Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy.

BACKGROUND: Optimal management of the endometrium in patients with oestrogen receptor-positive breast cancer taking extended tamoxifen therapy (for 10 years) remains uncertain. A meta-analysis was performed to determine the cumulative risk ratio (RR) for endometrial malignancy following extended compared with standard tamoxifen treatment. A systematic review was undertaken to identify whether routine endometrial surveillance in patients receiving tamoxifen is associated with earlier detection and reduced incidence of endometrial malignancy. METHODS: Two independent searches were undertaken in the Cochrane Library, PubMed and MEDLINE. A meta-analysis was performed of RCTs reporting on endometrial malignancy risk in extended tamoxifen therapy. A systematic review included prospective studies investigating the benefit of endometrial surveillance during tamoxifen therapy. RESULTS: Four RCTs reported on endometrial risk in extended tamoxifen therapy. The cumulative risk of endometrial malignancy increased twofold from 1·5 to 3·2 per cent with extended therapy compared with the standard 5 years of tamoxifen (RR 2·29, 95 per cent c.i. 1·60 to 3·28; P < 0·001). Four studies analysed the value of endometrial screening in 5-year cohorts. Endometrial cancer rates of up to 2 per cent were reported, which is higher than rates in the large extended tamoxifen trials. CONCLUSION: Extended adjuvant tamoxifen is associated with an increase in endometrial cancer. No clear benefit has been shown for routine endometrial surveillance in asymptomatic patients on tamoxifen therapy.

Segmental vs extended colectomy in the management of hereditary nonpolyposis colorectal cancer: a systematic review and meta-analysis.

AIM: The optimal surgical approach to the management of colorectal cancer in the setting of hereditary nonpolyposis colorectal cancer (HNPCC) is contentious. While some advocate total colectomy, others perform segmental resection followed by regular endoscopic surveillance. This systematic review evaluates the evidence for segmental colectomy (SC) and total (extended) colectomy (TC) in the management of HNPCC. METHOD: Two major databases (PubMed and Cochrane) were searched using predefined terms. All original articles, published in English, comparing the oncological outcomes of SC and TC in HNPCC patients from January 1950 to July 2013 were included. RESULTS: Eighty-four studies were identified. After applying exclusion criteria, six studies involving 948 patients were included (mean age 47.4 years, 51.8% male). SC was more commonly performed than TC (n = 780; 82.3%). Mean follow-up was 106.5 months. Metachronous high-risk adenomas were detected more often after SC, although the difference was not statistically significant (23.4% vs 9.6%; OR 2.258, P = 0.057). Metachronous cancers occurred more frequently after SC than after TC (23.5% vs 6.8%; OR 3.679, P < 0.005). However, there was no difference in overall survival (90.7% vs 89.8% for SC and TC, respectively; P = 0.085). Only one study reported operative mortality (0% in each group), there was no report of operative morbidity or functional outcome. CONCLUSION: The optimal surgical approach in the management of HNPCC remains unclear. More adenomas and cancers occur after SC than after TC but there certainly is no evidence to suggest that more radical surgery leads to improved survival.

The role of loose seton in the management of anal fistula: a multicenter study of 200 patients.

BACKGROUND: Perianal abscesses and fistulae-in-ano are a common anorectal complaint causing significant distress to patients, and present a considerable treatment challenge. Principal of treatment is achieving closure of the fistula while maintaining continence. There are numerous treatment approaches with large debate about which method is "ideal." Our aim was to assess the tolerance and efficacy of loose seton placement in the treatment for fistula-in-ano. METHODS: We performed a retrospective multicenter review of the management of anal fistulae with loose seton placement over a three-year period. All patients underwent a standardized procedure, and were rescheduled for an elective change of seton until fistula resolution. Patients' demographics, medical history, comorbidities, overall number and time interval between seton placements, tolerance, and morbidity of the procedure were recorded. RESULTS: A total of 200 consecutive patients had loose seton placement. 69.5 % (n = 139) were males, and mean age was 42.6 years. The median number of setons required for each patient was 3 (range 1-8; mean 2.84). The mean interval between changes was 3.08 months (range 2-4 months). All patients had successful clearance of fistula. The procedure was well tolerated in 96 % of patients (n = 187). Only 1 % (n = 2) could not tolerate the presence of seton due to significant discomfort. Fistula recurrence rate was 6 % (n = 12). CONCLUSIONS: Recently, newer treatment modalities have been reported with enthusiasm. However, there remains a lack of strong statistical evidence of efficacy to support their use. Overall, loose seton placement remains a well-tolerated, pragmatic low-cost solution to this common and difficult condition as evident by our study.

