BMC Gastroenterology

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Background Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease that limits to colon mucosa, which characterised by relapsing and remitting abdominal pain and diarrhea. Neurological complications in UC patients are usually underestimated. The most frequently reported neurological disorders associated with UC are peripheral neuropathy, cerebrovascular disease and demyelinating disease. However, acute transverse myelitis (TM) is rarely reported in UC patients. Case presentation We report a case of a 39-year-old man presented with fatigue, muscle weakness, numbness in the lower limbs and fingers with underlying UC. Laboratory results revealed elevated neutrophil count, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. Strip-shaped high signal intensity was identified in the cervical and thoracic spinal cord on T2-weighted magnetic resonance imaging. Acute TM was diagnosed. Significant improvements after intravenous high-dose methylprednisolone were observed. Conclusion We speculate that acute TM may be the extraintestinal manifestation of UC, which may be related to the abnormalities of cell-mediated and humoral immunity rather than the side effect of mesalazine.
 
In the January 2021 issue of BMC Gastroenterology, Elmokadem et al. report their findings on the use of gastric ultrasound (GUS) for the evaluation of feeding intolerance—defined as high gastric residual volume—in critically ill patients. We voice in this correspondence our concerns regarding certain methodological flaws and believe the study results should be interpreted with caution. The authors applied a model unvalidated for non-clear fluids as enteral feeding, the scanning protocol was not clearly described and essential anatomical landmarks required for correct interpretation are not visible in the presented images. Additionally, since GUS was not compared to a gold standard, we believe the authors’ conclusion may be overoptimistic and does not undoubtedly answer the primary outcome.
 
Mutational landscape, characteristics and mutational correlation in stage I hepatocellular carcinoma (HCC). A mutational landscape of 163 stage I HCC patients. The mutational status of the top 20 mutated genes is shown as indicated; B mutational characteristics of stage I HCC, including variant classification, type, rank and mutational burden. C Status of co-mutations and mutually exclusive mutations. The status and co-mutations or mutually exclusive mutations are indicated by colors and P values. SNV, single nucleotide variant; Del, deletion; Ins, insertion
Genes with significant stratification of prognosis by mutational status. The top 200 mutated genes in stage I hepatocellular carcinoma (HCC) were examined and those with significant stratification of prognosis are shown here. The mutational status is indicated by different colors and P values and hazard ratio (HR) values are shown as indicated. The unit for time is months. HR, hazard ratio; WT, wild type; CI, confidence interval
The stratification of patient prognosis by tumor mutational burden (TMB). The stratification status by a series of thresholds at different percentile is shown here. Only cutoff at 90th percentile was found to significantly stratify the patient prognosis, although all stratification showed a trend that low TMB group exhibited a better prognosis. The unit for time is months
Profile of transcriptional alterations of stage I hepatocellular carcinoma (HCC). A The heatmap shows the transcriptional status of the top 100 differentially transcripted genes. Blue bars represent normal tissues while pink bars represent cancer tissues. B Volcano plot shows the significantly up-regulated (red) or down-regulated (green) genes, with the names of the most significant ones labeled. C–E The results for GO (C), KEGG (D) and Reactome (E) enrichment analyses. The significantly altered functions or pathways are shown as indicated. GO, gene ontology; KEGG, Kyoto encyclopedia of genes and genomes; BP, biological process; CC, cellular compartment; MF, molecular function; FC, fold change; p.adjust, adjusted p value
The Nomogram model for predicting the prognosis of stage I hepatocellular carcinoma (HCC) patients. A series of clinicopathological factors, including sex, race, neoplasm histological grade, Child–Pugh grade, and the mutational status, represented by tumor mutational burden (TMB), and transcriptional levels of three genes, including MMRN1, OXT and COX6A2, were used to establish the model. TMB, tumor mutational burden; exp, expression; G, grade; Afr, African
Background The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels. Methods Here we first characterized the influencing factors of prognosis of stage I HCC patients by downloading and analyzing the whole-exome somatic mutation data, messenger ribonucleic acid (mRNA) transcription data, along with demographic and clinical information of 163 stage I HCC patients from the TCGA database. The relationship between the influencing factors and HCC prognosis was studied in detail, and a prediction Nomogram model was established. Figures and tables were plotted using the R software. Results TP53, CTNNB1, TTN, MUC16 and ALB were the top mutated genes in stage I HCC. A series of co-mutations and mutually exclusive mutations were identified. Twenty-nine genes with significant stratification on prognosis were identified, including highly mutated LRP1B, ARID1A and PTPRQ. Patients with wild type (WT) genes unanimously exhibited significantly better overall survival rate than those with mutants. Patients with the top 10% tumor mutational burden (TMB) exhibited significantly worse prognosis than the rest 90%. Further characterization of transcriptional profile revealed that membrane functions, cell skeleton proteins, ion channels, receptor function and cell cycle were comprehensively altered in stage I HCC. Univariate and multivariate analyses were performed at clinicopathological, mutational and transcriptional levels. The combined analysis revealed sex, race, TMB, neoplasm histologic grade, Child–Pugh grade, MMRN1, OXT and COX6A2 transcription as independent risk factors. These factors were used to establish a Nomogram model to predict the prognosis of individual HCC patients. Conclusions The influencing factors of prognosis of stage I HCC have been characterized for the first time at clinicopathological, mutational and transcriptional levels. A Nomogram model has been established to predict the prognosis. Further validation is needed to confirm the effectiveness and reliability of the model.
 
The CFA model of the RFIPC (standardised factor loadings)
Background Inflammatory bowel disease (IBD) has become a global public health problem. The prevalence of IBD in China increased annually in past two decades. Methods This study was to translate and validate the rating form of IBD patients' concerns (RFIPC), and to describe disease-related worries and concerns of patients with IBD. The simplified Chinese version of the RFIPC was developed according to translation and back-translation procedure. Patients with IBD were consecutively enrolled from the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The participants were assessed using the RFIPC and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Internal consistency, test–retest reliability, measurement error, confirmatory factor analysis (CFA) and correlation of the RFIPC with the SIBDQ were performed to evaluate the psychometric characteristics of the RFIPC. Results A total of 116 patients with IBD, 73 with ulcerative colitis (UC) and 43 with Crohn’s disease (CD), were enrolled in this study. Thirty-seven of them recompleted the questionnaires for the second time between 7 and 14 days after the first interview. The results of CFA indicated the original structure of the RFIPC was reasonable. Cronbach's alpha value of the RFIPC were 0.97. The intraclass correlation coefficients of four domains ranged from 0.85 to 0.92. The standard error of measurement was 7.10. The correlation coefficients between total score of the RFIPC and the SIBDQ score ranged from − 0.54 to − 0.70. Median total score of the RFIPC was 39.4 (IQR 24.0–59.3). Patients with severe symptoms reported higher scores of the RFIPC. The uncertain nature of disease, having surgery, having an ostomy bag, developing cancer, feeling out of control, being a burden on others and financial difficulties were highest concerns of patients with IBD. Comparing with patients with UC, patients with CD had more concerns of the ability to have children and being treated as different (P < 0.05). Conclusions The simplified Chinese version of RFIPC is a valid and reliable tool. It could be used for assessing disease-related worries and concerns of patients with IBD in China. Specific concerns of patients with UC and CD are different, therefore, health workers should consider the specific needs of UC and CD patients.
 
Study flow diagram. PEG, Polyethylene glycol; LB, Lubiprostone
Comparison of endoscopic findings between the two groups. PEG, Polyethylene glycol; LB, Lubiprostone
Comparison of total BBPS score between the two groups by PP analysis. BBPS, Boston Bowel Preparation Scale; PEG, Polyethylene glycol; LB, Lubiprostone; PP, per-protocol
Background Colonoscopy is a standard procedure for evaluating colon diseases and screening for colorectal cancer, and bowel cleanliness prior to colonoscopy is key. The aim of this study was to compare the bowel cleansing efficacy of low-volume (2 L) split-dose polyethylene glycol (PEG) plus single-dose (24 µg) lubiprostone (LB) and high-volume (4 L) split-dose PEG. Methods Patients scheduled to undergo outpatient colonoscopy between December 2019 and June 2021 at Rajavithi Hospital were enrolled and randomized into two groups: 2 L PEG + LB or 4 L PEG. Colon cleanliness was evaluated using the Boston Bowel Preparation Scale (BBPS) by reviewing images of the colon after completion of colonoscopy. Secondary outcomes comprised cecal intubation rate, procedure time, withdrawal time, polyp detection rate, adenoma detection rate, patient satisfaction, compliance (based on complete ingestion of bowel preparation regimen), willingness to repeat the preparation regimen, and associated adverse events. Results One hundred and forty patients were included, with 70 in each group. The mean total and segment-specific BBPS scores were not significantly different between groups. However, the rate of adequate bowel preparation was significantly higher in the 2 L PEG + LB group than the 4 L PEG group (100% [95% CI 94.6–100] versus 88.4% [95% CI 78.4–94.9], p = 0.004) in the per-protocol analysis. Colonic polyps were the most common finding. The polyp detection rate, adenoma detection rate, and all secondary outcomes were statistically similar in the two groups ( p > 0.05). Conclusions The combination of 2 L split-dose PEG plus LB improves bowel cleanliness (based on BBPS scores) to a comparable degree to the standard 4 L split-dose PEG, without additional adverse events and with a lower PEG volume.
 
ROC curves of ascitic ADA, ascitic total protein and ascitic cholesterol in differentiating PC from TBP
Scatter dot plot showing the distribution of ascitic ADA in the patients enrolled. Median with interquartile range is included, horizontal lines at 22.5 IU/L for ascitic ADA. (****, p < 0.0001)
Diagnostic performance of ascitic tumor markers in peritoneal carcinomatosis
Background Differential diagnosis between tuberculous peritonitis and peritoneal carcinomatosis remains challenging in clinical practice; thus, in-patients diagnosed with tuberculous peritonitis or peritoneal carcinomatosis were retrospectively enrolled, and diagnostic values of ascitic tumor markers and adenosine deaminase were determined. Methods Consecutive patients diagnosed with tuberculous peritonitis or peritoneal carcinomatosis were retrospectively enrolled. The pertinent data of 169 patients enrolled were collected. Results A panel of ascitic tumor makers (CEA, CA15-3, CA19-9) had high specificity (96.83%) and accuracy (94.67%) in the differentiation of peritoneal carcinomatosis from tuberculous peritonitis; and ascitic ADA was a good discriminator between these patients, with an accuracy of 91.72%. Combined use of ascitic tumor makers and ADA (ascitic ADA < 22.5 IU/L or ascitic CEA > 3.65 ng/mL or CA15-3 > 42.70 U/mL or CA19-9 > 25.10 U/mL) performed high sensitivity (99.06%) and accuracy (94.08%) for the diagnosis of peritoneal carcinomatosis. In addition, combined ascitic ADA and tumor marker (positive ascitic tumor makers and ADA < 22.50 IU/L) had 100% of the specificity in diagnosing peritoneal carcinomatosis. Conclusions Combined use of ascitic tumor markers and adenosine deaminase showed excellent efficiency in the differential diagnosis between tuberculous peritonitis and peritoneal carcinomatosis, thus these two simple and cost‐effective parameters should be determined when tuberculous peritonitis or peritoneal carcinomatosis was suspected in clinic practice.
 
Flow chart for selection of late HCV group and control group. HCV = hepatitis C virus; HCC = hepatocellular carcinoma; HBV = hepatitis B virus; ESRD = end stage of renal disease
Trend in late diagnosis of hepatitis C virus related hepatocellular carcinoma between 2012–2014 and 2017–2018
Demographic characteristics of patients with hepatitis C virus who were diagnosed late relative to hepatocellular carcinoma in Taiwan
Background New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan. Methods We conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis. Results A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis. Conclusions Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.
 
Study flow diagram. Two cohorts were evaluated in the present study. In Cohort 1, patients with long- and short-term disease durations were extracted and analyzed according to disease duration. In Cohort 2, all cases were divided into three groups in the order of disease duration such that the number of cases in each group was almost the same, and analysis was performed in these three groups
Bar graphs of the correlation coefficients between fecal biomarkers and Mayo endoscopic subscore (MES)/ ulcerative colitis endoscopic index of severity (UCEIS) scores categorized by disease duration. The dark-blue and orange bar graphs represent the fecal calprotectin (FC) and fecal immunochemical occult blood test (FIT) concentrations, respectively. The blue and red dashed lines indicate the correlation coefficients with FC and FIT concentrations in all cases, respectively. Bar graphs of the correlation coefficient between fecal biomarker concentrations and MES in the long-term (a) and short-term (b) disease-duration groups. Bar graphs of the correlation coefficients between fecal biomarker concentrations and UCEIS in long-term (c) and short-term (d) disease-duration groups
Bar graphs of the correlation coefficient between fecal biomarkers and the sum of Mayo endoscopic subscore (MES) by disease duration. The dark-blue and orange bar graphs represent the fecal calprotectin (FC) and fecal immunochemical occult blood test (FIT) concentrations, respectively. The blue and red dashed lines indicate the correlation coefficients with the FC and FIT concentrations in all cases, respectively. Bar graphs of the correlation coefficients with fecal biomarkers and the sum of MES in the long-term (a) and short-term (b) disease-duration groups
Receiver operating characteristic (ROC) curve analysis for predicting mucosal healing in the three groups according to disease duration. ROC curve of fecal calprotectin (FC) and fecal immunochemical occult blood test (FIT) in all cases (a). ROC curves of FC and FIT in the groups of disease duration 0–5 years (b), 6–12 years (c), and 13–38 years (d)
Background Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. Methods One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0–5, 6–13, and 14–38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. Results In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0–5, 6–13, and 14–38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0–5 year disease-duration group showed particularly higher values than those for the other two groups. Conclusions Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.
 
Background The aim of our study was to investigate the clinical characteristics and pathogenesis of tumor-induced acute pancreatitis (AP), and to develop a reliable prediction model of the clinical features to guide the diagnosis and treatment. Methods Patients with AP between January 2013 and December 2021 were enrolled in the study and were subdivided into the tumor group and the non-tumor group. The tumor group was subdivided into three groups based on the primary sites. Characteristic parameters, laboratory and imaging results were compared between groups. Least absolute shrinkage and selection operator regression model, XGBoost and random forest model were used to select the predictors associated with tumor-induced AP. Logistic regression analysis was used to validate the performance of the selected predictors and a nomogram was established to provide individualized probability of a tumor origin for AP. Results A total amount of 8970 patients were admitted for AP during the study period, and 8637 AP patients were enrolled in the study. Of these, 100 cases (1.16%) were tumor-induced AP. The tumor group was significantly older than the non-tumor group (t = 6.050, p = 0.000). Mild AP was observed in 90 cases, moderate AP in 9 cases and severe AP in one case. Tumors respectively originated from distal bile duct (14 cases), ampulla (13 cases) and pancreas (73 cases). The median time from initial AP to tumor diagnosis was 8.57 weeks and the median number of episode was 2 in the tumor group, which significantly surpassed the non-tumor group (p = 0.000). Age, white blood cell count, percentage of neutrophils, pancreatic or bile duct dilation and recurrent attacks were selected independent predictors for tumor origin. A nomogram model based on these factors was established. Conclusion For patients with agnogenic AP, elderly man, recurrent attacks, pancreatic or bile duct dilatation and continuous no significant increase of inflammatory markers prompt to further screening of pancreatic biliary and ampulla.
 
Objective: Evidence regarding the relationship between serum uric acid-to-creatinine (SUA/Scr) ratio and non-alcoholic fatty liver disease (NAFLD) in Chinese non-obese people is still limited. Therefore, the present study was undertaken to analyze the association between the SUA/Scr ratio and NAFLD. Methods: This study was a cross-sectional study that non-selectively and consecutively collected 182,320 non-obese individuals with a normal range of low-density lipoprotein cholesterol in a Chinese hospital from January 2010 to December 2014. A binary logistic regression model was used to evaluate the independent association between the SUA/Scr ratio and NAFLD. A generalized additive model (GAM) and smooth curve fitting (penalized spline method) was conducted to explore the exact shape of the curve between them. A series of sensitivity analyses were used to ensure the robustness of the results. Moreover, subgroup analyses were conducted. In addition, the diagnostic value of the SUA/Scr ratio for NAFLD was evaluated based on the area under the receiver-operating characteristic curve (AUROC). It was stated that the data had been uploaded to the DATADRYAD website. Results: The average participants' age was 40.96 ± 14.05 years old, and 90,305 (49.5%) were male. The prevalence of NAFLD was 13.7%, and the mean SUA/Scr was 3.62 ± 0.92. After adjusting covariates, the results showed that SUA/Scr ratio was positively associated with NAFLD (OR = 1.424, 95%CI: 1.396, 1.454). There was also a non-linear relationship between SUA/Scr ratio and NAFLD in participants with normal kidney function, and the inflection point of the SUA/Scr ratio was 4.425. The effect sizes (OR) on the left and right sides of the inflection point were 1.551 (1.504, 1.599) and 1.234 (1.179, 1.291), respectively. And the sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed a stronger association between SUA/Scr ratio and NAFLD in females and the population with age < 50 years, FPG ≤ 6.1 mmol/L, BMI < 24 kg/m2, and HDL-c ≥ 1 mmol/L. In contrast, the weaker association was probed in males and the population with age ≥ 50 years, BMI ≥ 24 kg/m2, FPG > 6.1 mmol/L, and HDL-c < 1 mmol/L. The SUA/Scr ratio had an AUC of 0.6624 (95% CI 0.6589, 0.6660) for diagnosing NAFLD. Based on the best cut-off value of 3.776, the negative predictive value of the SUA/Scr ratio for identifying NAFLD was 91.0%. Conclusion: This study demonstrates an independent positive association between SUA/Scr ratio and NAFLD in Chinese non-obese people with a normal range of low-density lipoprotein cholesterol. There is also a non-linear relationship between the SUA/Scr ratio and NAFLD in participants with normal kidney function, and the SUA/Scr ratio is strongly related to NAFLD when SUA/Scr ratio is less than 4.425. The SUA/Scr ratio has a certain reference value for determining NAFLD. When the SUA/Scr ratio is lower than 3.776, identifying NAFLD patients with low risk is a great reference.
 
Performance of non-invasive predictive model for predicting the onset of HCC in Changzhou cohort. A ROC curve analysis of the risk model and single variable for predicting the onset of HCC. B ROC curve analysis of the risk model and other score systems for predicting the onset of HCC. C ROC curve analysis of the risk model for predicting the onset of HCC in patients with different AJCC TNM stages. D Decision curve analysis demonstrates the clinical net benefit of the risk score model and other score systems for the onset of HCC in Changzhou cohort. E Clinical impact curve of the risk model. F Cumulative event between high risk and low risk groups at indicated time before clinical diagnosis
The longitudinal changes of the risk score for disease progression. A–D The smooth curve of risk score in selected datasets (A Changzhou cohort. B Patients with AJCC TNM stage I. C Patients with AJCC TNM stage II. D Patients with AJCC stage III and IV)
Validation of the risk model in Wuxi cohort. A Performance of the risk model for predicting the onset of HCC. B Performance of the risk model for predicting the onset of HCC in patients with different AJCC TNM stages. C Decision curve analysis demonstrates the clinical net benefit of the risk score model for the onset of HCC. D–E Clinical impact curve of the risk model. F Predictive value of the risk model for the onset of HCC in patients with small tumor (< 2 cm)
Abstract Background Early hepatocellular carcinoma (HCC) detection with non-invasive biomarkers remains an unmet clinical need. We aimed to construct a predictive model based on the pre-diagnostic levels of serum markers to predict the early-stage onset of HCC. Methods A total of 339 HCC patients (including 157 patients from Changzhou cohort and 182 patients from Wuxi cohort) were enrolled in our retrospective study. Levels of 25 baseline serum markers were collected. Propensity score matching (PSM) analysis was conducted to balance the distributions of patients’ gender, age, and the surveillance time between HCC group and control group. Then, Receiver operating characteristic (ROC) and Logistic regression analysis were performed to screen the independent predictive variables and construct a non-invasive predictive model. Subsequently, ROC curve and Kaplan–Meier (K–M) curve were used to evaluate the predictive values of the model. Clinical net benefit of the model was demonstrated by decision curve analysis (DCA) and clinical impact curve. Results Five independent predictive variables for HCC onset and two general characteristics of patients (age and gender) were incorporated into the score model. ROC and DCA curves showed that the score model had better predictive performance in discrimination and clinical net benefit compared with single variable or other score systems, with the area under the curve (AUC) of 0.890 (95% CI 0.856–0.925) in Changzhou cohort and 0.799 (95% CI 0.751–0.849) in Wuxi cohort. Meanwhile, stratification analysis indicated that the score model had good predictive values for patients with early tumor stage (AJCC stage I) or small tumors (
 
Patient selection flowchart. Abbreviations: ESD endoscopic submucosal dissection, ECC early colorectal cancer, SM submucosa, PM proper muscle
Kaplan–Meier curves demonstrating cumulative recurrence free survival rates in A overall enrolled ECC patients and B according to depth of cancer invasion
Kaplan–Meier curves demonstrating cumulative recurrence free survival rates A in curatively resected ECC patients and B according to depth in curatively resected patients
Clinical features of the recurrence cases
Background Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis. Methods This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence. Results The median follow-up period was 53.8 (12–138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% ( p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248). Conclusions Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.
 
Background Recent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies. Study design We identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012–2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL. Results In the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI: MBP [OR = 0.82, 95%CI: 0.70–0.96], ABP [0.69, 95%CI: 0.52–0.92]; AL: MBP [OR = 0.66, 95%CI: 0.51–0.86], ABP [0.56, 95%CI: 0.34–0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50–0.67; AL:OR = 0.46, 95%CI:0.36–0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13–0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open: SSI [OR = 0.51, 95%CI: 0.37–0.69], AL [OR = 0.47, 95%CI: 0.25–0.91]; Laparoscopic: SSI [OR = 0.58, 95%CI: 0.47–0.72, AL [OR = 0.49, 95%CI: 0.35–0.68]). Conclusions MBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.
 
Study flowchart of patient selection
Background Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). Methods This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD–PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. Results Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93–1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57–1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89–1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. Conclusion Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.
 
The flowchart of patient inclusion and pathways in this study
The comparison of pain relief time, oral refeeding time, length of hospital stay and ICU stay
The comparison of laboratory indicators
Background The effectiveness of pancreatic duct (PD) stenting in the early stages of acute pancreatitis (AP) remains controversial. This study aimed to investigate the efficacy and safety of PD stenting in the early stages of AP. Methods This is a retrospective cohort study. The clinical data of 131 patients with AP from 2018 to 2019 were analysed and divided into two groups: the study group (n = 46, PD stenting) and the control group (n = 85, standard treatment). Results There was a statistically significant reduction in pain relief, oral refeeding, hospitalization, and intensive care unit (ICU) stay in the study group compared with that of the control group ( P < 0.05). There were no significant differences in the incidence of complications between the two groups. Further multivariate analysis of risk factors for new-onset organ failure showed that the control group (odds ratio [OR] (95% confidence interval [CI]): 6.533 (1.104–70.181)) and a higher level of haematocrit (HCT) at admission (HCT > 46.1%, OR (95%CI): 8.728 (1.264–116.767)) were independent risk factors. Conclusions In the early phase of AP, PD stenting has the potential to reduce pain relief time, oral refeeding time, ICU stay time, and overall hospital stay time. This finding highlights a new route for the treatment of AP.
 
Background: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. Objectives: To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. Methods: For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. Results: Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n=4, 50%), portal vein thrombosis (n=25, 48.1%), splanchnic vein thrombosis (n=6, 42.8%), jaundice (n=1, 12.5%), raised liver enzymes (n=2, 7.7%), and autoimmune hepatitis (n=3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. Conclusion: Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.
 
Backgrounds and aims One of the most important risk factors for Helicobacter pylori (H. pylori) infection is nutrition. Balanced diets with high antioxidant properties may have protective effects against the consequences of this infection. In the current study, we aimed to investigate the association between the dietary antioxidant index and the risk of H. pylori infection among adults. Methods In a case–control study the dietary intake of patients with H. pylori infection was compared with healthy subjects. The dietary antioxidant index (DAI) was calculated using dietary intakes derived from a validated food frequency questionnaire (FFQ). Demographic information was obtained by a related questionnaire and Physical Activity was measured by International Physical Activity Questionnaire (IPAQ) were used to obtain information. Using logistic regression models, we evaluated the association between the DAI and H. pylori infection risk. The significance level was determined as P < 0.05. Results Finally, dietary data of 148 cases and 302 controls (mean age: 38.72 ± 10.61 (were analyzed. The mean of total DAI was significantly higher in controls (7.67) when compared with H. pylori cases (3.57) ( P < 0.001). After adjustment for covariates, participants with less than median DAI values had an increased risk of H. pylori onset (adjusted OR 1.08, 95% CI: 1.02–1.12, P < 0.001). Conclusions Appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of H. pylori infection risk .
 
Endoscopic appearance of severe ulcerative colitis
Background Guillain–Barré Syndrome is an immune mediated polyneuropathy. Ulcerative Colitis is an immune mediated chronic inflammatory condition mainly of the large intestine. Guillain–Barré Syndrome can present as a rare extraintestinal manifestation of Ulcerative Colitis when in remission or in a relapse. However, the concomitant presentation of Guillain–Barré Syndrome during a relapse of Ulcerative Colitis is very rare and only a few cases are reported to date. Case presentation A 24 year old young male diagnosed of Ulcerative Colitis presented with bloody diarrhea of frequency more than six times a day. He had been in clinical remission even after defaulting treatment for more than a year. He had also noted difficulty in walking prior to admission to the hospital. He was managed as for a severe relapse of Ulcerative Colitis and Guillain–Barré Syndrome. Appropriate management of both the illnesses helped him to recover. Conclusion Immune mediated diseases can have rare coexisting presentations. We report a case of Ulcerative Colitis with concomitant Guillain–Barré Syndrome. It is essential to be open minded and timely, appropriate treatment led to successful management of both the illnesses.
 
