Thoracoscopic removal of mediastinal parathyroid lesions: selection of surgical approach and pitfalls of preoperative and intraoperative localization.

BACKGROUND: Thoracoscopic surgery has replaced conventional sternotomy or thoracotomy for resection of mediastinal parathyroid lesions. We review our experience with this type of surgery with reference to selection of the appropriate approach and the pitfalls of lesion localization before and during surgery. METHODS: During a 14-year period, we treated 14 patients with hyperparathyroidism, in whom a mediastinal lesion had been localized preoperatively by sestamibi scan. Primary hyperparathyroidism was present in 12 patients (single adenoma in 11, associated with MEN 1 in one) and secondary hyperparathyroidism in 2. Thoracoscopic procedures were performed by the three-port method. RESULTS: The thoracoscopic procedure was successful in eight patients who were shown preoperatively to have a deep-seated (5 anterior, 3 middle) mediastinal lesions. Intraoperative visual confirmation of parathyroid adenoma was difficult only in a 19-year-old patient with a tumor embedded in the thymus, necessitating partial thymectomy. One of the eight mediastinal lesions resected thoracoscopically was a sestamibi-positive thymoma. Secondary hyperparathyroidism recurred 4 years after thoracoscopic mediastinal parathyroidectomy in one patient, necessitating additional thoracoscopic removal of this supernumerary lesion. However, seven patients with mediastinal parathyroid lesions localized at the aortic arch or upper region were treated successfully via a cervical approach. None of the patients suffered any surgical complications. CONCLUSIONS: Thoracoscopic surgery is safe and feasible for resection of deep mediastinal parathyroid lesions. Such lesions localized preoperatively at the aortic arch or upper region can be treated via a cervical approach. Preoperative sestamibi scan can sometimes give a false-positive result in cases of concurrent thymoma.

Bone mineral density before and after surgical cure of Cushing's syndrome due to adrenocortical adenoma: prospective study.

Osteoporosis is a major complication of Cushing's syndrome. The aim of the present study was to assess the chronologic effect of surgical cure on bone mineral density (BMD) in patients with Cushing's syndrome due to adrenal adenoma. BMD was examined in 28 patients before laparoscopic adrenalectomy; 17 patients with reduced BMD were then included in the longitudinal evaluation. BMD was determined using dual energy X-ray absorptiometry (DXA) before and at 3, 6, 12, 18, and 24 months after adrenalectomy. The prevalence of osteoporosis was 64% (95% confidence interval 44-81%). Preoperative BMD of the lumbar spine in the lateral projection was significantly lower than that of the femoral neck (mean+/-SD score: -3.53+/-0.75 vs. -1.54+/-0.22, p=0.003). A significant increase in BMD was observed at 3 months after surgery in the lumbar spine (p=0.0004). Improvement at both sites was maintained at 24 months after surgery. The postoperative percentage change in BMD of the lumbar spine was significantly higher than that of the femoral neck (mean+/-SD 36.7%+/-26.5% vs. 11.2%+/-12.1%, p=0.01). The change in the seven premenopausal patients was significantly higher than that in the three postmenopausal patients (p=0.0006). Surgical cure of hypercortisolism provides significant improvement in BMD in patients with Cushing's syndrome due to adrenal adenoma. The improvement is particularly apparent in the lumbar spine measured in the lateral projection. Premenopausal women are more likely to benefit from surgery in terms of secondary osteoporosis.

Functional parathyroid carcinoma: Long-term treatment outcome and risk factor analysis.

BACKGROUND: This study was conducted to evaluate the long-term outcome of surgical treatment in patients with functional parathyroid carcinoma and to clarify factors determining prognosis. METHODS: A retrospective review of 38 patients with parathyroid carcinoma was performed. The Ki-67 index was evaluated in 29 cases. Disease-free survival and cause-specific survival estimated using the Kaplan-Meier method were analyzed, and the median follow-up period was 119 months. RESULTS: Fifteen patients developed persistent or recurrent parathyroid carcinoma, and 9 patients died of the disease. Twenty-one of 41 reoperations normalized the serum calcium level for at least 6 months. Univariate and multivariate analyses showed that locoregional tumor extension at initial operation and Ki-67 index >or=5% were significant factors affecting cause-specific survival (P = .0008, P = .05) and disease-free survival (P = .0005, P = .005), respectively. Five of 6 patients whose tumor showed a Ki-67 index >or=10% developed recurrence within 3 years after initial operation, and 4 died of the disease. CONCLUSIONS: Parathyroid carcinomas with locoregional extension at initial surgery have potential for recurrence. Our data suggest that aggressive surgical resection of recurrent parathyroid carcinoma is beneficial for palliation of hypercalcemia in selected patients. Ki-67 staining may be a valuable prognostic factor for patients with parathyroid carcinoma, especially as tumors with indices greater than 10% are more likely to recur in the early postoperative period.

