A fatal case of amphetamine induced ischaemic colitis.

Amphetamine induced ischaemic colitis is an exceedingly rare presentation of amphetamine toxicity. The cases reported in the literature have described mild or transient disease. We present a fatal case of ischaemic colitis induced by amphetamine use in a 44-year-old woman who presented in extremis after a cardiac arrest en route to the emergency department. A short history of headache, abdominal pain, vomiting and agitation preceded her admission. Imaging revealed changes consistent with ischaemic colitis. Emergency laparotomy revealed widespread colonic necrosis necessitating a subtotal colectomy. Despite aggressive resuscitation and inotropic support from arrival, the patient deteriorated intraoperatively and died in the immediate postoperative period. Histology showed arterial type ischaemia/reperfusion injury of the area supplied by the superior mesenteric artery. The patient's serum amphetamine level was 0.52mg/l (peak therapeutic levels <0.2mg/l). The postmortem examination concluded that amphetamines were the likely cause of the vasospasm, leading to profound colonic ischaemia.

Management of iatrogenic recto-urethral fistula by transanal rectal flap advancement.

AIM: Recto-urethral fistulas are an uncommon, but devastating complication following rectal or urinary tract surgery. Repair is often difficult, and the optimal approach is unclear. We report our recent experience using an endorectal advancement flap. METHOD: A case note review of all patients undergoing repair of recto-urethral fistula in our institution was undertaken. Data on aetiology of the fistula, patient demographics, operative procedure and outcome both clinically and radiologically were extracted. RESULTS: Between 2002 and 2008, six transanal rectal advancement flaps in five patients were carried out. Four had undergone a laparoscopic radical prostatectomy, without any radiotherapy. Two types of fistula (type 1 associated with severe intra-abdominal sepsis and type 2 associated with localized sepsis) were found, with faecal diversion being less likely with the latter. Four (80%) patients underwent successful primary repair, with one patient requiring a second procedure. Postoperative cystography confirmed closure of the fistula in all five patients, and no recurrence has been observed at a mean follow-up time of 11 months. CONCLUSION: Rectal advancement flap is a simple, effective technique for iatrogenic recto-urethral fistula with minimal morbidity.

Composite abdominosacral resection for recurrent rectal cancer.

BACKGROUND: En bloc resection of the tumour and adjacent involved organs offers the only realistic curative option for patients with locally recurrent rectal cancer. This study assessed outcomes of composite resection for recurrent tumours involving the sacrum. METHODS: A consecutive series of patients underwent composite abdominosacral resection (abdominal mobilization and stoma construction followed by sacral division and tumour retrieval) for recurrent rectal cancer between 2001 and 2007. Patients were staged with preoperative computed tomography, magnetic resonance imaging and positron emission tomography. Data were collected prospectively. RESULTS: Forty patients (28 men; median age 59 (range 31-77) years) underwent surgery with sacral division at the S2/3 interface in 13, S3/4 level in 20 and S4/5 level in seven patients. One patient died and 24 had complications. An R0 resection was achieved in 20 patients and conferred benefit in disease-free interval over an R1 resection. The mean disease-free interval was 55.6 (95 per cent confidence interval (c.i.) 40.0 to 71.3) months for R0 and 32.2 (95 per cent c.i. 19.7 to 44.7) months for R1 resection (P = 0.048). CONCLUSION: Composite abdominosacral resection of locally recurrent rectal cancer is an effective treatment for a difficult clinical scenario.

Feasibility and functional outcome of laparoscopic sacrocolporectopexy for combined vaginal and rectal prolapse.

PURPOSE: Prolapse of multiple pelvic organs causes a variety of symptoms that impair a patient's quality of life. A laparoscopic procedure is described that uses a mesh fixation of the mid-compartment vagina to the sacrum with additional rectopexy to correct both the anatomical deformities and the dysfunction of the posterior compartment. METHODS: Patients with significant rectal and vaginal prolapse with or without rectocele were recruited. A thorough preoperative physiological assessment of each of the compartments of the pelvic floor was carried out. Patients also completed the Pelvic Floor Distress Inventory before and six months after surgery. RESULTS: Ten patients underwent the procedure of laparoscopic sacrocolporectopexy (median age 47 years, interquartile range 43-53). No mortality or morbidity occurred. Median global distress inventory scores were significantly lower postoperatively (8.3, interquartile range 0-20.8 vs. 37.5, interquartile range 16.6-60.4) P = 0.012. All three median subscales were also significantly lower postoperatively. The procedure corrected associated rectoceles and descent of the perineum on straining. CONCLUSION: The described laparoscopic procedure of mesh sacrocolpopexy with rectopexy was safe and feasible and conferred good symptomatic improvement in pelvic floor dysfunction.