Patient populations. *All patients randomly assigned to treatment for whom patient diary data could not rule out that they received at least one dose of NER1006. †Patients included in the safety population who had a normal sodium concentration at baseline and an increase from baseline to above the upper limit of normal (ULN) for sodium (143–148 mmol/L). ‡Reported as an adverse event based on test results on the day of colonoscopy; medical intervention was not required, and sodium levels returned to normal range within 2 ± 1 days post-colonoscopy. DAYB Day Before Arm MORA Morning Arm NOCT Nocturnal Pause Arm
Box and whisker plots of a median and b change from baseline in median sodium concentrations. Values were determined at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). Box shows median, and upper and lower quartile values; whisker designates upper and lower values. Circles in graph represent outliers. DAYB Day Before Arm MORA Morning Arm NOCT Nocturnal Pause Arm
Background This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006. Methods Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143–148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). Results A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3. Conclusion NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014])
 
A 5-years Kaplan–Meier survival analysis comparing subjects with malignant ascites with and without liver metastasis demonstrating higher mortality rates in those with liver metastasis. B 5-years Kaplan–Meier survival analysis comparing subjects with peritoneal carcinomatosis on cytology and or imaging to subjects without evidence of PC. C 3-years Kaplan–Meier survival analysis comparing subjects with peritoneal carcinomatosis on cytology and or imaging to subjects without evidence of PC. D 1-years Kaplan–Meier survival analysis comparing subjects with peritoneal carcinomatosis on cytology and or imaging to subjects without evidence of PC. E 5-years Kaplan–Meier survival analysis comparing subjects with pancreatic cancer and peritoneal carcinomatosis on cytology and or imaging to subjects without evidence of PC. F 1-years Kaplan–Meier survival analysis comparing subjects with pancreatic cancer and peritoneal carcinomatosis on cytology and or imaging to subjects without evidence of PC
Background Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites. Methods 241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis. Results Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC. Conclusions Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
 
Comparison of mean serum Ferritin concentrations by Ranson score, CTSI score, BISAP score, SIRS, Local complications, systemic complications and Persistent organ failure
Correlation between SF and other clinical indicators in AP patients
Comparison of receiver operating characteristic (ROC) curves for prediction of disease severity and organ failure since admission
Background Serum ferritin (SF), as an acute-phase response protein, is used to reflect the degree of oxidative stress and systemic inflammatory responses. This study was designed to assess the effect of elevated SF levels on the severity of acute pancreatitis (AP). Methods From January 2013 to December 2020, 200 consecutive patients with AP were retrospectively reviewed to analyze the relationships among the etiologies of pancreatitis, the severity of the disease and SF levels. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess whether elevated SF levels could predict the onset of organ failure in AP. Results 92 (46%) had high SF levels (> 275 ng/ml). SF levels were not associated with the etiology of AP disease. Among patients with high SF levels, there was a significant increase in the proportion of patients with severe AP (23.1% vs. 76.9%) and a higher proportion of systemic inflammatory response scores (25.9% vs. 44.6%) in comparison to patients with normal SF levels. The area under the ROC curve for SF in predicting persistent organ failure was 0.812 [95% confidence interval 0.721–0.904]. Conclusions F concentrations were positively correlated with the severity of AP, and quantitative assessment of SF can predict disease severity and organ failure in patients with AP.
 
Kaplan–Meier survival curves of patients with T1 colorectal cancer in months (P values were calculated by log-rank test). a Overall survival curves of poorly differentiated cluster grade; b Disease-free survival curves of poorly differentiated cluster grade; c Overall survival curves of depth of submucosal invasion; d Disease-free survival curves of depth of submucosal invasion
Survival time of T1 colorectal cancer patients with different poorly differentiated cluster grades
Survival time of T1 colorectal cancer patients with different depths of submucosal invasion
Kappa consistency test between our two pathologists for PDC grading
Background T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. Methods We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. Results Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR] G 3 = 0.001; 95% confidence interval [95% CI] G 3 = < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR] G 2 = 4.315; 95% CI G 2 = 1.506, 12.568; HR G 3 = 5.049; 95% CI G 3 = 1.326, 19.222) and disease-free survival (HR G 3 = 6.621; 95% CI G 3 = 1.472, 29.786). Conclusions Poorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.
 
Diagnosis of gastric antrum lymphangioma. a The surface of the overlying mucosa was normal. b EUS revealed an homogeneous echoless mass with a high echogenic separation inside. c No signs of blood flow. d Abdominal contrast-enhanced CT scan revealed a low density nodular mass without apparent enhancement. e Histopathological examination showed thin-walled, dilated lymphatic channels separated by fine fibrous stroma (hematoxylin‑eosin staining; magnification, × 40). f High power histopathological view showed flat endothelial cells lined the lymphatic canals (hematoxylin‑eosin staining; magnification, × 100)
Diagnosis of gastric body carcinoma. a White-light endoscopy showed a slightly elevated (IIa) and depressed (IIc) lesion. b Magnifying endoscopy with blue laser imaging (ME-BLI) showed demarcation line (DL), absent microsurface pattern (AMSP), and irregular microvascular pattern (IMVP). c EUS revealed a hypoechoic lesion infiltrating into the third layer. d Histopathological examination showed carcinoma cells infiltrating into the submucosa (hematoxylin‑eosin staining; magnification, × 40)
Background Gastric lymphangioma is one of the highly rare benign tumors characterized by multilocular or unilocular lymphatic spaces. Herein, we report a case of lymphangioma in the gastric antrum. Case presentation A 77-year-old male patient who had been experiencing epigastric discomfort for a year was presented to our hospital. A gastric subepithelial lesion was diagnosed by upper endoscopy and was entirely excised via diatal subtotal gastrectomy. Endoscopic ultrasonography revealed an echoless homogenous echo pattern in the third wall layer. A lymphangioma was diagnosed by pathologic investigation of the resected specimen. The PubMed, Embase and Web of Science databases were reviewed for literature in English while using the keywords of “gastric lymphangioma” or “lymphangioma of stomach” or “gastric lymphatic cyst” or “lymphatic cyst of stomach” and the results were discussed. Conclusion Gastric lymphangioma is a rarely occurring submucosal tumor that should be considered when diagnosing subepithelial lesions in the stomach.
 
