Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

Combining the amplification refractory mutation system and high-resolution melting analysis for KRAS mutation detection in clinical samples.

The success of personalized medicine depends on the discovery of biomarkers that allow oncologists to identify patients that will benefit from a particular targeted drug. Molecular tests are mostly performed using tumor samples, which may not be representative of the tumor's temporal and spatial heterogeneity. Liquid biopsies, and particularly the analysis of circulating tumor DNA, are emerging as an interesting means for diagnosis, prognosis, and predictive biomarker discovery. In this study, the amplification refractory mutation system (ARMS) coupled with high-resolution melting analysis (HRMA) was developed for detecting two of the most relevant KRAS mutations in codon 12. After optimization with commercial cancer cell lines, KRAS mutation screening was validated in tumor and plasma samples collected from patients with pancreatic ductal adenocarcinoma (PDAC), and the results were compared to those obtained by Sanger sequencing (SS) and droplet digital polymerase chain reaction (ddPCR). The developed ARMS-HRMA methodology stands out for its simplicity and reduced time to result when compared to both SS and ddPCR but showing high sensitivity and specificity for the detection of mutations in tumor and plasma samples. In fact, ARMS-HRMA scored 3 more mutations compared to SS (tumor samples T6, T7, and T12) and one more compared to ddPCR (tumor sample T7) in DNA extracted from tumors. For ctDNA from plasma samples, insufficient genetic material prevented the screening of all samples. Still, ARMS-HRMA allowed for scoring more mutations in comparison to SS and 1 more mutation in comparison to ddPCR (plasma sample P7). We propose that ARMS-HRMA might be used as a sensitive, specific, and simple method for the screening of low-level mutations in liquid biopsies, suitable for improving diagnosis and prognosis schemes.

Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression.

OBJECTIVE: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. DESIGN: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). RESULTS: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. CONCLUSION: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.

Participation in clinical trials increases the detection of pre-malignant lesions during colonoscopy.

BACKGROUND: colorectal adenoma detection has been associated with the effectiveness of cancer prevention. Clinical trials have been designed to determine the role of several interventions to increase the detection of pre-malignant lesions. We hypothesized that colonoscopy in the setting of clinical trials has a higher pre-malignant lesion detection rate. METHODS: a cross-sectional study was performed that compared the detection of pre-malignant lesions in 147 randomly sampled non-research colonoscopies and 294 from the control group of two prospective trials. Outpatients aged 40-79 years, with no personal history of colorectal cancer (CRC) were included. RESULTS: baseline characteristics were similar between the two groups. The pre-malignant lesion detection rate in the trial vs control group was 65.6 % vs 44.2 % (OR 2.411; 95 % CI: 1.608-3.614; p < 0.001), the polyp detection rate was 73.8 % vs 59.9 % (OR 1.889; 95 % CI: 1.242-2.876; p = 0.003), the adenoma detection rate was 62.6 % vs 44.2 % (OR 2.110; 95 % CI: 1.411-3.155; p < 0.001) and the sessile serrated lesion detection rate was 17 % vs 4.1 % (OR 4.816; 95 % CI: 2.014-11.515; p < 0.001). The mean number of pre-malignant and sessile serrated lesions was 1.70 vs 1.06 (p = 0.002) and 0.32 vs 0.06 (p = 0.001) lesions per colonoscopy, respectively. There was no significant change in any of the study outcomes according to the multivariate analysis with each single potential confounder. CONCLUSIONS: patients involved in colonoscopy trials may benefit from higher quality examinations, as shown by the higher detection rates. Institutions should consider supporting clinical research in colonoscopy as a simple means to improve colonoscopy quality and colorectal cancer prevention.

Comparative analysis of glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis. METHODS: We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted. RESULTS: For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.76-0.83), and areas under the ROC curve of .96 and .79, respectively. Glucose had a higher sensitivity (90%), with uncommon false-negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust. CONCLUSION: Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first-line test, particularly in small cysts with a limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis.

Mode of Delivery Does Not Affect the Risk of Inflammatory Bowel Disease.

BACKGROUND: Recent evidence suggests that exposures in early life that are known to influence microbiome development may affect the risk of developing inflammatory bowel disease (IBD). Cesarean section has been associated with altered colonization of commensal gut flora and is thought to predispose to immune-mediated diseases later in life. AIMS: To evaluate the risk of IBD, Crohn's Disease (CD), and Ulcerative Colitis (UC) according to mode of delivery (C-section vs vaginal delivery). METHODS: A systematic search was performed in PubMed and Embase. The primary outcome was the risk of IBD in individuals delivered vaginally compared to those born by C-section. Secondary outcomes were UC and CD risk according to mode of delivery and IBD risk in individuals born by emergent compared to elective C-section. Publication bias was evaluated by funnel plots and Egger's test. Study's quality was characterized using the Newcastle-Ottawa Scale. RESULTS: Ten studies fulfilled the inclusion criteria, of which seven were population-based. No publication bias was detected. Overall, 14.164 IBD patients and 4.206.763 controls were included. Being born by C-section was not associated with increased risk of IBD [OR 1.01, 95% CI (0.81-1.27), p = 0.92], CD [OR 1.15, 95% CI (0.94-1.42), p = 0.18] or UC [OR 0.94, 95% CI (0.61-1.45), p = 0.79]. No differences were found between emergent and elective C-section in IBD [OR 1.05, 95% CI (0.59-1,87), p = 0.87]. Substantial heterogeneity was found in statistical analysis, and further studies are needed. CONCLUSION: Overall, the risk of developing IBD was not affected by mode of delivery.

Should patients with symptomatic cholelithiasis before 30 years of age be tested for ABCB4 gene mutations?

BACKGROUND AND AIMS: Low phospholipid-associated cholelithiasis syndrome (LPAC) is characterized by recurrent symptomatic cholelithiasis in young adults associated with ABCB4 gene mutations. Current diagnosing criteria are complex and heterogeneous, making this a largely underdiagnosed entity. Also, although recommended, genetic testing is not necessary for the diagnosis and its real advantages are not clear. The aim of our study was to explore the prevalence of ABCB4 mutations in symptomatic patients with cholelithiasis before the age of 30. METHODS: We conducted a multicentric prospective cohort study including patients with symptomatic cholelithiasis presenting before 30 years of age in 4 Portuguese centres between January 2017 and December 2019. ABCB4 gene was analyzed by next generation sequencing (NGS) including all exons and flanking regions. In 17/32 patients ABCB11 and ATP8B1 variants were also analyzed by NGS. RESULTS: Thirty-two patients were included (75% females, median age of symptom onset was 23 ± 5 years). We found that 8/32 (25%) patients had mutations in ABCB4 gene, 3/17 (18%) in ATP8B1 gene and 1/17 (6%) in ABCB11 gene. 44% (8/18) of patients with LPAC syndrome criteria had identified variants, while the prevalence of mutations in patients with symptoms onset before 30 as sole criteria was 29%. CONCLUSION: Our results suggest that LPAC should be systematically suspected and investigated in patients with symptomatic cholelithiasis before age of thirty, but genetic testing should only be attempted in patients complying with the more stringent LPAC criteria.

Endoscopic ultrasound with fine needle aspiration is useful in pancreatic cysts smaller than 3 cm.

BACKGROUND: In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation). OBJECTIVE: To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. METHODS: Retrospective study of PCLs < 3 cm (2007-2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed. RESULTS: We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging-AUC = 0.80 versus AUC = 60. CONCLUSION: EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.

Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy.

PURPOSE: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients' health-related quality of life (HRQoL). METHODS: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. RESULTS: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms - lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (-4.646, 95% CI -6.953 to -2.339) and in the physical functioning (-9.622, 95% CI -17.061 to -2.183) and physical role functioning (-3.669, 95% CI -7.339 to 0.001) dimensions of the SF36. CONCLUSIONS: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.

Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts.

BACKGROUND: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described. AIMS: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis. MATERIALS AND METHODS: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological. RESULTS: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis. CONCLUSION: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

Irritable bowel syndrome: how can symptoms and quality of life be improved with diet?

PURPOSE OF REVIEW: This article aims to review the current scientific evidence of dietary approaches to control the symptoms of irritable bowel syndrome (IBS). RECENT FINDINGS: In the last decade, there was an important evolution in the study of the low fermentable oligo, di, mono-saccharides and polyols (FODMAP) diet (LFD). Current scientific evidence suggests a significant efficacy in the overall control of symptoms. LFD seems to be effective in improving quality of life. Recent studies suggest that LFD is effective and nutritionally well tolerated also in the long term, and longer adherence may contribute to greater effectiveness in improving depression. There is insufficient scientific evidence for the recommendation of gluten exclusion in IBS therapy, and some authors still suggest that the efficacy of this approach results from the limited ingestion of fructans. There is a promising efficacy of pre, pro, and symbiotic supplements, but there is no consensus on the most appropriate and effective strains in each case. SUMMARY: Given the poor evidence and the pathophysiological variability of IBS, the interest of each therapeutic option should be always evaluated individually. Nevertheless, LFD is currently the dietary approach with a higher degree of scientific evidence.

Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA.

BACKGROUND: Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS: To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS: We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS: There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS: In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.

Handgrip Dynamometry and Patient-Generated Subjective Global Assessment in Patients with Nonresectable Lung Cancer.

INTRODUCTION: Undernutrition is frequently associated with advanced lung cancer. Accurate nutritional assessment tools are important to provide the proper nutritional therapy. Handgrip dynamometry has already been used in these patients, and the findings suggest that it is a good indicator of nutritional status. AIMS: The aim of this study was to evaluate the association between nutritional status and handgrip strength (HGS) in patients with nonresectable lung cancer. METHODS: Cross-sectional study involving thirty-seven subjects with nonresectable lung cancer. Nutritional status was obtained using Patient Generated Subjective Global Assessment (PG-SGA), and muscle function was evaluated by HGS using a Jamar® handgrip dynamometer on the nondominant hand. The results of both methods were compared and correlated. RESULTS: According to PG-SGA, 73% (n = 27) of the patients were moderately undernourished, and 8% (n = 3) were severely undernourished. In total, 81% (n = 30) were undernourished. HGS was below the 50th percentile in 57% of the patients (n = 21). We found a significant association between nutritional status according to PG-SGA and HGS (P = 0.026, CI = 95%). CONCLUSIONS: Handgrip dynamometry can be a useful tool to evaluate the functional and nutritional status. It can be included in lung cancer patients evaluation, along with other nutritional assessment tools.

Non-anesthesiologist administration of propofol sedation for colonoscopy is safe in low risk patients: results of a noninferiority randomized controlled trial.

BACKGROUND AND STUDY AIMS: Propofol provides the best sedation in colonoscopy. The safety of non-anesthesiologist administration of propofol (NAAP) is still a matter of debate. The aim of the current study was to evaluate sedation safety, colonoscopy quality, and patient satisfaction with NAAP. PATIENTS AND METHODS: The study was a single-blinded, noninferiority, randomized controlled trial comparing NAAP (Group A) with anesthesiologist-administered sedation (Group B) performed at a single academic institution. Patients (18 - 80 years) who underwent colonoscopy and were at low anesthetic risk (American Society of Anesthesiologists class I - II) were included. The primary end point was the incidence of adverse events. Secondary end points were propofol dose, patient satisfaction and pain, colonoscopy quality indicators, and procedure and recovery times. RESULTS: A total of 277 patients were included in the analysis. The incidence of adverse events was 39.3 % in Group A and 39.0 % in Group B (absolute difference - 0.3 %, 95 % confidence interval [CI] - 12.0 % to 11.4 %; P = 0.959). There were no sentinel adverse events. The following interventions (Group A vs. Group B) were necessary: atropine administration (0 % vs. 5.5 %; P = 0.004); airway repositioning (8.7 % vs. 4.7 %; P = 0.196); increased oxygen administration (6.7 % vs. 3.9 %; P = 0.317), and increased fluid rate (2.7 % vs. 0.8 %; P = 0.379). There were no differences in cecal intubation and adenoma detection rates. Recovery times were longer in Group B (58 ±â€Š33 vs. 67 ±â€Š29 minutes; P = 0.032). There were no differences in mean propofol dose, withdrawal time, painless colonoscopy, satisfaction, and amnesia. All but two patients (Group B) were willing to repeat the colonoscopy. CONCLUSIONS: NAAP is equivalent to anesthesiologist-administered sedation in the rate of adverse events in a low risk population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02067065).

