Favorable surgical treatment outcomes for chronic constipation with features of colonic pseudo-obstruction

AIM: To determine long-term outcomes of surgical treatments for patients with constipation and features of colonic pseudo-obstruction.METHODS: Consecutive 42 patients who underwent surgery for chronic constipation within the last 13 years were prospectively collected. We identified a subgroup with colonic pseudo-obstruction (CPO) features, with dilatation of the colon proximal to the narrowed transitional zone, in contrast to typical slow-transit constipation (STC), without any dilated colonic segments. The outcomes of surgical treatments for chronic constipation with features of CPO were analyzed and compared with outcomes for STC.RESULTS: Of the 42 patients who underwent surgery for constipation, 33 patients had CPO with dilatation of the colon proximal to the narrowed transitional zone. There were 16 males and 17 females with a mean age of 51.2 ± 16.1 years. All had symptoms of chronic intestinal obstruction, including abdominal distension, pain, nausea, or vomiting, and the mean duration of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was 1.5 ± 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total colectomy, and one patient underwent diverting transverse colostomy. There was no surgery-related mortality. Postoperative histologic examination showed hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy (n = 3). Early postoperative complications developed in six patients with CPO; wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n = 1). Defecation frequencies 3 mo after surgery improved to 4.2 ± 3.2 times/d (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32 patients; all patients had improvements in constipation symptoms, but two patients needed intermittent medication for management of diarrhea. All 32 patients had distinct improvements in constipation symptoms (with a mean bowel frequency of 3.3 ± 1.3 times/d), social activities, and body mass index (20.5 kg/m² to 22.1 kg/m²) and were satisfied with the results of their surgical treatment. In comparison with nine patients who underwent colectomy for STC without colon dilatation, those in the CPO group had a lower incidence of small bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up.CONCLUSION: Chronic constipation patients with features of CPO caused by narrowed transitional zone in the left colon had favorable outcomes after total colectomy.     

The Effects of Surgical Cytoreduction Prior to Imatinib Therapy on the Prognosis of Patients with Advanced GIST

Background

Baseline tumor size is one of important prognostic factors for imatinib therapy in patients with advanced gastrointestinal stromal tumor (GIST). The purpose of this study was to determine whether surgical cytoreduction before imatinib therapy can improve the prognosis.

Methods

A total of 249 patients with advanced GIST were reviewed retrospectively. Patients were categorized into two groups according to the degree of initial cytoreduction: 35 patients with ≥75 % of initial tumor bulk removed (cytoreduction group) and the other 214 patients (no cytoreduction group). The median follow-up was 44.0 months.

Results

Patients in the cytoreduction group were younger, in better performance, showed more initially metastatic disease, peritoneal metastases, but fewer liver metastases. The baseline tumor size when starting imatinib became significantly reduced in the cytoreduction group, which made significant difference between the two groups. By multivariate analyses, mutational status, tumor size, and granulocyte count at presentation were associated with progression-free survival. Age and tumor size were associated with overall survival. However, initial cytoreduction was not significantly related to the prognosis.

Conclusions

Cytoreduction before imatinib therapy appears not to improve the prognosis. Imatinib therapy should still represent the initial treatment for advanced GIST.     

Bladder and bowel dysfunction following small-volume epidural blood patch for spontaneous intracranial hypotension

Epidural blood patch (EBP) is an effective procedure for the treatment of spontaneous intracranial hypotension (SIH). Neurological compromise following EBP, although rare, is recognized as a serious potential complication. We describe a 33-year-old female patient in whom long-term bladder and bowel dysfunction developed following a small volume (10 mL) EBP to treat SIH. We also discuss the possible pathophysiological mechanisms related to this complication in the postprocedure setting.     

Inhibition of Organic Anion Transporting Polypeptide 1B1 and 1B3 by Betulinic Acid: Effects of Preincubation and Albumin in the Media

Betulinic acid (BA), a plant-derived pentacyclic triterpenoid, may interact with the members of the organic anion transporting polypeptide 1B subfamily. Here, we investigated the interactions of BA and its analogs with OATP1B1/3 and rat Oatp1b2 in vitro and in vivo. BA inhibited the activity of OATP1B1/3 and rat Oatp1b2 in vitro. Systemic exposure of atorvastatin was substantially altered with the intravenous co-administration of BA (20 mg/kg). Preincubation (incubation with inhibitors, followed by washout) with BA led to a sustained inhibition of OATP1B3, which recovered rapidly in the media containing 10% fetal bovine serum. The addition of albumin to the media decreased intracellular concentrations of BA and expedited the recovery of OATP1B3 activity following preincubation. For asunaprevir and cyclosporin A (previously known to inhibit OATP1B3 upon preincubation), the addition of albumin to the media shortened recovery time with asunaprevir, but not with cyclosporin A. Overall, our results showed that BA inhibits OATP1B transporters in vitro and may incur hepatic transporter-mediated drug interactions in vivo. Our results identify BA as another OATP1B3 inhibitor with preincubation effect and suggest that the preincubation effect and its duration is impacted by altered equilibrium of inhibitors between intracellular and extracellular space (e.g., albumin in the media).