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Oesophageal adenocarcinoma is often treated with chemotherapy before surgery. Here, the authors sequence cancer samples before and after chemotherapy and examine how the genome changes, focusing on changes in driver gene mutations and differential clonal evolution between good and poor responders.

The field of artificial intelligence is rapidly evolving, and there has been an interest in its use to predict the risk of lymph node metastasis in T1 colorectal cancer. Accurately predicting lymph node invasion may result in fewer patients undergoing unnecessary surgeries; conversely, inadequate assessments will result in suboptimal oncological outcomes. This narrative review aims to summarize the current literature on deep learning for predicting the probability of lymph node metastasis in T1 colorectal cancer, highlighting areas of potential application and barriers that may limit its generalizability and clinical utility.

Abstract Adenomyomas are benign lesions that are most frequently found in the gallbladder but can also be rarely found in the biliary tract. Although benign, they present close similarity to malignant lesions and thus deserve important clinical consideration. We present a case of a 74‐year‐old Chinese man who presented acutely with fever and painless obstructive jaundice. CT imaging showed a large calculus within a dilated common bile duct (CBD) and, despite undergoing an endoscopic retrograde cholangiopancreatography (ERCP) with stone clearance, there was a persistent filling defect that was adherent to the wall of the proximal common bile duct. His CA 19–9 was also significantly raised. Intraductal ultrasonography (IDUS) showed a polypoid mass with papillary‐like projections, and ERCP forcep biopsies were unable to exclude a lesion with neoplastic potential. The patient subsequently underwent cholecystectomy with open CBD excision and Roux‐en‐Y hepaticojejunostomy, and histology showed features consistent with a biliary adenomyoma.

Abstract Background This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. Methods Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils 1. Baseline HR23B expression was assessed by immunohistochemistry. Results Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3–4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2–5.4) in solid-organ cancers and 2.6 months (95%CI 1.2–5.6) in lymphomas. HR23B status did not predict response. Conclusions CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. Trial registration ClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013.

Background/Aims Proximal colorectal cancers (CRCs) account for up to half of CRCs. Sessile serrated lesions (SSLs) are precursors to CRC. Proximal location and presence of dysplasia in SSLs predict higher risks of progression to cancer. The prevalence of dysplasia in proximal SSLs (pSSLs) and clinical characteristics of dysplastic pSSLs are not well studied. Methods Endoscopically resected colonic polyps at our center between January 2016 and December 2017 were screened for pSSLs. Data of patients with at least one pSSL were retrieved and clinicopathological features of pSSLs were analysed. pSSLs with and without dysplasia were compared for associations. Results Ninety pSSLs were identified, 45 of which had dysplasia giving a prevalence of 50.0%. Older age (65.9 years vs. 60.1 years, p=0.034) was associated with the presence of dysplasia. Twelve pSSLs were 10 mm or larger. After adjusting for age, pSSLs ≥10 mm had an adjusted odds ratio of 5.98 (95% confidence interval, 1.21–29.6) of having dysplasia compared with smaller pSSLs. Conclusions In our cohort of pSSLs, the prevalence of dysplasia is high at 50.0% and is associated with lesion size ≥10 mm. Endoscopic resection for all proximal serrated lesions should be en bloc to facilitate accurate histopathological examination for dysplasia as its presence warrants shorter surveillance intervals.

Brunner’s gland hamartoma (BGH) is a rare sub-epithelial tumour of the duodenum, which may cause haemorrhagic or obstructive gastrointestinal symptoms. Their accurate histological diagnosis often remains elusive before resection. Although endoscopic ultrasonography (EUS) is considered an excellent modality to study lesions within the gastrointestinal wall, only a few reports have described endosonographic characteristics of BGHs. A reliable pre-resection diagnosis with EUS may not only allay fear of malignancy but may as well avert a major surgery for the patients. In this report, we present a rare case of a large BGH in a young female who presented with acute gastrointestinal bleeding. Here, the endosonographic features assuaged the concern for malignancy while aiding in complete and uneventful surgical resection of the tumour via a submucosal plane.

Endoscopic ultrasound (EUS) is now well established as an important tool in clinical practice. From purely diagnostic imaging, it has progressed to include tissue acquisition, which provided the basis for therapeutic procedures. Even as interventional EUS developed, there has been ongoing progress in EUS diagnostic capabilities due to improved imaging systems, better needles for tissue acquisition and development of enhanced imaging functions such as contrast harmonic EUS (CHEUS) and EUS elastography. EUS is well established for differentiation of subepithelial lesions, for T-staging of luminal gastrointestinal and pancreaticobiliary malignancies, for differentiation of benign pancreaticobiliary disorders and for diagnostic tissue acquisition, which can be achieved by EUS-guided fine needle aspiration or by EUS-guided fine needle biopsy using dedicated biopsy needles. This review briefly describes the technique of performing EUS and then discusses its clinical utility in terms of gastrointestinal cancer staging, the evaluation of pancreaticobiliary disorders and tissue acquisition. Enhanced imaging techniques such as CHEUS and EUS elastography are briefly reviewed.

The field of artificial intelligence is rapidly evolving, and there has been an interest in its use to predict the risk of lymph node metastasis in T1 colorectal cancer. Accurately predicting lymph node invasion may result in fewer patients undergoing unnecessary surgeries; conversely, inadequate assessments will result in suboptimal oncological outcomes. This narrative review aims to summarize the current literature on deep learning for predicting the probability of lymph node metastasis in T1 colorectal cancer, highlighting areas of potential application and barriers that may limit its generalizability and clinical utility. [ABSTRACT FROM AUTHOR]

Background and aimsNon-invasive assessment of portal hypertension is an area of unmet need. This proof of concept study aimed to evaluate the diagnostic accuracy of a multi-parametric magnetic resonance technique in the assessment of portal hypertension. Comparison to other non-invasive technologies was a secondary aim.MethodsT1 and T2* maps through the liver and spleen were acquired prior to trans-jugular liver biopsy and hepatic vein pressure gradient (HVPG) measurement. T1 measurements reflect changes in tissue water content, but this relationship is confounded by the presence of iron, which in turn can be quantified accurately from T2* maps. Data were analysed using LiverMultiScan (Perspectum Diagnostics, Oxford, UK) which applies an algorithm to remove the confounding effect of iron, yielding the "iron corrected T1" (cT1). Sensitivity, specificity, diagnostic values and area under the curve were derived for spleen cT1, liver cT1, transient elastography, and serum fibrosis scores. HVPG was the reference standard.ResultsNineteen patients (15 men) with median age 57 years were included. Liver disease aetiologies included non-alcoholic fatty liver disease (n = 9; 47%) and viral hepatitis (n = 4; 21%). There was strong correlation between spleen cT1 and HVPG (r = 0.69; p = 0.001). Other non-invasive biomarkers did not correlate with HVPG. Spleen cT1 had excellent diagnostic accuracy for portal hypertension (HVPG >5 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) with an area under the receiver operating characteristic curve of 0.92 for both.ConclusionSpleen cT1 is a promising biomarker of portal pressure that outperforms other non-invasive scores and should be explored further.

We report the case of a patient with severe systemic symptoms (weight loss, malaise, and anorexia), eosinophilic oesophagitis, and raised inflammatory markers coinciding with the use of lisinopril. The onset of symptoms occurred after the administration of lisinopril and resolved shortly after cessation of the medication. Despite thorough investigation, no other cause of the systemic inflammation and anaemia of chronic disease was found. “Drug rash with eosinophilia and systemic symptoms” (DRESSs) syndrome describes a potentially serious multiorgan inflammatory response to certain classes of drugs; this includes the use of ACE inhibitors. Although this patient did not meet strict criteria for DRESSs, the subacute inflammatory syndrome with eosinophilic organ infiltration bears similar features. ACE inhibitors should be considered in the differential diagnosis in patients with nonspecific systemic inflammation and anaemia of chronic disease where no other cause is found.

