term survival among 10 gastric cancer patients with a positive peritoneal cytology. Also, 8 of these 10 patients developed clinical evidence of carcinomatosis. In 81 patients with a negative cytology, the 5-year survival rate was 70%, and only 2 patients developed clinical evidence of carcinomatosis. In this study of peritoneal cytology in gastric cancer patients, the presence of positive vs negative free intraperitoneal cancer cells was an even more definitive predictor of prognosis than positive vs negative lymph nodes.

Peritoneal cancer implantation is spontaneous in 20% to 30% of patients with primary gastrointestinal cancer as a result of full-thickness invasion of the bowel wall. There can be an iatrogenic component of carcinomatosis. The profound impact of a fresh wound induced by surgery on the likelihood of cancer cell implantation was clearly demonstrated by Zoetmulder (Amsterdam) in a thesis presentation. He showed in an experimental colon cancer model that a fresh surgical wound would increase the likelihood of tumor growth by a factor of 100; the peritoneal wound was observed to be a cancer promoter.[ 27] The smallest amount of tumor contamination at a surgically traumatized site will readily progress to clinical symptoms as a result of metastatic efficiency and tumor growth enhancement from healing tissues. 

Patterns of Intracoelomic Dissemination

The general surgical literature, especially manuscripts dealing with the spread of intraperitoneal infection, has described a characteristic pattern for the intracoelomic distribution of particles, bacterial organisms, or cancer cells. Autio identified six major compartments within the peritoneal cavity that could act as a reservoir for intracoelomic contaminants.[28] He also showed that there was a stream of peritoneal fluid from the lower abdomen along the right paracolic sulcus to the upper abdomen. Meyers studied the flow of intraperitoneal contrast radiologically and documented that intra-abdominal cancer cells in fluid disseminated via well-defined routes.[29] He emphasized that cancer dissemination in the presence of ascitic fluid was neither random nor limited to the immediate area of the primary neoplasm.

The role of lymphoid aggregates within the peritoneal surface and an associated peritoneal fluid resorption at these sites was described by Takahashi and colleagues.[30] They found a close correlation between infiltrating cancer cells and the density oflymphoid aggregates; these aggregates were shown to be foci of lymphoid tissue on the peritoneal surface through which fluid and small particles were absorbed from the peritoneal cavity into the subperitoneum. The lymphoid aggregates were abundant within the greater omentum, perigonadal tissue, and mesentery and could be identified by their uptake of activated carbon particles. The authors suggested that not only the flow of peritoneal fluid but also its absorption at specific anatomic sites, such as beneath the hemidiaphragms and within the greater omentum, were important mechanisms of intraperitoneal cancer dissemination.

Impact of Intraperitoneal Fluid on Dissemination Patterns

Sugarbaker described the profound impact of intraperitoneal fluid on the patterns of cancerous dissemination within the peritoneal cavity.[31] From observations collected from reoperative surgical procedures, he contrasted three important mechanisms of intracoelomic cancer dissemination. In the absence of intraperitoneal fluid and surgical intervention, gastrointestinal cancer cells metastasize in a randomfashion immediately adjacent to the primary neoplasm that has penetrated the serosal surface. A pattern of random and proximal spread is expected from invasive nonmucinous cancers. The cells adhere, implant, and then progress at the initial site of cell contact with the peritoneal surface. However, such a distribution pattern contrasts with that of cancers that invade the gastrointestinal cancer wall but also produce ascitic fluid or mucus. The fluid causes a characteristic "redistributed" pattern of implants. In this model, both the peritoneal compartments and the flow of intraperitoneal fluid determine the pattern of implant distribution. Mucinous adenocarcinoma progresses as cancer cells move with the flow of peritoneal fluid and become trapped within the large crevices between stationary surfaces or the fluid pools created by gravity.

