Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Sentinel lymph node biopsy for melanoma.

BACKGROUND: The most powerful predictor of survival for patients with melanoma is the status of the regional lymph nodes. Sentinel lymph node biopsy may provide improved staging accuracy without the morbidity of elective lymph node dissection (ELND). METHODS: Sixty-eight patients with intermediate thickness melanoma underwent gamma probe guided sentinel node biopsy without ELND and were followed up over a mean of 22 months. RESULTS: A sentinel node was found in all patients. Six patients (9%) had positive sentinel nodes; all underwent complete lymphadenectomy. Two patients (3%) with negative sentinel nodes developed nodal recurrence; 1 of these patients was found to have microscopic disease on reexamination of the sentinel node. Two patients (3%) developed systemic disease. CONCLUSION: Gamma probe guided sentinel node biopsy can be performed with a high rate of technical success. It provides accurate pathological staging with a low incidence of nodal basin failure.

Surgical morbidity, mortality, and long-term survival in patients with peripancreatic cancer following pancreaticoduodenectomy.

BACKGROUND: Surgical resection of the primary tumor in peripancreatic cancer has been associated with an improved survival and decreased morbidity in the recent literature. The purpose of this review was to analyze the results at a single institution. METHODS: Between 1985 and 1995, 88 patients underwent a pancreaticoduodenectomy for adenocarcinoma of the pancreatic head region and had complete long-term follow-up. Patient records were reviewed to determine morbidity, mortality, and survival. RESULTS: Tumor histology included pancreatic head adenocarcinoma (n = 46), ampullary adenocarcinoma (n = 28), duodenal adenocarcinoma (n = 8), and cholangiocarcinoma (n = 6). Morbidity occurred in 26 patients (29%). Perioperative mortality was seen in 6 patients (7%). No perioperative mortality was seen over the last 3 years, which included 33 patients. The mean follow-up was 29 months, with a median survival of 19 months. At last follow-up, 24 patients were alive without disease with an average survival of 43 months (1 to 141). There were 54 patients who died with cancer with an average survival of 21 months (1 to 117). Based on Kaplan and Meier statistical analysis the estimated survival was 47% at 2 years and 25% at 5 years. The location of the primary tumor (P = 0.0006) and the presence of positive lymph nodes (P = 0.05) was shown to have a negative impact on survival. CONCLUSION: Pancreaticoduodenectomy can be done with acceptable morbidity and mortality. The outlook with this disease remains poor, but long-term survival can be achieved in some patients.

Surgical management of thyroid cancer invading the airway.

BACKGROUND: Locally advanced thyroid cancer invading the tracheal cartilage represents a difficult treatment dilemma during thyroidectomy. METHODS: A retrospective chart review was performed to determine the results of laryngotracheal resection or tracheal cartilage shave with adjuvant radiotherapy in patients with locally advanced thyroid cancer invading the upper airway. RESULTS: Of 597 patients undergoing thyroidectomy for thyroid cancer, 40 were found to have laryngotracheal invasion. Thirty-five patients with superficial invasion underwent cartilage shave procedures with adjuvant radiotherapy; five with full-thickness invasion underwent radical resection, including tracheal sleeve resection (n = 3) or total laryngectomy (n = 2). Histologic subtypes included papillary (n = 32), follicular (n = 2), Hurthle cell (n = 1), medullary (n = 3), and anaplastic (n = 2). Of the cartilage shave group, 25 are currently alive with no evidence of disease at a mean follow-up of 81 months (range 1-290). Six developed isolated local/regional recurrence and were managed with total laryngectomy (n = 1), tracheal resection (n = 1), cervical lymphadenectomy (n = 1), or repeat radiotherapy (n = 3). All six patients remain free of disease at a mean follow-up of 5 years. Of those who underwent initial laryngotracheal resection, four remain free of disease at a mean follow-up of 5 years. The rates of 10-year disease-free survival and overall survival for all patients were 47.9% (95% confidence interval [CI] 24.8, 71.0) and 83.9% (95% CI 70.3, 97.5), respectively. CONCLUSIONS: These data suggest that adequate management of thyroid cancer with laryngotracheal invasion can be achieved with a more conservative surgical approach and adjuvant radiotherapy, reserving more radical resections for extensive primary lesions or locally recurrent disease.

Relationships of agonist properties to the single channel kinetics of nicotinic acetylcholine receptors.

The effects of the systematic variations of the acetylcholine molecule on the microscopic kinetics of channel activation were studied using the patch clamp technique. The modifications consisted of adding either halogens or a methyl group to the acetyl carbon of acetylcholine, which results in a change in both the steric and ionic character of that portion of the molecule. The ionic character of the bond affected both the opening and closing rates of the channel. An increase in the ionicity decreased the opening rate and increased the closing rate of the channel, suggesting that the open state was destabilized. Increasing the size of the substituent decreased both the association and dissociation rates for agonist binding but had little effect on the equilibrium constant. This indicates that the energy barrier for binding and unbinding was increased without a major change in the energy of the bound and unbound states. These results suggest that it is possible to assign changes in the structural characteristics of the ligand to changes in individual steps in a reaction scheme, which can lead to specific predictions for the properties of related compounds.

Coexistent multiple myeloma and primary hyperparathyroidism.

A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.

Convoluted secretory material in thyroid follicular epithelial tumors.

Electron microscopy may occasionally be useful, when routine histopathologic methods fail, in the typing of tumors, including those that present as metastases from occult primary sites. We describe a case in which the presence of an uncommon ultrastructural feature aided in establishing the thyroid gland as the source of a skeletal metastatic tumor.