Axillary dissection in the context of the biology of lymph node metastases.

BACKGROUND: Modern breast surgery, as the primary treatment of invasive breast carcinoma, has been evolving over the last century. Aggressive radical surgery, which included chest wall resection, complete axillary clearance and internal mammary node dissection, has slowly changed to a less aggressive approach. This has been based on an improved understanding of the biology of the disease. Over the years, randomized prospective trials, performed at centers all over the world, have demonstrated that axillary dissection does not impact on the overall survival while it helps with loco-regional control of breast cancer. Its major role, at the present time, is limited to staging and prognostication; functions that are equally well served by the limited approach of a sentinel node biopsy. SOURCES: This review is based on the available medical literature involving the biology and organ specificity of the metastatic process, not only in breast cancer but also in other malignancies. In addition, studies pertaining to clinical breast cancer, and the role of surgery in its treatment, were reviewed. The ongoing trials on the role of sentinel node biopsy in the management of the clinically node negative patients are discussed. CONCLUSIONS: This review covers the history, pathophysiology, and clinical basis of the current role of axillary dissection for invasive breast cancer. From the data presented we hope that the medical community will agree that there is no therapeutic role for extended axillary dissection at the current time.

Suppressor mutations in Escherichia coli methionyl-tRNA formyltransferase that compensate for the formylation defect of a mutant tRNA aminoacylated with lysine.

The specific formylation of initiator methionyl-tRNA by methionyl-tRNA formyltransferase (MTF) is important for the initiation of protein synthesis in eubacteria such as Escherichia coli. In addition to the determinants for formylation present in the initiator tRNA, the nature of the amino acid attached to the tRNA is also important for formylation. We showed previously that a mutant tRNA aminoacylated with lysine was an extremely poor substrate for formylation. As a consequence, it was essentially inactive in initiation of protein synthesis in E. coli. In contrast, the same tRNA, when aminoacylated with methionine, was a good substrate for formylation and was, consequently, quite active in initiation. Here, we report on the isolation of suppressor mutations in MTF which compensate for the formylation defect of the mutant tRNA aminoacylated with lysine. The suppressor mutant has glycine 178 changed to glutamic acid. Mutants with glycine 178 of MTF changed to aspartic acid, lysine, and leucine were generated and were found to be progressively weaker suppressors. Studies on allele specificity of suppression using different mutant tRNAs as substrates suggest that the Gly178 to Glu mutation compensates for the nature of the amino acid attached to the tRNA. We discuss these results in the framework of the crystal structure of the MTF.fMet-tRNA complex published recently.

Biologic and clinical significance of lymphadenectomy.

Interest in the lymphatic system and its relationship to metastases has developed owing to renewed interest in sentinel node biopsy. This article summarizes the anatomy, physiology, and biology of the lymphatic system and lymph node metastases, and reviews studies of lymph node metastases and surgical resection of cancers in different anatomic sites. On the basis of these studies, the authors conclude that lymph node metastasis functions as an indicator of prognosis, not the controlling or determining factor of prognosis. Thus, varying degrees of treatment of regional lymph nodes and metastases do not seem to be controlling factors in the outcome of cancer.

Critical preservation injury in rat fatty liver is to hepatocytes, not sinusoidal lining cells.

BACKGROUND: Fatty livers are more prone to primary nonfunction after transplantation. We hypothesized that sinusoidal lining cells (SLCs) in fatty livers of obese Zucker rats are more susceptible to ischemia/reperfusion injury than in normal livers. METHODS: Cold University of Wisconsin solution-preserved (30 min or 24 hr) livers from obese and lean Zucker rats were perfused ex vivo for 90 min with oxygenated warm acellular buffer containing hyaluronate. Bile output, alanine transferase, and hyaluronate clearance were measured during reperfusion. Trypan blue was infused at completion of reperfusion to assess cell membrane integrity. Another group of 24-hr preserved livers were reperfused with cold hypoxic buffer to differentiate the effects of preservation from reoxygenation. RESULTS: After 30 min of preservation, fatty livers had significantly decreased flow (1.9 vs. 2.6 ml/g/min), increased resistance, decreased hyaluronate clearance (17 vs. 35 microg/g liver) and lower bile output (13 vs. 42 microl/g) in comparison with normal livers. Hepatocyte and SLC trypan blue uptake were minimal and similar in both groups. After 24 hr of preservation, flow (2.0 vs. 2.0), resistance, hyaluronate clearance, and bile output were similar in both fatty and normal livers. The SLC trypan blue uptake was increased but similar in both groups (22 vs. 20%). In contrast, a significantly greater number of hepatocytes were trypan blue-stained in fatty livers (32 vs. 0.6%), accompanied by a marked increase in lactate dehydrogenase and alanine transferase release. Hypoxic reperfusion caused a significant decrease in hepatocyte and SLC trypan blue uptake. CONCLUSIONS: Fatty livers demonstrate impaired hepatocyte and SLC function, after even a very brief preservation. With increasing preservation, hepatocytes appear to be more susceptible to injury than SLCs. Reoxygenation appears to be important in triggering this event.