ObjectiveTo determine the likelihood of nonsentinel axillary metastasis in the presence of sentinel node metastasis from a primary breast carcinoma. Summary Background DataSentinel lymphadenectomy is a highly accurate technique for identifying axillary metastasis from a primary breast carcinoma. Our group has shown that nonsentinel axillary lymph nodes are unlikely to contain tumor cells if the axillary sentinel node is tumor-free, but as yet no study has examined the risk of nonsentinel nodaJ invoKlement when the sentinel node contains tumor calls. MethodsBetween 1991 and 1997, axillary lymphadenectomy was performed in 157 women with a tumor-involved sentinel node. Fifty-three axillae (33.5%) had at least one tumor-involved nonsentinel node. The authors analyzed the incidence of nonsentinel node involvement according to clinical and tumor characteristics. ResultsOnly two variables had a significant impact on the likelihood of nonsentinel node metastasis: the size of the sentinel node metastasis and the size of the primary tumor. The rate of nonsentinel node involvement was 7% when the sentinel node had a micrometastasis (.2 mm), compared with 55% when the sentinel node had a macrometastasis (>2 mm). In addition, the rate of nonsentinel node tumor involvement increased with the size of the primary tumor. ConclusionsIf a primary breast tumor is small and if sentinel node involvement is micrometastatic, then tumor cells are unlikely to be found in other axillary lymph nodes. This suggests that axillary lymph node dissection may not be necessary in patients with sentinel node micrometastases from T1/T2 lesions, or in patients with sentinel node metastases from Tl a lesions.Although surgical management of a primary breast cancer has evolved from radical mastectomy to breast-conserving techniques, surgical management of the axilla has changed little. The tumor status of lymph nodes excised during axillary lymph node dissection (ALND) is the best The increased use of screening mammography has resulted in the earlier detection and the smaller size of inva-

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Use of IHC increases the likelihood of detection of NSN metastasis, and the risk of IHC-detected metastasis increases with the size of the SN metastasis and the size of the primary tumor. If SN involvement is micrometastatic (< or =2 mm) or detected by using IHC, tumor cells are unlikely to be found in other axillary lymph nodes in patients with a small primary tumor. The clinical significance of micrometastatic disease in lymph nodes is controversial, and a prospective randomized study is necessary to resolve this important issue.

SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

ObjectiveThe authors determined whether caloric restriction (CR), either acutely or chronically, alters heat shock protein 70 (hsp70) gene expression in the gut. Summary Background DataCaloric restriction prolongs the life span and delays age-related disease (e.g., cancer) in mammals; the mechanisms responsible for these effects are not known. Heat shock proteins are a group of stress-responsive genes of which the most prominent member is hsp7O. MethodsIn the first experiment, adult (4-month-old) rats (n = 3/group) were killed after a 48-hour fast or 6 and 24 hours after refeeding. In addition, three rats (controls) were killed without fasting or refeeding. The stomach was removed and RNA was extracted for hsp70 gene expression. In the second experiment, aged (22-to 26-month-old) rats were fed ad libitum (AL) or a CR diet (60% caloric intake of AL diet). Rats were killed, the stomach and duodenum were removed, and RNA was extracted for determination of hsp70 gene expression. ResultsIn the first experiment, hsp70 mRNA levels were increased approximately threefold in the stomach of rats fasted for 48 hours; levels decreased to control values by 6 and 24 hours after refeeding. In the second experiment, hsp70 mRNA levels were increased significantly in both the stomach and duodenum of aged CR rats compared with AL controls. ConclusionsThe authors have demonstrated that hsp7o mRNA levels are increased in the proximal gut of young and old rats, either acutely-(with fasting) or with CR. Increased expression of the cytoprotective hsp70 gene in the gut may provide a possible cellular mechanism for the beneficial effects noted with CR.

The development of peptide-based vaccines that are useful in the therapeutic treatment of melanoma and other cancers ultimately requires the identification of a sufficient number of antigenic peptides so that most individuals, regardless of their major histocompatibility complex (MHC)-encoded class I molecule phenotype, can develop a cytotoxic T lymphocyte (CTL) response against one or more peptide components of the vaccine. While it is relatively easy to identify antigenic peptides that are presented by the most prevalent MHC class I molecules in the population, it is problematic to identify antigenic peptides that are presented by MHC class I molecules that have less frequent expression in the population. One manner in which this problem can be overcome is by taking advantage of known MHC class I supertypes, which are groupings of MHC class I molecules that bind peptides sharing a common motif. We have developed a mass spectrometric approach which can be used to determine if an antigenic peptide is naturally processed and presented by any given MHC class I molecule. This approach has been applied to the A3 supertype, and the results demonstrate that some, but not all, A3 supertype family-associated peptides can associate with all A3 supertype family members. The approach also demonstrates the shared nature of several newly identified peptide antigens. The use of this technology negates the need to test peptides for their ability to stimulate CTL responses in those cases where the peptide is not naturally processed and bound to the target MHC class I molecule of interest, thus allowing resources to be focused on the most promising vaccine candidates.

ObjectiveThe authors examined the effects of exogenous bombesin (BBS) on gut mucosal growth in chowfed rats and the mucosal regeneration after gut atrophy brought about by feeding an elemental diet and after intestinal injury produced by methotrexate (MTX). Summary Background DataBombesin is one of many gastrointestinal peptides implicated in the regulation of gut mucosal growth. Although BBS is known to stimulate growth of normal pancreatic tissue, the trophic effect of BBS on gut mucosa is less clear and its exact role in gut mucosal regeneration and repair is not known. MethodsRats were fed a regular chow diet (control) or an elemental diet plus either saline or BBS (10 sg/ kg). In another experiment, rats fed a chow diet and treated with saline or BBS were given MTX (20 gg/kg) or a single intraperitoneal injection. In all experiments, small and large bowel mucosa and pancreas were removed and analyzed for BBS-mediated proliferation.

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