Comparison between open repair with suprarenal clamping and fenestrated endovascular repair for unruptured juxtarenal abdominal aortic aneurysms.

BACKGROUND: Management of juxtarenal abdominal aortic aneurysms (JRAAA) remains challenging. Both open surgical and endovascular options are feasible, however, there is lack of level 1 evidence to support one modality over the other. Operative interventions frequently necessitate either open repair with a suprarenal clamp positioning (ORSRC) or complex endovascular repair (EVAR) with fenestrated (fEVAR) or parallel stent grafts (chEVAR). The aim of this study was to compare the renal function deterioration and mortality between ORSRC and fEVAR in patients who were operated on for unruptured JRAAA at a tertiary centre. METHODS: A retrospective review of prospectively collected data was performed on patients who underwent repair for unruptured JRAAA between March 2008 and October 2019. Analysis of short and mid-term outcomes after ORSRC (occlusion of the aorta above at least one of the main renal arteries) and fEVAR was conducted. Patients who underwent open repair of JRAAA with an infrarenal clamp were excluded. Procedural data as well as data regarding complications was noted. Acute kidney injury (AKI) and chronic kidney disease were defined using the KDIGO criteria (Kidney Disease: Improving Global Outcomes). Renal impairment data up to 1 year and mortality up to 5 years was recorded. RESULTS: During the study period, 162 patients who underwent JRAAA repair met the inclusion criteria (60.5% of them having ORSRC). Approximately, 85.8% of the population were males (80.6% in the open group compared to 93.7% in the endovascular group; P=0.019). The mean age for patients in the open group was 74.0 (SD=±5.5) years compared to 76.1 (SD=±7.2) years in the fEVAR group (P=0.035). More patients in the ORSRC group were symptomatic (18.4% versus 6.3% in the fEVAR group; P=0.028) and they also had larger aneurysms compared to the fEVAR group (66.9 (±12.7) mm versus 62.6 (±8.6) mm, respectively; P=0.021). In the ORSRC group, all patients required suprarenal clamping, with clamping above only one of the main renal arteries carried out in 43 patients (44.3%) of cases. At baseline, 37.0% and 44.5% of patients had CKD stage 3 or worse in ORSRC and fEVAR groups, respectively (P=0.759). Approximately 47.6% of patients having ORSRC had evidence of acute renal impairment on post-operative day 3 compared to 12.7% of those in the endovascular group (p<0.05). By 9-12 months, 54.6% of patients in the OR group had a CKD stage of 3 or worse, compared to 62.1% of patients in the fEVAR group (Pearson χ2, P=0.713). The median total length of stay (LOS) was 10 days for OR versus 6 days for fEVAR (p<0.05). Patients having fEVAR were more likely to require re-intervention (26.6% v/s 10.2%; P=0.006). Mortality at 30 days was 8.2% for ORSRC against 7.8% for complex EVAR (P=0.936). The corresponding figures at 1 and 5 years were 10.2% and 25.5% for ORSRC compared to 14.1% and 32.8% (P=0.456 and P=0.314, respectively). CONCLUSIONS: In the context of JRAAA, patients receiving fEVAR procedures tended to be older, with a smaller diameter aneurysm. Postoperatively, fEVAR was associated with shorter hospitalisation and less risk of AKI in the immediate post-operative course, but had a greater likelihood of requiring re-intervention over time. Both interventions had similar rate of renal function deterioration at 1 year and the five year mortality rate was comparable.

Transition to quantitative faecal immunochemical testing from guaiac faecal occult blood testing in a fully rolled-out population-based national bowel screening programme.

