Prostaglandin E2 receptors and their role in gastrointestinal motility - Potential therapeutic targets.

Prostaglandin E2 (PGE2) is found throughout the gastrointestinal tract in a diverse variety of functions and roles. The recent discovery of four PGE2 receptor subtypes in intestinal muscle layers as well as in the enteric plexus has led to much interest in the study of their roles in gut motility. Gut dysmotility has been implicated in functional disease processes including irritable bowel syndrome (IBS) and slow transit constipation, and lubiprostone, a PGE2 derivative, has recently been licensed to treat both conditions. The diversity of actions of PGE2 in the intestinal tract is attributed to its differing effects on its downstream receptor types, as well as their varied distribution in the gut, in both health and disease. This review aims to identify the role and distribution of PGE2 receptors in the intestinal tract, and aims to elucidate their distinct role in gut motor function, with a specific focus on functional intestinal pathologies.

Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

BACKGROUND: Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols. METHODS: A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death. RESULTS: A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001). CONCLUSIONS: Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification.

Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks.

BACKGROUND: Anastomotic leak (AL) represents a dreaded complication following colorectal surgery, with a prevalence of 1-19 per cent. There remains a lack of consensus regarding factors that may predispose to AL and the relative risks associated with them. The objective was to perform a systematic review of the literature, focusing on the role of preoperative, intraoperative and postoperative factors in the development of colorectal ALs. METHODS: A systematic review was performed to identify adjustable and non-adjustable preoperative, intraoperative and postoperative factors in the pathogenesis of AL. Additionally, a severity grading system was proposed to guide treatment. RESULTS: Of 1707 papers screened, 451 fulfilled the criteria for inclusion in the review. Significant preoperative risk factors were: male sex, American Society of Anesthesiologists fitness grade above II, renal disease, co-morbidity and history of radiotherapy. Tumour-related factors were: distal site, size larger than 3 cm, advanced stage, emergency surgery and metastatic disease. Adjustable risk factors were: smoking, obesity, poor nutrition, alcohol excess, immunosuppressants and bevacizumab. Intraoperative risk factors were: blood loss/transfusion and duration of surgery more than 4 h. Stomas lessen the consequences but not the prevalence of AL. In the postoperative period, CT is the most commonly used imaging tool, with or without rectal contrast, and a C-reactive protein level exceeding 150 mg/l on day 3-5 is the most sensitive biochemical marker. A five-level classification system for AL severity and appropriate management is presented. CONCLUSION: Specific risk factors and their potential correction or indications for stoma were identified. An AL severity score is proposed to aid clinical decision-making.

Incidental findings detected on emergency abdominal CT scans: a 1-year review.

INTRODUCTION: In recent years, there has been a substantial rise in the use of computed tomography (CT) in the emergency medicine setting. Accordingly, with increased CT usage there has been an upsurge in incidental pathology detection. METHODS: A retrospective review of all emergency CT abdominal scans performed at a university teaching hospital was examined. The frequency of incidental findings, their clinical significance and workload effect for the radiology department was assessed. RESULTS: 1155 patients had an emergency abdominal CT scan of which 700 had incidental findings detected. Of the incidental findings, 143 were deemed indeterminate requiring urgent investigations. Twenty-four occult neoplasms were confirmed subsequently. Additionally, 259 patients were recommended for additional diagnostics. The cumulative effect of the initial emergency abdominal CT was 15,015 relative value units (RVU). Subsequent imaging of incidental findings resulted in another 1674 RVU workload for radiology. CONCLUSION: Incidental findings cause considerable debate and concern over which patients require significant follow-up, investigations, and/or surveillance. This exerts significant pressures on sub-specialties for their expert input, with increased workload and implications on healthcare service provision.

An unusual cause for massive inflation.

Chagas disease is a rare condition but with an increasing incidence. Megacolon is a known sequelae. Surgical management remains the only disease modifying treatment option; with variable long-term success. We highlight an interesting case to emphasize attention to this rare condition as a differential diagnosis in any patient presenting with massive intestinal dilatation.

A Rare Case of BRCA2-Associated Breast Cancer in Pregnancy.

A 30-year old woman was referred to our department with symptomatic breast cancer at 35 weeks gestation. Genetic testing revealed a pathogenic BRCA2 mutation. Labour was induced at 38 weeks. Mastectomy and axillary clearance were performed with a view to adjuvant chemotherapy, radiation and hormonal therapy. Multidisciplinary involvement is crucial for management of BRCA-associated breast cancer, especially in the context of pregnancy. Bilateral mastectomy may be indicated given the increased risk of ipsilateral and contralateral breast cancers. Tamoxifen may lower contralateral breast cancer risk in those in whom risk-reducing surgery is not performed.

