Paul H. Sugarbaker

The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.

Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m2), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (71% and 78% at five years; p2 = 0.75) or overall survival rates (83% and 88% at five years; p2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p1 less than 0.0001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p1 = 0.0008) and overall survival (95% vs. 74%; p1 = 0.04). Thus limb-sparing surgery, radiation therapy, and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity.

A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases.

Sixty-four patients were entered into a randomized trial that evaluated intra-arterial (I.A.) versus intravenous (I.V.) 5-fluorodeoxyuridine (FUDR) for colorectal liver metastases. There was a significant improved response rate for I.A. (62%) compared with I.V. (17%) treatment (p less than 0.003). However, the improved response rate for patients in whom I.A. therapy was used did not translate to a significantly improved survival rate. The 2-year actuarial survival rates for the groups for which I.A. and I.V. therapy was used were 22% and 15% respectively, with the survival curves not differing significantly (p = 0.27). These results may have been due to the inclusion of patients with tumor in draining hepatic lymph nodes. The presence of tumor in hepatic lymph nodes was associated with a poorer prognosis. Analysis of a subgroup of patients with negative hepatic lymph nodes suggested an improved actuarial survival rate in patients for whom I.A. versus I.V. therapy was used (p less than 0.03). The toxicity of I.A. FUDR was considerable, and side effects included chemical hepatitis (79%), biliary sclerosis (21%), peptic ulcers (17%), and gastritis/duodenitis (21%). The only major effect of toxicity of I.V. FUDR was severe diarrhea (59%). Regional I.A. FUDR allowed more drug delivery to liver tumors, which resulted in increased tumor responses when compared with use of systemic therapy. However, the small gain in survival seen in a select subgroup of patients with negative hepatic nodes appeared to be offset by the toxicity of I.A. FUDR.

Clinical perspective of human colorectal cancer metastasis.

SummaryDeath from colorectal cancer frequently results from manifestations of recurrent local or metastatic disease following initial ‘curative’ therapy. Presently, the attempted curative treatment of recurrent colorectal cancer lays in the hands of the surgeon. This paper reviews the natural history of surgically treated large bowel cancer and summarizes published and National Cancer Institute experience with the surgical therapy of recurrent disease. A schema with rationale is offerred for follow-up of the patient following ‘curative’ bowel resection. The treatment of recurrent disease incorporating the use of CEA initiated second-look laparotomy is advocated. Hepatic and pulmonary resections for metastatic disease are accepted as important therapeutic endeavours, and are discussed in some detail.It is concluded that of all patients diagnosed as having large bowel cancer, roughly 70% are resectable for cure at time of presentation, and 45% will indeed be cured by primary resection. Of the 25% who fail primary therapy, approximately 20% (5% of all colorectal cancer patients) can be cured by local re-resection or hepatic or pulmonary resection.

Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases

Data from fifty-five patients who had hepatic resections for colorectal liver metastases at the National Cancer Institute (NCI) were analyzed to determine the effect of perioperative blood transfusions on disease recurrence and overall survival. Besides blood transfusions, other factors included in the analysis were size, number, and distribution of metastases, margin status of resected metastases, length of disease-free interval, Dukes stage of the primary tumor, type of hepatic resection, and anesthesia time. Using the Cox proportional hazards model, the amount of blood transfused was found to be a significant prognostic factor. For each additional unit of blood transfused the risk of disease recurrence and death was increased by 5% (p = 0.0015) and 7% (p = 0.0013), respectively. The median disease-free survival for patients who received 3-5, 6-10, and greater than or equal to 11 transfused units was 26, 12.1, and 11.4 months, respectively. The median overall survival for patients who received 3-5, 6-10, and greater than or equal to 11 transfused units was greater than 44, 39.2, and 33.6 months, respectively. The number of resected nodules (1-2 vs. greater than or equal to 3), type of resection (anatomic lobectomy vs. wedge resection), and nodule size (less than or equal to 3.0 cm vs. greater than 3.0 cm) were additional factors that were further evaluated to determine the effect of blood transfusions. Analyses stratified for each of these factors revealed that patients who received greater than or equal to 11 units of blood had a significantly decreased disease-free and overall survival compared with patients who received 3-10 units of blood. It is concluded that the amount of perioperative blood transfused is an independent prognostic factor that adversely effects disease-free and overall survival.