Colonoscopy with endoscopic resection of detected colonic adenomas interrupts the adenoma-carcinoma sequence and reduces the incidence of colorectal cancer and cancer-related mortality. In the past decade, there have been significant developments in instruments and techniques for endoscopic polypectomy. Guidelines have been formulated by various professional bodies in Europe, Japan and the United States, but some of the recommendations differ between the various bodies. An expert professional workgroup under the auspices of the Academy of Medicine, Singapore, was set up to provide guidance on the endoscopic management of colonic polyps in Singapore. A total of 23 recommendations addressed the following issues: accurate description and diagnostic evaluation of detected polyps; techniques to reduce the risk of post-polypectomy bleeding and delayed perforation; the role of specific endoscopic resection techniques; the histopathological criteria for defining endoscopic cure; and the role of surveillance colonoscopy following curative resection. [ABSTRACT FROM AUTHOR]

Colonoscopy is the reference standard procedure for the prevention and diagnosis of colorectal cancer, which is a leading cause of cancer-related deaths in Singapore. Artificial intelligence systems are automated, objective and reproducible. Artificial intelligence-assisted colonoscopy has recently been introduced into clinical practice as a clinical decision support tool. This review article provides a summary of the current published data and discusses ongoing research and current clinical applications of artificial intelligence-assisted colonoscopy. [ABSTRACT FROM AUTHOR]

Background/Aims: Proximal colorectal cancers (CRCs) account for up to half of CRCs. Sessile serrated lesions (SSLs) are precursors to CRC. Proximal location and presence of dysplasia in SSLs predict higher risks of progression to cancer. The prevalence of dysplasia in proximal SSLs (pSSLs) and clinical characteristics of dysplastic pSSLs are not well studied. Methods: Endoscopically resected colonic polyps at our center between January 2016 and December 2017 were screened for pSSLs. Data of patients with at least one pSSL were retrieved and clinicopathological features of pSSLs were analysed. pSSLs with and without dysplasia were compared for associations. Results: Ninety pSSLs were identified, 45 of which had dysplasia giving a prevalence of 50.0%. Older age (65.9 years vs. 60.1 years, p=0.034) was associated with the presence of dysplasia. Twelve pSSLs were 10 mm or larger. After adjusting for age, pSSLs ≥10 mm had an adjusted odds ratio of 5.98 (95% confidence interval, 1.21--29.6) of having dysplasia compared with smaller pSSLs. Conclusions: In our cohort of pSSLs, the prevalence of dysplasia is high at 50.0% and is associated with lesion size ≥10 mm. Endoscopic resection for all proximal serrated lesions should be en-bloc to facilitate accurate histopathological examination for dysplasia as its presence warrants shorter surveillance intervals. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD.Methods: We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed.Results: A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy.Conclusion: Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss the effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gastroenterology. Also cited are the gastrointestinal (GI) involvement and manifestations of infection, the temporal relationship between fever/respiratory symptoms and onset of GI symptoms, as well as the possible chronic or recurrent GI symptoms in GI patients like inflammatory bowel disease and irritable bowel syndrome.

Cholangiocarcinoma is the second most common hepatobiliary cancer following hepatocellular carcinoma, and 20% to 25% are intrahepatic. We describe 2 cases of intrahepatic cholangiocarcinoma arising within unusual and rare hepatic lesions, fibropolycystic liver disease form of ductal plate malformation and biliary adenofibroma, whose association with malignancy is rarely reported in the literature. [ABSTRACT FROM AUTHOR]

Introduction: Patients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging, it is now possible to characterize colonic lesions with higher levels of confidence than previously. We have reviewed the diagnostic yield of polyp-adjacent biopsies in IBD. Materials and Methods: A systematic search of our histopathology database revealed cases in which polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, and patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes. Results: Three hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. The median polyp size was 4 mm (range 1-45), and the predominant morphology was Paris 0-Is (n = 98, 32%). The histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), and was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%). Conclusion: The diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high-definition technology and chromoendoscopy, it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia. [ABSTRACT FROM AUTHOR]

Background and Aims: Histological remission and low faecal calprotectin are positive prognostic factors in ulcerative colitis [UC]. Intramucosal calprotectin [iMC], which can be readily determined by immunohistochemistry, has not so far been evaluated as a predictor of outcome in UC. We aimed to investigate the relationship between iMC and clinical, endoscopic, and histological measures of remission in UC, and the independent prognostic value of iMC. Methods: Ambulant patients with UC were recruited for a study comparing clinical activity indices. Sigmoidoscopy and biopsy were performed at the index visit. Clinical, endoscopic, and histological activity were scored and iMC semi-quantitatively measured using immunohistochemistry for the S100A8/9 heterodimer on colonic biopsies, scored as the mean number of positive cells in five high-power fields [HPF]. At the end of follow-up [6 years], data on steroid use, hospitalisation, and colectomy ['adverse outcomes'] were collected. Results: iMC was determined in 83 patients and 20 controls, and correlated with clinical, endoscopic, and histological activity [r = 0.51, 0.65, 0.53, p > 0.001, respectively]. iMC was lowest (median 2.4, interquartile range [IQR]: 5.2-5, p < 0.001) in patients with concordance between clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcome (hazard ratio [HR] 3.36, confidence interval [CI] 1.58, 7.15, p < 0.001). Only 53%, 33%, and 25% of patients in histological remission with iMC > 5 cells/HPF avoided an adverse outcome after 1, 3, and 6 years, respectively. Conclusions: iMC was lowest in patients with concordant clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcomes despite histological remission. Therefore iMC is a potentially useful independent marker of activity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to investigate the interobserver agreement for categorical and quantitative scores of liver fibrosis.Methods: Sixty-five consecutive biopsy specimens from patients with mixed liver disease etiologies were assessed by three pathologists using the Ishak and nonalcoholic steatohepatitis Clinical Research Network (NASH CRN) scoring systems, and the fibrosis area (collagen proportionate area [CPA]) was estimated by visual inspection (visual-CPA). A subset of 20 biopsy specimens was analyzed using digital imaging analysis (DIA) for the measurement of CPA (DIA-CPA).Results: The bivariate weighted κ between any two pathologists ranged from 0.57 to 0.67 for Ishak staging and from 0.47 to 0.57 for the NASH CRN staging. Bland-Altman analysis showed poor agreement between all possible pathologist pairings for visual-CPA but good agreement between all pathologist pairings for DIA-CPA. There was good agreement between the two pathologists who assessed biopsy specimens by visual-CPA and DIA-CPA. The intraclass correlation coefficient, which is equivalent to the κ statistic for continuous variables, was 0.78 for visual-CPA and 0.97 for DIA-CPA.Conclusions: These results suggest that DIA-CPA is the most robust method for assessing liver fibrosis followed by visual-CPA. Categorical scores perform less well than both the quantitative CPA scores assessed here. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis. Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden. Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] > 10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk. Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy. [ABSTRACT FROM AUTHOR]

Background Testing for BRAF mutations in colorectal carcinoma (CRC) is important in the screening pathway for Lynch syndrome and is of prognostic value to guide management. This is a diagnostic accuracy study of the Idylla system, a novel and automated alternative PCR system. Methods 100 consecutive formalin-fixed, paraffin-embedded CRC resection cases were tested for BRAF mutations using the Idylla automated platform and compared with standard (Cobas) PCR. Results The sensitivity of the Idylla BRAF test was 100% and the specificity was 96%. Only one discordant Idylla positive/standard PCR negative result occurred and on Droplet Digital PCR demonstrated a mutation not identified by traditional PCR in this case. Conclusion This study has validated the Idylla system for BRAF testing in CRC and demonstrated a possibly greater sensitivity, in addition to cost effectiveness and shorter turnaround time, when compared with standard PCR. [ABSTRACT FROM AUTHOR]

Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumor progression.Myofibroblasts previously have been distinguished from normal fibroblasts mostly by the expression of α smooth muscle actin (αSMA). We now have identified AOC3 (amine oxidase, copper containing 3), a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast- reacting mAb PR2D3. The normal and tumor tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by nonenzymatic procedures. Whole-genome microarray mRNA-expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly differentially expressed in these two cell types: NKX2-3 and LRRC17 in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. TGFβ substantially down-regulated AOC3 expression in myofibroblasts but in skin fibroblasts it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and increased expression of the fibroblast-associated gene SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3, and other markers, are a distinctly different cell type from TGFβ-activated fibroblasts. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs. [ABSTRACT FROM AUTHOR]

The development of hepatocyte cell models that represent fatty acid partitioning within the human liver would be beneficial for the study of the development and progression of nonalcoholic fatty liver disease (NAFLD). We sought to develop and characterize a novel human liver cell line (LIV0APOLY) to establish a model of lipid accumulation using a physiological mixture of fatty acids under low- and high-glucose conditions. LIV0APOLY cells were compared with a well-established cell line (HepG2) and, where possible, primary human hepatocytes. LIV0APOLY cells were found to proliferate and express some mature liver markers and were wild type for the PNPLA3 (rs738409) gene, whereas HepG2 cells carried the Ile148Met variant that is positively associated with liver fat content. Intracellular triglyceride content was higher in HepG2 than in LIV0APOLY cells; exposure to high glucose and/or exogenous fatty acids increased intracellular triglyceride in both cell lines. Triglyceride concentrations in media were higher from LIV0APOLY compared with HepG2 cells. Culturing LIV0APOLY cells in high glucose increased a marker of endoplasmic reticulum stress and attenuated insulin-stimulated Akt phosphorylation whereas low glucose and exogenous fatty acids increased AMPK phosphorylation. Although LIV0APOLY cells and primary hepatocytes stored similar amounts of exogenous fatty acids as triglyceride, more exogenous fatty acids were partitioned toward oxidation in the LIV0APOLY cells than in primary hepatocytes. LIV0APOLY cells offer the potential to be a renewable cellular model for studying the effects of exogenous metabolic substrates on fatty acid partitioning; however, their usefulness as a model of lipoprotein metabolism needs to be further explored. [ABSTRACT FROM AUTHOR]

Background Traditional serrated adenoma (TSA) is a very characteristic type of serrated polyp that has a predilection for the left colon. Recent molecular advances have shown two molecular phenotypes of TSA: one associated with BRAF mutations and the other with KRAS mutations. The former is associated with hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs), while the latter is associated with more conventional adenomatous dysplasia. Aims The association of TSAs with so-called precursor lesions (HPs and SSAs) is not well recognised and the purpose of this study was to explore the coexistent presence of HPs, SSAs and adenomatous polyps within a large cohort of TSAs. Methods In total 149 TSAs were examined for the presence of HP, SSA and adenomatous polyps. Results Seen in 83 men and 65 women ranging in age from 32 to 89 years and 127 were left sided with 22 in the right colon. Seventy-eight of the 149 TSAs showed evidence of another polyp (52.34%): 32 were low-grade tubular/tubulovillous adenomas (TAs/TVAs; 41%), 28 were HPs (36%) and 18 were SSAs (23%). Eleven of the 22 right-sided TSAs were associated with a precursor lesion (1 HP and 7 SSA). In addition, five TSAs showed more than one polyp type: TSA with TA/TVA and HP (3); TSA with TA/TVA and SSA (2). The TAs/TVAs were adjacent to the TSA but occurred as a separate discrete polyp, while HPs and SSAs were intermingled with the TSA and present at the base and surface of the lesion. Conclusions More than 50% of TSAs are associated with a precursor lesion or adjacent TA/TVA. Their recognition is important as this may have surveillance and management ramifications. [ABSTRACT FROM AUTHOR]

Aim The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P). Methods A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America. Results Forty-three of 45 pathologists agreed to participate. The vast majority (88%) had a special interest in gastrointestinal (GI) pathology, had great exposure to GI polyps in general with 40% diagnosing SSA/P at least once a week if not more, abnormal architecture was thought by all participants to be histologically diagnostic, and 11% would make the diagnosis if a single diagnostic histological feature was present in one crypt only, while a further 19% would diagnose SSA/P in one crypt if more than one diagnostic feature was present. The vast majority agreed that deeper sections were useful and 88% did not feel proliferation markers were useful. More than one-third did not know whether, or did not feel that, their clinicians were aware of the implications of SSA/P. Conclusions 98% of pathologists surveyed are aware that SSA/P is a precursor lesion to colorectal cancer, the majority agree on diagnostic criteria, and a significant number feel that there needs to be greater communication and awareness among pathologists and gastroenterologists about SSA/P. [ABSTRACT FROM AUTHOR]

Aim An audit of serrated polyps diagnosed over a 4-year period: 2009 to 2012 was undertaken to ascertain the reporting trends of sessile serrated polyps (SSP). Methods All right sided hyperplastic polyps (HP) proximal to the splenic flexure and all polyps designated SSP were retrieved from the study period. Three pathologists blinded to the original diagnosis re-examined the slides. Recent American College of Gastroenterology guidelines for the diagnosis of SSP was utilised. Results No cases of SSP were diagnosed in 2009. In 2010, 32 right-sided cases were encountered, 83 confirmed in 2011 and 134 confirmed in 2012. The vast majority of these were right-sided. With regards to right-sided HP that were re-classified as SSP the data is as follows: 20 of 66 in 2009 (30%); 58 of 91 in 2010 (64%); 42 of 106 (40%) in 2011 and 69 of 206 in 2012 (33%). Conclusions This study has demonstrated an almost exponential increase in the diagnosis of SSP over a 4-year period. In addition, 30 to 64% of right-sided HP were re-classified as SSP over the 4-year period suggesting that greater awareness of the diagnostic criteria for SSP is required. SSP is an important precursor lesion in the serrated pathway of colorectal cancer. Its recognition is important for surveillance and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aims: Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice. Methods arid results: A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1-3 cytokeratin-immunostained, whole-slide digital scans from 50 pT1-pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants' experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding-positive cases with all methods compared to H&E-stained slides, but did not influence agreement levels. Conclusions: An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement. [ABSTRACT FROM AUTHOR]

Aims With changing indications for performing medical liver biopsies, we aimed to develop a tool to allow pathologists to evaluate the current usefulness, value and impact of their medical liver biopsy service. Methods We designed and piloted a questionnaire-based clinico-pathological audit for medical liver biopsies. Results The audit tool was simple to implement and provided useful information about our service. Hepatologists felt that 96% of reports were clinically useful. 56% of biopsies confirmed clinical diagnoses, 46% helped differentiate between diagnoses and 42% were able to exclude possible diagnoses. 74% resulted in a change of management and 27% of liver biopsies resulted in a diagnosis which was not clinically suspected. Conclusions We demonstrate the usefulness of an audit tool in providing evidence of the value of the liver pathology service in a large UK regional centre. [ABSTRACT FROM AUTHOR]

The routine use of 18F-fluorodeoxyglucose-positron emission tomography (PET)/ computed tomography scans for staging and assessment of treatment response for cancer has resulted in a large number of thyroid abnormalities being detected as incidental findings ("incidentalomas"). Since most PET/CT scans are performed in the setting of a known nonthyroid malignancy, the need for "incidentalomas" to be further investigated and managed depends on the stage, prognosis, and current treatment plan for the known malignancy. We present a case describing the management of an incidental F-fluorodeoxyglucose-avid thyroid nodule detected in a patient with known metastatic colorectal cancer. On the basis of this case, we discuss the management of incidental PET-detected thyroid nodules in patients with metastatic cancer. Thyroid "incidentalomas" must be seen in the context of the prognosis and treatment plan for the known malignancy. [ABSTRACT FROM AUTHOR]

Medical liver biopsy reporting is challenging, and maintaining competency with small case numbers is potentially difficult. This study evaluates the discrepancies identified in cases referred to a specialist centre between the specialist reports and those of the referring general departments. Fifty consecutive recently referred cases were selected, and original and final reports were compared. Discrepancies were classified as per the Royal College of Pathologists guidelines and scored for potential clinical impact. The overall rate of discrepancy was 38% with most of these due to differences in interpretation of morphology. Seventy per cent of these discrepancies were judged to have major clinical impact (26% of all referred cases). This study highlights the need for robust systems of quality control of liver biopsies in a general setting. [ABSTRACT FROM AUTHOR]

Needle core biopsy is a key tool in diagnosis and assessment of many medical liver diseases, but there is evidence that the combination of small size of the specimen obtained and the patchy nature of many of these diseases can result in misdiagnosis or incorrect staging. The Royal College of Pathologists has therefore published guidelines for assessment of adequacy. To assess whether these guidelines were being observed, we reviewed cases reported in our department over a 15-year period. Results showed that only 19.8% of cores would be considered adequate, 56.4% were suboptimal and 23.8% were inadequate. We discuss the issues around recommendations on the minimum size of liver biopsies, potential factors limiting biopsy size and whether further refinement of the guidelines for adequacy is required. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 79-year old woman with a 2-month history of a right breast lump linked with blood-stained nipple discharge. The patient was diagnosed with a primary osteogenic sarcoma of the breast, which is inferred to be a rare tumor originating from totipotent mesenshymal cells of breast stroma. The risk factor of primary osteosarcoma of the breast is highlighted.

