Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence.

The Registry of Hepatic Metastases has collected data on consecutive patients from 24 institutions who have undergone hepatic resection for colorectal carcinoma metastases. Patterns of recurrence were examined in a subgroup of 607 patients who had undergone curative resection of isolated hepatic metastases. Forty-three percent of these patient have had recurrences in the liver and 31% have had recurrences in the lung (either alone or in combination with other organs). A multivariate analysis showed that patients with positive pathologic margins or bilobar metastases were at an increased risk of having a recurrence in the liver (68% and 64%, respectively). We conclude that: hepatic resection effectively controls hepatic tumor in a substantial number of patients, adjuvant therapy after hepatic resection should be directed at both the lung and liver to significantly increase survival, and patients with positive pathologic margins or bilobar metastases are at an increased risk for hepatic recurrence.

En bloc resection of primary melanoma with regional lymph node dissection.

En bloc resection of the primary melanoma with the regional lymph node drainage basin as a method of controlling disease within the area was used in 281 patients with stage I or II melanoma arising on the extremities (proximal to wrist or ankle) or on the trunk from 1954 through 1964. The en bloc operation was performed in 212 patients with a five-year cure of 73.5% (156 of 212). Seventy-six percent had histologically negative nodes. Only 2% developed regional recurrence. Sixty-nine patients had a discontinuous dissection. The five-year cure was comparable: 68% (47 of 69). The incidence of histologically negative nodes was similar (77%), but the regional recurrence rate was 14%. This difference is significant at P < .01. The incontinuity or en bloc procedure appears highly effective for its designed purpose.

Proximal extrahepatic bile duct tumors. Analysis of a series of 52 consecutive patients treated over a period of 13 years.

Fifty-two consecutive patients with proximal extrahepatic bile duct tumors were treated by one of us (J.G.F.) between 1974 and 1987 at Memorial Sloan-Kettering Cancer Center, New York, NY. Thirty-eight patients (73%) underwent palliative procedures aimed at relieving the biliary obstruction (group A) and 14 patients (27%) were operated on with curative intent (group B). The choice of the surgical procedure employed to relieve the biliary obstruction did not significantly influence the length of survival of patients in group A in whom the median survival was 13.5 months and the in-hospital mortality was 15.7%. Fifty percent of the patients in group B underwent major liver resections to macroscopically encompass the tumor. In this group, although 35% of the patients experienced major complications, no in-hospital mortalities were encountered and the median actuarial survival was 38 months. The projected and crude 5-year survival rates were 28% and 21%, respectively. Age, gender, extent of resection, microscopic status of margins of resection, and grade of the lesion did not affect the length of survival in patients in group B. Locoregional failure, either isolated or as a component of peritoneal failure, was detected in the 6 patients in whom the disease has recurred. Eighty-three percent of the patients in whom the disease has recurred were dead within 12 months of the diagnosis of recurrence. Two long-term survivors (14%) developed second primary tumors in the follow-up period.

Twenty-two year experience with periampullary carcinoma at Memorial Sloan-Kettering Cancer Center.

The resectability rate was high (84 per cent) for patients with periampullary cancer. The incidence of lymph node metastases was also high, being 50 per cent for those with small tumors (2 cm or less). The 5 year cure rate was 67 per cent for patients with negative nodes but 0 per cent for those with positive nodes.

Selective use of wide excision with elective lymph node dissection for malignant melanoma.

One hundred and eighty individuals with clinically negative regional lymph nodes are the basis of this study. One hundred and ten of these underwent an elective lymph node dissection. The incidence of histologically positive lymph nodes was 0 percent, 17 percent, and 42 percent for those with thin, intermediate thickness and deeply invasive lesions. Of these 25 patients with histologically positive lymph nodes, the metastases were micro in size (less than or equal to 2 mm) in 75 percent of the intermediate thickness group compared with 38 percent of the deeply invasive group. At the present time, the size of lymph node metastases appears to correlate with disease-free estimates: at 2 years, the disease-free estimates are 70 percent for those with micro metastases and 24 percent for those with macro metastases. Therapeutic success is influenced greatly by the number of circulating cancer cells challenging the host's defense mechanism. The large cell mass of clinically evident metastatic disease would appear to present most patients with an uncontrollable number.

Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy.

