Endoscopic transstomal stent insertion: a novel approach for a stenosed stoma in a challenging patient.

Transstomal stent deployment to maintain the patency of stoma in a challenging patient who developed stoma stenosis, is a minimal invasive, novel technique. This is a new and alternative approach in management of stoma stenosis in a difficult case using a biodegradable stent for end colostomy.

Mesh safety in pelvic surgery: Our experience and outcome of biological mesh used in laparoscopic ventral mesh rectopexy.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) continues to be a popular treatment option for rectal prolapse, obstructive defecation/faecal incontinence and rectoceles. In recent years there have been concerns regarding the safety of mesh placements in the pelvis. AIM: To assess the safety of the mesh and the outcome of the procedure. METHODS: Eighty-six patients underwent LVMR with Permacol (Biological) mesh from 2012 to 2018 at University Hospital Wishaw. Forty were treated for obstructive defecation secondary to prolapse, rectocele or internal rectal intussusception, 38 for mixed symptoms obstructive defecation and incontinence, 5 for pain and bleeding secondary to full thickness prolapse and 3 with symptoms of incontinence. Questionnaires for the calculation of Wexner scores for constipation and incontinence were completed by the patients who were followed up in the clinic 12 wk after surgery and again in 6-12 mo. The average review of their notes was 18.3 ± 4.2 mo. RESULTS: The median Wexner scores for constipation pre-operatively and post-operatively were 14.5 [Interquartile range (IQR): 10.5-18.5] and 3 (IQR: 1-6), respectively, while the median Wexner score for faecal incontinence was 11 (IQR: 7-15) and 2 (IQR: 0-5), respectively (P < 0.01). There were 4 (4.6%) recurrences, 2 cases that presented with erosion of a suture through the rectum and one with diskitis. No mesh complications or mortalities were recorded. CONCLUSION: LVMR using a Permacol mesh is a safe and effective procedure for the treatment of obstructive defecation/faecal incontinence, rectal prolapse, rectoceles and internal rectal prolapse/intussusception.

A novel endoscopic treatment for anastomotic leakage post anterior resection: Padlock over the scope clip.

BACKGROUND: Anastomotic dehisense is a serious complication of anterior resections. We have had success in our centre utilising Endosponge therapy to salvage anastomotic leaks but this requires multiple endoscopic sessions and can take around 6 weeks to heal in some cases. This can delay further management such as chemotherapy. AIM: We describe the novel use of Padlock over the scope clips to manage patients with anastomotic dehisense post anterior resection. METHOD: Padlock over the scope clips were used to manage three patients who presented with anastomotic breakdown post laparoscopic anterior resection between February 2016 and July 2017. RESULTS: These patients were initially managed conservatively with IV antibiotics and fluids. One case was first managed with Endosponge treatment before a Padlock clip was utilised to bridge a narrow defect. The other cases were managed initially with CT-guided percutaneous drains before clip deployment. Patients were followed up with regular clinic and sigmoidoscopies. All three cases demonstrated anastomotic salvage and satisfactory healing. This allowed the patients to be fit for their chemotherapy in less than 4 weeks from presentation. There were no complications from utilising the Padlock clips in these cases. CONCLUSION: Utilising over the scope endoclips previously has been thought to be limited by the size of defect. Our experience details novel combination techniques that allow for quick resolution and the expeditious commencement of further management such as chemotherapy. These clips also proved to be cost-effective in our centre, utilising less inpatient and outpatient resources than alternative management plans.

The effect of peri-stomal infiltration with bupivacaine/epinephrine on post-operative pain, nausea and ease of surgery in reversal of loop ileostomies.

PURPOSE: Evidence to support the routine use of local anaesthetic in the reversal of loop ileostomy is equivocal. This randomized control study looked at the use of peri-operative infiltration of stoma with 0.25% bupivacaine with 1/200,000 epinephrine on the ease of surgery and its effect on post-operative pain and nausea. METHODS: Sixty patients were randomized to receive peri-stomal infiltration with either 0.25% bupivacaine with 1/200,000 epinephrine or normal saline. The surgeon graded the surgery as straightforward, intermediate or difficult, and the time for the operation was also recorded. Post-operatively, analgesia was provided via PCA for 24 h. Post-operative pain and nausea scores and total morphine usage median (inter-quartile range) were compared using the Mann-Whitney U test with p < 0.05 considered significant. RESULTS: There was no difference between the local anaesthetic groups and controls with respect to opiate consumption (p = 0.4), post-operative pain (p = 0.72) or nausea (p = 0.78). Shorter total anaesthetic and operative times were noted in study group, but this was not significant (p = 0.55). However, surgery was found to be easier in the local anaesthetic group (p = 0.0046). CONCLUSION: Peri-stomal infiltration with 0.25% bupivacaine with 1/200,000 epinephrine does not impact on post-operative pain and nausea scores or opiate analgesia use. However, its use is recommended as an aid to dissection in surgery.

Alterations of beta-tubulin isotypes in breast cancer cells resistant to docetaxel.

Docetaxel is one of the most active drugs used to treat breast cancer. The cellular target of docetaxel is the microtubule, specifically the beta-tubulin subunit, that comprises a series of isotypes and that can modulate function. This study has examined the role of alteration in beta-tubulin isotypes in vitro and has sequenced the beta-tubulin gene to determine if there were mutations, both of which may represent important mechanisms of acquired resistance to docetaxel. Breast cancer cells, MCF-7 (oestrogen-receptor positive) and MDA-MB-231, (oestrogen-receptor negative) were made resistant to docetaxel in vitro. Expression of beta-tubulin isotypes (class I, II, III, IVa, IVb, and VI) was determined at the RNA and protein level using RT-PCR and western analysis, respectively. DNA sequencing evaluated the beta-tubulin gene. At the mRNA level, class I, II, III, and IVa beta-tubulin mRNA isotypes were over-expressed in docetaxel-resistant MCF-7 cells when compared with the docetaxel-sensitive parental cells. However, class VI beta-tubulin mRNA isotype expression was decreased in resistant cells. In MDA-MB-231 cells, there was a decrease in expression of the class I and class IVa beta-tubulin mRNA. However, there were increased expressions in class II, IVb, and VI beta-tubulin mRNA isotypes in resistant cells. Western analysis has confirmed corresponding increases in beta-tubulin protein levels in MCF-7 cells. However, in MDA-MB-231 cells, there were decreased protein levels for class II and class III beta-tubulin. This study demonstrates that altered expression of mRNA beta-tubulin isotypes and modulation of beta-tubulin protein levels are associated with acquired docetaxel resistance in breast cancer cells. This allows further understanding and elucidation of mechanisms involved in resistance to docetaxel.

Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells.

INTRODUCTION: Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects. METHODS: We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively. RESULTS: Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively). CONCLUSIONS: This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies.