Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Clear cell carcinoma of the liver with spontaneous regression of metastases.

The purpose of this report is to establish in some detail a case of spontaneous regression of metastases secondary to a clear cell hepatocellular carcinoma. A review of the hepatocellular carcinomas from this department has been previously reported, and this particular study focuses on the two lesions that have the microscopic classification referred to above. One young female patient was 23 at the time of resection of the clear cell carcinoma of the liver plus diffuse intrahepatic metastases. She has been followed carefully over the years and has been seen as recently as June 1993. At that time, studies including ultrasonic and CT scan examinations of liver were carried out, all of which were negative for any evidence of residual disease. The evidence presented in this report would seem to establish conclusively that a spontaneous regression of the metastases from a clear cell carcinoma of the liver had occurred without any medication and without any obvious alteration in diet or state of health.

Effect of combined modality therapy on the surgical management of locally advanced rectal carcinoma.

The treatment of locally advanced rectal carcinoma is one of the more complicated problems in the management of colorectal carcinoma. More than any other site successful treatment requires a multimodality approach as surgery alone is frequently insufficient to completely eradicate all disease. This review focuses primarily on the management of patients who present without prior treatment and discusses the role of preoperative radiation therapy as well as intraoperative radiation therapy. Although much less gratifying, patients who present after failing previous therapy may also benefit from an aggressive multimodality approach.

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.

Intraoperative radiation therapy for carcinoma of the gallbladder.

The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation. The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity. Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.

Surgical therapy for recurrent liver metastases from colorectal cancer.

Forty percent of patients whose disease recurs after hepatic resection for liver metastases from colorectal cancer initially will have liver-only metastases. We have retrospectively reviewed our experience with repeated surgical treatment for liver-only recurrence after previous hepatic resection for colorectal metastases. Repeated hepatic procedures were performed with no mortality in 10 patients. Intraoperative ultrasound allowed identification of three unsuspected metastases and determination of unresectability of two metastases during 11 procedures. Three patients were free of disease at 31, 41, and 48 months from the first hepatic procedure and at 15, 31, and 43 months from the second procedure. Five patients have remained free of hepatic disease. Patients whose initial metastases were less than 6 cm in diameter and had single liver recurrences after hepatic resection appeared to be the best candidates for further surgical therapy. These data and a review of the literature suggest that surgical treatment of recurrent liver metastases from colorectal cancer can be performed safely, and it is associated with long-term disease-free survival in up to 38% of highly selected patients.

The Budd-Chiari syndrome and hepatic veno-occlusive disease. Recognition and treatment.

In a review of 29 patients who were surgically treated by combined hepatic and portal decompression for intractable ascites, 18 were identified as falling into the category of the Budd-Chiari syndrome, with varying causes. Of this group, 2 patients were distinguished by the classical hepatic venous endophlebitis described by Chiari and later by Bras et al. Recently, this disease entity has been recognized as being due to the toxic effects of pyrrolizidine alkaloids contained in the Senecio and Crotolaria plants. In the first of these two cases the patient had emigrated from Jamaica and was exposed to "bush trees," but no chemical measurements were done. The second patient had consumed a large amount of comfrey teas, which were shown to contain high levels of pyrrolizidine alkaloids. These two cases add further weight to the existing evidence of the toxic effect of these alkaloids, and also demonstrate the effectiveness of hepatic and portal decompression.

Intraoperative radiation therapy for biliary tract carcinoma: results of a 5-year experience.

The results of a 5-year experience with use of intraoperative radiation therapy (IORT) in the management of locally advanced bile duct carcinoma are presented. Fifteen patients received IORT doses between 5 and 20 Gy for localized disease, which was either primary and resected with microscopic residual (2 patients), primary and unresected (10 patients), or recurrent (3 patients). Thirteen patients also received postoperative radiation therapy. The median survival of the 12 patients with primary disease was 14 months, with disease controlled in the porta hepatis in 5 of 10 evaluable patients. The three patients with recurrent disease survived 2, 9, and 11 months. There were two operative deaths, for an operative mortality of 13%. Acute and chronic complications are reviewed. Cholangitis is the most frequent in both categories. This aggressive approach in the therapy for advanced disease has an acceptable level of morbidity and may warrant the use of IORT as part of the management of biliary tract cancer.

Primary cancer of the liver. Evaluation, treatment, and prognosis.

