William S. Fletcher

Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA‐directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty‐two second‐look patients remain free of disease 5 years after their second operaton. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months. Cancer 55:1284‐1290, 1985.

Breast carcinoma in situ: A retrospective review of 112 cases with a minimum 10 year follow-up☆☆☆

We have retrospectively reviewed 112 cases of in situ carcinoma of the breast treated between 1960 to 1972, with a minimum 10 year follow-up to correlate treatment with outcome. We concluded that bilateral simple mastectomy with low axillary dissection is the treatment of choice for intraductal or lobular carcinoma in situ. This conclusion was based on the early age at diagnosis, the high incidence of bilaterality, and the long latency and probable progression from the in situ stage to the invasive stage. Lesser procedures can be endorsed for those patients of advanced age or who have associated medical problems whose life expectancy is estimated to be 10 years or less. Patients who refuse bilateral mastectomy should undergo biopsy of the involved or opposite breast at 3 to 5 year intervals regardless of physical findings or mammographic suspicions, especially when severe epithelial dysplasia is encountered in the biopsy specimens. This nonpalpable but potentially curable lesion remains difficult to detect even by mammography.

Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization

BACKGROUND Overall survival and quality of life in patients with metastatic carcinoid tumors depend on control of tumor growth and suppression of amine-induced symptoms. METHODS We report on a series of 10 patients with carcinoid tumors metastatic to the liver who were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), sequential intra-arterial 5-fluorouracil (5-FU) infusions, and hepatic tumor chemoembolization. RESULTS All 10 patients remained asymptomatic or had extremely mild symptoms after combined modality therapy (mean follow-up duration of 51.5 months). Sixty percent of the patients had a > 50% reduction of their tumor size (mean duration 42 months). An additional 30% experienced stabilization of tumor growth for 6 months or longer. Five of the 10 patients are currently alive. The mean group survival is 58 months since diagnosis (range 33 to 115) and 40 months since starting therapy (range 12 to 65). CONCLUSIONS Combining octreotide acetate, intra-arterial 5-FU, and tumor chemoembolization effectively retards tumor growth while providing excellent symptom control.

Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate

Survival in patients with metastatic carcinoid tumors is dependent on control of tumor growth and adequate palliation of vasoactive amine-induced symptoms of flushing, diarrhea, wheezing, and valvular heart disease. Eight patients with carcinoid tumors metastatic to the liver were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), intra-arterial 5-fluorouracil infusion (2 g/day x 5 days), and hepatic tumor chemoembolization. All eight patients became asymptomatic and have remained so with a mean follow-up duration of 22 months from the time of first infusion. Following institution of subcutaneous octreotide acetate, intra-arterial infusion, and tumor chemoembolization, all patients are alive with a mean survival of 40 months from the time of diagnosis of carcinoid syndrome (range: 2 to 108 months). Four patients had greater than a 50% decrease in tumor size after therapy (mean follow-up duration: 10.6 months), and the other four patients have had stable disease after institution of therapy. It appears that combinations of long-term subcutaneous administration of octreotide acetate, intra-arterial 5-fluorouracil, and tumor chemoembolization effectively control progressive liver metastasis and provide excellent symptomatic palliation in patients with hepatic metastasis from functional carcinoid tumors.

Genesis of nonocclusive mesenteric ischemia

T HE DEVELOPMENT Of Signs and SymptOmS of &hernia in the absence of organic vascular occlusion has become an increasingly apparent clinical syndrome. The occurrence of necrosis of the bowel in the absence of arterial or venous obstruction was first documented in the American literature in 1943 by Thorek [I]. Since that date, approximately 500 additional case reports have appeared in the English medical journals [2-101. This presentation deals with eighteen patients we observed both clinically and pathologically who were found to have nonocclusive mesenteric ischemia. The clinical picture which allows for the diagnosis in the majority of cases is described. A laboratory investigation into one area considered to be etiologically related to the development of the disease has been carried out.

Effect of octreotide acetate on pancreatic exocrine function

Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.

Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities

Fifty-nine patients with melanoma or soft tissue sarcoma of the extremities underwent hyperthermic isolated limb perfusion utilizing cisplatin and wide local excision. Doses of cisplatin ranged from 0.75 to 2 mg/kg. The mortality and morbidity rates were 0 and 6.8 percent, respectively. Pharmacokinetic studies indicate that cisplatin is rapidly bound to perfused tissues and remains bound for 1 month. Maximum tumor response in sarcomas occurs 1 to 2 weeks after perfusion, compared with 1 month after perfusions with l-phenylalanine mustard and actinomycin D. Local and regional recurrence rates were 0 and 3.4 percent, respectively, at 1 year. Further studies of hyperthermic limb perfusions with cisplatin are warranted.

Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer

PURPOSE A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.

Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung. A Southwest Oncology Group Study.

Using a randomized prospective trial design, chemotherapy with 5-fluorouracil, vincristine, and mitomycin C (FOMi) was compared with cyclophosphamide, doxorubicin, and cisplatin (CAP) and with FOMi alternating with CAP (FOMi/CAP) in 452 eligible patients with metastatic large-cell undifferentiated and adenocarcinoma of the lung. Objective responses were obtained in 26%, 17%, and 22% of patients treated with FOMi, CAP, and FOMi/CAP, respectively. The median survival was similar for FOMi, CAP, and FOMi/CAP therapies (20, 24, and 23 weeks, respectively), but the overall survival (log rank test), 1-year survival, and remission duration were longer for FOMi/CAP-treated patients. Survival was significantly longer for fully ambulatory FOMi/CAP-treated patients compared with either FOMi (P = .01) or CAP (P = .04). Younger patients treated with full doses of therapy responded more often than older patients receiving reduced drug doses (26% and 11%, respectively; P = .003). A prognostic factor regression analysis of all eligible patients indicates that sex, performance status, stage, and treatment assigned were important independent variables determining survival (P less than .05). Toxicity was comparable in each treatment group.

Preoperative irradiation for carcinoma of the colon and rectum: A preliminary report

Summary Twenty-seven patients undergoing preoperative irradiation to a tumor dose of 5,000 r for carcinoma of the colon and rectum are reported. Tumor regression was noted in twenty-six patients. One tumor 10 cm. in diameter disappeared and two patients were converted from an inoperable to an operable state. The irradiation was well tolerated by all but one patient and the technical difficulties of operation were not significantly increased. There was no operative mortality and the complication rate was considerably better than in a previously studied nonirradiated group of 191 patients from the same population.