P. Lasser

Curative Treatment of Peritoneal Carcinomatosis Arising from Colorectal Cancer by Complete Resection and Intraperitoneal Chemotherapy

Peritoneal carcinomatosis (PC) is fatal, despite standard systemic chemotherapy. A new approach that combines maximal surgery with maximal regional chemotherapy has potential to cure selected patients who have colorectal PC. The authors have reported the oncologic results of this combined treatment.

Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases

Extrahepatic disease has always been considered an absolute contraindication to hepatectomy for liver metastases. The present study reports the long‐term outcome and prognostic factors of patients undergoing resection of extrahepatic disease simultaneously with hepatectomy for liver metastases.

Surgery for lung metastases from colorectal cancer: analysis of prognostic factors.

PURPOSE To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer. PATIENTS AND METHODS A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Coxs model) analyses of survival were used to identify significant prognostic factors. RESULTS Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level. CONCLUSION Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.

Squamous cell carcinoma of the anal canal: treatment by external beam irradiation.

External beam radiation therapy alone or in combination with curietherapy is the recommended treatment for anal canal carcinoma in some countries. In others, surgery is the sole accepted treatment. The results for 64 patients treated by external radiotherapy alone show excellent survival for stage T1T2 tumors but results are poor for large tumors (stage T4). The overall 5 year crude survival rate is 46%. The 5-year results are better for stage T1T2 (72%) than for stage T3T4 (35%). The presence of inguinal node involvement at first examination is a very poor prognostic sign. Local recurrences and metastases are infrequent for stage T1T2, but are more common for stage T3 and T4. Complications follow radiotherapy more frequently in those with stage T3 and T4 tumors. The analysis of local recurrences, complications and survival shows that radiation therapy may be sufficient treatment for stage T1 and T2 and for some stage T3 tumors. The importance of anal sphincter involvement and the poor quality of life for patients who are cured but develop complications, shows the need for combined treatment with surgery and perhaps with chemotherapy. For small tumors the results obtained by external radiotherapy alone are comparable with those obtained by external radiotherapy and curietherapy in terms of survival and complications.

Resection of liver metastases from colorectal cancer : the real impact of the surgical margin

AIMS The benefit of liver resection for metastatic colorectal cancer is now established. Nevertheless if the surgical margin on pre-operative imaging is considered to be less than 10 mm, this is considered an absolute contraindication to surgery by some, and a relative contraindication by others, so its real impact on prognosis is not clear. METHODS From 1984 to 1996, 269 patients underwent hepatectomy for liver metastases and were prospectively studied. The only two objectives of this surgery were to be curative (or achieve complete R0 resection), and to avoid mortality. Of the 269, 187 patients had surgical margins inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had extrahepatic metastatic sites. Their clinical and pathological factors were specifically studied. RESULTS The crude 5-year survival of these 187 patients (including the 2% post-operative mortality) was 24.7%, and the disease-free survival was 18.8%. The surgical margin was 0 mm in 60 cases and was histologically invaded in 20 cases. The most important prognostic factor was whether the resection was considered palliative (R1-R2 resection according to UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded, there was not prognostic difference between the 107 patients with a margin of 0-4 mm and the 143 patients with a margin greater than 4 mm. However, a surgical margin greater than 9 mm appears to be a second prognostic factor (P = 0.001), when these 187 patients are compared to others. The reasons behind this are that there is a close relationship between narrow margins and extensive disease (high number of metastases, bilateral localization and extended hepatectomy), and also an increased possibility of microscopic satellite lesions within 10 mm around the metastases. CONCLUSION The real prognostic impact of the surgical margin must not be overestimated. Hepatectomy for metastases can provide long-term survival in patients with supposed poor prognostic factors. Resection is justified so long as it is complete and with minimal risk. An experienced, specialized centre can be a prognostic determinant.

Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis

Combined chemotherapy has demonstrated a degree of efficacy in gastric carcinoma. As 5-fluorouracil (5FU) and cisplatinum are two of the most active drugs, we have tested the efficacy of combined 5FU and cisplatinum in a prospective phase II trial. Cycles were administered every 4 weeks and consisted of 5FU 1000 mg/m2/day 5 days continuous intravenous (i.v.) infusion and cisplatinum 100 mg/m2 on day 2. Cycles were repeated according to tolerance and efficacy. 87 patients entered the study, 57 with metastatic or recurrent tumour (M) and 30 with locally advanced gastric cancer (LAGC). The response rate for the 83 evaluable patients was 43% [95% confidence interval (CI) 30-56%]. There were four complete responses (5%), 32 partial responses (39%), 34 cases of stable disease and 13 cases of progressive disease. Responses were more frequent in patients with a good performance status (P = 0.02), with their primary located in the cardia (P = 0.003), with a non-linitis plastica tumour form (P = 0.003) or a tumour containing less than 50% of independent cells (P = 0.016). Median survival was 9 months for the total population. It was better in patients with a good performance status (P = 0.01), and those who did not have linitis plastica (P = 0.005). Toxicity was acceptable, although grade 3-4 neutropenia was reported in 22% of the cycles, mucositis in 14% and 3 patients died of septic complications. The combination of 5FU and cisplatinum is effective in terms of tumour response in advanced gastric cancer and warrants testing with the other active regimens.