Barrett’s oesophagus is associated with an increased risk of oseophageal cancer, but its cell of origin is unclear. Here the authors show, using single-cell RNA sequencing of biopsies from six patients and two unaffected subjects, that cells in Barrett’s oesophagus show a transcriptional profile that is similar to that of cells in oesophageal submucosal glands.

The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

Background and study aims Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

Background and aims: Radical endoscopic excision of Barrett’s epithelium performing 4 – 6 endoscopic resections during the same endoscopic session results in complete Barrett’s eradication but has a high stricture rate (40 – 80 %). Therefore radiofrequency ablation is preferred after endoscopic mucosal resection (EMR) of visible nodules. We investigated the clinical outcome of non-radical, stepwise endoscopic mucosal resection with a maximum of two endoscopic resections per endoscopic session. Methods: We analysed our prospectively maintained database of patients undergoing esophageal EMR for early neoplasia in Barrett’s esophagus from 2009 to 2014. EMR was performed using a maximum of two band ligation mucosectomies per endoscopic session; thereafter, follow-up was 3-monthly and EMR was repeated as required for Barrett’s eradication. Results: In total, 118 patients underwent staging EMR for early Barrett’s neoplasia. Subsequently, 27 patients underwent surgery/chemotherapy due to deep submucosal or more advanced tumor stages or were managed conservatively. The remaining 91 patients with high grade dysplasia (48), intramucosal (38) or submucosal cancer (5) in the resected nodule underwent further endoscopic therapy with a mean follow-up of 24 months. Remission of dysplasia/neoplasia was achieved in 95.6 % after 12 months treatment. Stepwise endoscopic Barrett’s resection resulted in complete Barrett’s eradication in 36/91 patients (39.6 %) in a mean of four sessions; 40/91 patients (44.0 %) had a short circumferential Barrett’s segment (

There is a 10% shortfall in the number of proximal colorectal cancer cases detected by the UK Bowel Cancer Screening Programme and the actual number of UK-registered proximal colorectal cancers. Sessile serrated adenomas/polyps (SSA/P) are common premalignant lesions in the proximal colon and are notoriously difficult to spot endoscopically. Missed or dismissed SSA/Ps might contribute to this UK proximal colon cancer detection disparity. In Oxfordshire, a service evaluation audit and histological review has shown a linear increase in the detection rate of these lesions over the past 4 years. This is the result of increased endoscopist and pathologist awareness of these lesions and improved interdisciplinary communication. This is the result of increased endoscopist and pathologist awareness of these lesions, together with improved interdisciplinary communication, and we predict that this will lead to a comparable detection increase nationwide. Ongoing surveillance of an increasing number of these premalignant lesions could become a significant endoscopic resource requirement once UK guidelines on serrated lesion follow up are established. [ABSTRACT FROM AUTHOR]

Background: In histopathology, the quantitative assessment of various morphologic features is based on methods originally conceived on specific areas observed through the microscope used. Failure to reproduce the same reference field of view using a different microscope will change the score assessed. Visualization of a digital slide on a screen through a dedicated viewer allows selection of the magnification. However, the field of view is rectangular, unlike the circular field of optical microscopy. In addition, the size of the selected area is not evident, and must be calculated. Materials and Methods: A digital slide morphometric system was conceived to reproduce the various methods published for assessing tumor budding in colorectal cancer. Eighteen international experts in colorectal cancer were invited to participate in a web-based study by assessing tumor budding with five different methods in 100 digital slides. Results: The specific areas to be tested by each method were marked by colored circles. The areas were grouped in a target-like pattern and then saved as an .xml file. When a digital slide was opened, the .xml file was imported in order to perform the measurements. Since the morphometric tool is composed of layers that can be freely moved on top of the digital slide, the technique was named digital slide dynamic morphometry. Twelve investigators completed the task, the majority of them performing the multiple evaluations of each of the cases in less than 12 minutes. Conclusions: Digital slide dynamic morphometry has various potential applications and might be a useful tool for the assessment of histologic parameters originally conceived for optical microscopy that need to be quantified.