OBJECTIVE: The purpose of this study was to evaluate the regional pancreatectomy as surgical therapy for ductal adenocarcinoma of the pancreas and to evaluate potential prognostic factors. SUMMARY BACKGROUND DATA: Regional pancreatectomy was developed as a more adequate surgical procedure for pancreatic cancer in an attempt to improve the cure rate for this highly lethal disease. Few studies have evaluated large numbers of patients treated with this technique, and in recent years the emphasis has been on more limited surgery for pancreatic cancer. METHODS: Fifty-six patients with ductal adenocarcinoma of the pancreatic head were treated by regional subtotal or total pancreatectomy. Clinical and pathologic parameters were reviewed and potential prognostic factors were compared statistically. The three patients who died within 30 days of the operation were excluded from the survival analysis. RESULTS: Primary tumor size was the strongest determinant of prognosis. The mean tumor size was 3.9 cm (range, 1-7 cm). Eighty-five percent of patients had peripancreatic soft tissue invasion microscopically, and 58% had regional lymph node metastasis. Kaplan-Meier survival curves indicated a 33% 5-year survival for patients with tumor 2.5 cm or less in diameter (n=12) and 12% for patients with larger tumors (n=39). No patient with a tumor larger than 5 cm survived more than 5 years. Mean tumor size was not significantly associated with lymph node metastases, but 5 of 12 patients (42%) with primary tumor < or =2.5 cm had lymph node metastases. Twenty-four percent of patients with negative lymph nodes and 14% with positive lymph nodes survived 5 years. The difference was not statistically significant (p=0.3), but this is likely related to sample size. The 30- day operative mortality was 5.3%. The most common complications were infection, gastrointestinal bleeding, and gastric stasis. CONCLUSIONS: After regional pancreatectomy, tumor size is the strongest predictor of prognosis. A multi- institutional randomized prospective trial of regional pancreatectomy versus pancreaticoduodenectomy is warranted in previously untreated, noninfected cases.

Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection.

In the United States, there are an estimated 5000 to 6000 new patients annually who might be candidates for major hepatic resection to treat their recurrent colon cancer. Since 1971, the program reported here has evaluated various factors that might influence the curative potential of such an approach. Sixty-five patients had a major hepatic resection from March 1971 through May 1982. Using a stepwise proportional hazard analysis, all data that had been stored in CLINFO (a data analysis system by Bolt, Beranek and Newman; Boston, MA) were evaluated for the effect of multiple variables on the survival of patients with resected hepatic metastases. Twenty-seven had a right hepatic lobectomy; 14 had extended right hepatectomy with one having the caudate lobe also removed; ten had left lobectomy, nine had left lateral segmentectomy; and five had a major hepatic resection with three-dimensional wedge excision of a metastatic deposit in the contralateral lobe. The 30-day operative mortality rate was 7% (4/58) for patients undergoing the standard major hepatic resection. It was 14% for seven patients in whom the isolation-hypothermic perfusion technique was used early in the series. In ten patients, wedge excision only was required to remove the tumor. Stage I disease is defined as tumor confined to the resected portion of the liver without invasion of major intrahepatic vessels or bile ducts. Stage II disease is regional spread and Stage III disease is metastasis to lymph nodes or extraregional sites. The 3-year survival estimate was 66% for the 37 patients with Stage I disease. The 3-year survival estimate for 13 patients with Stage II disease was 58%. Five of the nine patients with Stage III disease are presently alive from 3 to 23 months; one of the other four died at 35 months of disease. The stage of liver disease was the most significant variable in this survival analysis (p = 0.02); Dukes' classification of colorectal primary was significant at p less than 0.05. Those factors found not to be significant determinants of survival were: number of metastatic hepatic deposits, site of colon primary, age, sex, preoperative liver function tests, and CEA.

Multivariate analysis of a personal series of 247 patients with liver metastases from colorectal cancer. II. Treatment by intrahepatic chemotherapy.

One hundred and seventeen patients with colorectal hepatic metastases had insertion of catheters for infusional chemotherapy. The two-year survival estimate of patients with less than 50% hepatic replacement and no other adverse factors was 37%. Nine of 39 patients in this group are alive at 24 months. The catheters were placed into the hepatic artery (HA), 23; into the portal venous system (PV), 18; into both HA and PV, 64; or into an accessory HA following ligation, 12. Fifty-nine patients had ligation of the common HA also. The 30-day postoperative mortality rate was 1.7% (2/117) and morbidity was 37.6%. The majority of complications were related to fever (61%, 27/44). Over the past 2 years, 87% of patients have been discharged within 10 days following surgery. Preoperative CEA ranged from 0.5-12,150 ng/ml (median 165 ng/ml); 93% (78/84) had plasma CEA levels exceeding 5 ng/ml. All patients had careful intraoperative staging: per cent hepatic replacement (PHR) ranged from 5-95% (median 60%); portal, celiac, or periaortic lymph node metastases were observed in 31% (36/117). Initial intrahepatic chemotherapy programs consisted of either CAMF (9 patients), MAFL (60 patients), BFS (22 patients), continuous infusion FUDR (14 patients), or miscellaneous drugs (4 patients). Median survival time of 109 evaluable patients was 11.5 months. The effect of 20 variables on the observed survival time was analyzed using a multivariate proportional hazard model. Three variables were found to have influenced survival: PHR emerged as the most significant, p = 0.000001. Increased PHR was associated with decreased survival time. Lymph node metastases and prior chemotherapy were prognostic factors also, p = 0.0006 and p = 0.03, respectively. No patient with PHR greater than 80% lived more than 8 months. Utilization of these variables would appear to be necessary for accurate stratification and evaluation of future chemotherapy trials in patients with colorectal hepatic metastases.

