Gostout, Christopher J.

Abstract Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI®Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%ΔACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5–34) and 8 (0–37) at baseline and postintervention, respectively. The median (SD) for %ΔACF was 5.6 (−69% to 143%), −18.6 (−83% to 160%), −3.6 (−88% to 83%), and −10.0 (−100% to 117%) in the atorvastatin, sulindac, ORAFTI®Synergy1 and control arms, respectively. Neither within-arm (P = 0.12–0.59) nor between-arm (P = 0.30–0.92) comparisons of %ΔACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI®Synergy1, although statistical power was limited by the relatively small sample size. Cancer Prev Res; 4(2); 259–69. ©2011 AACR.

Natural orifice translumenal endoscopic surgery (NOTES) is a novel surgical concept that may provide a multitasking platform for minimally invasive surgery in the 21st century. With NOTES, natural hollow organs are used to gain access to body cavities via the mouth, anus, vagina, and urethra, thereby eliminating skin incisions. Access to the body cavity through the entry portal for the NOTES procedure and closure of the portal after surgery are important treatment considerations. In this review, access and closure techniques for NOTES-related procedures are discussed. Technical descriptions for access are also described. Closure techniques using experimental and commercially available devices are also reviewed. Based on the experimental and early clinical experiences to date, the future of NOTES appears quite promising. Nonetheless, ongoing fundamental research is necessary to determine the safety and benefit of these procedures. While technical challenges are currently present, the issues are being resolved with the development of optimal instrumentation and techniques. We believe that once standardized safe and reliable access and closure techniques are established, a major shift in minimally invasive surgery will likely be inevitable.

AbstractTherapeutic endoscopy (TE) has provided a new means for treating peptic ulcer disease, prompting a reevaluation of surgery's role. The aim of this study was to determine if surgical therapy of bleeding duodenal ulcers has changed since the advent of TE. This retrospective review involved consecutive time periods during which TE was (1985–1990) and was not (1980–1984) widely available. Exclusion criteria were prior gastric surgery, nonpeptic conditions, and untreated ulcers. Inclusion standards were met by 252 patients (180 men, 72 women) whose mean age was 67 years. Patients were grouped by the initial therapeutic intervention. Groups were similar in age, medical condition (mean APACHE II score 16), and morbidity. Seventy‐five patients had surgery alone during 1980–1984 and 38 during 1985–1990. TE was initially performed on 134 patients during 1985–1990. Bleeding (n=30) and perforation (n=1) prompted emergent operation in 23% of cases following TE. Thus 69 (38+31) patients underwent surgery between 1985 and 1990. Preprocedure transfusions averaged 4.1 units in the endoscopic group and 8.2 units in the operative groups (p<0.0001). Disagreement existed between the endoscopic and surgical descriptions of ulcer location in 53% of cases. Emergent surgery was required in 45% of hemodynamically unstable patients versus 14% of stable patients who initially underwent TE (p<0.0001). Sixty‐one percent of incompletely visualized TE‐treated lesions required operation, and 18% of well visualized ulcers underwent operation (p<0.0001). Hospital mortality was similar (8% versus 16%) in the endoscopic and operated groups (p=0.7). Mean follow‐up was 540 days. The number of operations performed for bleeding duodenal ulcer did not change significantly during the TE era, and a significant subset (23%) of endoscopically treated patients required surgical therapy. TE failure was portended by hemodynamic instability or incomplete endoscopic visualization.