Surgical management of primary anorectal melanoma

This aim of this study was to analyse outcome after surgery for primary anorectal melanoma and to determine factors predictive of survival.

Hepatectomy for liver metastases from breast cancer

Thirty-two selected patients underwent laparotomy in an attempt to resect one or more isolated liver metastases (LM) from breast cancer. Only 21 of them had hepatectomy and systematic lymph node picking of the hepatic pedicle. In six patients (19%), the discovery of diffuse metastatic disease contraindicated hepatectomy and in five patients (16%), the diagnosis of LM was erroneous, for lesions proved to be benign liver tumours. Nineteen of the resected cases received preoperative chemotherapy, 12 received post-operative chemotherapy and two had repeated hepatectomy. Eight patients (38%) had more than one LM and (24%) had positive hepatic lymph nodes. No post-operative mortality occurred. After the beginning of this combined treatment, median survival was 38.2 months and 2- and 5-year survival rates were, respectively, 78% and 24%. After the hepatectomy, median survival was 26 months and 2- and 5-year survival rates were, respectively, 50% and 9%. When a recurrence did occur (mean time to recurrence after hepatectomy was 14.8 months) the liver was involved in 75% of the cases and was the first place of recurrence in 56% of the patients. In this limited series, the number of LM, the number of positive pedicular lymph nodes, and a response to preoperative chemotherapy were not significant prognostic factors. However, patients with negative nodes tended to have a better prognosis, as did those with the first and only site of relapse being the liver. These selected patients, treated with hepatectomy, had a median survival at least three-fold that of patients treated with standard, non-surgical treatment. However, hepatectomy appeared to be mainly a cytoreductive procedure, and the efficiency of this combined treatment was mainly hampered owing to the inefficacy of current chemotherapy programmes. Only a prospective randomized study, in well-defined patients with isolated LM from breast cancer, comparing conventional treatment with or without hepatectomy, will demonstrate whether hepatectomy does indeed increase survival rates.

Human Pharmacokinetic Study of Heated Intraperitoneal Oxaliplatin in Increasingly Hypotonic Solutions after Complete Resection of Peritoneal Carcinomatosis

Purpose: We studied the pharmacokinetics of heated intraoperative intraperitoneal (i.p.) oxaliplatin (LOHP) solution and its safety profile in increasingly hypotonic solutions. This is the first clinical study of i.p. chemohyperthermia with hypotonic solutions. Methods: Patients with peritoneal carcinomatosis (PC) underwent complete cytoreductive surgery followed by intraoperative i.p. chemohyperthermia (IPCH) with successive dextrose solutions of 300, 200, 150 and 100 mosm/l. LOHP (460 mg/m2) was administered in 2 liters of solution/m2 at an i.p. temperature of 42–44°C for 30 min. IPCH was performed using an open procedure (skin pulled upwards) with a continuous closed circuit. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before IPCH to maximize the effect of LOHP. i.p. plasma and tissue samples were analyzed by means of atomic absorption spectrophotometry. Sixteen consecutive patients with PC of either gastrointestinal or peritoneal origin were treated. The safety of the procedure was studied. Results: Pharmacokinetics: The mean duration of the entire procedure was 7.7 ± 2.6 h. Half the LOHP dose was absorbed within 30 min at all dose levels. Absorption was not higher with hypotonic solutions than with isotonic solutions. The area under the curve of LOHP in plasma did not increase with decreasing osmolarity of the i.p. solutions. Intratumoral LOHP penetration was high; it was similar to that at the peritoneal surface, and about 18 times higher than that in nonbathed tissues. LOHP penetration was not significantly increased by using hypotonic solutions. Safety: There was a very high incidence of unexplained postoperative peritoneal bleeding (50%) and unusually severe thrombocytopenia in the 150 and 100 mosm/l groups. Conclusion: Contrary to experimental studies, this clinical study showed no increase in tumoral or systemic penetration of LOHP with i.p. hypotonic solutions (200, 150 or 100 mosm/l) during IPCH. A high incidence of i.p. hemorrhage and thrombocytopenia was observed.

Neoadjuvant chemotherapy in locally advanced gastric carcinoma-A phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum.

Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates.