The oral UFT/LV regimen failed to achieve improved TTP; however, the study confirms significant safety improvements compared with bolus IV 5-FU/LV for the first-line treatment of metastatic CRC.

Background and aims: This study evaluated the effect of transanal endoscopic microsurgery (TEM) on anorectal sphincter functions and determined the risk factors for anorectal dysfunctions (including incontinence). Patients and methods: A study group of 33 patients with small, mobile rectal tumors (adenoma and carcinoma) located up to 12 cm from the anal verge underwent anorectal motility studies (using pull-through anorectal manometry and rectal barostat) and endoanal ultrasound prior to surgery and 3 weeks and 6 months after TEM; controls were 20 healthy volunteers. Results: Resting and squeeze anal pressures were reduced 3 weeks after TEM. Resting anal pressure remained reduced 6 months after surgery; the changes were related to low preoperative levels and to the internal anal sphincter defects rather than to the procedure duration or the type of surgery. High-pressure zone length and vector volume were decreased 3 weeks after TEM and restored 6 months later. Rectoanal inhibitory reflex, reflex sphincter contraction, rectoanal pressure gradients, threshold and maximal tolerable volume of rectal sensitivity, and compliance were significantly changed 3 weeks after TEM; only rectal wall compliance remained low at 6 months. The rectoanal inhibitory reflex, reflex sphincter contraction, rectal sensitivity, and compliance were related to the extent and type of excision (partial or full thickness). Anal ultrasound revealed internal anal sphincter defects in 29% of patients studied 3 weeks after TEM. Only 76% of patients were fully continent. Disturbed anorectal function (including partial fecal incontinence) was observed in up to 50% of patients at 3 weeks. Partial and moderate anorectal dysfunction was found in 21% patients 6 months after surgery. The main risk factors of anorectal dysfunctions following TEM included: postoperative internal anal sphincter defects, low preoperative resting anal pressure, disturbed rectoanal coordination, extent (>50% of wall circumference) and the depth (full thickness) of tumor excision. Conclusion: TEM has a relevant but temporary effect on anorectal motility. As a result of TEM procedures 21% of the patients had disturbed anorectal functions, mostly due to the extent or depth of tumor excision (influencing rectal compliance and rectoanal coordination), and to the sphincter defects lowering resting anal pressure. Preoperative anorectal motility studies and anal ultrasound allow the identification of patients with the risk of postoperative anorectal dysfunctions.

Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and (13)C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.

Lymph node ratio seems to be a new promising prognostic factor in patients with respectable node-positive pancreatic head cancer.