The dominant regions for redistributed cancer progression would be the space between the right diaphragm and liver, the lower part of the left paracolic sulcus, and the cul-de-sac of Douglas. Of course, fluid drawn to milky spots within the greater or lesser omentum, gonadal or perigonadal tissue, and mesenteric border of the small bowel would also accumulate a larger proportion of the intraperitoneal malignant cells. A prospective study documenting the profound impact that intraperitoneal mucin has on the patterns of intraperitoneal cancer dissemination was presented by Carmignani and colleagues.[32]

Tumor Cell Entrapment

The third pattern of intraperitoneal cancer dissemination is caused by surgical dissection; this mechanism of cancer dissemination is referred to as "tumor cell entrapment." The anatomic sites associated with an increased incidence of cancerous implants would be all the traumatized peritoneal surfaces. Cancer implants would be observed at anastomotic sites, at sites where bowel was repeatedly handled, within the abdominal closure, and within the raw tissues created by a retroperitoneal dissection.[31] In summary, fibrin plus cancer cells results in cancer implants at specifictraumatized sites; ascites plus cancer cells results in a redistributed pattern of dissemination.

Motion Hypothesis

The paper by Carmignani et al documented a fourth mechanism influencing the distribution of intraperitoneal cancer cells in mucinous or serous ascitic fluid.[32] These investigators described the "motion hypothesis" in which the movement of an intra-abdominal structure largely determines the volume of malignancy associated with its peritoneal surface. Many structures within the abdomen are largely stationary, whereas others, such as the surfaces of the small bowel and its mesentery, are in continuous motion by peristalsis. This motion greatly influences the distribution of tumor and, therefore, the surgical management of mucinous carcinomatosis. If the small bowel is largely clear of tumor nodules, then peritonectomy procedures can remove the remainder of the disease from other peritoneal surfaces.

FIGURE 1


Distribution of Mucinous Adenocarcinoma

The thin wall of the smooth muscle tube that constitutes the small bowel creates a difficult anatomic site for peritonectomy. Nodules of invasive cancer on the small bowel surface must be left in place by the surgeon, or a portion of the small bowel must be resected. Nodules of cancer on the liver, stomach, undersurface of the diaphragm, or pelvic sidewalls can be peritonectomized with negative margins. The observation that mucinous adenocarcinomas spare the small bowel surfaces but are located in large volume at other sites, especially within the omental cake and in dependent areas, is the original observation that led to a rationale for a curative approach to mucinous peritoneal carcinomatosis (Figure 1).[33]

Distribution of Mucinous/ Nonmucinous Adenocarcinoma

The studies by Carmignani et al quantitatively documented differences in the distribution of mucinous adenocarcinoma and nonmucinous adenocarcinoma throughout the abdomen and pelvis.[32] The lesser omentum was involved with mucinous tumors in a majority of patients and wascinous tumors. The undersurface of the right hemidiaphragm was nearly always involved with mucinous tumors, but was rarely involved with nonmucinous tumors. The same could be said for the surface of the liver.

For high-grade nonmucinous malignancies from colorectal cancer, the proximity of the tissue to the primary cancer for which the incidence of implants was determined was very important. The bladder surface was frequently involved by ovarian malignancy but seldom by mucinous or nonmucinous adenocarcinoma. Also, the vaginal cuff opened at the time of hysterectomy showed a high incidence of metastases with ovarian cancer but was rarely, if ever, involved in other types of cancer.

Prior Limited Benefits With Intraperitoneal Chemotherapy

Many oncologists seeing a resurgence of interest in intraperitoneal chemotherapy are skeptical of its possible benefits. They cite 2 decades of work in this field that have yielded only modest improvements. Those who have previously used intraperitoneal chemotherapy usually conclude that the difficulties with this route of administration outweigh any small benefits. However, prior use of intraperitoneal chemotherapy may have been flawed for three prominent reasons.

Limited Drug Penetration

REFERENCE GUIDE

Therapeutic Agents
Mentioned in This Article

Cisplatin
Docetaxel (Taxotere)
Doxorubicin
Fluorouracil (5-FU)
Gemcitabine (Gemzar)
Mitomycin (Mutamycin)
Mitoxantrone (Novantrone)
Oxaliplatin (Eloxatin)
Paclitaxel

Brand names are listed in parentheses only if a drug is not available generically and is marketed as no more than two trademarked or registered products. More familiar alternative generic designations may also be included parenthetically.

First, intracavitary chemotherapy instillation produces a limited penetration of drug into tumor nodules. Only the outermost layer (approximately 1 mm) of the cancer nodule is exposed to the high concentration of drug delivered local-regionally. Also, as soon as chemotherapy enters any tissue, it is rapidly cleared into the systemic circulation. This means that only minute tumor nodules or individual cancer cells can be definitively treated. In most patients, oncologists have attempted to treat established disease with visible nodules. This improper selection of patients has resulted in disappointment with intraperitonealdrug use. Microscopic residual disease is the theoretically reasonable target for intraperitoneal chemotherapy.

Nonuniform Drug Distribution

Second, drug distribution with intraperitoneal chemotherapy is nonuniform. A majority of patients treated in this manner have undergone extensive prior surgery, which invariably results in the scarring of peritoneal surfaces. The adhesions create multiple barriers to the free access of fluid. Although the instillation of a large volume of fluid will partially overcome the problems of nonuniform drug distribution, large surfaces inevitably have no access or limited access to the chemotherapy solution. Unfortunately, this limited access due to adhesions is impossible to predict, and it generally worsens with repeated cycles of chemotherapy.

Not only do adhesions interfere with the distribution of chemotherapy, they also prevent the chemotherapy solution from achieving direct contact with the cancer. Surgery causes fibrin deposits on the surfaces that have been traumatized by the resection. Free intraperitoneal cancer cellsbecome entrapped within the fibrin. As collagen is laid down within fibrin, the tumor cells become entrapped within a scar tissue matrix that is dense and impenetrable by intraperitoneal chemotherapy. 

Another aspect of nonuniform intraperitoneal drug distribution can be attributed to gravity. Water-density fluid placed within the peritoneal cavity will displace the lipid-density bowel and find a pool for the accumulation of chemotherapy solution within the pelvis and other dependent areas, including the paracolic gutters and right retrohepatic space. Unless the patient actively pursues frequent and radical changes in position (thereby affecting gravity distribution), the surfaces between the small bowel loops and especially between the small bowel loops and the anterior abdominal wall will remain untreated.

Problematic Technology

A final obstacle to the successful use of long-term intraperitoneal chemotherapy concerns the problematic technology for administration. With such chemotherapy treatments continuing for many weeks and months, the maintenance of long-term peritoneal access has proven difficult, and no optimal technical solution has been developed. Repeated instillations of large volumes of chemotherapy solution can be achieved through repeated paracentesis. However, bowel perforation, pain upon instillation, and failure to gain intraperitoneal access have frequently occurred.

Insertion of a permanent intraperitoneal port is an option. Failure to infuse, pain upon instillation, and a gradual reduction of free intraperitoneal space due to an indwelling foreign body have all been problematic.Infection of the intraperitoneal port occurs especially in patients with ascites. At present, prolonged peritoneal access is a logistic challenge with no known solution.

Rationale for Intraperitoneal Chemotherapy in Gastrointestinal Cancer

Conceptual Changes in Chemotherapy Administration

Systemic chemotherapy has produced increasingly higher response rates in patients with gastrointestinal cancer and has become a standard part of the treatment of unresectable metastatic disease and of adjuvant treatment following complete resection of the primary malignancy. In order to modify the use of chemotherapy in patients with carcinomatosis, conceptual changes regarding its use have been proposed.

First, a change in the route of drug administration is necessary. Chemotherapy is administered intraperitoneally or perhaps with multidrug therapy, both intraperitoneally and intravenously. Intravenous chemotherapy for carcinomatosis has not been shown to prolong survival. Currently, systemic chemotherapy is sometimes used as induction therapy in carcinomatosis patients with a poor prognosis, to reduce the volume of disease prior to definitive cytoreductive surgery plus intraperitoneal chemotherapy.

A second conceptual change involves the timing of drug administration. With carcinomatosis, the only successful management plans employ perioperative intraperitoneal chemotherapy. Usually, drug administration is initiated in the operating room using a heated chemotherapy solution. The drugs selected for intraoperative use are synergized by hyperthermia, and most frequently include mitomycin (Mutamycin), doxorubicin, cisplatin, and oxaliplatin (Eloxatin). In the early postoperative period, drugs that require cell replication are most appropriate. These drugs are administered in a large volume of fluid for the first 5 to 7 days postoperatively and include 5-FU, paclitaxel, and docetaxel (Taxotere).

A third conceptual change involves patient-selection criteria. The greatest benefit will be observed in patients with noninvasive mucinous appendiceal tumors and the less aggressive peritoneal mesotheliomas. Of the minimally invasive cancers, even large-volume carcinomatosis not located on small bowel surfaces can be definitively eradicated by peritonectomy. For malignancies that have invasive capabilities, the lesion size and distribution of the peritoneal implants are of great importance. Patients with small peritoneal tumor nodules that have limited distribution within the abdomen and pelvis can sometimes be made visibly free of disease by surgical resection. A proportion of these patients show long-term benefits when cytoreductive surgery is combined with perioperative intraperitoneal chemotherapy. However, aggressive treatment of an advanced and widely distributed invasive cancer on peritoneal surfaces is unlikely to produce any long-term benefits; the cytoreduction will be incomplete and intraperitoneal chemotherapy ineffective.

FIGURE 2


Selection of Patients for a Complete Cytoreduction Based on Implant Size and Invasive Nature

Also, these surgically heroic procedures result in a high incidence of morbidity and mortality. From a technical perspective, treatment of peritoneal carcinomatosis must be initiated as early as possible in the natural history of the disease in order to provide the greatest benefit (Figure 2).[34]

Peritoneal Space-to-Plasma Barrier

Selected chemotherapy agents demonstrate a prolonged retention within the abdominopelvic space. Therefore, the exposure of peritoneal surfaces to a high concentration of drug over a long period will be much greater than systemic drug exposure. This marked difference in drug exposure results in a much higher response rate at the peritoneal surface. For intraperitoneal chemotherapy, the differences in drug exposure at the peritoneal surface vs systemic exposure in the treatment of gastrointestinal cancer are shown in Table 2.

TABLE 2


AUC Ratios of Peritoneal Fluid to Plasma for Drugs Used to Treat Gastrointestinal Cancer

The common adverse effects of chemotherapy, even when delivered via the intraperitoneal route, are bone marrow and gastrointestinal mucosaldamage. Indeed, one should not assume that intraperitoneal administration of chemotherapy eliminates systemic toxicity. Although the drugs are sequestered for prolonged periods within the peritoneal space, they are cleared into the systemic circulation. For this reason, the safe dose of most drugs instilled into the peritoneal cavity is similar to the intravenous dose. The exceptions are drugs with hepatic metabolism, such as 5-FU and gemcitabine (Gemzar). The dose of 5-FU can be increased by approximately 50% with intraperitoneal vs intravenous administration. The intravenous dose of 5-FU for 5 consecutive days is approximately 500 mg/m2/d; for intraperitoneal 5-FU, it is 750 mg/m2/d.

Two drugs that have vesicant effects locally are doxorubicin and mitoxantrone (Novantrone). For doxorubicin, the intraperitoneal dose is limited to 15 mg/m2 in 3 L of dialysis solution with manual distribution in the operating room. This dose, when used with moderate heat (41-42oC) for 90 minutes, will produce a tolerable level of peritoneal fibrosis. Multiple cycles of doxorubicin or higher doses of intraperitoneal drug will produce profound intestinal fibrosis and may dramatically interfere with normal peristalsis.

Intraperitoneal mitoxantrone has been extensively used to treat malignant ascites. Link and colleagues have reported success in the elimination of excess peritoneal fluid in 90% of 143 patients.[35] The dose of mitoxantrone was 30 mg/m2, and up to three treatments were necessary to achieve the desired effect. Systemic toxicity was rarely seen (2.0%).

