Steven G. Economou

Complications of laparoscopic cholecystectomy: A national survey of 4,292 hospitals and an analysis of 77,604 cases

Complications of laparoscopic cholecystectomy were evaluated by a survey of surgical department chairpersons at 4,292 US hospitals. The 77,604 cases were reported by 1,750 respondents. Laparotomy was required for treatment of a complication in 1.2% of patients. The mean rate of bile duct injury (exclusive of cystic duct) was 0.6% and was significantly lower at institutions that had performed more than 100 cases. Bile duct injuries were recognized postoperatively in half of the cases and most frequently required anastomotic repair. Intraoperative cholangiography was practiced selectively by 52% of the respondents and routinely by 31%. Bowel and vascular injuries, which occurred in 0.14% and 0.25% of cases, respectively, were the most lethal complications. Postoperative bile leak was recognized in 0.3% of patients, most commonly originating from the cystic duct. Eighteen of 33 postoperative deaths resulted from operative injury. These data demonstrate that laparoscopic cholecystectomy is associated with low rates of morbidity and mortality but a significant rate of bile duct injury.

L‐phenylalanine mustard (L‐PAM) in the management of primary breast cancer: An update of earlier findings and a comparison with those utilizing L‐PAM plus 5‐fluorouracil (5‐FU)

In 1972, a prospective, randomized, multi‐institutional, cooperative clinical trial was begun to evaluate the efficacy of prolonged 1‐phenylalanine mustard (L‐PAM) administration following operation in lengthening the disease free interval of patients with primary breast cancer. That protocol using a single agent was the first of a series directed toward evaluating successively more complex chemotherapeutic regimens in an attempt to define subsets of patients which might be responsive to less therapy than others. When it was observed that L‐PAM prolonged the disease free interval, particularly of premenopausal patients, findings were reported and a new evaluation comparing L‐PAM with L‐PAM plus 5‐fluorouracil (5‐FU) was begun. Upon completion of patient accrual in that protocol, an additional trial comparing L‐PAM and 5‐FU with L‐PAM, 5‐FU and Methotrexate was implemented. The present report updates findings from the initial study and presents those from the second. It compares results across the first two protocols as well as between groups within a protocol. While insufficient time has elapsed for determining the ultimate worth of the modalities employed, findings from the second protocol confirm those previously reported indicating that L‐PAM lengthens the disease free interval following mastectomy. The combination of L‐PAM with 5‐FU resulted in a reduction of treatment failure at 12 months which is as good or better than that observed with L‐PAM in the first protocol lending further credibility to the earlier findings. While at the end of the first year following mastectomy there was alomst a 50% reduction in treatment failures in patients aged 50 or over (post‐menopausal), by 18 months the reduction was 23% and at two years, based on small numbers of patients, only 5%. Examination of results from the first protocol (placebo vs L‐PAM) after two years reveals a most highly significant effect of L‐PAM in pre‐menopausal women with one to three positive nodes. There is an 89% reduction of treatment failures. A similar but less striking effect is noted for those under 50 with ≥four positive nodes. In older patients in both nodal categories, the early observed effect for L‐PAM has decreased with time. Inter‐protocol comparisons relative to survival are premature. At two years survival in L‐PAM patients is 36% greater than in those receiving placebo. It is somewhat better in every subgroup for those receiving L‐PAM. Information relative to the effect of these agents on patient toxicity and loco‐regional treatment failures is presented. All of the findings stress the urgency for obtaining results on subsets of patients rather than on a population as a whole and they lend support to the thesis that since breast cancer is an eponym to describe a heterogeneous group of tumors residing in a heterogeneous group of women, it is unlikely that uniformly qualitative and quantitative systemic regimens of therapy will be required for every patient.

Predicting lymph node metastases in rectal cancer.

For properly selected rectal cancers, local excision is a sphincter-saving alternative to abdominoperineal resection. If histologic assessment of a locally excised tumor reveals ominous features, further treatment with radical resection or irradiation may be necessary to treat potential lymph node metastases. PURPOSE: We wished to determine which features, if any, were predictors of nodal metastases. METHODS: Nine histologic and morphologic features of 62 radically excised rectal cancers were reviewed to determine which factors, if any, were associated with nodal disease. RESULTS: Using a chi-squared analysis, we found worsening differentiation (P=0.0001), increasing depth of penetration (P=0.026), a microtubular configuration of 20 percent or more (P=0.023), and the presence of venous (P=0.001) or perineural invasion (P=0.002) to significantly influence nodal disease. Lymphatic invasion was witnessed too infrequently to determine significance but, when present, was associated with nodal metastases in every case. Exophytic tumor morphology, mitotic count, and tumor size were not significant predictors. An analysis of variables determined that, of all factors or combination of factors examined, Broders classification was the strongest predictor of nodal disease. CONCLUSIONS: If a rectal cancer is accessible and of small size to facilitate local excision, an in-depth histologic assessment is needed to determine if nodal metastases are likely on a statistical basis.

Importance of Repeat Fine-Needle Biopsy in the Management of Thyroid Nodules

Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patients choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant.

Thoracotomy for colon and rectal cancer metastases

Between 1978 and 1990, 23 patients underwent 35 thoracotomies for metastatic colorectal cancer. The pulmonary disease was diagnosed within an interval of 0 to 105 (average, 33.4) months after colon resection. Fifteen patients underwent a single thoracotomy; 12 patients had solitary lesions, and three patients had multiple nodules. Eight patients underwent multiple thoracotomies. The median survival following thoracotomy was 28 months; three-year survival was 45 percent, and five-year survival was 16 percent. Factors that had no significant bearing on survival included origin and stage of the primary tumor and patient age and sex. An interval before thoracotomy of three years had an impact on survival approaching statistical significance (P=0.17). Patients who underwent multiple thoracotomies had a significantly prolonged survival (P=0.04). Patients who underwent a single thoracotomy for a solitary lesion had a significantly prolonged survival compared with patients who had a single thoracotomy for multiple metastases. After thoracotomy, 14 patients eventually developed recurrent disease, which was confined to the lung in only four patients. Of these 14 patients, 11 subsequently died of cancer. We conclude that thoracotomy for metastatic disease should be considered when the primary tumor is controlled, the lungs are the only site of metastatic disease, and there is adequate lung reserve to withstand surgery. Survival following thoracotomy may be influenced by the interval before diagnosis, the number of pulmonary nodules, and the number of thoracotomies performed.

Hormone receptor studies in axillary metastases from occult breast cancers

The authors describe 11 patients with occult breast carcinoma, who initially presented with axillary nodal metastases of unknown origin. In all 11 cases, physical examination and mammography results were normal. Steroid hormone receptor studies were done on tissue from all 11 axillary masses and 2 masses underwent lactalbumin staining as well. In 8 of the 11 patients these studies were positive, suggesting breast as the primary tumor site. Estrogen (30 to 445 fmol/g) or progesterone (30 to 1059 fmol/g) receptors, or both, were positive in seven cases. Although a breast carcinoma was subsequently found in all 11 patients, receptor studies on the primary tumor could not be done in every instance. The authors conclude that performing steroid hormone receptor assays on axillary metastases from occult tumors not only may provide information regarding the identity of the primary tumor but also may be the sole opportunity to determine its hormone receptor status. Cancer 59:1170‐1172, 1987.

Sodium molybdate increases the amount of progesterone and estrogen receptor detected in certain human breast cancer cytosols.

When sodium molybdate is added at a final concentration of 20 mM, additional 8S and 4S progesterone (3H-R5020) receptor can be detected in the cytosols from a number of human breast cancers. Additional estrogen receptor also could be measured in some cytosols, and a quantitative temperature-dependent conversion of 8S to 4S binding molecules achieved. Sodium molybdate also prevented the loss of binding activity that occurred when cytosols were incubated at 30 degrees in the absence of added estradiol. In addition to increasing the amount of progesterone receptor, and to a lesser extent estrogen receptor that may be detected, elicidation of the mechanism by which this salt stabilized receptors should contribute to further understanding of how cytosol steroid receptor content and function is regulated.

Radiation carcinogenesis in man: new primary neoplasms in fields of prior therapeutic radiation

Nine patients are presented in whom new malignant neoplasms developed in fields of prior irradiation. The prior irradiation had been administered to these patients for previously confirmed cancers, lesions suspected of being cancer (but never confirmed as such), and for non‐neoplastic disorders. Each of these cases is relatively unique and several present the first association between prior radiation therapy and the subsequent neoplasm or neoplasms which developed.

The approach to the irradiated thyroid.

Nodular thyroid disease and cancer are frequently associated with a history of prior irradiation. Mass screening and patient recall programs have identified those at risk. Treatment involves careful evaluation followed by total or near-total thyroidectomy for patients with cancer.

Fibrin glue improves the healing of irradiated bowel anastomoses

Many surgeons are reluctant to construct a bowel anastomosis with irradiated intestine. Previous studies have demonstrated diminished tensile strength of rat small bowel anastomoses that have been irradiated intraoperatively. To determine whether fibrin glue, a known tissue adhesive, improves the healing of these anastomoses, 69 male Sprague-Dawley rats were randomized into three anastomotic groups: Group 1, sutured ileal anastomosis without radiation or fibrin glue; Group 2, irradiated sutured ileal anastomosis without fibrin glue; and Group 3, irradiated ileal anastomosis with fibrin glue added to the suture line. Groups 2 and 3 received a single dose of 2,000 R intraoperatively. At seven days, the rats were sacrificed and the anastomotic segment was tested for breaking (tensile) strength. Anastomotic collagen content was evaluated using a hydroxyproline assay. Tensile strength results demonstrated that Group 2 was significantly weaker than Groups 1 and 3 (P=0.001) and that the hydroxyproline content of Group 3 was significantly greater than that of Group 2 (P=0.015). These results show that the addition of fibrin glue to an intraoperatively irradiated small bowel anastomosis improves healing, as demonstrated by both tensile strength and hydroxyproline content studies.