OBJECTIVE: Faecal immunochemical tests (FIT) are replacing guaiac faecal occult blood tests (FOBT) in colorectal cancer (CRC) screening. Data from the first year of FIT screening were compared with those from FOBT screening and assumptions based on a pilot evaluation of FIT. DESIGN: Data on uptake, positivity, positive predictive value (PPV) for CRC and higher-risk adenoma from participants in the first year of the FIT-based Scottish Bowel Screening Programme (n=919 665), with a threshold of 80 µg Hb/g faeces, were compared with those from the penultimate year of the FOBT-based programme (n=862 165) and those from the FIT evaluation (n=66 225). RESULTS: Overall, uptake of FIT was 63.9% compared with 56.4% for FOBT. Positivity was 3.1% and 2.2% with FIT and FOBT; increases were seen in both sexes, and across age range and deprivation. More CRC and adenomas were detected by FIT, but the PPV for CRC was less (5.2% with FIT and 6.4% with FOBT). However, for higher-risk adenoma, PPV was greater with FIT (24.3% with FIT and 19.3% with FOBT). In the previous FIT evaluation, uptake was 58.5% with FIT compared with 54.0% with FOBT; positivity was 2.5% with FIT and 2.0% with FOBT. CONCLUSION: Transition to FIT from FOBT produced higher uptake and positivity with lower PPV for CRC and higher PPV for adenoma. The FIT pilot evaluation underestimated uptake and positivity. Introducing FIT at the same threshold as the evaluation caused a 67.2% increase in colonoscopy demand instead of a predicted 10%.

Case report: cystic artery pseudoaneurysm presenting as a massive per rectum bleed treated with percutaneous coil embolization.

BACKGROUND: Cystic artery pseudoaneurysms are rare. It usually occurs as a complication of laparoscopic cholecystectomy, but can arise uncommonly as a complication of acute cholecystitis. Ruptured cystic artery aneurysms present with haemobilia, intraperitoneal or upper gastrointestinal bleeding. We present an unusual case of cystic artery aneurysm presenting as a massive lower gastrointestinal bleed. CASE PRESENTATION: A 47-year-old man was admitted with a thoracic abscess and was noted incidentally on CT to have acute cholecystitis. Subsequently the patient then presented with massive fresh PR bleeding. This was found on CT to be the result of a cystic artery pseudoaneurysm with associated gallbladder fistulation to the hepatic flexure, secondary to cholecystitis. The patient was treated with coil embolisation of the cystic artery made a full recovery and was discharged with a view to performing an elective cholecystectomy. CONCLUSION: Cystic artery pseudoaneurysm is a rare complication of cholecystitis which can present as massive lower gastrointestinal haemorrhage secondary to cholecystocolic fistula. Percutaneous embolization is a safe and effective treatment in the acute phase.

Nivolumab and immune-mediated colitis.

Nivolumab is associated with a number of immune-regulated adverse events, including immune-mediated colitis and may present following the discontinuation of treatment. Current guidance suggests lower doses of methylprednisolone; however, we described faster resolution of the patient's symptoms compared to previous reported cases, using higher dosing, thereby minimizing hospitalization.

Occult blood in faeces is associated with all-cause and non-colorectal cancer mortality.

OBJECTIVE: An association between detectable faecal haemoglobin (f-Hb) and both the risk of death from colorectal cancer (CRC) and all-cause mortality has been reported. We set out to confirm or refute this observation in a UK population and to explore the association between f-Hb, as indicated by a positive guaiac faecal occult blood test (gFOBT) result, and different causes of death. DESIGN: All individuals (134 192) who participated in gFOBT screening in Tayside, Scotland between 29/03/2000 and 29/03/2016 were studied by linking their test result (positive or negative) with mortality data from the National Records of Scotland database and following to 30/03/2016. RESULTS: Those with a positive test result (n=2714) had a higher risk of dying than those with a negative result, from CRC: HR 7.79 (95% CI 6.13 to 9.89), p<0.0001, (adjusted for, gender, age, deprivation quintile and medication that can cause bleeding) and all non-CRC causes: HR 1.58 (95% CI 1.45 to 1.73), p<0·0001.· In addition, f-Hb detectable by gFOBT was significantly associated with increased risk of dying from circulatory disease, respiratory disease, digestive diseases (excluding CRC), neuropsychological disease, blood and endocrine disease and non-CRC. CONCLUSION: The presence of detectable f-Hb is associated with increased risk of death from a wide range of causes.

Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer.

This corrects the article DOI: 10.1038/bjc.2016.363.

Fluid signal changes around the knee on MRI are associated with increased volumes of subcutaneous fat: a case-control study.