Spot urinary protein analysis for excluding significant proteinuria in pregnancy.

The aim of this research was to compare the accuracy of urinary protein/creatinine ratio (PCR) and albumin/creatinine ratio (ACR) in defining optimal cut-off points to rule-out significant proteinuria (>300 mg/24 h) in pregnancy. The secondary outcome measure was to determine the investigation of choice to evaluate proteinuria used by maternity units in the UK. PCR and ACR were calculated on first (PCR1, ACR1) void urine samples of the 24-hour urinary protein collection (24UP). Sensitivity and specificity was calculated for different cut-off points for PCR1 and ACR1 to rule-out significant proteinuria. An online survey was sent to RCOG members questioning them on their investigation of choice to evaluate proteinuria. We concluded from our results that both PCR and ACR are good rule-out tests for significant proteinuria in pregnancy using cut-off points of <20 mg/mmol and <2.5 mg/mmol. PCR is the investigation of choice in 56% of UK units studied.

Systemic mirnas as potential biomarkers for malignancy.

MiRNAs are a class of short, endogenous, single-stranded RNA molecules that play a role in the regulation of gene expression. They have been shown to modulate a number of cellular processes including cell differentiation, growth and apoptosis and as a result have been implicated in carcinogenesis. They are detectable in tumour tissue, and altered expression levels have been identified in various cancer types. Of interest, miRNAs have recently been detected and identified to be dysregulated in the circulation of patients with breast cancer. The fact that a minimally invasive test can distinguish the presence or absence of disease illustrates the immense potential these molecules hold as predictive markers. This review serves to identify those systemic miRNAs that are upregulated or downregulated in malignancy and how treatment impacts on their circulating levels. In addition, this review questions the source of these small molecules in the bloodstream and how they may possibly play a role in the future detection of cancer as either prognostic or predictive markers.

Systematic review of outcomes after intersphincteric resection for low rectal cancer.

BACKGROUND: For a select group of patients proctectomy with intersphincteric resection (ISR) for low rectal cancer may be a viable alternative to abdominoperineal resection, with good oncological outcomes while preserving sphincter function. The purpose of this systematic review was to evaluate the current evidence regarding oncological outcomes, morbidity and mortality, and functional outcomes after ISR for low rectal cancer. METHODS: A systematic review of the literature was undertaken to evaluate evidence regarding oncological outcomes, morbidity and mortality after ISR for low rectal cancer. Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The review included all original articles reporting outcomes after ISR, published in English, from January 1950 to March 2011. RESULTS: Eighty-four studies were identified. After applying inclusion and exclusion criteria, 14 studies involving 1289 patients were included (mean age 59.5 years, 67.0 per cent men). R0 resection was achieved by ISR in 97.0 per cent. The operative mortality rate was 0.8 per cent and the cumulative morbidity rate 25.8 per cent. Median follow-up was 56 (range 1-227) months. The mean local recurrence rate was 6.7 (range 0-23) per cent. Mean 5-year overall and disease-free survival rates were 86.3 and 78.6 per cent respectively. Functional outcome was reported in eight studies; among these, the mean number of bowel motions in a 24-h period was 2.7. CONCLUSION: Oncological outcomes after ISR for low rectal cancer are acceptable, with diverse, often imperfect functional results. These data will aid the clinician when counselling patients considering an ISR for management of low rectal cancer.

Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.

BACKGROUND: Following neoadjuvant chemoradiotherapy (CRT) and interval proctectomy, 15-20 per cent of patients are found to have a pathological complete response (pCR) to combined multimodal therapy, but controversy persists about whether this yields a survival benefit. This systematic review evaluated current evidence regarding long-term oncological outcomes in patients found to have a pCR to neoadjuvant CRT. METHODS: Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The systematic review included all original articles reporting long-term outcomes in patients with rectal cancer who had a pCR to neoadjuvant CRT, published in English, from January 1950 to March 2011. RESULTS: A total of 724 studies were identified for screening. After applying inclusion and exclusion criteria, 16 studies involving 3363 patients (1263 with pCR and 2100 without) were included (mean age 60 years, 65·0 per cent men). Some 73·4 per cent had a sphincter-saving procedure. Mean follow-up was 55·5 (range 40-87) months. For patients with a pCR, the weighted mean local recurrence rate was 0·7 (range 0-2·6) per cent. Distant failure was observed in 8·7 per cent. Five-year overall and disease-free survival rates were 90·2 and 87·0 per cent respectively. Compared with non-responders, a pCR was associated with fewer local recurrences (odds ratio (OR) 0·25; P = 0·002) and less frequent distant failure (OR 0·23; P < 0·001), with a greater likelihood of being alive (OR 3·28; P = 0·001) and disease-free (OR 4·33, P < 0·001) at 5 years. CONCLUSION: A pCR following neoadjuvant CRT is associated with excellent long-term survival, with low rates of local recurrence and distant failure.

Gastrointestinal surgery for obesity and diabetes: weight loss and control of hyperglycemia.

Obesity is associated with a variety of weight-related metabolic comorbidities. Bariatric surgery (metabolic/gastrointestinal surgery) not only achieves significant and sustainable weight loss, but also induces extraordinary effects on nearly all obesity-related comorbidities, particularly remission of type 2 diabetes mellitus (T2DM). The mechanisms underlying such effects are slowly being elucidated, and it appears that the metabolic benefits of bariatric surgery are not only attributable to weight loss, but there are also weight independent mechanisms at play. This article outlines the metabolic effects of the most commonly performed bariatric procedures, with a particular emphasis on how they affect glucose metabolism and T2DM.

Bariatric surgery for treatment of obesity.

This article focuses on recent trends and outcomes of bariatric surgery. The outcomes discussed include perioperative morbidity and mortality, weight loss, long-term complications and the impact of bariatric surgery on comorbidities, cardiovascular risk and mortality.

A focus on surgical preoperative evaluation of the bariatric patient--the Cleveland Clinic protocol and review of the literature.

Bariatric surgery is well established as a safe and effective treatment for morbid obesity and related metabolic diseases. As an elective procedure, it is critical that individuals considering bariatric surgery should be carefully selected, extensively evaluated, and optimized in order to achieve optimal outcomes. This patient population has unique and challenging issues, including an extensive range of potential medical, psychiatric, and psychological comorbidities, and often patients have unrealistic expectations of the surgery. Therefore, a multidisciplinary, comprehensive and timely assessment preoperatively is of great importance. Individual bariatric units utilise different preoperative patient evaluation protocols. There is at present no uniformly accepted or recommended practice. In this article we describe what we believe are the essential components of a preoperative bariatric surgery evaluation, with supporting evidence for each recommendation. We also present a protocol currently in practice at a high volume bariatric center of excellence; the Bariatric and Metabolic Institute in the Cleveland Clinic, Ohio.

Clinical and Survival Outcomes Using Percutaneous Cholecystostomy Tube Alone or Subsequent Interval Cholecystectomy to Treat Acute Cholecystitis.

BACKGROUND: Percutaneous cholecystostomy (PCT) is a safe method of gallbladder drainage in the setting of severe or complicated acute cholecystitis (AC), particularly in patients who are high-risk surgical candidates. Small case series suggest that PCT aids resolution of acute cholecystitis in up to 90% of patients. However, reluctance is observed in utilising PCT more frequently, due to concerns that we are committing comorbid patients to an interval surgical procedure for which they may not be suitable. AIM: The aim of this study was to assess the clinical and survival outcomes of PCT use, with particular emphasis on a subgroup of patients who did not proceed to cholecystectomy. METHODS: A retrospective analysis was performed of all patients with severe acute cholecystitis who required PCT insertion in a tertiary referral hospital from 2010 to 2015. Patient demographics and clinical data including systemic inflammatory response (SIRS) scores at presentation, readmissions and clinical and survival outcomes were analysed. Statistical analysis was performed using SPSS v.22 and GraphPad Prism v.7. RESULTS: In total, 157 patients (59% males) with AC underwent PCT insertion during the study period. Median age at presentation was 71 years (range 29-94). A median SIRS score of 3 was noted at presentation. Patients required a median of two cholecystostomy tube changes/replacements (range 1-10) during treatment. Transhepatic tube placement was the preferred approach (69%) with 31% of tubes being placed via transabdominal approach. Only 55% proceeded to interval cholecystectomy. Of the 70 patients treated with PCT alone, their median age was 75 years. In this subgroup, only 12.9% (n = 9) developed recurrent biliary sepsis necessitating readmission following initial resolution of symptoms and tube removal. All episodes of recurrent biliary sepsis presented within 6 months of index presentation, and definitive PCT removal in this group was performed at a median of 3 months. No difference in survival was observed between both groups. CONCLUSION: Almost 90% of patients with AC who are managed definitively with a PCT will recover uneventfully without recurrent sepsis following PCT removal. This is a viable option for older, comorbid patients who are unfit for surgical intervention and is not associated with significantly increased mortality.

Bouveret's syndrome--a rare presentation of gallstone ileus.

We present the case of an elderly Irish male with Bouveret's syndrome--a very unusual cause of gallstone ileus, where a large gallstone occludes the gastric outlet or duodenum causing obstruction. Management of this condition is often controversial. We discuss the various medical, radiological and surgical therapies available for treatment of this rare entity. Bouveret's Syndrome--A Rare Presentation of Gallstone Ileus

Segmental duodenal resection: indications, surgical techniques and postoperative outcomes.

INTRODUCTION: Segmental duodenal resections (DR) have been increasingly performed for the treatment of primary duodenal tumours. The aim of the study is to review the indications for, clinical and operative details, and outcomes of patients undergoing elective DR. MATERIAL AND METHODS: We retrospectively reviewed all patients who underwent elective segmental DR for the treatment of primary duodenal tumours, at a single institution between January 2007 and December 2013. Demographic data, clinical presentation, preoperative investigations, operative details, postoperative complications/mortality and histopathological results were recorded. RESULTS: In the study period, 11 duodenal resections were performed (7 male, median age 61 years). Thirty-six percent of the patients presented with anaemia. Surgical resection included two or more segments in seven patients. The most frequently resected part of the duodenum was segment 3 (n = 7). Median operative time was 191 min and blood loss was 675 ml. End-to-end and end-to-side anastomoses were performed in equal numbers. The pathology of resected specimens included adenocarcinoma (n = 4), gastrointestinal stromal tumour (GIST) (n = 1), adenoma (n = 5) and lymphoma (n = 1). Median hospital stay was 14 days. Overall, 30-day morbidity rate was 82% (78% Clavien 2 or less). CONCLUSIONS: Segmental duodenal resection is a safe and effective surgical technique for the resection of primary duodenal tumours.

Extreme heatstroke causing fulminant hepatic failure requiring liver transplantation: a case report.

INTRODUCTION: Exertional heatstroke with liver involvement is a rare and potentially fatal condition. In this setting, fulminant hepatic failure (FHF) occurs as a result of severe hypoxic hepatitis. CASE REPORT: We report the case of a young male athlete who developed exertional heatstroke associated with rhabdomyolysis and hypoxic hepatitis while running the final stages of an ultra-marathon (62 km). The patient rapidly developed multiorgan failure, including fulminant hepatic failure, requiring intensive care admission for mechanical ventilation, hemodialysis, and inotropic support. He failed to improve with supportive measures and underwent an emergency hepatectomy followed by orthotopic liver transplant, after which he recovered completely. CONCLUSIONS: We discuss the rationale for liver transplantation in this setting, possible alternative treatments, and the pathophysiology of fulminant liver failure in this rare case.

Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy, cavotomy, and thrombectomy.

Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation.

Pancreatectomy for metastatic disease: a systematic review.

AIM: Tumours rarely metastasise to the pancreas. While surgical resection of such metastases is believed to confer a survival benefit, there is limited data to support such management. We present a systematic review of case series of pancreatic metastasectomy and analysis of survival outcomes. METHODS: A literature search was performed using the PubMed and Cochrane databases and the reference lists of relevant articles, searching for sizeable case series of pancreatic metastasectomy with curative intent. Data extracted included basic demographics, histological primary tumour, presentation, operative management, complications and survival, while the MINORS index was used to assess study quality. RESULTS: 18 studies were found which met our inclusion criteria, involving 399 patients. Renal cell carcinoma (RCC) was the commonest malignancy metastasising to the pancreas, responsible for 62.6% of cases, followed by sarcoma (7.2%) and colorectal carcinoma (6.2%). While survival data was not uniformly reported, the median survival post-metastasectomy was 50.2 months, with a one-year survival of 86.81% and five-year survival of 50.02%. Median survival for RCC was 71.7 months with 70.4% five-year survival. Median survival was similar in patients with synchronous and metachronous pancreatic metastases, but patients with additional extrapancreatic metastases had a significantly shorter survival than patients with isolated pancreatic metastases (26 versus 45 months). Study quality was poor, with a median MINORS score of 10/16. CONCLUSIONS: Within the limitations of a review of non-randomised case series, it would appear that pancreatic metastasectomy confers a survival benefit in selected patients. Better evidence is required, but may prove difficult to acquire.