Anaemia in Patients with Inflammatory Bowel Disease - A Nationwide Cross-Sectional Study.

BACKGROUND: Anaemia is the most common complication in patients with inflammatory bowel disease (IBD). This study aims to assess the prevalence of anaemia in IBD patients and to know its characteristics with regard to the main IBD clinical features. METHODS: An observational cross-sectional multicentre study was conducted. We included all patients who had an appointment at the 15 participating centres during the period of 1 month, and who met the following selection criteria: age ≥18, diagnosis of IBD. Disease activity was evaluated by Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), and by Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). RESULTS: One thousand three hundred and thirteen patients, were included: 54.8% female, mean age 42.8 (interquartile range (25th-75th): 31-53 years), 59% had a diagnosis of CD, 39% of UC and 2% IBD unclassified. The median follow-up since diagnosis was 7 years. The ongoing treatment was aminosalicylates (63.1%), corticosteroids (11.6%), immunomodulators (36.4%) and anti-tumour necrosis factor (27.3%). Anaemia was identified in 244 patients, representing a prevalence of 18.6% (95% CI 16.6-20.9). A majority of cases (90%) have mild/moderate anaemia (mean haemoglobin 11.3 ± 0.8 g/dl). Anaemia was significantly higher in females (p = 0.006), but there were no differences between CDs (19.1%) and UCs (17.7%; p = 0.688). Anaemia was more frequent in patients with active disease (HBI >4; SCCAI >2) than in those in clinical remission (33.6 vs. 15.6%, p < 0.001) and in patients on steroids (36.8%) vs. other treatments (p < 0.001). Only 47% of patients with anaemia were under any specific treatment (oral iron 67%; intravenous iron 41%). CONCLUSION: Anaemia was more frequent in patients with active disease and in those on corticosteroids. The treatment of anaemia still seems undervalued, whereas more than half of anaemic patients were not receiving any specific treatment and the use of oral iron prevails contrarily to current recommendations.

Body composition and Crohn's disease behavior: Is adiposity the main game changer?