Peritonectomy Procedures

If a surgeon elects to manage patients with a peritoneal surface component of gastrointestinal cancer, it is imperative that the technical skills required for completion of the peritonectomy be mastered. During the peritonectomy, all visible cancer is removed in an attempt to leave the patient with only microscopic residual disease. Knowledge of the dissemination patterns of gastrointestinal cancer to peritoneal surfaces is essential, andunless all sites are rigorously inspected and all foci of cancerous implants removed, patients will be left with gross disease and a poor long-term outcome. 

Isolated tumor nodules are removed using electroevaporation. Normal peritoneum is not excised; only the peritoneum involved by the malignant process is electrosurgically resected. If the visceral peritoneum requires removal and if a complete cytoreduction is contemplated, then resection of portions of the small bowel, colorectum, or stomach is indicated.

Common Anatomic Sites of Visceral Involvement

Mucinous peritoneal carcinomatosis has its greatest propensity for a large volume of visceral involvement at three definite anatomic sites. These are the sites where the bowel is anchored to the retroperitoneum, and motion resulting from peristalsis is restricted. The force of gravity also causes cancer cells to accumulate.

The most common intestinal resection required with peritonectomy involves the rectosigmoid colon. The peritoneal surfaces of the distal colon are nonmobile portions of bowel fixed within a dependent site. This dependent portion of the bowel is, therefore, frequently layered by carcinomatosis. A complete pelvic peritonectomy, which requires stripping of the abdominopelvic sidewalls, the peritoneum overlying the bladder, the culdesac of Douglas, and resection of approximately 18 in. of rectosigmoid colon, is necessary.

The ileocecal valve and terminal ileum constitute a second area where limited mobility may lead to a large volume of carcinomatosis and the need for a bowel resection. Resection of the terminal ileum and a small portion of the right colon are often necessary.

A final site frequently requiring gastrointestinal resection is the antrum or the entire stomach. The antrum is fixed to the retroperitoneum at the pylorus. Large volumes of tumor may accumulate on the pylorus and gastric antrum extending from the hepatoduodenal ligament across the stomach to the greater omentum. Also, tumor may enter the lesser sac through the foramen of Winslow and accumulate in the subpyloric space.[36] Tumor at these two sites surrounding the gastric outlet may cause outlet obstruction. Large volumes of tumor in the lesser omentum combined with disease in the subpyloric space will sometimes cause a confluence of disease involving the left gastric artery, necessitating a total gastrectomy with lesser omentectomy for complete cytoreduction.

Surgical Overview

In order to adequately perform cytoreductive surgery with peritonectomy, the surgeon must use an electroevaporative technology. Electroevaporative surgery involves a high voltage from an electrosurgical generator, a pure cut mode, and a ball electrosurgical tip. An attempt at peritonectomy using the traditional scissor- and-knife dissection will result in unnecessary blood loss. Also, the highvoltage electrosurgery creates a margin of heat necrosis that is devoid of viable tumor cells and less likely to develop recurrence.

The peritonectomy procedures can be briefly described as follows.[3] After abdominal exposure is achieved with a long midline abdominal incisionand a self-retaining retractor, a greater omentectomy and splenectomy are performed. If the spleen and undersurface of the left hemidiaphragm are layered by tumor, then a left subphrenic peritonectomy is necessary. This dissection elevates the spleen and distal pancreas prior to the division of the splenic artery and vein. The third peritonectomy is usually a right subphrenic peritoneal stripping. Electroevaporative surgery is also used to strip away Glisson's capsule and the tumor layered on the liver surface.

Following these upper abdominal dissections, the surgeon generally initiates a complete pelvic peritonectomy; ie, a peritoneal stripping of the pelvic sidewalls and the bladder and resection of the female internal genitalia and the rectosigmoid colon along with the adjacent cul-de-sac. The vaginal cuff is copiously irrigated and must be closed prior to initiating heated intraoperative intraperitoneal chemotherapy, or leakage of the chemotherapy solution will occur. Usually, the final peritonectomy involves a cholecystectomy, lesser omentectomy, and stripping of the omental bursa.

It should be emphasized that no intestinal suturing is performed prior to the completion of heated intraoperative intraperitoneal chemotherapy. The only closure that is indicated is closure of the vaginal cuff to eliminate the loss of chemotherapy solution through this dependent site.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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