Pancreatic metastasectomy: experience of the Irish National Surgical Centre for Pancreatic Cancer.

BACKGROUND: Metastatic tumours of the pancreas are rare and the optimal management of these tumours remains unclear, given the paucity of data existing in the literature. We report our experience of pancreatic metastasectomy. METHODS: Data were reviewed on all patients who underwent pancreatic resection for pathologically confirmed metastatic lesions over a consecutive 7-year period. RESULTS: Seven patients (two men and five women) underwent a pancreatectomy for a metastatic pancreatic tumour. The primary tumours were renal cell carcinoma (n = 3), colorectal carcinoma (n = 2) and leiomyosarcoma (n = 2). There was no operative mortality. Postoperative morbidities occurred in two patients. The median follow-up was 49 months (range 17-76). Overall 1- and 2-year survivals were 100 and 86 %, respectively, with a 2-year disease-free survival of 72 %. CONCLUSIONS: Our series further supports that pancreatic metastasectomy can be performed safely and achieves acceptable survival outcomes.

Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers.

BACKGROUND: Omental fat accumulation is associated with development of the metabolic syndrome, although its molecular characteristics are poorly understood. Mi(cro)RNAs (miRNAs), a class of small noncoding RNAs, are known to regulate various metabolic processes, although their role in obesity and the metabolic syndrome is not clearly defined. This study sought to characterize the miRNA expression in omentum, sc fat and in the circulation of obese and nonobese individuals. Their potential as noninvasive metabolic biomarkers was also explored. METHODS: miRNA was extracted from paired omentum and sc fat tissues, and blood samples, from a total of 50 obese and nonobese patients. A miRNA microarray was performed and a panel of differentially expressed miRNAs validated using RQ-PCR. RESULTS: The miRNA expression profiles were unique for omentum and paired sc fat; no correlation in miRNA expression was observed between these two fat depots. Expression of two miRNAs (miR-17-5p and miR-132) differed significantly between obese and nonobese omental fat (P = 0.048 and P = 0.016). This expression pattern was reflected in the circulation in which these same two miRNAs were also significantly dysregulated in blood from obese subjects. The miRNA expression in omental fat and blood from obese patients correlated significantly with body mass index, fasting blood glucose, and glycosylated hemoglobin. CONCLUSION: This study demonstrates that candidate metabolic miRNAs are altered in adipose tissue and circulation of the obese. Omental fat tissue and systemic miRNA levels reflect components of the metabolic syndrome, highlighting their potential as novel biomarkers for this complex syndrome.

Quality of life after immediate breast reconstruction and skin-sparing mastectomy - a comparison with patients undergoing breast conserving surgery.

BACKGROUND: Historically breast cancer surgery was associated with significant psychosocial morbidity and suboptimal cosmetic outcome. Recent emphasis on women's quality of life following breast cancer treatment has drawn attention to the importance of aesthetic outcome and potential benefits of immediate breast reconstruction (IBR). Our primary aim was to assess patient's quality of life after IBR, compared to a matched group undergoing breast conservation. We also investigated the oncological safety and morbidity associated with immediate reconstruction. METHODS: A prospectively collected database of all breast cancer patients who underwent IBR at a tertiary referral breast unit was reviewed. Patients were reviewed clinically, and administered two validated quality of life questionnaires, at least one year after completing their treatment. RESULTS: 255 patients underwent IBR following mastectomy over a 55 month period. Reconstruction with ipsilateral latissimus dorsi flap was most commonly performed (88%). After mean follow-up of 36 months, IBR patients' quality of life was comparable to a group of age-matched women (n = 160) who underwent breast conserving surgery (p = 0.89). No patient experienced local recurrence (0%), distant metastases developed in 4.8% and disease related mortality was 2.2%. Post-operative morbidities included wound infection (11.8%), chronic pain (2.0%), capsular contracture (11%; 36% of whom had radiotherapy) and fat necrosis (14.1%). No patient experienced flap loss. CONCLUSIONS: IBR is a highly acceptable form of treatment for women requiring mastectomy. With high rates of patient satisfaction, low associated morbidity, and proven oncological safety, it is an appropriate recommendation for all women requiring mastectomy.