Minimally invasive and surgical management strategies tailored to the severity of acute diverticulitis.

BACKGROUND: The severity of acute diverticulitis ranges from mild, simple inflammation to pericolic abscesses, or perforation with faeculent peritonitis. Treatment of diverticulitis has evolved towards more conservative and minimally invasive strategies. The aim of this review is to highlight recent concepts and advances in management. METHODS: A literature review was performed on the electronic databases MEDLINE from PubMed, Embase and the Cochrane Library for publications in English. The keywords 'diverticulitis', 'diverticular' were searched for the past decade (to September 2013). RESULTS: Diverticulitis occurs frequently in the Western world, but only one in five patients develops complications (such as abscess and perforation) during the first acute presentation. The reported perforation rate is 3.5 per 100,000 population. Based on recent data, including the AVOD and DIVER trials, antibiotic therapy for mild episodes may be unnecessary and outpatient management reasonable in most patients. Antibiotics and admission to hospital is required for complicated diverticulitis confirmed on imaging and for patients with sepsis. Diverticular abscesses (about 5 per cent of patients) may require percutaneous drainage if antibiotics alone fail. Laparoscopic management of non-faecal perforated diverticulitis is feasible in selected patients, and peritoneal lavage in combination with antibiotic therapy may avoid colonic resection and a stoma. However, the collective, published worldwide experience is limited to fewer than 800 patients, and results from ongoing randomized trials (LapLAND, SCANDIV, DILALA and LADIES trials) are needed to inform better decision-making. CONCLUSION: The treatment of diverticulitis continues to evolve with a trend towards a more conservative and minimally invasive management approach. Judicious use of antibiotics in uncomplicated cases, greater application of laparoscopic techniques, and primary resection and anastomosis are of benefit in selected patients.

Clinical review: surgical management of locally advanced and recurrent colorectal cancer.

AIM: Recurrent and locally advanced colorectal cancers frequently require en bloc resection of involved organs to achieve negative margins. The aim of this review is to evaluate the most current literature related to the surgical management of locally advanced and recurrent colorectal cancer. METHODS: A literature review was performed on the electronic databases MEDLINE from PubMed, EMBASE and the Cochrane library for publications in the English language from January 1993 to July 2013. The MeSH search terms 'locally advanced colorectal cancer', 'recurrent colorectal cancer' and 'surgical management' were used. RESULTS: A total of 1,470 patients with recurrent or locally advanced primary colorectal cancer were included in 22 studies. Surgical removal of the tumour with negative margins (R0) offers the best prognosis in term of survival with a 5-year survival of up to 70 %. MVR is needed in approximately 10 % with the most commonly involved organ being the bladder. The mean post-operative morbidity is 40 %, mainly relating to superficial surgical site infection, pelvic collections and delayed wound healing. Most patients will undergo radiotherapy and/or chemotherapy pre- or post-operatively. The mean 5-year overall survival for R0 resection is 50 % for recurrent and locally advanced primary tumours while survival following R1 or R2 is 12 and <5 %, respectively. CONCLUSION: Multimodal therapy and extended surgery to achieve clear margins offers good prognosis to patients with recurrent and locally advanced colorectal cancers.

Surgical mortality - an analysis of all deaths within a general surgical department.

BACKGROUND: Post-operative mortality is one of the most universal and important outcomes that can be measured in surgical practice and is increasingly used to measure quality of care. The aim of this study was to evaluate overall mortality within a surgical department and to analyse factors associated with operative and non-operative death. METHODS: We analysed prospectively collected data detailing all surgical admissions, procedures and mortalities over a twelve year period (2000-2012) from a regional Irish hospital. We evaluated type of operation, patient factors and cause of death. RESULTS: A total of 62 085 patients were admitted under surgical care between the 1st of January 2000 and the 31st of December 2011. There were a total of 578 deaths during this period (0.93% overall mortality rate). 415 deaths (71.8%) occurred in non-operative patients in which advanced cancer (36.5%), sepsis (14.9%), cardiorespiratory failure (13.2%) and trauma (11%) were the primary causes. A total of 22 788 surgical procedures were performed with an operative mortality rate of 0.71%. Mortality rate following elective surgery was 0.17% and following emergency surgery was 10-fold higher (1.7%). The main cause of post-operative death was sepsis (30.02%). Emergency operations, increasing age and major procedures significantly increased mortality risk (p < 0.001). CONCLUSION: Post-operative deaths comprise a small proportion of overall deaths within a surgical service. Mortality figures alone are not an accurate representation of surgical performance but in the absence of other easily available quality outcome measures they can be used as a surrogate marker when all confounding factors are accounted for.

Exploration of chest wall perforator vascular anatomy on standard breast MRI: A potential aid to chest wall perforator flap planning.

