Mercy University Hospital

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

OBJECTIVE: The commensal microbiota, host immunity and metabolism participate in a signalling network, with diet influencing each component of this triad. In addition to diet, many elements of a modern lifestyle influence the gut microbiota but the degree to which exercise affects this population is unclear. Therefore, we explored exercise and diet for their impact on the gut microbiota. DESIGN: Since extremes of exercise often accompany extremes of diet, we addressed the issue by studying professional athletes from an international rugby union squad. Two groups were included to control for physical size, age and gender. Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing. Each participant completed a detailed food frequency questionnaire. RESULTS: As expected, athletes and controls differed significantly with respect to plasma creatine kinase (a marker of extreme exercise), and inflammatory and metabolic markers. More importantly, athletes had a higher diversity of gut micro-organisms, representing 22 distinct phyla, which in turn positively correlated with protein consumption and creatine kinase. CONCLUSIONS: The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.

INTRODUCTION: The prevalence of frailty at population level is unclear. We examined this in population-based studies, investigating sources of heterogeneity. METHODS: PubMed, Embase, CINAHL and Cochrane Library databases were searched for observational population-level studies published between 1 January 1998 and 1 April 2020, including individuals aged ≥50 years, identified using any frailty measure. Prevalence estimates were extracted independently, assessed for bias and analysed using a random-effects model. RESULTS: In total, 240 studies reporting 265 prevalence proportions from 62 countries and territories, representing 1,755,497 participants, were included. Pooled prevalence in studies using physical frailty measures was 12% (95% CI = 11-13%; n = 178), compared with 24% (95% CI = 22-26%; n = 71) for the deficit accumulation model (those using a frailty index, FI). For pre-frailty, this was 46% (95% CI = 45-48%; n = 147) and 49% (95% CI = 46-52%; n = 29), respectively. For physical frailty, the prevalence was higher among females, 15% (95% CI = 14-17%; n = 142), than males, 11% (95% CI = 10-12%; n = 144). For studies using a FI, the prevalence was also higher in females, 29% (95% CI = 24-35%; n = 34) versus 20% (95% CI = 16-24%; n = 34), for males. These values were similar for pre-frailty. Prevalence increased according to the minimum age at study inclusion. Analysing only data from nationally representative studies gave a frailty prevalence of 7% (95% CI = 5-9%; n = 46) for physical frailty and 24% (95% CI = 22-26%; n = 44) for FIs. CONCLUSIONS: Population-level frailty prevalence varied by classification and sex. Data were heterogenous and limited, particularly from nationally representative studies making the interpretation of differences by geographic region challenging. Common methodological approaches to gathering data are required to improve the accuracy of population-level prevalence estimates. PROTOCOL REGISTRATION: PROSPERO-CRD42018105431.

OBJECTIVE: A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. DESIGN: We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples ('ON' and 'OFF' the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. RESULTS: The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. CONCLUSIONS: CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.

AIMS: Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour 'budding' and attempted to establish its appropriate criteria. METHODS AND RESULTS: A total of 638 rectal cancer specimens was examined. We defined tumour 'budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of 'budding' foci within a microscopic field of x 250. Rectal cancer with high-grade 'budding' (>or= 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5-year survival rates (40.7%) than patients with low-grade 'budding' (84.0%) (P < 0.0001). Based on multivariate analysis, tumour 'budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two-graded tumour 'budding' in the intraobserver study was 0.84. CONCLUSIONS: Because of its value as a prognostic indicator and its reproducibility, tumour 'budding' would be a good index to estimate the aggressiveness of rectal cancer.

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2) CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS(+)) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS(+) B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial-host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts.

Errors and discrepancies in radiology practice are uncomfortably common, with an estimated day-to-day rate of 3-5% of studies reported, and much higher rates reported in many targeted studies. Nonetheless, the meaning of the terms "error" and "discrepancy" and the relationship to medical negligence are frequently misunderstood. This review outlines the incidence of such events, the ways they can be categorized to aid understanding, and potential contributing factors, both human- and system-based. Possible strategies to minimise error are considered, along with the means of dealing with perceived underperformance when it is identified. The inevitability of imperfection is explained, while the importance of striving to minimise such imperfection is emphasised. TEACHING POINTS: • Discrepancies between radiology reports and subsequent patient outcomes are not inevitably errors. • Radiologist reporting performance cannot be perfect, and some errors are inevitable. • Error or discrepancy in radiology reporting does not equate negligence. • Radiologist errors occur for many reasons, both human- and system-derived. • Strategies exist to minimise error causes and to learn from errors made.