Nativity, complications, and pathology are determinants of surgical results for gastric cancer.

BACKGROUND: About half the patients involved in the current study were born outside of the United States. Epidemiologic and histologic features and survival estimates were compared with persons born in the United States. Results of gastrectomy with lymph node dissection were studied. METHODS: Records of 187 patients with adenocarcinoma of the stomach were reviewed. Seventy-six with a curative gastrectomy were staged retrospectively. Univariate and multivariate analyses were done. RESULTS: Seventy-six percent of histologically reviewed curative resections had the intestinal subtype with the same frequency in U.S.-born and foreign-born patients. Fewer patients with proximal third lesions were foreign born. Thirty-six percent had complications. The overall 5-year Kaplan-Meier survival estimate was 46%: 77% for patients with negative nodes and 33% for patients with positive nodes. N1 survival estimate was 44%; N2, 25%; N3(M1), 0%. All six patients with early gastric cancer are alive 50-147 months after surgery. Other stage I patients had estimated survival of 65%; Stage II, 52%; Stage III, 40%; and Stage IV, 0%. Multivariate analysis revealed four significant prognostic variables: nativity, histologic subgroup, presence of complications, and number of positive nodes. CONCLUSIONS: Proximal gastric cancer was more common in U.S.-born persons. Gastric cancer may be more malignant in U.S.-born persons than in foreign-born persons because their survival was significantly poorer. Complications, a significant adverse factor, were more common in U.S. series. Pancreatectomy with gastrectomy is rarely indicated, because microscopic involvement is rare and complications frequent. The prognostic advantage of a regional lymphadenectomy remains unclear.

Major hepatic resection for neoplasia: personal experience in 108 patients.

One hundred eight patients have undergone major hepatic resection by the senior author during the eight year period April 1970 to April 1978. Primary liver cancer was present in 36; metastatic colorectal cancer in 25, miscellaneous metastatic cancers in 15, hepatoblastoma in 5, gallbladder cancer in 4, and bile duct cancer in 3. Benign tumors, principally giant hemangioma, were resected in 20 additional patients. The 30 day operative mortality rate was 9% overall. Prior to 1975, 41 of the resections were done using the vascular isolation perfusion technique. The operative mortality rate of 17% for this technique is a reflection of early experience and the advanced stage of disease of many patients. The operative mortality for the standard resection has been only 4%. Subphrenic abscess has developed in only 13% of patients during the past three years. Postoperative hospitalization has been shortened, being a median of 13 days. The resectability rate for malignant disease was 33%. Forty-six percent of the resections were performed with curative intent. Fifty-four per cent were palliative, performed in individuals with regional spread or distant metastasis. After curative surgery, three year survival was 88% for individuals with primary liver cancer and 72% with metastatic colorectal cancer. After palliative resection, the rates were 31 and 0%, respectively. The three year survival rate is 46% overall, being 81% for the curative resection group and 18% for the palliative group. Tumor markers proved useful in monitoring patients after hepatic resection.

The seventies evolution in liver surgery for cancer.

During the past decade, one of the major changes in the field of oncology has been in the surgical approach to primary and secondary cancer of the liver. As a result of data and experience gained in liver transplantation programs and with the application of vascular surgical principles, resectability rates have been increased. The present rate of 32% has been achieved with an overall 30-day operative mortality rate of 9%. More sophisticated intraoperative and postoperative supports have been essential in achieving these results. The median operating time is now 4 3/4 hours in length. Complications are minimal. The median postoperative hospital stay is now 13 days. During the past decade, 436 patients with liver tumors were treated by the authors. It has become apparent in this experience and in that reported by others that an increasing number of patients with primary liver cancer or metastatic cancer in the liver can be cured by surgery with minimal operative risk. Adjuvant chemotherapy may increase the salvage rate. Current therapeutic results are best evaluated after staging of the liver disease: Stage I (no involvement of margins of resection, hepatic vascular structures or bile ducts; all gross disease removed): 85% three-year survival estimate, using the Kaplan-Meier method, for individuals with primary liver cancer; 71% for those with metastatic colorectal cancer. Stages II and III (regional or extrahepatic spread): 22% three-year survival for individuals with primary liver cancer but no survivors at two years with metastatic colorectal cancer. These data permit better selection of patients who are most likely to benefit from surgery.

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.