Citations

AbstractIdentification of multiple clinical and pathologic prognostic factors in differentiated thyroid cancer has permitted some degree of risk stratification. However, these clinical indices fail to distinguish potential intrinsic differences in tumor virulence. The nm23 gene has been identified as a potential metastasis suppressor gene that is homologous to nucleoside diphosphate kinases. Studies in human breast cancer have shown a significant inverse correlation between nm23 levels and nodal involvement/tumor recurrence. Given the possible clinical utility of a marker of metastatic potential in the management of thyroid carcinoma, we examined 34 thyroid neoplasms and a human medullary thyroid cancer (MTC) cell line (TT) for nm23 expression. Normalized nm23 expression was assessed by Northern analysis of tumor RNA. nm23 Expression (tumor expression/TT cell expression, mean ±SE) was 1.14 ±0.15* in MTCs (n =5), 0.70 ±0.10* in follicular cancers (n=6), 0.51 ±0.11 in papillary cancers (n=19), and 0.31 ±0.03 in follicular adenomas (n=4) (*p< 0.05 when compared to adenomas). Within histologicgroups, we found no correlation between nm23 expression and nodal involvement or distant métastases. Our results indicate that thyroid neoplasms of different histologies express varying levels of the nm23 transcript. Although nm23 expression seems diminished in metastatic breast cancer, it appears not to be the case in metastatic thyroid cancer. The nm23 gene may therefore have different roles in the evolution and metastases of different neoplasms.

AbstractThe EEA stapler is a convenient, well‐designed, and reliable instrument. It will anastomose the bowel with reliability and speed at least equivalent to hand‐sewn techniques, and probably offers a technical advantage in performing very low rectal anastomoses. Unfortunately, intraoperative misadventures are greater with this device than with hand‐sewn techniques, and its use would seem best restricted to those situations in which it has its greatest advantage. Postoperative complications are not increased by its use, but the long‐term incidence of anastomotic stricture and possibly increased rate of local recurrence need to be clarified.

AbstractEighty‐nine patients underwent adrenal exploration for Cushing's syndrome at our institution during the period 1970–1979. On the basis of clinical and histological findings related to the initial adrenal operation, patients were divided into 6 major subgroups: (a) adrenocortical adenoma; (b) adrenocortical carcinoma; (c) proven ectopic ACTH adrenocortical hyperplasia; (d) Cushing's disease; (e) uncertain diagnostic group (probably ectopic ACTH syndrome—site unknown); and (f) “non‐ACTH‐dependent” hypercortisolism due to micronodular hyperplasia.Results of pathologic examination included 25 adrenal adenomas, 15 adrenocortical carcinomas, 40 bilateral adrenocortical hyperplasias, and a single case of micronodular hyperplasia. The postoperative mortality rate was 5.6%, and significant morbidity occurred in 40% of patients. Four of the 5 patients who died within 30 days of operation were in the subgroups with adrenal carcinoma (2 patients) and Cushing's disease (2 patients). Survival in patients with adrenocortical adenomas was significantly decreased at 2 years (relative adrenocortical insufficiency?), but thereafter, it paralleled the expected survival. Patients with the ectopic ACTH syndrome and adrenocortical carcinoma had significantly decreased survival, with only one‐third of carcinoma patients alive 2 years postoperatively. The survival of patients with Cushing's disease was lower than expected at both 5 and 10 years.These results confirm that the diagnosis of patients with endogenous hypercortisolism is usually straightforward and accurate, surgical intervention in this group of patients is still accompanied by significant short‐term mortality and morbidity, and long‐term survival in all subgroups is decreased.

SummarySmith–Lemli–Opitz syndrome is a rare autosomal recessive disorder characterized by multiple congenital anomalies and various degrees of cognitive deficits. This condition results from a deficiency of 7‐dehydrocholesterol reductase, a critical step in cholesterol biosynthesis. Children with Smith–Lemli–Opitz syndrome have frequent infections, particularly of the respiratory tract. Immunodeficiency, however, is not recognized as a part of this metabolic condition. Frequent infections are usually attributed to a decreased patient mobility and reduced respiratory effort secondary to muscular hypotonia and mental retardation, which are often present in affected individuals. We describe a patient with Smith–Lemli–Opitz syndrome and recurrent respiratory infections who was found to have a selective antibody deficiency. The immunological diagnosis was based on an absent immune response to Pneumovax. She also had no immunological response to hepatitis B vaccine and was unable to break down red cells with isoagglutinin B. Therapy with intravenous IgG (IVIG) was initiated. Infections were less severe, although they still occurred in a high frequency after initiation of the IVIG therapy. This finding prompts the need for a higher index of suspicion for an underlying immune deficiency in patients with Smith–Lemli–Opitz syndrome who present with recurrent and chronic infections. Early recognition and appropriate therapeutic interventions may decrease the severity of infections, prevent potentially fatal infections, and eventually improve the quality of life in these patients.

Abstract We hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio &lt; 0.26 or &gt; 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P &lt; .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non–immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (≥ 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).

Purpose There is a need for a simple, reliable staging system for multiple myeloma that can be applied internationally for patient classification and stratification. Patients and Methods Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. Potential prognostic factors were evaluated by univariate and multivariate techniques. Three modeling approaches were then explored to develop a staging system including two nontree and one tree survival assessment methodologies. Results Serum beta 2 -microglobulin (Sβ 2 M), serum albumin, platelet count, serum creatinine, and age emerged as powerful predictors of survival and were then used in the tree analysis approach. A combination of Sβ 2 M and serum albumin provided the simplest, most powerful and reproducible three-stage classification. This new International Staging System (ISS) was validated in the remaining patients and consists of the following stages: stage I, Sβ 2 M less than 3.5 mg/L plus serum albumin ≥ 3.5 g/dL (median survival, 62 months); stage II, neither stage I nor III (median survival, 44 months); and stage III, Sβ 2 M ≥ 5.5 mg/L (median survival, 29 months). The ISS system was further validated by demonstrating effectiveness in patients in North America, Europe, and Asia; in patients less than and ≥ 65 years of age; in patients with standard therapy or autotransplantation; and in comparison with the Durie/Salmon staging system. Conclusion The new ISS is simple, based on easy to use variables (Sβ 2 M and serum albumin), and recommended for early adoption and widespread use.

Extracellular proteolysis plays a key role in many pathophysiologic processes including cancer, inflammatory diseases, and cardiovascular conditions such as atherosclerosis and restenosis. Whereas matrix metalloproteinases are their best known member, many others are becoming better known. The extracellular proteases are a complex and heterogeneous superfamily of enzymes. They include metalloproteinases (matrix metalloproteinases, adamalysins, or pappalysins), serine proteases (elastase, coagulation factors, plasmin, tissue plasminogen activator, urokinase plasminogen activator), and the cysteine proteases (such cathepsins). In addition to their matrix degradation capabilities, they have other less well known biologic functions that include angiogenesis, growth factor bioavailability, cytokine modulation, receptor shedding, enhancing cell migration, proliferation, invasion, and apoptosis. This review discusses extracellular proteases relevant to the vasculature, their classification and function, and how protease disorders contribute to arterial plaque growth, including chronic atherosclerosis, acute coronary syndromes, restenosis, and vascular remodeling. These broad extracellular protease functions make them potentially interesting therapeutic targets.