Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis:A Prospective Study of Interrater and Intrarater Reliability

INTRODUCTION: In patients with familial adenomatous polyposis, the Spigelman classification is recommended for staging and risk stratification of duodenal adenomatosis. Although the classification has been used for decades, it has never been formally validated. METHODS: We included consecutive FAP patients undergoing upper gastrointestinal endoscopic surveillance and evaluated the inter- and intrarater reliability of the Spigelman classification. RESULTS: The interrater reliability of the endoscopic parameters and the Spigelman classification was good and excellent, respectively. The intrarater reliability of the endoscopic parameters and the Spigelman classification was moderate and good, respectively. DISCUSSION: The results support continued use of the Spigelman classification as the primary end point for future studies and as key endoscopic performance measure

Laparoscopic Lavage Is Feasible and Safe for the Treatment of Perforated Diverticulitis With Purulent Peritonitis:The First Results From the Randomized Controlled Trial DILALA

To evaluate short-term outcomes of a new treatment for perforated diverticulitis with purulent peritonitis in a randomized controlled trial. BACKGROUND: Perforated diverticulitis with purulent peritonitis (Hinchey III) has traditionally been treated with surgery including colon resection and stoma (Hartmann procedure) with considerable postoperative morbidity and mortality. Laparoscopic lavage has been suggested as a less invasive surgical treatment. METHODS: Laparoscopic lavage was compared with colon resection and stoma in a randomized controlled multicenter trial, DILALA (ISRCTN82208287). Initial diagnostic laparoscopy showing Hinchey III was followed by randomization. Clinical data was collected up to 12 weeks postoperatively. Results: Eighty-three patients were randomized, out of whom 39 patients in laparoscopic lavage and 36 patients in the Hartmann procedure groups were available for analysis. Morbidity and mortality after laparoscopic lavage did not differ when compared with the Hartmann procedure. Laparoscopic lavage resulted in shorter operating time, shorter time in the recovery unit, and shorter hospital stay. CONCLUSIONS: In this trial, laparoscopic lavage as treatment for patients with perforated diverticulitis Hinchey III was feasible and safe in the short-term

Incisional hernia repair after caesarean section: a population based study

BACKGROUND Incisional hernias occur at surgical abdominal incision sites but the association with caesarean section (CS) has not been examined. AIM: To determine whether CS is a risk factor for incisional hernia repair. MATERIAL and METHODS: Population-based cohort study in Australia using linked birth and hospital data for women who gave birth from 2000 to 2011. (n=642,578) Survival analysis was used to explore the association between CS and subsequent incisional hernia repair. Analyses were adjusted for confounding factors including other abdominal surgery. The main outcome measure was surgical repair of an incisional hernia. RESULTS: 217,555 women (33.9%) had at least one CS and 1,554 (0.2%) had an incisional hernia repair. The frequency of incisional hernia repair in women who had ever had a caesarean section was 0.47%, compared to 0.12% in women who never had a caesarean section. After controlling for different follow up lengths and known explanatory variables, the adjusted hazard ratio (aHR) was 2.73 (95%CI 2.45-3.06, P <0.001). Incisional hernia repair risk increased with number of caesarean sections: women with two CS had a threefold increased risk of incisional hernia repair, which increased to 6 fold after five CS (aHR=6.29, 95%CI 3.99-9.93, P<0.001) compared to women with no CS. Prior abdominal surgery including other hernia repair also increased the risk of incisional hernia repair (all p<0.001). CONCLUSIONS: There was a strong association between maternal CS and subsequent incisional hernia repair, which increased as the number of CSs increased, but the absolute risk of incisional hernia repair was low.We thank the New South Wales (NSW) Ministry of Health for access to the population health data and the NSW Centre for Health Record Linkage for linking the data sets. This work was supported by an Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant (1001066). CLR is supported by a NHMRC Senior Research Fellowship (#APP1021025)

Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin

In skin penetration studies, HPLC-MS/MS analysis on extracts of heat-separated epidermis and dermis provides an estimate of the amount of drug penetrated. In this study, MALDI-MSI enabled qualitative skin distribution analysis of endogenous molecules and the drug molecule, tofacitinib and quantitative analysis of the amount of tofacitinib in the epidermis. The delivery of tofacitinib to the skin was investigated in a Franz diffusion cell using three different formulations (two oil-in-water creams, C1 and C2 and an aqueous gel). Further, in vitro release testing (IVRT) was performed and resulted in the fastest release of tofacitinib from the aqueous gel and the lowest from C2. In the ex vivo skin penetration and permeation study, C1 showed the largest skin retention of tofacitinib, whereas, lower retention and higher permeation were observed for the gel and C2. The quantitative MALDI-MSI analysis showed that the content of tofacitinib in the epidermis for the C1 treated samples was comparable to HPLC-MS/MS analysis, whereas, the samples treated with C2 and the aqueous gel were below LOQ. The study demonstrates that MALDI-MSI can be used for the quantitative determination of drug penetration in epidermis, as well as, to provide valuable information on qualitative skin distribution of tofacitinib

Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry

Background: Studies suggest that vascular invasion may be a superior prognostic marker compared with traditional selection criteria, e.g. Milan criteria. This study aimed to investigate the prognostic value of micro and macrovascular invasion in a large database material. Methods: Patients liver transplanted for HCC and cirrhosis registered in the European Liver Transplant Registry (ELTR) database were included. The association between the Milan criteria, Up-to-seven criteria and vascular invasion with overall survival and HCC specific survival was investigated with univariate and multivariate Cox regression analyses. Results: Of 23,124 patients transplanted for HCC, 9324 had cirrhosis and data on explant pathology. Patients without microvascular invasion, regardless of number and size of HCC nodules, had a five-year overall survival of 73.2%, which was comparable with patients inside both Milan and Up-to-seven criteria. Patients without macrovascular invasion had an only marginally reduced survival of 70.7% after five years. Patients outside both Milan and Up-to-seven criteria without micro or macrovascular invasion still had a five-year overall survival of 65.8%. Conclusion: Vascular invasion as a prognostic indicator remains superior to criteria based on size and number of nodules. With continuously improving imaging studies, microvascular invasion may be used for selecting patients for transplantation in the future

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study

BackgroundFraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population.MethodsFENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders.ResultsThe median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46–64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10–26) vs. 13 ppb (IQR 8–18.), p &lt; 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p &lt; 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50–5.15, p &lt; 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37–7.20, p = 0.007)].ConclusionThe liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation

A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery

The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed