Ninety-six five-year survivors after liver resection for metastatic colorectal cancer.

BACKGROUND: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years. STUDY DESIGN: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed. RESULTS: Five-year survivors (n = 96) were more likely to have a Duke's B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%. CONCLUSIONS: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.

Hepatic resection for noncolorectal, nonneuroendocrine metastases: a fifteen-year experience with ninety-six patients.

BACKGROUND: The role of liver resection for hepatic metastases from noncolorectal, nonneuroendocrine (NCNN) cancers is unknown. This study examines a large, single institutional experience of hepatic resection for NCNN metastases. METHODS: Records of 96 patients who underwent liver resection for metastatic NCNN cancer from 1980 to 1995 at a single institution were reviewed. Survival after liver resection in this cohort of patients is reported, and factors predictive of survival are analyzed. RESULTS: Resection was performed for liver metastases from genitourinary primary tumors (n = 34), soft tissue primary tumors (n = 41), and metastases from other primary cancers (n = 21). Extent of liver resection included wedge (n = 32), lobectomy (n = 44), and extended hepatic lobectomy (n = 20). No operative deaths occurred. Overall survival rate after resection at 1, 3, and 5 years was 80%, 45% and 37%, respectively (median survival, 32 months), with 12 actual 5-year survivors. There was no difference in survival according to the type of liver resection, bilateral versus unilateral disease, or resection of extrahepatic disease. Disease-free interval of less than 36 months before discovery of liver metastases, curative resection, and primary tumor group (genitourinary was greater than soft tissue, which was greater than gastrointestinal) were predictors of a significantly better survival by multivariate analysis. CONCLUSIONS: Primary tumor type, disease-free interval, and curative resection predict those patients who benefit from hepatic resection. Hepatic resection for patients with NCNN metastasis has value in carefully selected patients.

Liver resection for colorectal metastases.

PURPOSE: More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome. MATERIALS AND METHODS: Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed. RESULTS: The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%. CONCLUSION: Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.

Outcome of treatment for distal bile duct cancer.

All patients with distal bile duct tumours over a 10-year period (October 1983 to December 1993) were identified by means of a prospective database. The medical records of 104 patients were reviewed. Univariate and multivariate analysis for predictors of outcome was performed. Median age of the patients was 65 (range 30-89) years. Patients presented with a clinical picture indistinguishable from that of pancreatic ductal adenocarcinoma. Twenty patients had no surgical treatment and 23 had a diagnostic laparotomy only. Biliary bypass was performed in 16 patients and radical resection was performed in 45 (pancreaticoduodenectomy, 39; bile duct excision, six). Operative mortality occurred in two of 45 patients having radical resection and complications in 17. Resection provided significant survival benefit. By univariate and multivariate analysis, resectability and negative node status (P < 0.001) were the only predictors of favourable outcome. Sex, age, preoperative stenting, grade of tumour and bilirubin level did not predict outcome. The 5-year survival rate for radically resected, node-negative tumours was 54 per cent. Surgical resection is effective therapy for distal bile duct tumours. These patients have a better outlook than those having resection of pancreatic adenocarcinoma.

Long-term results after resection for gallbladder cancer. Implications for staging and management.

BACKGROUND: The surgical management of gallbladder cancer is controversial. There is no consensus among surgeons as to the indications for reoperation or radical resection. OBJECTIVE: The purpose of this study was to examine results of reoperation after an incidental finding of gallbladder cancer after cholecystectomy, and results of radical resection in patients with advanced disease. METHODS: A retrospective review of 149 patients with the diagnosis of gallbladder cancer treated from 1985 to 1993 was performed. Fifty-eight patients were explored and 23 underwent resection for cure. Resection included trisegmentectomy in nine patients and bile duct resection in ten patients. Seventeen patients underwent re-exploration after an incidental finding of gallbladder cancer at initial cholecystectomy. RESULTS: Surgical resection is associated with an actuarial 51% 5-year disease-free survival rate, with a median follow-up time of 48 months. Eight patients are alive beyond 50 months. There were no operative deaths; the perioperative morbidity rate was 26%. Nodal status is the most powerful predictor of outcome. Two patients with T4, NO disease are alive without evidence of disease beyond 4 years. Thirteen of the 17 patients (76%) undergoing reoperation after simple cholecystectomy for T2 or T3 tumors had residual disease. CONCLUSIONS: Patients with nodal metastasis beyond the pericholedochal nodes should not be considered for curative resection. Tumors staged T4, NO should be included with stage III disease, and resection should be considered. Re-resection of T2 or T3 tumors after simple cholecystectomy is likely to include residual disease and should thus provide the only chance for long-term survival.