OBJECTIVE: We investigated the association between body composition upon diagnosis and complicated phenotypes and time until surgery in patients with Crohn's disease (CD). METHODS: We conducted a retrospective cohort study including patients with CD who had a computed tomography enterography or a magnetic resonance enterography performed ≤6 mo of diagnosis. Skeletal muscle and visceral and subcutaneous adipose tissue cross-sectional areas were determined with computed tomography or magnetic resonance images at the third lumbar vertebral level, processed with the sliceOmatic (TomoVison, Magog, QC, Canada) and ABACS plugin. RESULTS: We included 63 patients: 33 (52%) men, median age 35 y. Disease location (L) and behavior (B) according to the Montreal classification were L1 (ileal disease) = 28 (44%), L2 (colonic disease) = 13 (21%), L3(ileocolonic disease) = 18 (28%), L1 + L4 (ileal and isolated upper disease) = 1 (2%), L3 + L4 (ileocolonic and isolated upper disease) = 3 (5%), B1 (non-stricturing) = 39 (62%), B2 (stricturing) = 11 (17%), and B3 (penetrating)= 13 (21%); 20 (32%) patients had perianal disease. Visceral obesity was present in 12 (19%) patients and was associated with higher age of CD onset (median 60 versus 34 y; P = 0.002) and complicated disease behavior (B2 and B3) (66.7% versus 31.7%; P = 0.021). After adjusting for age and perianal disease, total adipose tissue was associated with a 4% increase in the odds of complicated behavior per 10 cm2 of total adipose tissue (odds ratio [OR] = 1.004; 95% confidence interval [CI], 1.00-1.008; P = 0.043). Median follow-up time was 3.35 y, during which 15 (24%) of patients underwent abdominal surgery. Visceral obesity was associated with 5.10-times higher risk of abdominal surgery (95% CI, 1.52-17.09; P = 0.008); after adjusting for disease behavior, visceral obesity maintained a near-significant association with a 2.90-times higher risk of surgery (95% CI, 0.83-10.08; P = 0.09). CONCLUSION: Total fat was associated with complicated disease phenotype and visceral obesity, with higher risk of abdominal surgery and shorter time until surgery.

Narrow Band Imaging versus White Light for the Detection of Sessile Serrated Colorectal Lesions: A Randomized Clinical Trial.

Background: Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. Methods: We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. Results: Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, p = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, p = 0.58) and SSL detection rate (6.8% vs. 7.5%, p = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, p = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, p = 0.052). Conclusions: The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.

Introdução: O cancro do cólon e reto é a neoplasia mais frequente considerando os dois géneros. . A deteção de lesões pré-malignas por colonoscopia está associada a uma redução da incidência e da mortalidade. Estudos sobre a utilização da luz de banda estreita (NBI) na deteção de lesões serreadas tiveram resultados promissores, mas heterogéneos. Métodos: Realizámos um ensaio clínico randomizado para comparar o número médio de lesões serreadas e lesões hiperplásicas ≥10 mm com NBI ou luz branca de alta-definição (HD-WL). Como resultados secundários comparámos a prevalência e as taxas de deteção de lesões serreadas sésseis, adenomas e todas as lesões. Resultados: Foram randomizados 782 doentes (392 no grupo HD-WL e 390 no grupo NBI). O número médio de lesões serreadas e hiperplásicas ≥10 mm não apresentou diferença estatisticamente significativa entre dois grupos (0.118 vs. 0.156, p = 0.44). A taxa de deteção de adenomas (55.2% vs. 53.2%, p = 0.58) e a taxa de deteção de lesões serreadas sésseis (6.8% vs. 7.5%, p = 0.502) também não foram diferentes. O tempo de retirada foi maior no grupo NBI (10.88 vs. 9.47 min, p = 0.004) e o tempo total de procedimento teve um ligeiro aumento não atingindo significância estatística (20.97 vs. 19.30 min, p = 0.052). Conclusão: A utilização da luz NBI por rotina não aumenta a deteção de lesões serreadas nem de qualquer lesão pré-maligna e aumenta o tempo de retirada na colonoscopia.

Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

Update on the Role of Rifaximin in Digestive Diseases.

Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota have been firmly implicated in digestive diseases such as hepatic encephalopathy, irritable bowel syndrome and diverticular disease. However, while these three conditions may all be related to dysfunction of the gut-liver-brain axis, the precise pathophysiology appears to differ somewhat for each. Herein, current knowledge on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are reviewed, with a special focus on the gut microbiota modulation associated with these disorders during therapy with rifaximin. In general, the evidence for the efficacy of rifaximin in hepatic encephalopathy appears to be well consolidated, although it is less supported for irritable bowel syndrome and diverticular disease. We reviewed current clinical practice for the management of these clinical conditions and underlined the desirability of more real-world studies to fully understand the potential of rifaximin in these clinical situations and obtain even more precise indications for the use of the drug.