Between 1970 and 1985, a diagnosis of primary hepatocellular carcinoma was established in 98 patients. Sixty-one cases developed in the presence of chronic liver disease, and only six of these were considered resectable. Of these, the median survival was 19 months. There was one perioperative death. Of the 98 tumors, 37 arose in normal livers. Of the 16 patients with tumors in normal livers that were resected, all survived operation. The long-term median survival was 32 months. Two subsets of the fibrolamellar and clear-cell variants appeared to carry a more favorable prognosis.

Experience with colorectal carcinoma metastatic to the liver.

The predilection of colorectal cancer metastases for the liver is probably the result of several factors, including the blood supply, the "homing" characteristics of the tumor cells, and the state of the liver. Five-year survival rates after hepatic resection for colorectal cancer metastases range from 20 to 40 per cent, and some other patients obtain palliative benefit. The authors discuss the three presentations of liver metastases, operative techniques, and prognostic factors.

Surgical treatment of biliary cystadenoma. A report of 15 cases.

Mucinous biliary cystadenomas are rare intrahepatic or, less commonly, extrahepatic neoplasms that may produce massive enlargement, hemorrhage, rupture, secondary infection, jaundice, or vena caval obstruction. Radiologic criteria differentiate biliary cystadenomas from more common parasitic or simple cysts. Treatment has included sclerosis, marsupialization, internal drainage, or resection, but without resection the patient is at risk for enlargement, infection, or progression of an unrecognized malignant neoplasm. We report the course of 15 patients who underwent resection for biliary cystadenoma to elucidate the clinical presentation, preoperative evaluation, and surgical treatment. Nine patients had had previous radiologic or surgical intervention other than excision, and complications of sepsis and tumor recurrence had developed. Following complete resection, however, only five postoperative complications were encountered, and no patient experienced recurrence of tumor. Thus, we recommend complete surgical resection as the preferred therapy.

Avoidance of transhepatic drainage prior to hepaticojejunostomy for obstruction of the biliary tract.

We retrospectively reviewed the course of 14 consecutive patients with symptomatic hepatic duct bifurcation obstruction of the biliary tract because of unresectable non-Klatskin malignant disease to clarify issues of diagnostic and therapeutic strategy. All patients were symptomatic with pruritus and were expected to survive three months or more. Ten patients underwent percutaneous transhepatic cholangiography preoperatively. In no instance did the study influence operative decision making, and complications included septic shock in two patients. Decompression of the biliary tract in one patient made the duct technically inadequate for internal drainage. The remaining 13 patients underwent surgical drainage of the biliary tree. Ten had peripheral hepaticojejunostomies, which offers the best palliation of symptomatic obstruction of the biliary tract due to unresectable malignant disease at the hepatic duct bifurcation. Percutaneous transhepatic cholangiographic drainage should not be used for diagnostic studies prior to hepaticojejunostomy for malignant obstruction as it interferes with surgical drainage.

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

Amino acid clearance in cirrhosis. A predictor of postoperative morbidity and mortality.

The central plasma clearance rate of amino acids (CPCR-AA), the ratio of peripheral amino acid entry rate into blood plasma to arterial amino acid concentration, was measured preoperatively in 149 noninfected cirrhotic patients. In 50 survivors of shunting or general surgical procedures, the mean (+/- SEM) CPCR-AA was 201 +/- 17 mL/m2/min; in 39 subsequent deaths, the mean ratio was 87 +/- 14 mL/m2/min. Comparing Child's classification with CPCR-AA reveals the following values: class A (mortality, two of ten patients) survivors, 152 +/- 23 mL/m2/min; class A deaths, 96 +/- 54 mL/m2/min; class C (mortality, 13 of 19 patients) survivors, 214 +/- 47 mL/m2/min; class C deaths, 101 +/- 13 mL/m2/min. The preoperative CPCR-AA of 46 patients receiving liver transplants was 91 +/- 9 mL/m2/min; 69% of these patients survived. Preoperative CPCR-AA values correlated significantly with rates of hepatic protein synthesis in incubated liver slices obtained by biopsy at operation in 22 patients. Thus, CPCR-AA determination is a true liver function test, valuable in predicting surgical mortality and selecting transplantation or other operations for cirrhotic patients.

Management of recurrent pelvic tumors.

The management of regional tumor recurrence in the pelvis traditionally has been a difficult problem for surgeons and oncologists. The only meaningful therapy for these patients is a potentially curative re-resection. The records and operative reports of 29 patients with regional pelvic tumor recurrence treated between 1981 and 1986 were reviewed. The operative procedures performed included three bowel resections, six abdominoperineal resections, eight pelvic exenterations, eight resections of tumor recurrence, and four conservative procedures. There was one operative death in this group. Significant morbidity was noted in the group but was clustered in a small number of patients operated on early in the series. The median follow-up in this series was 13 months (range, two to 51 months). Nineteen (65%) of the patients are surviving at a median follow-up of ten months (range, two to 51 months). The median survival (following resection) in the ten patients (35%) who died was 18 months. In 15 (52%) of the patients, a complete resection was performed. In this group, the survival is 80% with a median follow-up of 11 months. Seven (37%) are surviving with no evidence of disease. Palliation of symptoms occurred in 23 (79%) of the 29 patients. Radical resection of tumor recurrence in the pelvis can be performed with acceptable mortality and complication rates. This therapy should be considered for further clinical trials combining surgical and adjuvant therapy in patients with regional pelvic tumor recurrence.

Systemic mastocytosis with extensive large cutaneous mastocytomas: surgical management.

A case of systemic mastocytosis is reported with an observation period of 20 years. During these two decades multiple manifestations of the disease appeared including urticaria pigmentosis, episodic histamine release, gastro-intestinal involvement and hepatosplenomegaly. The most extraordinary, and possibly unique phenomenon, has been the development of a massive proliferation of large mastocytomas mainly, but not exclusively, limited to the lower extremities. For different reasons (mechanical disability, bleeding, cosmesis), these tumors have required repeated admissions for surgical removal. The most successful technique has involved use of the ultrasonic scalpel.

Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements.

Venocclusive disease, a form of Budd-Chiari syndrome, was diagnosed in a 49-yr-old woman. The patient had portal hypertension associated with obliteration of the smaller hepatic venules. A liver biopsy specimen showed centrilobular necrosis and congestion. Analysis of food supplements the woman regularly consumed showed the presence of pyrrolizidine alkaloids. The major source was a powder purporting to contain ground comfrey root (Symphytum sp). We calculated that during the 6 mo before the woman was hospitalized, she had consumed a minimum of 85 mg of pyrrolizidine alkaloids (15 micrograms/kg body wt X day). The clinical and analytic findings were consistent with chronic pyrrolizidine intoxication, indicating that low-level, chronic exposure to such alkaloids can cause venocclusive disease.

Portoazygous disconnection for bleeding esophageal varices.

Between 1971 and 1982, 20 portoazygous disconnections (modified Tanner's operation) were performed in patients with bleeding esophagogastric varices who were anatomically portosystemic shunting. Immediate control of variceal hemorrhage was achieved in all patients, although rebleeding occurred after eight operations at intervals from 2 days to 7.5 years postoperatively, requiring additional surgery at a mean interval of 2.5 years. There were eight perioperative deaths. Analysis has suggested increased mortality in patients with more severely impaired liver function according to Child's classification, and in patients who require urgent or emergent operations. There was an 80 percent incidence of major and minor complications. Portoazygous disconnection is not a satisfactory alternative to portosystemic shunting, except in a selected group of patients with intact hepatic function and with anatomic characteristics that preclude usual shunting procedures.

Major hepatic resection for metachronous metastases from colon cancer.

Hepatic resection of metastatic colorectal cancer is being performed with increasing frequency. Reports describe wide variations in survival after resection of solitary of multiple metastases. In 23 consecutive patients having major hepatic resection for metachronous metastases from colorectal cancers, 18 patients had one, two, or three metastases and five had four or more individual metastases; the cure rate of one, two, or three metachronous metastases was comparable to reports of resected solitary simultaneous metastases. The median maximum diameter of metastases in patients both surviving and dead was 7 cm. Features separating surviving from dead patients were resection margins of at least 1 cm and fewer than four metastatic nodules. All patients with four or more hepatic metastases died of disease, 80% with further liver metastases. Only three of 18 (17%) patients with one, two, or three metastases developed further hepatic lesions. This study suggests that the biology of the hepatic metastatic disease is paramount; timing of the hepatic resection is of little importance. Delayed resection of suitable biologic situations does not impair survival opportunities, and early resection of inappropriate biologic situations with more than three hepatic metastases does not improve survival. Therefore, programs of early detection with the use of carcinoembryonic antigen (CEA) screening or "second look" operations will not increase cure rates.