This revised staging system will be officially adopted for use in tumor registries in January 2003.

The model of cecal ligation and puncture (CLP) in rodents has been used extensively to investigate the clinical settings of sepsis and septic shock. This model produces a hyperdynamic, hypermetabolic state that can lead to a hypodynamic, hypometabolic stage, and eventual death. Blood cultures are positive for enteric organisms very early after CLP. The model has been widely used over the past 26 years and is highly versatile in adapting to a range of severity and testing objectives. It is inexpensive to prepare and technically straightforward. Aspects of sepsis research investigated using CLP include energetics, metabolism, resuscitation, antibiotic therapy, microbial factors, cardiovascular responses, immune function, mediator release, and cytokine expression patterns. The challenge of the small circulating blood volume in rodents can be overcome by using micromethods that enable analysis of small volumes, or alternatively, by using a large number of animals to obtain serial samples.

These results demonstrate that the prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. A minimum of 13 lymph nodes should be examined to label a T3 colon cancer as node negative. These data suggest that adjuvant trials for T3N0 colon cancer should stratify according to the number of lymph nodes examined.

MBC is a rare tumor with different characteristics than IDC: it presents with larger tumor size, less nodal involvement, higher tumor grade, and hormone receptor negativity. Patients with MBC are treated more aggressively than IDC (more often with mastectomy and chemotherapy) because of a higher stage at presentation, but are being treated by the same principles as IDC. Follow-up will determine the long-term results of the current treatment.

MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gbetagamma-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17beta-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERbeta, but not ERalpha, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Galphas subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17alpha-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.

Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.

Hypothesis: Lifestyle is a priority among senior medical students when selecting a career specialty. The trend toward controllable lifestyle vs noncontrollable lifestyle specialties is affecting the number of students desiring a career in general surgery. Design: The Medical Student Graduation Questionnaire is published and distributed by the Association of American Medical Colleges to all US medical schools for senior medical students to complete before graduation. The results from the survey are published each year in the All Schools Report. We evaluated these reports to track the percentage of students pursuing a career in general surgery during the past decade. The National Resident Matching Program also publishes a report each year outlining the match results. We reviewed these results from 1978 through 2001 and used them to determine the percentage of students choosing to enter general surgery. Main Outcome Measures: First choice of specialty among graduating senior students from US medical schools; positions matched by US and foreign medical students and students from osteopathic medical schools; factors that influenced the decision-making process in choice of specialty; and factors that influenced students to change their mind from one career to another. Results: An established trend of decreasing interest in general surgery exists and has the potential to affect the number of positions that are filled each year in the match. Linear projections confirm that, should the current trend continue (negative slope; P =.01), by 2005 only 4.8% of US graduating senior medical students will be interested in general surgery. This established trend of decreasing interest in general surgery, which began in the early 1980s, did not affect the match until 2001, when the number of positions offered exceeded the number of students interested in general surgery. At present, the specialty of general surgery is at risk for significant numbers of positions remaining unfilled. Our match projections estimate that for 2005, only 76.6% of positions will be filled by US senior students (negative slope; P=.001). Conclusions: If the trend continues, the students matching in general surgery will not be as competitive as in years past, and there will be a potential shortage of these specialists in the United States.