Influence of surgical techniques on survival in patients with colorectal cancer

This review was undertaken in an attempt to accumulate and critically evaluate all evidence that suggests that special techniques may alter survival rates of patients undergoing surgery for large-bowel cancer. Data suggesting reduced survival with a distal margin of resection less than 5 cm in patients undergoing anterior resection were found to be inconsistent.En bloc removal of the primary tumor and an adhesed adjacent structure seemed important, for 30 to 60 per cent survival has been reported using this approach, and adhesions were found to contain malignant cells at the interface of the primary tumor and adjacent structure in 40 to 100 per cent of patients. No statistically significant differences in survival rates were found in studies comparing conservative segmental bowel resection with radical hemicolectomy. This was true for colonic as well as rectal resections; while patient morbidity was not markedly increased for radical colectomy, it was found to be much greater with radical rectal resections. No data to support the use of “no-touch techniques” could be uncovered. Data to support the use of techniques for control of intraluminal tumor cells were sparse; however, because these maneuvers cost the patient little in terms of added morbidity, they should be used. Important aspects of the techniques for large-bowel surgery need to be investigated by prospective controlled clinical trials.

A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk

Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high‐grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000–6300 rads over 7–8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (⩽550 mg/m2), cyclophosphamide (⩽5500 mg/m2), and methotrexate (⩽1000 mg/kg). Three‐year actuarial disease‐free survival in the chemotherapy arm was 77%, compared to 49% in the no‐chemotherapy arm (P = 0.075). Three‐year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3‐year actuarial disease‐free survival in the chemotherapy arm was 92%, compared to 47% in the no‐chemotherapy arm (P = 0.006). Actuarial 3‐year overall survival in the chemotherapy arm was 82%, compared to 61% in the no‐chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow‐up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3‐year actuarial disease‐free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease‐free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease‐free survival (P < 0.001). The most significant toxicity associated with chemotherapy was doxorubicin‐induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease‐free survival, but additional patients and longer follow‐up are necessary to determine if improved overall survival will result. Cancer 55:1206‐1214, 1985.

Lymphatic dissemination of hepatic metastases. Implications for the follow-up and treatment of patients with colorectal cancer

Hepatic spread of colorectal cancer is a prominent cause of treatment failure, but selected patients with liver metastases may attain long‐term palliation or cure with liver resection. A review of the records of 81 patients seen at the National Cancer Institute for treatment of colorectal hepatic metastases revealed 7 instances of metastases discovered at operation within the hepatic lymphatic drainage in the absence of other extrahepatic tumor. These patients were studied with reference to location and stage of the primary colon cancer and location of metastases at the time of planned liver resection. All seven patients had their extrahepatic lymphatic disease limited to nodes draining the liver, implicating lymphatic dissemination from hepatic metastases as the mechanism of tumor spread. This pattern of spread rendered these patients unresectable for cure. If lymphatic metastases occur from hepatic tumor this implies a need for frequent and thorough follow‐up of patients following resection of a primary colon cancer, and indicates urgency in treatment of liver metastases.

A prospective analysis of laboratory tests and imaging studies to detect hepatic lesions.

A prospective study of the ability of laboratory tests and liver imaging tests to detect hepatic metastases was performed. Eighty patients at risk for hepatic metastases but without clinical evidence of disease were tested with 13 laboratory tests and three liver imaging tests. No single laboratory test had greater than 65% accuracy in the detection of hepatic lesions. No combination of the laboratory tests increased this accuracy. If the laboratory tests were used with one of the liver imaging tests, the accuracy was improved in some combinations to 76%. The CEA assay when analyzed in patients with colorectal primaries had an accuracy of 79%. The results show that the laboratory tests alone are not sufficiently accurate to detect liver metastases. Additional accuracy can be obtained by the combined use of a single liver imaging test and selected laboratory tests. Use of all the liver imaging tests and laboratory tests lowers the accuracy and increases the expense and thus is unnecessary.

Congenital duplication of the gallbladder associated with an anomalous right hepatic artery

A case report describing the incidental finding of a double gallbladder associated with an anomalous anteriorly displaced right hepatic artery has been presented. The literature has also been reviewed and the appropriate surgical intervention for supranumerary gallbladder suggested.

Perineal and bladder necrosis following bilateral internal iliac artery ligation report of a case

Abdominoperineal resection with pelvic sidewall dissection is not uncommonly performed for treatment of bulky primary or locally recurrent rectal neoplasms. Usually, the internal iliac arteries and veins are ligated bilaterally early in the course of the procedure to reduce intraoperative blood loss and to facilitate subsequent dissection of the pelvic sidewalls. No complications related to bilateral internal iliac artery ligation in this setting have been described previously. In this report, profound vesical and perineal necrosis after bilateral internal iliac artery ligation occurred in a female patient operated on for recurrent rectal cancer. If the internal iliac artery is ligated below the take-off of the gluteal vessels, prineal necrosis can be prevented.