BACKGROUND: Fluid in the subcutaneous fat is a common finding anterior to the knee on MRI. This may be caused by chronic low-grade shearing injuries in patients who are overweight. The purpose of this study was to determine if there is a difference in the amount of subcutaneous fat around the knee between patients with these appearances and controls. METHODS: This was a retrospective case-control study. Following a sample size calculation on pilot data, eighteen sequential patients demonstrating hyper-intense subcutaneous signal changes around the knee on fat-saturated T2-weighted MRI were identified from PACS (18 females, mean age 45, range 31-62). Age and gender-matched patients without abnormal T2 MR signal changes were selected. Two observers independently drew regions of interest representing cross-sectional areas of bone and fat. The location of T2 signal hyper-intense lesions was characterized by consensus. RESULTS: Inter and intra-rater intraclass reproducibility was "excellent" (ICC > 0.8). The mean cross-sectional area of bone for patients with T2 hyper-intense lesions was 31.79cm2 (SD 2.57) and for controls 30.11cm2 (SD 3.20) which was not significantly different (p = 0.09). The median cross-sectional area of fat for the study group was 62.29cm2 (IQR 57.1-66.5) and for controls was 32.77cm2 (IQR 24.8-32.3) which was significantly different (p < 0.0001). Consensus agreement demonstrated all T2 hyper-intense lesions were anterior to the knee extensor mechanism. CONCLUSION: Subcutaneous fluid around the knee is associated with an increased amount of subcutaneous fat, anterior to the knee extensor mechanism. This may be caused by shearing injuries in fat with reduced elasticity associated with metabolic syndrome.

Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer.

BACKGROUND: Although the nuclear factor-erythroid 2-related factor 2 (NRF2) pathway is one of the most frequently dysregulated in cancer, it is not clear whether mutational status is a good predictor of NRF2 activity. Here we utilise four members of the aldo-keto reductase (AKR) superfamily as biomarkers to address this question. METHODS: Twenty-three cell lines of diverse origin and NRF2-pathway mutational status were used to determine the relationship between AKR expression and NRF2 activity. AKR expression was evaluated in lung cancer biopsies and Cancer Genome Atlas (TCGA) and Oncomine data sets. RESULTS: AKRs were expressed at a high basal level in cell lines carrying mutations in the NRF2 pathway. In non-mutant cell lines, co-ordinate induction of AKRs was consistently observed following activation of NRF2. Immunohistochemical analysis of lung tumour biopsies and interrogation of TCGA data revealed that AKRs are enriched in both squamous cell carcinomas (SCCs) and adenocarcinomas that contain somatic alterations in the NRF2 pathway but, in the case of SCC, AKRs were also enriched in most other tumours. CONCLUSIONS: An AKR biomarker panel can be used to determine NRF2 status in tumours. Hyperactivation of the NRF2 pathway is far more prevalent in lung SCC than previously predicted by genomic analyses.

Extramammary Paget disease of the perianal region: the potential role of imiquimod in achieving disease control.

Extramammary Paget disease (EMPD) is a rare perineal neoplasia associated with a high rate of local recurrence. Surgical excision is the standard treatment; however, this has high rates of post-operative morbidity in combination with potentially mutilating results. Previous literature has demonstrated good response with imiquimod 5% cream in patients with vulval EMPD, yet its effectiveness in primary perianal disease is unknown.We describe the case of a 40-year-old woman presenting with EMPD of the perianal region, providing detailed histological and pictoral evidence of its response to topical imiquimod 5% cream over a 16-week period, which initially resulted in remission prior to metastatic lymph node recurrence. This case demonstrates the potential for topical imiquimod cream to avoid major surgery and its associated complications in patients presenting with EMPD of the perianal region. We discuss the current evidence for treating this rare condition with medical therapy, how this case adds to current literature and possible future directions.

Molecular Profiling of Multiplexed Gene Markers to Assess Viability of Ex Vivo Human Colon Explant Cultures.

