A case and review of bowel perforation secondary to metastatic lung cancer.

Gastrointestinal tract perforation (GITP) secondary to metastatic lung cancer is extremely rare. We present a case of small bowel perforation secondary to metastatic lung cancer. The objective of this study was to review the current literature and further characterize the incidence, histology, and risk of GITP secondary to lung cancer metastasis. A Medline search was done to identify all the cases of GITP attributed to metastatic lung cancer reported in the literature. Data was collected and analyzed from a collection of cases in the medical literature since 1960. We identified 98 cases of perforated lung cancer metastasis to the small intestine. Four gastric perforations, three colonic perforations, and one appendiceal perforation were also identified but not analyzed. The mean age was 64.5 years. There was a male predominance of 89 per cent versus 11 per cent female. Perforations occurred most often in the jejunum (53%) followed by ileum (28%). Combined jejunum-ileum lesions accounted for 4 per cent of perforations. No duodenal perforations were reported, though a specific site was not determined in 13 per cent of cases. Small bowel perforations were most often caused by adenocarcinoma (23.7%), squamous cell carcinoma (22.7%), large cell carcinoma (20.6%), and small cell carcinoma (19.6%). The prevalence of small bowel perforation secondary to a given primary lung cancer histology varied by region. The mean survival was 66 days with 50 per cent of patients not surviving past 30 days. Despite a high incidence of lung cancer, small bowel perforation secondary to lung cancer metastasis remains relatively rare. Perforated metastases occur more often in men and are found more commonly in the jejunum. Small bowel perforations are caused most often by adenocarcinoma; however, squamous cell and large cell carcinoma metastases are more likely to result in perforation. Small bowel perforation in this setting has a significant impact on mortality, decreasing 1-year survival to less than 3 per cent.

Hepatic artery ligation for liver metastasis in colorectal carcinoma.

From April 1975 to January 1982, 97 patients with greater than or equal to 50% of the liver involved with metastasis from colorectal carcinoma underwent hepatic artery ligation. The purpose was to evaluate median survival times in relation to performance status, synchronous intraabdominal metastasis, pulmonary metastasis, liver function tests (alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), total bilirubin, and Dukes' staging. Results reveal that for performance status 0 to 1 (normal or symptoms, but ambulatory), median survival time was 12.3 months; status 2 to 3 (in bed less than or greater than 50% of time), 8.3 months; status 4 (100% bedridden), 2.6 months, (P less than 0.01). Median survival time in patients with only intrahepatic metastasis was 10 months versus 7 months for synchronous intraabdominal metastasis (P less than 0.01). For 20 patients with pulmonary metastasis undergoing hepatic artery ligation, the median survival time was 8.8 months (P less than 0.05). The median survival time in patients whose alkaline phosphatase was 2 times normal was 12.4 months, whereas, if alkaline phosphatase was 2 times to 4 times or greater than 4 times normal, median survival times were 7.1 and 6.9 months, respectively (P less than 0.01). Factors that adversely affect survival for hepatic artery ligation are extrahepatic metastasis, poor performance status, and elevated liver function tests (alkaline phosphatase 2 times normal). The overall median survival time in this study is 9.5 months with certain subgroups achieving 12.4 months' survival.

The use of colonoscopy in the study of synchronous colorectal neoplasms.

Over a 5-year period, 185 patients with primary colorectal carcinoma were studied by colonoscopy for synchronous neoplasms. Twenty-eight patients had incomplete examinations due to obstructing tumors, and 157 had total colonoscopy. Sixty patients (35.9%) had synchronous neoplasms, of which 43 (25.7%) were adenomatous polyps, 5 (3%) were villous polyps, and 12 (7.2%) were carcinomas. The planned surgical procedure was altered on 7 of 12 synchronous cancers (58.3%), 10 of 38 adenomatous polyps, and 17 of 157 (10.8%) patients who underwent total colonoscopy. Preoperative colonoscopy is deemed essential for the optimal management of the patient with colorectal carcinoma.

Enhancement of T lymphocyte proliferative response to mitogens by indomethacin in breast and colorectal cancer patients.

The present study confirms previous observations that in vitro T lymphocyte proliferative response to mitogens is depressed in only some untreated patients with advanced or metastatic breast and colorectal cancer. Indomethacin, a prostaglandin synthetase inhibitor, at 1.0 microgram or 0.1 microgram/ml concentration significantly enhances the PHA, Con A or PWM response in these patients with breast and colorectal cancer (P less than 0.05 - P less than 0.01). Indomethacin has no mitogenic activity. Ethyl alcohol (0.01%), in which indomethacin is dissolved, also has no mitogenic or cytotoxic activity. Although the in vitro effect of indomethacin has been well-demonstrated, the in vivo effect of this agent on cell-mediated immunity in man has not yet been thoroughly investigated and thus, further studies of the effect of indomethacin administration on in vivo and in vitro cellular immunity seem warranted.

