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Purpose: To compare single-incision laparoscopic (SIL) with multiport laparoscopic (LAP) colectomy in patients with colon cancer to assess oncologic resection and 1-year outcomes., Methods: We compared patients who underwent SIL colectomy for colon cancer with an equal number of case-matched LAP colectomy patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) score, previous abdominal operations, and operation type. Results of oncologic resection included lymph node (LN) yield and margins. One-year outcomes included cancer recurrence and death., Results: Twenty-six patients were identified for SIL and LAP colectomy groups with no differences in case matching (age, P = .70; gender, P > .99; BMI, P = .74; ASA score, P > .99; previous abdominal operation, P > .99; and operation-type, P > .99). Oncologic resection was similar for both groups. Mean LN yield was 17 (P = .88). There were no positive margins and 2 (8%) patients had proximal/distal margin of <5 cm in each group. The mean follow-up was 13 and 21 months for the SIL and LAP groups, respectively (P < .001), with 2(8%) recurrences in each group, and no port-site recurrences or deaths. Disease-free survival at 1 year was 92% for both groups., Conclusion: These data suggest that SIL colectomy for cancer provides equivalent oncologic resection and 1-year outcomes compared with a standard LAP technique. Further studies are required to determine long-term oncologic outcomes, including recurrence and survival rates., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Enterocolitis is the major toxicity of methotrexate-based cancer chemotherapy, which limits its clinical applications. Methotrexate induces gut mucosal apoptosis in vivo; however, little is known about the molecular mechanism involved. The effectors of apoptosis include the caspase family of proteases, which are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were (1) to establish an in vitro model of methotrexate-induced gut apoptosis and (2) to determine the role of caspases in methotrexate-induced apoptosis in intestinal epithelial cells., Methods: Rat intestinal epithelial cells (RIE-1) were treated with methotrexate in the absence or presence of ZVAD-fluoromethyl ketone, a general caspase inhibitor. Apoptosis was quantified by means of deoxyribonucleic acid (DNA) fragmentation assays and Hoechst nuclear staining. Caspase activation was measured with the use of fluorogenic substrates., Results: Methotrexate induced apoptosis and decreased cell number in RIE-1 cells. DNA fragmentation was preceded by the sequential activation of caspases 9, 2, and 3, whereas caspases 1 and 8 remained inactive. ZVAD-fluoromethyl ketone inhibited methotrexate-induced caspase activation, DNA fragmentation, and nuclear condensation., Conclusions: These results indicate that methotrexate activates specific caspases and induces apoptosis in RIE-1 cells. Furthermore, caspases may play an important role in methotrexate-induced apoptosis in RIE-1 cells and may be potential therapeutic targets to attenuate methotrexate-induced enterocolitis.

Background: The prognosis for gastric cancer remains dismal; novel agents that target specific molecular pathways are needed as adjuvant therapy. Camptothecin (CPT), on inhibitor of topoisomerase I, is effective in the treatment of certain solid tumors; its effects on gastric cancer are largely undefined. The purpose of this study was to (1) characterize the effects of CPT on the growth of a human gastric cancer and (2) assess potential cellular mechanisms responsible for CPT-mediated growth inhibition., Methods: The human gastric cancer SIIA was transplanted subcutaneously into athymic nude mice. After tumors reached approximately 100 mm2, mice were randomized into 3 groups to receive either CPT (5 or 10 mg/kg) or vehicle (control) intraperitoneally 3 days per week for 3 weeks; tumor size was measured biweekly. To assess potential mechanisms of CPT-mediated inhibition, SIIA cells were treated with CPT (20 mumol/L) and cells were counted over a time course; apoptosis was assessed by Hoechst stain and DNA laddering. Expression of p53 (a tumor suppressor), p21Waf1 and p27Kip1 (cell cycle inhibitors), and Bcl-2 and Bcl-XL (antiapoptotic proteins) was determined., Results: CPT (5 and 10 mg/kg) significantly inhibited tumor growth of SIIA gastric cancers compared with controls. CPT-mediated inhibition of SIIA cell proliferation was associated with an increase in apoptosis. Moreover, CPT treatment resulted in induction of p53, p21Waf1, and p27Kip1 and a decrease in Bcl-2 and Bcl-XL RNA and protein levels., Conclusions: Treatment with CPT effectively inhibited the growth of the human gastric cancer SIIA; the mechanism involved was induction of apoptosis mediated by up-regulation of p53, p21Waf1/Cip1, and p27Kip1 and the down-regulation of Bcl-2 and Bcl-XL. Novel agents such as CPT, which target specific molecular pathways, may prove clinically useful in the adjuvant treatment of gastric cancers.