Local chest wall perforator flaps (CWPFs) are a volume replacement technique permitting breast-conserving surgery in patients who otherwise may require a mastectomy. These flaps are based on one or more perforating arteries arising from the lateral chest wall that travel through the soft tissue and into the sub-dermal plexus to perfuse the flap. Examples include the lateral intercostal and lateral thoracic artery perforators (LICAP and LTAP, respectively). Cross-sectional imaging of perforating vessels is not routinely performed, and vessels are mapped pre- and peri-operatively using a hand-held acoustic doppler device. As many breast cancer patients undergo pre-operative MRI scanning for oncological purposes, we investigated the role of MRI in mapping the vascular anatomy to aid with the surgical planning of CWPFs. We collated data retrospectively on a cohort of breast cancer patients who underwent breast MRI as part of routine pre-operative imaging. Axial 3D high-resolution dynamic contrast-enhanced MRI sequences with multiplanar reconstructions were analysed by a consultant radiologist. The presence and calibre of lateral chest wall perforator vessels were assessed. Fifty patients were suitable for inclusion. A consistent pattern of lateral chest wall vasculature was observed. Forty-eight patients (96%) demonstrated a bilateral lateral thoracic artery (LTA) descending inferiorly along the chest wall with two-thirds of these communicating with perforating intercostal vessels. True independent LICAP vessels were identified in six patients. From our observations, lateral CWPFs are dependent on an intricate intercommunication between intercostal vessels and the LTA which in turn supply perforators to the lateral chest wall donor site.

How I do it: the stapled ileal J pouch at restorative proctocolectomy.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) following proctocolectomy is the preferred option for patients with medically refractory ulcerative colitis, indeterminate colitis, and familial adenomatous polyposis. However, it remains a procedure associated with morbidity and mortality. Pelvic sepsis, pouch fistulae, and anastomotic dehiscence predispose to pouch failure. We report our experience with an adaptation for the formation of the stapled ileal J pouch using the GIA™ 100 stapling device (Covidien, Mansfield, Massachusetts, USA). When creating the J pouch, we remove the bevelled plastic protector from the thin fork of the stapling device, allowing the staple line to be completed to the tip of the stapled efferent limb of the pouch, thereby minimizing potential blind ending in the efferent limb and injury to the transverse staple line. METHODS: Patients undergoing elective IPAA at our institution over a 5-year period using this adapted stapling technique for creation of the ileal J pouch were reviewed. Data were collected from a prospectively maintained inflammatory bowel disease database, theater records, and patient chart review. RESULTS: Forty-one patients underwent IPAA using this technique at our institution during the study period. Postoperative morbidity was encountered in 11 of 41 patients including pelvic sepsis, pouch fistulae, anastomotic stricture, or leak. There was no morbidity observed related to a blind efferent limb or transverse staple line disruption. No mortality was observed in this series. CONCLUSION: Maximizing the length of the efferent fork of the GIA stapling device can reduce the length of redundant efferent J limb of the ileal J pouch. This may reduce the incidence of torsion, volvulus, distension, fistulae/sinuses, and pelvic sepsis/anastomotic leak following IPAA.

Use of an electrothermal bipolar sealing device in ligation of major mesenteric vessels during laparoscopic colorectal resection.

BACKGROUND: A variety of approaches are available for division of major vascular structures during laparoscopic colorectal resection. Ultrasonic coagulating shears (UCS), vascular staplers, plastic or titanium clips and electrothermal bipolar vessel sealing (EBVS) are currently available. We report our experience with an EBVS device, LigaSure™ (Covidien AG), used in division of the ileocolic, middle colic and inferior mesenteric arteries during laparoscopic colorectal resection. METHODS: We report the immediate outcome of 802 consecutive unselected patients who underwent elective laparoscopic colorectal cancer resection performed with use of the LigaSure™ (5 and 10 mm) at our institution over a 5-year period. Operative procedures included right hemicolectomy (n = 180), left hemicolectomy (n = 96), sigmoid colectomy (n = 347) and anterior resection (n = 179). Data were collected from a prospectively maintained cancer database and operative records. The procedures were performed primarily by three consultant surgeons with an interest in laparoscopic colorectal resection. RESULTS: Of 802 cases in which the LigaSure™ device was employed to divide major vascular structures, immediate effective vessel sealing was achieved in 99.8% (n = 800). Two patients experienced related adverse events both following division of the inferior mesenteric artery with a 5 mm LigaSure™. Both patients had immediate uncontrolled haemorrhage that required laparotomy. CONCLUSIONS: Use of the LigaSure™ device to seal and divide the major mesenteric vessels during laparoscopic colorectal resection is very effective, with a high success rate of 99.8%. Caution should be exercised in elderly atherosclerotic patients, particularly when using the 5-mm LigaSure™ device.