An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

Introduction: Intravenous(IV) immunoglobulin(Ig) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Methods: Sepsis was induced by cecal ligation perforation(CLP) in rats. The animals were divided into five groups; sham, control, CLP + saline, CLP + immunoglobulin G IgG(250 mg/kg,iv), and CLP + immunoglobulins enriched with immunoglobulin M-IgGAM(250 mg/kg,iv). Blood and brain samples were taken in two sets of experiments after CLP to see the early(24 hrs) and late(10 days) effects of treatment. Total complement activity, complement 3(C3) and soluble complement C5b-9 levels were measured in sera of rats using ELISA-based methods. Cerebral complement content was analyzed by Western Blot. Immune cell infiltration and gliosis were examined by immunohistochemistry using cluster of differentiation 3, CD4, CD8, CD11b, CD19 and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining and Western Blot-based semi-quantitative evaluation of brain homogenates by bax and bcl-2 antibodies. Results: IV IgG and IgGAM administration significantly reduced systemic complement activity but increased serum C3 and soluble C5b-9 levels. Likewise, Western Blot data showed slightly increased C5b-9 expression and significantly reduced C1q expression in brain samples of IgGAM-treated but not IgG-treated septic rats especially in the first day of administration. No cerebral cellular infiltrates were observed in treated and non-treated septic rats. By contrast, IV IgG and IgGAM treatment induced considerable amelioration in glial cell proliferation which was increased in non-treated rats. IgG and IgGAM treated rats exhibited significantly reduced numbers of apoptotic neurons and cerebral expression levels of bax and bcl-2 as compared to nontreated rats. Conclusions: We suggest that IV IgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might be suppressing classical complement pathway by reducing C1q expression.

OBJECTIVE: To define the incidence of problematic common bile duct calculi in patients undergoing laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: In patients selected for laparoscopic cholecystectomy, the true incidence of potentially problematic common bile duct calculi and their natural history has not been determined. We evaluated the incidence and early natural history of common bile duct calculi in all patients undergoing laparoscopic cholecystectomy with intraoperative and delayed postoperative cholangiography. METHODS: Operative cholangiography was attempted in all patients. In those patients in whom a filling defect was noted in the bile duct, the fine bore cholangiogram catheter was left securely clipped in the cystic duct for repeated cholangiography at 48 hours and at approximately 6 weeks postoperatively. RESULTS: Operative cholangiography was attempted in 997 consecutive patients and was accomplished in 962 patients (96%). Forty-six patients (4.6%) had at least one filling defect. Twelve of these had a normal cholangiogram at 48 hours (26% possible false-positive operative cholangiogram) and a further 12 at 6 weeks (26% spontaneous passage of calculi). Spontaneous passage was not determined by either the number or size of calculi or by the diameter of the bile duct. Only 22 patients (2.2% of total population) had persistent common bile duct calculi at 6 weeks after laparoscopic cholecystectomy and retrieved by endoscopic retrograde cholangiopancreatography. CONCLUSIONS: Choledocholithiasis occurs in 3.4% of patients undergoing laparoscopic cholecystectomy but more than one third of these pass the calculi spontaneously within 6 weeks of operation and may be spared endoscopic retrograde cholangiopancreatography. Treatment decisions based on assessment by operative cholangiography alone would result in unnecessary interventions in 50% of patients who had either false positive studies or subsequently passed the calculi. These data support a short-term expectant approach in the management of clinically silent choledocholithiasis in patients selected for LC.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).

BACKGROUND: The standard approach to generalized peritonitis due to perforated diverticulitis involves open surgery and diversion of faecal content. This study assessed the feasibility of laparoscopic peritoneal lavage. METHODS: A prospective multi-institutional study of 100 patients was undertaken. All consenting patients with perforated diverticulitis causing generalized peritonitis underwent attempted laparoscopic peritoneal lavage. The degree of peritonitis, according to the Hinchey grading system, was recorded. Primary endpoints were operative success and resolution of symptoms. RESULTS: Patients had a median age of 62.5 (range 39-94) years, a male : female ratio of 2 : 1 and a median American Society of Anesthesiologists grade of III (range II-V). Eight patients with grade 4 diverticulitis had conversion to an open Hartmann's procedure. The remaining 92 patients were managed by laparoscopic lavage, with morbidity and mortality rates of 4 and 3 per cent respectively. Two patients required postoperative intervention for a pelvic abscess. Only two patients re-presented with diverticulitis at a median follow up of 36 (range 12-84) months. CONCLUSION: Laparoscopic management of perforated diverticulitis with generalized peritonitis is feasible, with a low recurrence risk in the short term.