Erythromycin stimulates gastric emptying after esophagectomy with gastric replacement: a randomized clinical trial.

UNLABELLED: Delayed gastric emptying after esophagogastrectomy can pose a significant early postoperative problem. Because erythromycin, which stimulates the gastric antral and duodenal motilin receptor, has been shown to significantly increase gastric emptying in patients with diabetic gastroparesis, we decided to evaluate its effect on gastric emptying after esophagogastrectomy. METHODS: Twenty-four patients (18 men and six women, age range 41 to 79 years, median 66 years) were randomized to receive either erythromycin lactobionate (200 mg in 50 ml normal saline solution intravenously) (n = 13) or placebo (50 ml normal saline solution intravenously (n = 11) 11 days after esophagogastrectomy (with pyloric drainage procedure). After erythromycin or placebo had been infused over a 15-minute period, patients ingested a solid meal (scrambled egg with bread) labeled with technetium 99m sulfur colloid (500 microCi) over approximately 15 minutes. Dynamic images of the stomach were then acquired over 90 minutes in the supine position by gamma imaging. Results were expressed as percentage of counts retained in the stomach (percent gastric retention) over time. RESULTS: There were no side effects of erythromycin. In the placebo group, the mean percent of radiolabeled meal retained in the stomach after 90 minutes was 88%, which was significantly greater than in the erythromycin group, 37% (p < 0.001). In addition, analysis of covariance demonstrated that the rate of gastric emptying (slope of the line) was significantly greater in the erythromycin-treated group than in the placebo group (p < 0.0001). CONCLUSION: Early satiety after esophagogastrectomy may be due to delayed gastric emptying and not due to a decrease in the gastric reservoir. Intravenous erythromycin significantly improves gastric emptying in patients after esophagogastrectomy by stimulating gastric motility.

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.

Pancreatic or liver resection for malignancy is safe and effective for the elderly.

BACKGROUND: Liver resection, or pancreaticoduodenectomy, has traditionally been thought to have a high morbidity and mortality rate among the elderly. Recent improvements in surgical and anesthetic techniques, an increasing number of elderly patients, and an increasing need to justify use of limited health care resources prompted an assessment of recent surgical outcomes. METHODS: Five hundred seventy-seven liver resections (July 1985-July 1994) performed for metastatic colorectal cancer and 488 pancreatic resections (October 1983-July 1994) performed for pancreatic malignancies were identified in departmental data bases. Outcomes of patients younger than age 70 years were compared with those of patients age 70 years or older. RESULTS: Liver resection for 128 patients age 70 years or older resulted in a 4% perioperative mortality rate and a 42% complication rate. Median hospital stay was 13 days, and 8% of the patients required admission to the intensive care unit (ICU). Median survival was 40 months, and the 5-year survival rate was 35%. No differences were found between results for the elderly and those for younger patients who had undergone liver resection, except for a minimally shorter hospital stay for the younger patients (median, 12 days vs. 13 days; p = 0.003). Pancreatic resection for 138 elderly patients resulted in a mortality rate of 6% and a complication rate of 45%. Median stay was 20 days, and 19% of the patients required ICU admission, results identical to those for the younger cohort. Long-term survival was poorer for the elderly patients, with a 5-year survival rate of 21% compared with 29% for the younger cohort (p = 0.03). CONCLUSIONS: Major liver or pancreatic resections can be performed for the elderly with acceptable morbidity and mortality rates and possible long-term survival. Chronological age alone is not a contraindication to liver or pancreatic resection for malignancy.

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.

Inadvertent spread of cancer at surgery.

Surgical cure requires that a given cancer be removed without inadvertent spillage of cancer cells by technical error. Potential mishaps include pressing a ligature, while tying, against a protruding tumor and cutting into it; inserting a hemostat into the tumor area to gain control of an escaped short pancreaticoduodenal artery stump which has retracted; grasping a lymph node with forceps which invariably fragments it spilling any cancer cells it may contain; and injecting local anesthesia into or adjacent to a lesion for biopsy. If the lesion is a cutaneous melanoma or other cancer the resulting pressure may force cancer cells into the lymphatic or bloodstream. Other misadventures include touching that portion of a biopsy needle which has been in the tumor and doing an intraoperative biopsy which allows blood or tissue fluid to flow out the opening from the tumor. Sensitivity to such dangers appears essential to avoiding spillage of cancer cells and obtaining maximal benefit from surgery.

Resection of hepatic and pulmonary metastases from colorectal cancer.

Resection of hepatic metastases of colorectal origin has gained wide acceptance, but when patients have synchronous or metachronous pulmonary metastases, they are often considered incurable and are offered systemic therapy only. We performed a retrospective review of the patients at Memorial Sloan-Kettering Cancer Center who underwent resection of both hepatic and pulmonary metastases of colorectal origin between 1970 and 1990. Ten patients were identified who met the above criteria. Median survival after hepatic and pulmonary resections were 34 and 18 months, respectively. Actuarial 1-, 3- and 5-year survivals are 89%, 78% and 52%, respectively. With a median of 18 months after second operation, three patients have no evidence of disease (NED), four are alive with disease (AWD) and three are dead of disease (DOD). In the absence of effective chemotherapy, selected patients with hepatic and pulmonary metastases of colorectal origin should be considered for resection as it offers the only possibility for long-term survival.

Metabolic consequences of (regional) total pancreatectomy.

Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery.

Brachytherapy in the treatment of solitary colorectal metastases to the liver.

It is well-established that 30-40% of patients with solitary liver metastases from primary colorectal tumors can be cured by resection. Conventional radiation therapy has had only a palliative role in treating liver metastases because the dose that the liver will tolerate is far below a tumoricidal dose. In contrast, brachytherapy allows one to deliver a tumoricidal dose to the tumor while limiting the dose to surrounding normal tissue to the tolerance dose. As a pilot study, 125I seeds were implanted into unresectable hepatic metastases, or positive margins of resection, at the time of surgery. This report concerns six patients whose liver lesions were the only known site of disease and in whom precipitous drops in carcinembryonic antigen (CEA) levels followed the implants. Recurrence was observed in only one of the 11 implanted site, with a median follow-up of 12 months.

Hepatic resection in the elderly.

Between July 1, 1970 and December 31, 1988, 453 patients underwent hepatic resection by the senior author. Ninety of these patients were more than 64 years old and are the subject of this review. The 30-day operative mortality rate for all patients undergoing hepatic resection was 3.3%: major hepatic resection was 4.4% and subsegmental resection was 1.4%. The operative mortality rate for patients undergoing major hepatic resection increased incrementally with age: for patients up to age 55 years it was 0.70%, for those between 55 and 64 years it was 3.6%, and for patients older than 64 years it increased to 11.1%. This higher operative mortality rate in the elderly reflects the mortality rate for extended right hepatic lobectomy in this age group of 30.7%. If this procedure is excluded, the operative mortality rate for patients older than age 64 was 7.6%. Sixty per cent of the operative deaths were due to hepatic insufficiency. The data presented demonstrate that major hepatic resection can be performed in the elderly with a low but somewhat increased mortality risk. However, because of its markedly increased operative risk, extended right hepatic lobectomy should be performed in elderly patients only in selected cases until better methods of estimating hepatic reserve are available.

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.

"Radical" abdominal cancer surgery: current state and future course.

Biologically driven cancer surgery is essential for the best care of the cancer patient. Modern technology and support have improved the safety and operative results of radical surgery. Better understanding of tumor biology with technical advances permit rational, en bloc resection of the primary cancer and regional lymphatic drainage with better cure rates. The author has operated on 1103 patients with liver tumors since 1970. The liver tumors were resected in 415 patients, with major hepatic resections being done in 359. Since 1979, the author carried out 62 regional pancreatectomies. Thirty-three were for stage 1 or 2 adenocarcinomas of the head of the pancreas. The 5-year actual survival was 31 per cent. There has been similar improvement in treating ampullary and periampullary cancer, gallbladder cancer, or extrahepatic bile duct cancer. These data show significant improvement in the results of treating cancer by radical or biologically driven surgery. Abdominal cancer is not a generalized disease until late in its course.

Recurrence of colorectal cancer after hepatic resection.

Survival estimates of 95, 65, and 49 percent at 1, 3, and 5 years, respectively, after hepatic resection in 77 patients when all gross metastatic cancer was removed compare favorably with the series of Wagner et al [20] of untreated, apparently comparable patients. In the present series, recurrent disease was evident after hepatic resection, most commonly in the lungs; the liver; and locally, in that order. About half of the 45 patients with a second recurrence were operated on, and the recurrence was completely removed in roughly half of these patients. A median survival estimate of 31 months (range 1 to 67 months) after complete removal of the second recurrence was better than the survival estimate of 14 months (range 1 to 18 months) for those in whom the recurrence could not be removed (p less than 0.01). An elevated carcinoembryonic antigen level as the only indicator of recurrence after hepatic resection has proved to be an ominous prognostic sign.