A novel structural fold in polysaccharide lyases: Bacillus subtilis family 11 rhamnogalacturonan lyase YesW with an eight-bladed beta-propeller.

Rhamnogalacturonan (RG) lyase produced by plant pathogenic and saprophytic microbes plays an important role in degrading plant cell walls. An extracellular RG lyase YesW from saprophytic Bacillus subtilis is a member of polysaccharide lyase family 11 and cleaves glycoside bonds in polygalacturonan as well as RG type-I through a beta-elimination reaction. Crystal structures of YesW and its complex with galacturonan disaccharide, a reaction product analogue, were determined at 1.4 and 2.5 A resolutions with final R-factors of 16.4% and 16.6%, respectively. The enzyme is composed of an eight-bladed beta-propeller with a deep cleft in the center as a basic scaffold, and its structural fold has not been seen in polysaccharide lyases analyzed thus far. Structural analysis of the disaccharide-bound YesW and a site-directed mutagenesis study suggested that Arg-452 and Lys-535 stabilize the carboxyl group of the acidic polysaccharide molecule and Tyr-595 makes a stack interaction with the sugar pyranose ring. In addition to amino acid residues binding to the disaccharide, one calcium ion, which is coordinated by Asp-401, Glu-422, His-363, and His-399, may mediate the enzyme activity. This is, to our knowledge, the first report of a new structural category with a beta-propeller fold in polysaccharide lyases and provides structural insights into substrate binding by RG lyase.

Plant cell wall degradation by saprophytic Bacillus subtilis strains: gene clusters responsible for rhamnogalacturonan depolymerization.

Plant cell wall degradation is a premier event when Bacillus subtilis, a typical saprophytic bacterium, invades plants. Here we show the degradation system of rhamnogalacturonan type I (RG-I), a component of pectin from the plant cell wall, in B. subtilis strain 168. Strain 168 cells showed a significant growth on plant cell wall polysaccharides such as pectin, polygalacturonan, and RG-I as a carbon source. DNA microarray analysis indicated that three gene clusters (yesOPQRSTUVWXYZ, ytePQRST, and ybcMOPST-ybdABDE) are inducibly expressed in strain 168 cells grown on RG-I. Cells of an industrially important bacterium, B. subtilis strain natto, fermenting soybeans also express the gene cluster including the yes series during the assimilation of soybean used as a carbon source. Among proteins encoded in the yes cluster, YesW and YesX were found to be novel types of RG lyases releasing disaccharide from RG-I. Genetic and enzymatic properties of YesW and YesX suggest that strain 168 cells secrete YesW, which catalyzes the initial cleavage of the RG-I main chain, and the resultant oligosaccharides are converted to disaccharides through the extracellular exotype YesX reaction. The disaccharide is finally degraded into its constituent monosaccharides through the reaction of intracellular unsaturated galacturonyl hydrolases YesR and YteR. This enzymatic route for RG-I degradation in strain 168 differs significantly from that in plant-pathogenic fungus Aspergillus aculeatus. This is, to our knowledge, the first report on the bacterial system for complete RG-I main chain degradation.

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adrenal-preserving laparoscopic surgery in selected patients with bilateral adrenal tumors.

BACKGROUND: There have been few reports of laparoscopic adrenal-sparing surgery for bilateral adrenal tumors. We review our experience with this type of surgery with the aim of evaluating its feasibility and safety. METHODS: Over a 4-year period, we treated 9 patients with bilateral benign adrenal tumors. Seven patients had bilateral pheochromocytomas (MEN 2: 5, VHL: 1, sporadic: 1), and 2 patients had Cushing's syndrome caused by bilateral adrenocortical adenomas. Laparoscopic procedures were performed by a flank approach. The mean diameter of the tumors was 3.7 cm (range, 2.0-8.5 cm). RESULTS: All the tumors were removed laparoscopically. Four patients with hereditary pheochromocytomas underwent bilateral total adrenalectomy because of the large tumor size and multiplicity. The other 5 patients were treated successfully with preservation of adrenocortical function. In 4 of these 5 patients, the adrenal tumors were 3 cm or less in diameter. None of the patients experienced surgical complications. At a mean follow-up of 16 months (range, 4-40 months), none of the 5 patients who were treated by adrenal-sparing surgery required corticosteroid replacement. CONCLUSION: Laparoscopic surgery is feasible for the treatment of bilateral adrenal tumors. Adrenal-preserving laparoscopic surgery may be practicable for the removal of these tumors, if the tumor on either side is 3 cm or less in diameter; however, our follow up is short (mean, 16 months).