This is a condensed summary of an international multisociety statement on ethics of artificial intelligence (AI) in radiology produced by the ACR, European Society of Radiology, RSNA, Society for Imaging Informatics in Medicine, European Society of Medical Imaging Informatics, Canadian Association of Radiologists, and American Association of Physicists in Medicine. AI has great potential to increase efficiency and accuracy throughout radiology, but it also carries inherent pitfalls and biases. Widespread use of AI-based intelligent and autonomous systems in radiology can increase the risk of systemic errors with high consequence and highlights complex ethical and societal issues. Currently, there is little experience using AI for patient care in diverse clinical settings. Extensive research is needed to understand how to best deploy AI in clinical practice. This statement highlights our consensus that ethical use of AI in radiology should promote well-being, minimize harm, and ensure that the benefits and harms are distributed among stakeholders in a just manner. We believe AI should respect human rights and freedoms, including dignity and privacy. It should be designed for maximum transparency and dependability. Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future. The radiology community should start now to develop codes of ethics and practice for AI that promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes. This article is a simultaneous joint publication in Radiology, Journal of the American College of Radiology, Canadian Association of Radiologists Journal, and Insights into Imaging. Published under a CC BY-NC-ND 4.0 license. Online supplemental material is available for this article.

Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.

Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma.

Background: The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL‐10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL‐10 knockout mice using the probiotic Lactobacillus salivarius ssp. s alivarius UCC118. Aim: To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL‐10 knockout mice. Methods: Twenty IL‐10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens , bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed. Results: L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls ( P &lt; 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice ( P &lt; 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice. Conclusion: In this placebo controlled trial, modification of enteric flora in IL‐10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.

We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin. Chemosensitive cell lines exhibited apoptosis whereas chemoresistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PCD). Cell populations that respond with autophagy are more resistant and will recover following withdrawal of the chemotherapeutic agents. Specific inhibition of early autophagy induction with siRNA targeted to Beclin 1 and ATG7 significantly enhanced the effect of 5-FU and reduced the recovery of drug-treated cells. Pharmacological inhibitors of autophagy were evaluated for their ability to improve chemotherapeutic effect. The PtdIns 3-kinase inhibitor 3-methyladenine did not enhance the cytotoxicity of 5-FU. Disruption of lysosomal activity with bafilomycin A 1 or chloroquine caused extensive vesicular accumulation but did not improve chemotherapeutic effect. These observations suggest that an autophagic response to chemotherapy is a survival mechanism that promotes chemoresistance and recovery and that selective inhibition of autophagy regulators has the potential to improve chemotherapeutic regimes. Currently available indirect inhibitors of autophagy are, however, ineffective at modulating chemosensitivity in these esophageal cancer cell lines.

OBJECTIVES: The management of incidentally detected gallbladder polyps on radiological examinations is contentious. The incidental radiological finding of a gallbladder polyp can therefore be problematic for the radiologist and the clinician who referred the patient for the radiological examination. To address this a joint guideline was created by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). METHODS: A targeted literature search was performed and consensus guidelines were created using a series of Delphi questionnaires and a seven-point Likert scale. RESULTS: A total of three Delphi rounds were performed. Consensus regarding which patients should have cholecystectomy, which patients should have ultrasound follow-up and the nature and duration of that follow-up was established. The full recommendations as well as a summary algorithm are provided. CONCLUSIONS: These expert consensus recommendations can be used as guidance when a gallbladder polyp is encountered in clinical practice. KEY POINTS: • Management of gallbladder polyps is contentious • Cholecystectomy is recommended for gallbladder polyps >10 mm • Management of polyps <10 mm depends on patient and polyp characteristics • Further research is required to determine optimal management of gallbladder polyps.

A role for the intestinal microbiota is routinely cited as a potential aetiological factor in colorectal cancer initiation and progression. As the majority of bacteria in the gut are refractory to culture we investigated this ecosystem in subjects with colorectal cancer and with adenomatous polyposis who are at high risk of developing colorectal cancer, using culture-independent methods. Twenty colorectal cancer and 20 polypectomized volunteers were chosen for this analysis. An exploration of the diversity and temporal stability of the dominant bacteria and several bacterial subgroups was undertaken using 16S rRNA gene denaturing gradient gel electrophoresis and ribosomal intergenic spacer analysis (RISA). Metabonomic analysis of the distal gut microbiota's environment was also undertaken. A significantly reduced temporal stability and increased diversity for the microbiota of subjects with colorectal cancer and polyposis was evident. A significantly increased diversity of the Clostridium leptum and C. coccoides subgroups was also noted for both disease groups. A clear division in the metabonome was observed for the colorectal cancer and polypectomized subjects compared with control volunteers. The intestinal microbiota and their metabolites are significantly altered in both colorectal cancer and polypectomized subjects compared with controls.