Malignant peritoneal mesothelioma. Case-report demonstrating pitfalls of diagnostic laparoscopy.

Patients with peritoneal mesothelioma present with abdominal distension and clinical syndrome of debilitating ascites. Cytology of the peritoneal fluid obtained by laparocentesis often does not result in a diagnosis. Laparoscopy with biopsy of peritoneal nodules is a valuable method by which a histological diagnosis is established. However laparoscopy can greatly complicate the management of peritoneal mesothelioma by facilitating tumor dissemination to port sites. The patient presented was treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Although palliation of intra-abdominal tumor and ascites was achieved, port sites-disease required extensive resection of the abdominal wall. Our experience with this patient suggests that if a malignant source of ascites is suspected and a diagnosis is not obtained by paracentesis, laparoscopy should be used to establish a diagnosis. However, trocars should only be placed along the midline of the abdominal wall so that port sites can be excised at the time of cytoreductive surgery. This diagnostic strategy is applicable to the majority of patients undergoing laparoscopy when there is known or suspected intraabdominal malignancy.

Anastomotic leak after double-stapled low colorectal resection.

PURPOSE: Anastomotic leaks after double-stapled low anterior resection were associated with a number of factors related to patient condition, level of anastomosis, and variety of surgery-related and antitumor therapy-related factors. This retrospective analysis of a group of patients with consistent length of rectal stump was undertaken to determine the risk factors of anastomotic leak after low colorectal resection related to surgery and to intraperitoneal chemotherapy. METHODS: A group of 165 patients treated with surgery only, surgery with early postoperative intraperitoneal chemotherapy, and surgery with hyperthermic intraoperative and early postoperative intraperitoneal chemotherapy. All patients underwent surgery that used the double-stapled technique with transection of the rectum through its middle third. In univariate and multivariate analysis, the relationship between anastomotic leak rate and extent of colon resection, length of residual colon, presence of left colon, and type of applied treatment was studied. RESULTS: With a full length of residual colon, leak rate was 1 percent but increased progressively with the extent of proximal colon resection. Removal of the left colon was associated with the 2.7 odds ratio for anastomotic disruption. Leak rate after surgery only was 6 percent; surgery with normothermic intraperitoneal chemotherapy was 5 percent; and surgery with heated intraperitoneal chemotherapy was 20 percent. CONCLUSIONS: In this group of patients with consistent length of residual rectum, the incidence of anastomotic disruption was related to extent of proximal colon resection. Anastomotic integrity was not compromised by normothermic intraperitoneal chemotherapy. Hyperthermic intraperitoneal chemotherapy was associated with high leak rate only when extensive resection of the colon was performed. Variables other than extent of rectal excision are important in causing a leak of colorectal anastomosis.

Strategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer.

Two main approaches are suggested to improve treatment results in resectable gastric cancer: extended lymphadenectomy and adjuvant antitumour therapy. Progress is to some extent stalled by the perception of gastric cancer as a pathophysiologically uniform disease; it has been demonstrated, however, that there are variants of gastric cancer associated with predominantly intra-abdominal spread or with haematogenous metastases. Recent clinicopathological studies have provided information about the mechanisms of this metastatic diversity. A review of clinical trials suggests that no single method of treatment can efficiently address all variants of gastric cancer spread, but new treatment strategies may be based on defining the pathophysiological variant of gastric cancer and selecting adjuvant therapy according to the most probable mode of tumour spread. Treatment should start with surgery which includes a 'reasonably' extended lymphadenectomy aimed at achieving an increased rate of curative resection and more accurate staging. Risk factors for peritoneal spread of tumour require the perioperative use of intraperitoneal chemotherapy. Subsequent adjuvant therapy may be indicated in patients at high risk of further cancer spread or occult metastases, as determined by pathological examination of the resected specimen.

Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinoma has been regarded as a uniformly lethal clinical entity. A treatment plan combining cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy (HIIC) was devised and tested to treat such patients. The purpose of this study was to evaluate the morbidity and mortality associated with this treatment approach. METHODS: Sixty patients with peritoneal carcinomatosis from adenocarcinoma of the colon or appendix were included in the study. Extensive cytoreductive surgery was combined with heated intraperitoneal mitomycin in an intraoperative lavage technique followed by one cycle of early postoperative intraperitoneal 5-fluorouracil. Eleven clinical variables were selected and statistically correlated with morbidity and mortality. RESULTS: Twenty-five complications occurred in 21 patients (morbidity = 35%). Morbidity related to gastrointestinal function included anastomotic leak (n=6), bowel perforations (n=5), bile leak (n=3), and pancreatitis (n=2). Four patients presented with severe hematologic toxicity (Grade 3 or 4). There were three cases of postoperative bleeding, one case of abdominal wound dehiscence, and one case of pulmonary embolism. Morbidity was significantly associated with three clinical factors: male sex, high intraabdominal temperature during HIIC, and duration of the surgical procedure. Enteral complications (bowel fistula and anastomotic leak) occurred in patients with a significantly higher number of peritonectomy procedures and a significantly longer operation. Three patients died within 8 weeks after the procedure (mortality = 5%). Mortality was significantly associated with age and intraabdominal temperature. CONCLUSIONS: Cytoreductive surgery combined with HIIC is associated with a 35% morbidity rate and a 5% mortality rate. Extensive surgery (duration and number of peritonectomy procedures) and high intraabdominal temperature represent the major risk factors for postoperative morbidity and mortality of patients treated with this new therapeutic approach.

Hyperthermic intraoperative intreperitoneal chemotherapy (HIIC) with mitomycin C.

Dedrick et al. published a mathematical model in 1978 that described the theoretical rationale for in- traperitoneal administration of chemotherapeutic agents.' Numerous authors have provided substantial clinical and experimental evidence supporting Dedrick's model. Lukas et al.' and Torres et al.' have de- scribed the pharmacokinetics involved in the transport of drugs from the peritoneal cavity into the portal and systemic circulation. These investigations and others gave birth to the pharmacologic concept known as the peritoneal plasma barrier (PPB). The PPB has been described as a complex diffusion barrier, consisting of the endothelium, the mesothelium, and the intervening interstitium, along with the fluid in the blood and the dialysate.t This physiologic barrier limits the resorption of hydrophilic drugs such as mitomycinC, doxoru- bicin, and cisplatin from the peritoneal cavity into the blood.

Recurrent intraabdominal cancer causing intestinal obstruction: Washington Hospital Center experience with 42 patients managed by surgery and intraperitoneal chemotherapy.

Reoperative surgery was used as a treatment for patients with recurrent obstructing cancer. In this group of patients intraperitoneal chemotherapy was used in an attempt to prolong the beneficial effects of treatment. This aggressive approach may be recommended irrespective of patient performance status if the patient is not terminally ill. This treatment was associated with a high rate of postoperative complications (55%) but low mortality (7%). To avoid or reduce the incidence of postoperative complications, this treatment should be performed only by an experienced surgical oncologist. Long-term benefits of this treatment were related to biologic factors reflected by cancer origin in the appendix, low-grade tumor histopathology, and a free interval of > 2 years. Treatment-related factors were completeness of cytoreduction and administration of intraperitoneal chemotherapy. The best outcome was achieved with pseudomyxoma peritonei of appendiceal origin with a time interval between surgeries of 2 or more years, a complete cytoreduction, and treatment with intraperitoneal chemotherapy. This treatment modality can be recommended for palliation of patients with recurrent obstruction due to other gastrointestinal and ovarian malignancies, although, long-term results may not be so encouraging as with appendix tumors. In the group of colorectal cancer patients treated by aggressive reoperative surgery and intraperitoneal chemotherapy, 35.3 percent survived 1 year, which differs significantly from the 4-5 month survival after treatment by the standard approach.

Peritoneal mesothelioma: treatment approach based on natural history.

A more modern treatment strategy for diffuse malignant peritoneal mesothelioma may be suggested (figure 3). Clinical suspicion of diffuse malignant mesothelioma (peritoneal carcinomatosis) calls for laparoscopy with evaluation of parietal and visceral peritoneum and multiple biopsies sufficient for definitive histologic diagnosis. Cytologic examination of ascitic fluid is not likely to be of benefit. CT of chest, abdomen, and pelvis is needed for evaluation of visceral involvement and the presence of distant metastases. Contrast enhancement of the gastrointestinal and urinary tract is necessary with the CT. Additional radiologic techniques for detection of distant metastases should be used if there are clinical or laboratory signs of extraperitoneal spread. After histologic diagnosis and extent of tumor spread have been documented, and if no symptoms of intestinal obstruction are present, the patient may be subjected to two to three courses of induction intraperitoneal chemotherapy. This will provide the clinician with important information on tumor response to chemotherapy, minimize tumor accumulation on bowel surfaces, and provide time for surgical conditioning. The time devoted to induction chemotherapy will allow occult distant metastases to be detected. In patients with a response or stable disease, cytoreductive surgery is attempted approximately 2 months after completion of induction chemotherapy. Surgery must be aimed at achieving complete or near-complete cytoreduction through the use of peritonectomy procedures [46,47]. Additional intraperitoneal chemotherapy should be administered intraoperatively and in the early postoperative period (figure 3). This treatment strategy may be the most feasible one according to existing knowledge of the natural history of diffuse malignant peritoneal mesothelioma. Only further phase II clinical trials can reveal the extent to which it is beneficial. Because of the rare occurrence of this disease, the quickest answer would come as a result of cooperative study by several groups experienced in these treatment modalities.