Human colon tissue explant culture provides a physiologically relevant model system to study human gut biology. However, the small (20-30 mg) and complex tissue samples used present challenges for monitoring tissue stability, viability, and provision of sufficient tissue for analyses. Combining molecular profiling with explant culture has potential to overcome such limitations, permitting interrogation of complex gene regulation required to maintain gut mucosa in culture, monitor responses to culture environments and interventions. Human ex vivo colon explant gene expression profiles were assayed using an in-house custom-designed hCellMarkerPlex assay at culture time points 0, 1, 2, 4, and 14 h. Characteristic profiles of epithelial cell markers linked to differentiation, cellular polarization, and apoptosis were correlated with visible histochemical changes in explant epithelium during culture and tissue donors. The GenomeLab System provides effective assay of multiple targets not possible from small tissue samples with conventional gene expression technology platforms. This is advantageous to increase the utility of the ex vivo human colon model in applications to interrogate this complex and dynamic tissue environment for use in analytical testing.

Do Multidisciplinary Team (MDT) processes influence survival in patients with colorectal cancer? A population-based experience.

BACKGROUND: MDT (multidisciplinary team) meetings are considered an essential component of care for patients with cancer. However there is remarkably little direct evidence that such meetings improve outcomes. We assessed whether or not MDT (multidisciplinary team) processes influenced survival in a cohort of patients with colorectal cancer. METHODS: Observational study of a population-based cohort of 586 consecutive patients with colorectal cancer diagnosed in Tayside (Scotland) during 2006 and 2007. RESULTS: Recommendations from MDT meetings were implemented in 411/586 (70.1 %) of patients, the MDT+ group. The remaining175/586 (29.9 %) were either never discussed at an MDT, or recommendations were not implemented, MDT- group. The 5-year cause-specific survival (CSS) rates were 63.1 % (MDT+) and 48.2 % (MDT-), p < 0.0001. In analysis confined to patients who survived >6 weeks after diagnosis, the rates were 63.2 % (MDT+) and 57.7 % (MDT-), p = 0.064. The adjusted hazard rate (HR) for death from colorectal cancer was 0.73 (0.53 to 1.00, p = 0.047) in the MDT+ group compared to the MDT- group, in patients surviving >6 weeks the adjusted HR was 1.00 (0.70 to 1.42, p = 0.987). Any benefit from the MDT process was largely confined to patients with advanced disease: adjusted HR (early) 1.32 (0.69 to 2.49, p = 0.401); adjusted HR(advanced) 0.65 (0.45 to 0.96, p = 0.031). CONCLUSIONS: Adequate MDT processes are associated with improved survival for patients with colorectal cancer. However, some of this effect may be more apparent than real - simply reflecting selection bias. The MDT process predominantly benefits the 40 % of patients who present with advanced disease and conveys little demonstrable advantage to patients with early tumours. These results call into question the current belief that all new patients with colorectal cancer should be discussed at an MDT meeting.

A pathologist's survey on the reporting of sessile serrated adenomas/polyps.

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.

Ultra-high resolution and long scan depth optical coherence tomography with full-phase detection for imaging the ocular surface.

We used a unique combination of four state-of-the-art technologies to achieve a high performance spectral domain optical coherence tomography system suitable for imaging the entire ocular surface. An ultra-high resolution, extended depth range, full-phase interferometry, and high-speed complementary metal-oxide semiconductor transistor camera detection provided unprecedented performance for the precise quantification of a wide range of the ocular surface. We demonstrated the feasibility of this approach by obtaining high-speed and high-resolution images of a model eye beyond the corneal-scleral junction. Surfaces determined from the images with a segmentation algorithm demonstrated excellent accuracy and precision.

Learning from partially annotated OPT images by contextual relevance ranking.

Annotations delineating regions of interest can provide valuable information for training medical image classification and segmentation methods. However the process of obtaining annotations is tedious and time-consuming, especially for high-resolution volumetric images. In this paper we present a novel learning framework to reduce the requirement of manual annotations while achieving competitive classification performance. The approach is evaluated on a dataset with 59 3D optical projection tomography images of colorectal polyps. The results show that the proposed method can robustly infer patterns from partially annotated images with low computational cost.

Novel multiplex method to assess insulin, leptin and adiponectin regulation of inflammatory cytokines associated with colon cancer.

The role of altered levels of insulin, leptin and adiponectin in contributing to the observed increased risk of colon cancer associated with obesity remains to be determined. Elevated insulin and leptin associated with obesity are linked to inflammatory responses. Conversely, adiponectin levels are reduced in obese individuals and this hormone is generally associated with anti-inflammatory responses. Inflammatory cytokines are key components of processes linked with carcinogenesis. Insulin, leptin and adiponectin receptor expression profiles were assessed in human normal, adenomatous polyp and tumour tissue. Insulin, leptin and adiponectin regulation of inflammatory cytokines previously identified as being associated with early events in colon carcinogenesis were further investigated here using a surrogate colon epithelial cell line and a custom designed GeXP assay of the inflammatory cytokines (CCL20, CXCL1, CXCL2, CXCL3, CXCL11, IL1RN, CXCL4, IL8, CCL19, CCL21, CCL23, CCL5, IL10RB and TNFRSF1A). Mean insulin, leptin and adiponectin receptor expression levels were lower in adenomatous polyp samples in comparison with normal and tumour tissue. In contrast to leptin, insulin significantly reduced CCL20 and CXCL11 and increased CXCL3 expression. Full length adiponectin, but not globular adiponectin, induced CCL5, CXCL1, CXCL3 and CCL20 gene expression. GeXP assay permitted measurement of changes in gene expression of cytokines in response to insulin and adiponectin, indicating the potential for insulin and adiponectin regulation of mediators of inflammation associated with early events in colon carcinogenesis.

Migration-stimulating factor as a novel biomarker in salivary gland tumours.

BACKGROUND: The identification of novel stratification biomarkers would benefit the clinical management of patients with salivary gland tumours. Migration-stimulating factor (MSF) is a potent stimulator of cell invasion, matrix remodelling and angiogenesis. The aim of this study was to determine whether MSF was expressed in salivary gland tumours and its potential value as a diagnostic biomarker. METHODS: Paraffin-embedded archival specimens of small salivary gland tumours were stained with an MSF-specific antibody. The specimens included 27 malignant and seven benign tumours; histologically normal salivary gland adjacent to the tumour was present in 16 specimens. MSF expression was assessed by consensus of 2-4 independent observers according to various indices, including 'overall MSF grade', 'percentage of area stained' and 'intensity of the staining'. The motogenic effect of MSF on a salivary gland tumour cell line, HSG, was examined in the transmembrane assay. RESULTS: Overall MSF expression increased significantly in a step-wise fashion from normal salivary gland to benign and malignant tumours (P = 0.04-0.0001); with moderate/strong positive specimens representing 6%, 33% and 74% of the normal, benign and malignant specimens, respectively. MSF was heterogeneously expressed in both carcinoma and stromal cell compartments, its expression being higher in malignant than benign tumours regarding various MSF indices. In tissue culture studies, exogenous MSF stimulated the migration of HSG cells. CONCLUSIONS: These immunohistochemical and functional studies suggest that MSF expression is a potentially useful biomarker of salivary gland tumour progression.

Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol.

AIMS: The heterogeneity within individual distinct cancer types in terms of behaviour, response to therapy and prognosis is well recognized. A major goal of translational research projects has therefore been to define clinically significant subgroups of individual tumour types by analysis of mRNA as well as protein expression. An essential premise of such investigations is that expression of these key molecules is a true reflection of conditions present within the neoplastic cells in vivo. The aim was to investigate the effect of methods of tissue handling and storage on expression of mRNA. METHODS AND RESULTS: mRNA expression in 60 biopsy samples obtained from 10 patients with colorectal tumours was examined. The mRNA expression profile and the level of expression of specific mRNA species were significantly affected by the procedures used for collection and storage of tissue samples. Significant variation in the level of expression (both increased and decreased) of transcripts was detectable after 15 min, and by 120 min there was a fourfold increase in the number of genes with a more than twofold change in the level of expression. CONCLUSIONS: Reliable interpretation of results of gene expression at the mRNA level requires standardized protocols for tissue procurement.