Background: Conventional adjuvant therapy for advanced carcinoid tumors remains disappointing; novel therapeutic agents are needed. We have shown previously that inhibiting polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) slows the growth of carcinoid tumors. However, the clinical utility of DFMO has been limited by its cytostatic property. Synthetic polyamine analogs such as 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) appear to be cytotoxic against several human tumors. The purpose of our study was to determine whether BE-4-4-4-4 is a more effective antiproliferative and cytotoxic agent than DFMO on human carcinoid (BON) cells in vitro., Methods: BON cells were treated with either 5 mmol/L DFMO, 0.5 to 10 mumol/L BE-4-4-4-4, or vehicle (control). Ornithine decarboxylase activity was determined by the rate of 14CO2 production, and intracellular polyamine levels were determined by chromatography. Cell number and viability were determined by Coulter counter and trypan blue exclusion, respectively., Results: BE-4-4-4-4 inhibited ornithine decarboxylase activity and depleted all 3 polyamines. BE-4-4-4-4 decreased cell numbers by 81% compared with control and 27% compared with DFMO. BE-4-4-4-4 also induced a 2-fold increase in cell death compared with control or DFMO., Conclusions: BE-4-4-4-4 is cytotoxic and more effective than DFMO in inhibiting growth of BON cells. Polyamine analogs such as BE-4-4-4-4 may be effective adjuvant therapeutic agents for advanced carcinoid tumors.

Background: Glutamine is the most abundant amino acid in the blood, and its deprivation leads to gut mucosal atrophy. The small intestinal mucosa is maintained by a balance between cell proliferation and cell death by apoptosis. We reported that glutamine is required for nitrogen-stimulated proliferation in intestinal epithelial cells. We do not know whether glutamine regulates apoptosis in the gut. The purpose of this study is to determine whether glutamine deprivation induces apoptosis in rat intestinal epithelial (RIE-1) cells and to compare the effect of glutamine starvation with that of methionine and cysteine (Met/Cys) starvation., Methods: RIE-1 cells were deprived of either glutamine or Met/Cys for 24 hours. Cell numbers were determined by cell counting and tetrazolium enzymatic assay. Apoptosis was quantified by Annexin V assay and confirmed by DNA gel electrophoresis and Hoecsht nuclear staining., Results: Deprivation of glutamine or Met/Cys resulted in decreased cell numbers. However, only the glutamine-deprived group showed significant induction of apoptosis with increased Annexin V staining, DNA laddering, and nuclear condensation., Conclusions: This study provides biochemical and morphologic evidence that glutamine deprivation induces apoptosis in rat intestinal epithelial cells. In contrast, Met/Cys starvation suppresses cell number without induction of apoptosis. These results suggest that glutamine serves as a specific survival factor in enterocytes.

Background: Recent reports have demonstrated an increase in the number of complications associated with delayed timing of fasciotomy for trauma. This study examines the effectiveness of early (less than 12 hours) versus late (more than 12 hours) fasciotomy in the injured extremity., Methods: This is a retrospective review of 88 patients undergoing fasciotomy for extremity trauma admitted to the University of Cincinnati from January 1990 through December 1995. Records were reviewed for demographics, compartment pressures, time and type of fasciotomy, complications, limb salvage, and mortality. Statistical analysis was determined with chi-squared, multivariant regression analysis, and Student's t test with significance at p less than 0.05., Results: Sixty-one (69%) patients had fasciotomy performed before 12 hours and twenty-seven (31%) after 12 hours. Although the rates of infection differed significantly between the two groups (7.3% for early versus 28% for late), the rates of limb salvage and neurologic sequelae were similar. Age, mechanism, shock, associated injuries, and time to fasciotomy were not predictive of complications., Conclusions: Fasciotomy for trauma is most efficacious when performed early. However, when performed late, it results in similar rates of limb salvage as compared with early fasciotomy but at the increased risk of infection. These results support aggressive use of fasciotomy in extremity trauma regardless of time of diagnosis.