Tumour-induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction.

Gastrointestinal carcinomas frequently disseminate within the abdominal cavity to form secondary peritoneal metastases. Invasion of the peritoneal mesothelium is fundamental to this process, yet the underlying invasive mechanisms remain unclear. Preliminary in vitro work suggested that tumour cells can induce mesothelial apoptosis, representing a novel mechanism of peritoneal invasion. We examined the role of tumour cell-induced mesothelial apoptosis and explored the role of the death ligand/receptor system, Fas Ligand/Fas, as mediators of the apoptotic process. Cultured human mesothelial cells were used to establish in vitro co-culture models with the SW480 colonic cancer cell line. Tumour-induced mesothelial apoptosis was confirmed by phase-contrast microscopy and apoptotic detection assays. Human mesothelial cells and SW480 tumour cells constitutively expressed Fas and Fas Ligand mRNA and protein as determined by RT-PCR and confocal fluorescent microscopy. Stimulation of human mesothelial cells with anti-Fas monoclonal antibody or crosslinked soluble Fas Ligand-induced apoptosis, confirming the functional status of the Fas receptor. Pretreatment of SW480 cells with a blocking recombinant anti-Fas Ligand monoclonal antibody significantly reduced mesothelial apoptosis, indicating that tumour-induced mesothelial apoptosis may, in part, be mediated via a Fas-dependent mechanism. This represents a novel mechanism of mesothelial invasion and offers several new targets for therapeutic intervention.

Extracellular matrix proteins and chemoradiotherapy: alpha5beta1 integrin as a predictive marker in rectal cancer.

AIMS: To investigate the effects of extracellular matrix (ECM) protein expression on the rates of apoptosis and proliferation in rectal cancers and subsequent response to chemoradiotherapy (CRT). METHODS: The expression of fibronectin, collagen IV, laminin and the fibronectin receptor (FnR, alpha5beta1 integrin) were analysed in 32 pre-treatment rectal cancer biopsies by immunohistochemistry. ECM expression was correlated with tumour mitotic index (MI), apoptotic index (AI) and histopathological response to CRT. RESULTS: 18/32 cancers showed a poor response and 14/32 a good response (5/14 with complete pathological response) to CRT. Moderate to strong staining was seen in 22/32 cancers for fibronectin, 5/32 for collagen IV and 18/32 for laminin. Tumour FnR was related to stromal fibronectin content, and was significantly associated with CRT response; good responders having higher FnR expression compared to poor responders. No association was found between FnR expression and either MI or AI in pre-treatment biopsies, nor between MI or AI and CRT response. CONCLUSIONS: Tumour FnR expression is independent of MI and AI, and may serve as a useful marker for CRT response in rectal cancer.

Control of pollen tube tip growth by a Rop GTPase-dependent pathway that leads to tip-localized calcium influx.

We have shown that Rop1At, a pollen-specific Rop GTPase that is a member of the Rho family of small GTP binding proteins, acts as a key molecular switch controlling tip growth in Arabidopsis pollen tubes. Pollen-specific expression of constitutively active rop1at mutants induced isotropic growth of pollen tubes. Overexpression of wild-type Arabidopsis Rop1At led to ectopic accumulation of Rop1At in the plasma membrane at the tip and caused depolarization of pollen tube growth, which was less severe than that induced by the constitutively active rop1at. These results indicate that both Rop1At signaling and polar localization are critical for controlling the site of tip growth. Dominant negative rop1at mutants or antisense rop1at RNA inhibited tube growth at 0.5 mM extracellular Ca(2+), but growth inhibition was reversed by higher extracellular Ca(2+). Injection of anti-Rop antibodies disrupted the tip-focused intracellular Ca(2+) gradient known to be crucial for tip growth. These studies provide strong evidence for a Rop GTPase-dependent tip growth pathway that couples the control of growth sites with the rate of tip growth through the regulation of tip-localized extracellular Ca(2+) influxes and formation of the tip-high intracellular Ca(2+) gradient in pollen tubes.