Extensive resections of isolated metastasis from carcinoma of the colon and rectum.

The results of this study show that hepatic resection for metastatic carcinoma of the colon and rectum is an effective treatment modality. The duration and quality of survival are better than those achieved by an other treatment modalities. The results of this study also show that hepatic resection is a safe procedure; however, a 50 per cent, two of four, mortality rate in patients undergoing a trisegmentectomy for metastatic disease points toward a need for better selection of patients. Adjuvant chemotherapy following hepatic resection has not been shown to be of any benefit in this series.

Surgical treatment of isolated abdominal wall metastasis in colorectal cancer.

Isolated abdominal wall recurrence, following resection of a primary large bowel adenocarcinoma, is an infrequent finding. Over a ten year period, 22 patients were submitted to en bloc resection of such localized neoplastic foci. In 13 cases, recurrent tumor was located in a previous midline or para median incision. Nine patients underwent palliative radiotherapy and/or chemotherapy once the recurrent disease was identified, and were operated on when uncontrolled progression was clinically evident. In all cases, 4-5 cm disease-free margins were obtained. In eight patients it was possible to close the defect primarily and 14 patients required marlex mesh. Twelve patients were alive at two years and ten patients at five-years follow-up mark. Mucin-producing or poorly differentiated adenocarcinoma had the worse prognosis. Synthetic prosthesis allowed for adequate resections with little morbidity and acceptable cosmesis. Symptomatic relief and long-term palliation can be achieved with aggressive surgery. The role of adjuvant chemotherapy and radiation therapy still needs to be evaluated. The aggressiveness of poorly differentiated and the mucin producing adenocarcinoma should temper radical surgical exercises.

Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas.

The effects of thymidine (dThd) coadministration on the pharmacokinetics and metabolism of 5-fluorouracil (FUra) were investigated in 29 colorectal cancer patients. Five patients received 5-day i.v. infusion of FUra at 15 mg/kg/day and 24 patients received infusion of FUra (7.5 mg/kg/day, 5 days) and dThd (216 mg/kg/day, 6 days) preceded by a bolus dose of dThd (405 mg/kg). Plasma and urine concentrations of FUra, 5-fluorodeoxyuridine (FdUrd), thymine, and dThd were quantitated by a high-pressure liquid chromatographic assay. Concurrent dThd administration reduced the plasma clearance of FUra at steady state from 389.1 +/- 153.5 (S.D.) to 56.0 +/- 36.4 liters/kg/day. The mean steady-state plasma concentration of FUra in patients receiving FUra alone was 0.38 microM and was significantly lower than the 1.30 microM in patients receiving FUra-dThd. Plasma concentrations of FUra were linearly dependent on those of thymine. Furthermore, the metabolic and renal clearances of FUra decreased inversely with thymine concentrations indicating that the elimination of FUra was reduced by thymine. In contrast to the absence of FdUrd as a circulating metabolite in patients treated with FUra alone, microM concentrations of FdUrd were detected in plasma of most of the patients treated with FUra-dThd. This together with the linear correlation of FdUrd and dThd concentrations indicates that the interconversion of FUra to FdUrd was enhanced by dThd. The incidence of dose-limiting leukopenia in the FUra-dThd combination therapy was 40%. There is an inverse correlation between the plasma clearance of FUra at steady state and hematological toxicity. The plasma clearance of FUra in the toxic population was 32.0 +/- 16.8 liters/kg/day and was significantly lower than the clearance of 72.0 +/- 37.3 liters/kg/day in the nontoxic population (p less than 0.001). The corresponding critical toxic steady-state FUra plasma concentration was 1.5 microM. The biochemical effects of dThd on the incorporation of FUra and FdUrd into RNA and into acid-soluble 5-fluorodeoxyuridine monophosphate (FdUMP) in human colon tumor cells were studied in vitro. At 100 microM, dThd increased the incorporation of FUra into RNA up to 4-fold but diminished the acid-soluble FdUMP pool. Similarly, the incorporation of FdUrd into acid-soluble FdUMP was inhibited by dThd. The response rate of colorectal carcinoma to FUra was not improved by coadministration of dThd; only one of the 11 patients who had no prior FUra therapy achieved partial remission. The lack of clinical response in these patients may be partly due to the inhibition of anabolism of FUra and FdUrd to FdUMP by dThd.

EEA stapler in low anterior anastomosis.