Krukenberg syndrome as a natural manifestation of tumor cell entrapment.

In summary, confusion exists among clinicians regarding the possibilities of treatment for ovarian metastases in general, and of the Krukenberg tumors in particular. The ovaries themselves are easily removable irrespective of their sizes, but disappointing long-term results of oophorectomy alone leave most surgeons with only the choice of conservative therapy unless there is a debilitating tumor mass. In most patients nothing is done until surgical palliation becomes mandatory. There is a group of patients with isolated peritoneal dissemination of gastrointestinal cancers who are eligible for new treatment strategies. This group includes patients who have small-volume peritoneal spread or who can be completely cytoreduced, and those who have no evidence of liver or extraabdominal metastases. An aggressive approach with cytoreductive surgery and intraperitoneal chemotherapy with or without additional systemic chemotherapy should be considered for the treatment of selected patients.

Cancer recurrence following laparoscopic colectomy. Report of two patients treated with heated intraperitoneal chemotherapy.

PURPOSE: Use of laparoscopic techniques for resection of colon and rectal cancer has raised considerable controversy. There is increasing concern that wound recurrence and peritoneal dissemination may represent a potentially fatal complication of this technique. METHODS: The surgical literature was reviewed, and clinical course of two patients is presented. RESULTS: Our two patients had tumor recurrence in the laparoscopy port sites within one year after laparoscopic assisted colectomy for Dukes B adenocarcinoma of the colon. At laparotomy, diffuse peritoneal carcinomatosis without lymph node or liver metastases were found in both patients. They were treated by surgical resection of recurrent disease combined with heated intraoperative intraperitoneal mitomycin C chemotherapy and five days of early postoperative intraperitoneal 5-fluorouracil. These patients are clinically free of disease at 1.5 years after treatment of peritoneal implants. CONCLUSIONS: Cancer recurrence in abdominal wall incisions after laparoscopic colectomy has been reported in an increasing number of patients. It is possible that this technique should be abandoned. Cytoreductive surgery combined with intraperitoneal chemotherapy may represent the most adequate treatment of recurrent cancer that occurs following laparoscopic colectomy.

Abdominal wall metastasis and peritoneal carcinomatosis after laparoscopic-assisted colectomy for colon cancer.

We report a case of a port-site recurrence with diffuse peritoneal carcinomatosis after laparoscopic-assisted right hemicolectomy. The interval between resection of the colonic adenocarcinoma and diagnosis of the recurrence was short (1 month), suggesting that intraperitoneal dissemination and tumour implantation on surgical wounds may represent the principal mechanism of recurrence after laparoscopic surgery. Review of the literature shows an alarming increase in the occurrence of this devastating complication. Although beneficial to the patient in the immediate post-operative period, the adequacy of laparoscopic-assisted colectomy in tumour is increasingly under question.

Pharmacokinetic studies of intraaortic stop-flow infusion with 14C-labeled mitomycin C.

This pharmacokinetic study attempted to improve the exposure of gastrointestinal tract tissues to chemotherapy by increasing the transit time of a first pass of a drug through the vascular system. Bolus infusion of 9 mg mitomycin (MMC) mixed with 1 mg of MMC labeled by 50 microCi of 14C was performed in 18 mongrel dogs. Pharmacokinetics of MMC in peripheral, portal, and aortic blood were studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted a control group. In 15 dogs MMC was infused intraaortically with the catheter's tip at the level of the celiac and superior mesenteric artery. Vascular flow was controlled in four different ways for 30 min: Type I-Type IV. In Type IV the abdominal aorta and vena cava inferior were occluded after surgical exclusion of all nongastrointestinal branches of aorta. Blood samples were obtained during a 90-min period. After solubilizing the samples, 14C-labeled MMC activity was counted by a scintillation counter. For stop-flow infusion Type I, II, III, and IV, area under the curve (AUC) ratios for portal blood versus systemic circulation were 1.6:1, 2.9:1, 2.9:1, and 8.8:1, respectively (statistically significant for Types II, III, and IV). The highest value of AUC, peak MMC concentration, and lowest clearance in portal blood were achieved in SFI Type IV. Exposure to MMC was the greatest with SFI Type IV, making this type of aortic stop-flow infusion the most favorable mode of drug administration from a pharmacokinetic perspective.

Intraaortic stop-flow infusion: pharmacokinetic feasibility study of regional chemotherapy for unresectable gastrointestinal cancers.

BACKGROUND: This study attempted to increase the exposure of gastrointestinal tract tissues to chemotherapy by prolonging the first pass of intraaortically administered drug by temporary occlusion of vascular structures. METHODS: Bolus infusion of 14C-labeled mitomycin C (MMC) mixed with unlabeled MMC was performed in dogs. Distribution of MMC in gastrointestinal tract tissues was studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted the control group. Vascular flow was controlled in four ways for 30 min: type I--stop-flow infusion (SFI) with clamping of the abdominal aorta above the celiac and below inferior mesenteric artery; type II--with additional clamping of the inferior vena cava above the diaphragm; type III with additional clamping of the portal vein in the hepatoduodenal ligament; and type IV--with surgical exclusion of nongastrointestinal branches of the aorta in addition to type II clamping. RESULTS: Type II and IV produced a 3-10-fold increase in exposure to MMC of major gastrointestinal tissues as compared with intravenous infusion. Area under the curve ratios with type IV were most prominent in the following tissues: stomach, pancreas, liver, and mesenteric lymph node. CONCLUSION: Access of MMC to several gastrointestinal tissues was increased through SFI. Type IV infusion was the most effective. Tissue exposure to MMC was especially advantageous for stomach, pancreas, liver, and mesenteric lymph node.

Surgical technique and colorectal cancer: impaction on local recurrence and survival.

The survival of patients with large bowel cancer continues to improve. This may be explained by an evolution in surgical technique for cancer resection. Survival statistics between 30% and 75% can be found for the same stage of disease by different surgeons and at different institutions. The absolute requirement for survival is a complete resection of cancer with free margins of dissection. The etiology of local recurrence was suggested to be spilled tumor cells from venous blood, trasected lymphatics or from tissue trauma at narrow margins of dissection. Blunt dissection technique may be responsible for an increased incidence of local recurrence and cancer related death especially in metastatically insufficient cancers. Although no touch technique may not be important, the wide dissection that it promotes is of benefit. Even if adjacent structures are involved, an anatomically disciplined en bloc sharp or electrosurgical dissection are the surgical techniques that are of paramount importance. Adjuvant intraperitoneal cytostatic agents may in the future be used to eliminate spilled tumor cells that may occur even though the surgical approach is optimized.

The use of drains in elective surgery for colorectal cancer: always, never or selectively?

Indications for the use of drains of the peritoneal and pelvic cavity following elective surgery for colorectal cancer provide a source of continuing controversy. Analysis of the experimental and clinical studies indicates that routine drainage in needless with standard elective surgery for colon cancer. Some risk factors justify the selective use of drains when there is an increased risk of postoperative morbidity. In contrast, surgery for rectal cancer is associated with high risk of wound site complications and usually requires drainage with or without the filling of a pelvic "dead space" with well-vascularized soft tissues.

Recurrent intraabdominal cancer with intestinal obstruction.

The objective of this study was to evaluate short and long term results of management of recurrent intraabdominal malignancy causing intestinal obstruction using surgery and intraperitoneal chemotherapy and determine the clinical features that suggest favorable outcome. Forty two consecutive patients who were treated by cytoreductive surgery with or without intraperitoneal chemotherapy were retrospectively analyzed. There were 20 patients with primary tumors of appendix, 13 with cancer of colon or rectum, and 9 patients with cancer of other origins. All 42 patients were explored and extensively evaluated intraoperatively. Surgery included bowel resections and peritonectomy procedures. In 30 patients early postoperative intraperitoneal chemotherapy was administered. The overall morbidity was 55% while mortality was 7.14%. The projected three year survival for this group of patients was 32.7%. Among the most significant clinical features that reflect favorable prognosis were low histologic grade of malignancy, recurrence 2 and more years after primary surgery, and cancer that could be completely surgically excised. As a result of treatment patients' performance status improved in 47.6% of cases. An aggressive reoperative approach may be considered for palliation of selected patients with recurrent cancer causing intestinal obstruction.