Preservation of the anal sphincter is a goal of all surgeons treating colorectal malignancies. In the hands of many, transsacral and low anterior resections with end-to-end anastomosis have been associated with high morbidity and leakage. The EEA stapler represents an alternative in re-establishing bowel continuity. Fifty-eight patients with adenocarcinoma of the rectum were treated over a three-year period at Roswell Park Memorial Institute. Forty-nine procedures judged to be curative and nine, palliative. All patients had an EEA stapler introduced through the anus. No protective colostomies were needed. No case of clinically significant anastomotic leakage was seen. Minor spotting or bleeding was documented, but no patient required blood transfusions. Two patients developed constipation; 16 patients had temporary soiling, two had prolonged soiling. Frank incontinence was not observed. The EEA stapler is an evolutionary instrument derived from the Russian PKS model. It is safe, reliable, and simple to operate. With adequate training of the surgeon, precious time can be saved. Intraoperative sigmoidoscopies, as well as postoperative barium enema examinations, were not needed. Gaps in the stapled anastomotic line (when present) were easily repaired. It is too early to tell whether anastomotic and local recurrence rates will increase, as more sphincter-saving procedures are performed. Five-year follow up is crucial to establish criteria for the use of the EEA stapler.

Metachronous ovarian metastases from adenocarcinoma of the colon and rectum.

Our observations indicate that the menopausal status of a patient, the anatomic location or the histologic differentiation of a primary adenocarcinoma of the colorectal area does not seem to affect the incidence of ovarian metastases. Tumors initially classified as Dukes' B2 and, later, associated with ovarian metastases have consistently poorer prognosis. The reason that ovarian metastases attain a relatively large size, while other metastatic foci remain small, is unknown. Regardless of the surgical findings, patients with ovarian metastases from a primary adenocarcinoma of the colorectal area tend to have short survival with widespread distribution of the tumors at death. This would suggest that these metastases occur primarily by the hematogenous route rather than by an orderly invasion to contiguous structures and draining lymph nodes. Patients with resectable solitary ovarian metastases and prospectives of cure must be a rare event in carcinoma of the colon and rectum.

Mesothelial cysts associated with metastases to ovary from primary colonic carcinoma.

The three cases herein reported concern metachronous ovarian metastases from primary adenocarcinomas of the colon associated with mesothelial cysts. Although the etiology of these cysts remains obscure, the cases were of interest because the cysts did not contain tumor cells despite the intimate relationship to the tumor. Metastases were localized to the ovary and were resectable. All signs and symptoms disappeared, affording excellent palliation and an extended survival.

Treatment of recurrence of adenocarcinoma of the colon and rectum at the anastomotic site.

Resection of recurrent adenocarcinoma of the colon and rectum at the anastomotic site was performed in 30 patients. In the majority of the patients, the recurrence was apparent within two years of the initial operation. In 27 patients, the recurrence was diagnosed based upon persistent signs and symptoms or if the tumor was clinically palpable. In 15 patients, complete resection of the recurrent tumor was feasible, and the median survival time was 59 months, with a five year survival rate of 49 per cent. In ten other patients, minimal tumor was left behind. The median survival time was 17 months and 12 per cent survived five years.

Surgical treatment of metastatic colorectal adenocarcinoma.

Ninety-one patients with recurrent or metastatic colorectal adenocarcinomas were studied according to the anatomic areas of the recurrent tumor. In Group A, 30 patients with anastomotic recurrence, diagnosis was made in the majority within two years from initial surgery; most of them had specific symptomatology. A significant number of patients had blood in the stools. In half of the patients, complete resection of the recurrent tumor was feasible. In Group B, 47 patients with intra-abdominal recurrence, there was some delay in diagnosis; the symptomatology was less specific, and fewer patients were rendered free of tumor following reresection. The medial survival and estimated five-year survival rate were, in both groups, strongly related to the completeness of the resection. In Group C, with distant metastasis (eight patients with pulmonary and six with liver metastasis), the disease-free interval was longer compared to the previous groups. The metastatic tumor was found in three patients, four or more years after the initial surgery. The medial survival was the same as in the two other subgroups with complete resection of the recurrent tumor.

Indications for cholecystectomy in ligation of the hepatic artery.

Ligation of the hepatic artery has been successfully used in the management of massive bleeding, secondary to hepatic trauma, and in the treatment of metastatic neoplastic disease. The indications for a concomitant cholecystectomy are less well defined. It is generally accepted that cholecystectomy should be performed when ligation is used to control bleeding. In our study, ligation of the hepatic artery was performed, leaving the gallbladder in situ. At autopsy, no pathologic process could be detected in the gallbladder. Microscopic analysis showed fibrosis in the mucosal surface, mild chronic inflammation and nonspecific mononuclear infiltration. We conclude that the changes are insufficient to warrant the removal of a normal gallbladder when ligation of the hepatic artery is performed as treatment for neoplastic disease.