Chest computed tomography showing mucus hypersecretion (black arrows), thickening of the peri-bronchiolar walls (white arrowheads) and a “tree-in-bud” pattern reflecting bronchiolar mucoid impaction with additional involvement of adjacent alveoli (black arrowheads)
Serum protein electrophoresis. The numbers represent the electrophoretic run of different patients. When the sample is applied and the electric current is turned on, the serum proteins migrate differentially. Then, they are fixed and stained in blue. The most stained band is albumin, followed by alpha 1 globulin, alpha 2 globulin, beta globulin and gamma globulin. Column 6 shows a normal pattern of gamma globulin intensity and width. Column 7 is from the case reported, showing a marked reduction in the gamma globulin region. Column 8 was obtained from a patient with a monoclonal peak just after the beta globulin band and reduced gamma region. Column 3 displays a polyclonal gamma globulin augmentation (polyclonal hypergammaglobulinemia). After staining, the results are read by spectrometry to quantify each band
Background Common variable immunodeficiency (CVID) is a rare disease that affects children and adults and is often difficult to diagnose. Despite being one of the most frequent causes of immunodeficiency, involving gastrointestinal (GI), respiratory, and hematological systems, the disease onset can have heterogeneous and intermittent symptoms, frequently leading to diagnostic delay. GI symptoms are common and can include diarrhea, but the asymptomatic periods lead to overlooking the recurrent pattern. The same can occur with respiratory infections, thus delaying CVID suspicion. The starting point for CVID diagnosis is the decreased gamma globulin levels in serum protein electrophoresis (SPE), also observed through direct immunoglobulin’s dosage. Case presentation The patient is a 38 years-old man who had intermittent diarrhea and recurrent airway infections for 19 years, but the CVID diagnosis was achieved only after SPE was carried out. At that time, he was already malnourished, and developed other complications related to CVID in a short period. Conclusions SPE is readily available and inexpensive, but is not part of the laboratory approach in diarrhea. According to the case presented herein, it can be useful for patients with recurrent infections or other clues of the disease.
 
Flowchart describing the patient identification and selection process
Receiver operating characteristic curves. Performance of the predictive model in comparison to a single laboratory parameters, b the APACHE II score, and c applied to the entire patient collective
Association of blood parameters with infected pancreatic necrosis
Multivariate logistic regression model for prediction of infected pancreatic necrosis
Background In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet. Methods This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection. We conducted a retrospective analysis from the hospital information and reimbursement data system and screened 705 patients hospitalized with diagnosis of acute pancreatitis who underwent contrast-enhanced computed tomography and additional diagnostic puncture or drainage of necrotic collections. Both clinical and laboratory parameters were analyzed for an association with a microbiologically confirmed infected pancreatic necrosis. A prediction model was developed using a logistic regression analysis with stepwise inclusion of significant variables. The model quality was tested by receiver operating characteristics analysis and compared to single parameters and APACHE II score. Results We identified a total of 89 patients with necrotizing pancreatitis, diagnosed by computed tomography, who additionally received biopsy or drainage. Out of these, 59 individuals had an infected necrosis. Eleven parameters showed a significant association with an infection including C-reactive protein, albumin, creatinine, and alcoholic etiology, which were independent variables in a predictive model. This model showed an area under the curve of 0.819, a sensitivity of 0.692 (95%-CI [0.547–0.809]), and a specificity of 0.840 (95%-CI [0.631–0.947]), outperforming single laboratory markers and APACHE II score. Even in cases of missing values predictability was reliable. Conclusion A model consisting of a few single blood parameters and etiology of pancreatitis might help for differentiation between infected and non-infected pancreatic necrosis and assist medical therapy in acute necrotizing pancreatitis.
 
Patient flow diagram. A total of 231 patients were eligible for study purposes. After exclusions, data from 110 patients were included. Early allograft dysfunction (EAD) was defined according to the Olthoff criteria. Elevated aminotransferase level on the first 2 postoperative days (AST or ALT > 2000 IU/L) was defined as a sign of ischemia–reperfusion-injury (IRI). IRI patients were classified according to their PCT level into IRI patients with PCT > 15 mcg/l and IRI patients with PCT < 15 mcg/l
Procalcitonin during the first week after liver transplantation. Panel A. Whole study cohort. Panel B. EAD versus non-EAD patients. Panel C. IRI versus non-IRI patients. Panel D. IRI patients with graft survival versus IRI patients with graft loss. Bar charts represent median PCT level, IQR is represented by the vertical black line. P-values are indicated by ns (not significant) and * (significant)
Kaplan Meier Analysis of graft and patient survival of non-IRI patients and IRI patients with PCT > 15 mcg/l versus IRI patients with PCT < 15 mcg/l. Panel A. 12-month graft survival of non-IRI patients was 56/64 (87.5%). 12-month graft survival of IRI patients with PCT > 15 mcg/l did not differ from that of non-IRI patients (25/27 (92.6%); p=0.483) and was lower in IRI patients with PCT < 15 mcg/l (11/19 (57.9%); p=0.002). Panel B. 12-month patient survival of non-IRI patients was 56/64 (87.5%). 12-month patient survival of IRI patients with PCT > 15 mcg/l did not differ from that of non-IRI patients (25/27 (92.6%); p = 0.483) and was lower in IRI patients with PCT < 15 mcg/l (13/19 (68.4%); p = 0.034)
Background: Ischemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT. Methods: Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed. Results: Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD. Conclusion: Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.
 
The flow chart diagram for the patient enrollment. UAS, upper abdominal surgery; AICU, anesthesia intensive care unit
Receiver operator characteristic curve of the individual variables for predicting SPCs. Lac, Lactate; SII, Systemic immune-inflammation index; CRP, C-reactive protein; AUC, area under the receiver operating characteristic curve
Receiver operator characteristic curve of the combined model for predicting SPCs. AUC, area under the receiver operating characteristic curve
Background Systemic pro-inflammatory factors play a critical role in mediating severe postoperative complications (SPCs) in upper abdominal surgery (UAS). The systemic immune-inflammation index (SII) has been identified as a new inflammatory marker in many occasions. The present study aims to determine the association between SII and the occurrence of SPCs after UAS. Methods Included in this study were 310 patients with upper abdominal tumors who received UAS and subsequently were transferred to the anesthesia intensive care unit between November 2020 and November 2021 in Nanjing Drum Hospital. SPCs, including postoperative pulmonary complications (PPCs), major adverse cardiac and cardiovascular events, postoperative infections and delirium, were recorded during the hospital stay. The clinical features of the patients with and without SPCs were compared by Student’s t-test or Fisher’s exact test as appropriate. Risk factors associated with SPC occurrence were evaluated by univariable and multivariable logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to establish a cut-off level of SII value to predict SPCs. Results Of the 310 patients receiving UAS, 103 patients (33.2%) presented at least one SPC, including PPCs (n = 62), adverse cardiovascular events (n = 22), postoperative infections (n = 51), and delirium (n = 5). Both preoperative SII and 1-h postoperative SII in patients with SPCs were significantly higher than those in patients without SPCs. Multivariate analysis showed that 1-h postoperative SII was an independent predictor for SPC occurrence (OR = 1.000, 95% CI 1.000–1.000, P = 0.007), together with postoperative C-reactive protein, postoperative arterial lactate, postoperative oxygenation-index and older age. The ROC curve showed that the optimal cutoff value of 1-h postoperative SII to predict SPCs was 754.6078 × 10 ⁹ /L, with an 88.3% sensitivity and a 29% specificity. Multivariate analysis also confirmed that 1-h postoperative SII > 754.6078 × 10 ⁹ /L was associated with increased SPC occurrence (OR = 2.656, 95% CI 1.311–5.381, P = 0.007). Conclusion Our findings demonstrated an association between the higher level of 1-h postoperative SII and SPCs, suggesting that 1-h postoperative SII, especially categorized 1-h postoperative SII using cutoff value, may be a useful tool for identifying patients at risk of developing SPCs.
 
Pooled analysis of the PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms variant alleles on hepatic enzymes including a ALT and b AST. The frequencies of the respective risk alleles were as follows; 0 risk alleles = 246, 1 risk allele = 127, 2 risk alleles = 39, and 3 risk alleles = 07
Proportion of a significant hepatic fibrosis (≥ F2), b advanced hepatic fibrosis (≥ F3), and c hepatic cirrhosis (F4) in all CHC patients with 0, 1, 2 and 3 risk alleles of PNPLA3 and TM6SF2 variants
Background The present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients. Methods In total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated. Results Genotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy–Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis ( p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load ( p = > 0.05). Conclusions PNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.
 
Skeletal muscle measurements at L3 level before and after neoadjuvant therapy
Flow chart of the study. SML: Significant muscle loss. A: Male; B: Female
ROC curve to determine the optimal cut-off value for ΔSMI (%)/250 days
Postoperative pathological regression response after neoadjuvant therapy in patients with LA-GIST
A 3-year survival of pre-treatment sarcopenia versus pre-treatment non-sarcopenia; B 3-year survival between post-treatment sarcopenia and post-treatment non-sarcopenia; C 3-year survival between the appearance of SML and No-SML during neoadjuvant therapy in men. D 3-year survival between the appearance of SML and No-SML during neoadjuvant therapy in women
Background: Currently, the effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) remains unclear. This study aims to investigate the relationship between changes in skeletal muscle and postoperative complications, survival and tumor response in patients with LA-GIST during neoadjuvant therapy with imatinib. Methods: We retrospectively analyzed pre- and post-treatment computed tomography images of 57 GIST patients who underwent radical surgery after neoadjuvant therapy with imatinib from January 2013 to March 2019. Skeletal muscle index (SMI) was measured at the L3 vertebral level in all patients. A cut-off value (SMI < 52.3 cm2/m2 and < 38.6 cm2/m2 for men and women, respectively) published in a previous study was used to define sarcopenia. Based on gender, we defined ΔSMI (%)/250 days above 9.69% for men and ΔSMI (%)/250 days above 7.63% for women as significant muscle loss (SML). Factors associated with postoperative complications and tumor response were analyzed using logistic regression, and predictors affecting patient prognosis were analyzed using Cox regression. Results: Of the 57 patients, sarcopenia was present before and after neoadjuvant therapy in 20 (35.09%) and 28 (49.12%) patients, respectively. It was not associated with immediate or long-term clinical outcomes. However, patients with SML during neoadjuvant therapy had a higher incidence of postoperative complications (60.00% vs. 25.00%, p = 0.008), worse pathological regression (44.00% vs. 75.00%, p = 0.017) and worse 3-year survival (Male, 68.75% vs. 95.45%, p = 0.027; Female, 66.67% vs. 100.00%, p = 0.046) than patients without SML. Conclusion: The development of SML during neoadjuvant therapy in LA-GIST patients, rather than pre- and post-treatment sarcopenia, is a major prognostic factor for the long-term prognosis and is also associated with recent postoperative complication rates and pathological regression.
 
Background Hepatocellular carcinoma (HCC) is a serious malignant disease with high incidence, high mortality and poor prognosis. This study aimed to establish a novel signature based on apoptosis-related genes (ARGs) to predict the prognosis of HCC. Methods Expression data of HCC from TCGA database and the list of 160 ARGs from MSigDB were downloaded. The genes included in apoptosis-related signature were selected by univariate Cox regression analysis and lasso Cox regression analysis. Subsequently, a prognostic risk model for scoring patients was developed, and then separates patients into two groups. Kaplan–Meier and receiver operating characteristic analysis were performed to evaluate the prognostic value of the model in TCGA, GEO and ICGC databases. The characteristics of immune cell infiltration between two groups of HCC were investigated. Finally, a nomogram was plotted to visualize the prognosis prediction. Results Nine genes (CDC25B, DAP3, ETF1, GSR, LGALS3, MGMT, PPP2R5B, SQSTM1 and VDAC2) were included in the prognostic risk model. Survival was lower in the high-risk group. Surprisingly, the high-risk group was significantly more in immune cell infiltration and with higher immunoscore and stromalscore than in the low-risk group. In addition, the risk score was an independent prognostic factor for HCC. Conclusions Prognostic signature comprising nine ARGs could be used as a potential prognostic factor for HCC. It also provides an important idea for further understanding the immunotherapy of HCC.
 
Four running patterns of the left gastric vein. Yellow and green arrowheads point to the left gastric veins. The running patterns indicated by the yellow arrowheads were more frequently ligated than the patterns indicated with green arrowheads. LGV, left gastric vein; CHA, common hepatic artery; SpA, splenic artery; DGA, duodenal gastric artery; PHA, proper hepatic artery; PV, portal vein; SpV, splenic vein; SMV, superior mesenteric vein
Mechanism of reducing the development of delayed gastric emptying after subtotal stomach-preserving pancreatoduodenectomy by preserving the left gastric vein as suggested. Double black lines indicate the ligation point. PV, portal vein; SpV, splenic vein; SMV, superior mesenteric vein; GCT, gastrocolic trunk; LGV, left gastric vein; RGV, right gastric vein; SGV, short gastric vein; RGEV, right gastroepiploic vein
Running pattern of LGV frequency and association between running patterns of the left gastric vein and ligation rate
Univariate and multivariate analysis of the association between delayed gastric emptying and operative factors
Univariate and multivariate analysis of the association between delayed gastric emptying and operative factors in LGV ligation group
Background This study aimed to determine which running pattern of the left gastric vein (LGV) is most frequently ligated in subtotal stomach-preserving pancreatoduodenectomy (SSPPD) and how LGV ligation affects delayed gastric emptying (DGE) after SSPPD. Methods We retrospectively analysed 105 patients who underwent SSPPD between January 2016 and September 2021. We classified the running pattern of LGV as follows: type 1 runs dorsal to the common hepatic artery (CHA) or splenic artery (SpA) to join the portal vein (PV), type 2 runs dorsal to the CHA or SpA and joins the splenic vein, type 3 runs ventral to the CHA or SpA and joins the PV, and type 4 runs ventral to the CHA or SpA and joins the SpV. Univariate and multivariate analyses were used to identify differences between patients with and without DGE after SSPPD. Results Type 1 LGV running pattern was observed in 47 cases (44.8%), type 2 in 23 (21.9%), type 3 in 12 (11.4%), and type 4 in 23 (21.9%). The ligation rate was significantly higher in type 3 (75.0%) LGVs ( p < 0.0001). Preoperative obstructive jaundice ( p = 0.0306), LGV ligation ( p < 0.0001), grade B or C pancreatic fistula ( p = 0.0116), and sepsis ( p = 0.0123) were risk factors for DGE in the univariate analysis. Multivariate analysis showed that LGV ligation was an independent risk factor for DGE (odds ratio: 13.60, 95% confidence interval: 3.80–48.68, p < 0.0001). Conclusion Type 3 LGVs are often ligated because they impede lymph node dissection; however, LGV preservation may reduce the occurrence of DGE after SSPPD.
 
Flow chart showing the selection of cases. Abbreviation: BMI-SDS, body mass index standard deviation score
Histogram that shows when major complications occurred following PLB among the total cases. Abbreviation: PLB, percutaneous liver biopsy
Aim Although major complication rates following percutaneous liver biopsy (PLB) have been reported to be higher in children than in adults, scarce data are available regarding pediatric patients stratified by native and transplanted liver. We aimed to assess the factors associated with major complications after percutaneous biopsy of native or transplanted liver using a nationwide inpatient database. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients who underwent PLB between 2010 and 2018. We described major complication rates and analyzed factors associated with major complications following PLB, stratified by native and transplanted liver. Results We identified 3584 pediatric PLBs among 1732 patients from 239 hospitals throughout Japan during the study period, including 1310 in the native liver and 2274 in the transplanted liver. Major complications following PLB were observed in 0.5% (n = 18) of the total cases; PLB in the transplanted liver had major complications less frequently than those in the native liver (0.2% vs. 1.0%, p = 0.002). The occurrence of major complications was associated with younger age, liver cancers, unscheduled admission, anemia or coagulation disorders in cases with native liver, while it was associated with younger age alone in cases with transplanted liver. Conclusions The present study, using a nationwide database, found that major complications occurred more frequently in pediatric cases with native liver and identified several factors associated with its major complications.
 
Flowchart of the study population
Meandering main pancreatic duct (MMPD) at the head of the pancreas. a Reverse-Z subtype C1 where the more upstream turn is tight and < 90° and the second turn is smoother and > 90°. b Reverse-Z subtype C2 where the more upstream turn is > 90° and the second turn is tight and < 90°. c Reverse-Z subtype C3 where there are two tight and < 90° turns in the horizontal direction along the same plane. d C3 subtype with the duct of Santorini which attaches to the right tight turn and drains into the minor papilla. e Loop-up configuration. f Loop-down configuration. g N-shape where the duct forms a deep notch. h N-shape where the ansa pancreatica attaches to the notch and drains into the minor papilla
Schematic and MRI images of non-MMPD type courses at the head of the pancreas. a Descending course. b Sigmoid course with a sigmoid curve. c Vertical course draining straight down
Background No previous studies have examined the possible relationship between intraductal papillary mucinous neoplasm (IPMN) and the developmental ductal variations of the pancreas, such as an ansa pancreatica and a meandering main pancreatic duct (MMPD). Methods This retrospective cross-sectional study enrolled 214 patients, 108 with IPMN disease and 106 subjects from a community at the tertiary care unit. The main pancreatic duct (MPD) was evaluated in the head of the pancreas by its course, which were non-MMPD: descending, vertical, and sigmoid, or MMPD including loop types, reverse-Z subtypes, and an N-shape, which was identified for the first time in this study. IPMN patients were also evaluated for worrisome features (WF) or high-risk stigmata (HRS), and the extent of IPMN cysts. Results Among IPMN patients, 18.4% had MMPD, which we observed in only 3.0% of the control group ( P < 0.001). Patients with MMPD were more likely to belong to the IPMN group compared with non-MMPD patients [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2–24.9]. Compared with a descending shape MPD, IPMN patients with an N-shaped MPD were more likely to have a cystic mural nodule (OR 5.9, 95% CI 1.02–36.0). The presence of ansa pancreatica associated with more extent IPMN disease (OR 12.8, 95% CI 2.6–127.7). Conclusions IPMN patients exhibited an MMPD more often than control patients. Ansa pancreatica associated with multiple cysts. Furthermore, an N-shape in IPMN patients associated with cystic mural nodules, suggesting that this shape serves as a risk factor for more severe IPMN.
 
Background Painless gastrointestinal endoscopy is widely used for the diagnosis and treatment of digestive diseases. At present, propofol is commonly used to perform painless gastrointestinal endoscopy, but the high dose of propofol often leads to a higher incidence of cardiovascular and respiratory complications. Studies have shown that the application of propofol combined with ketamine in painless gastrointestinal endoscopy is beneficial to reduce the dosage of propofol and the incidence of related complications. Esketamine is dextrorotatory structure of ketamine with a twice as great anesthetic effect as normal ketamine but fewer side effects. We hypothesized that esketamine may reduce the consumption of propofol and to investigate the safety of coadministration during gastrointestinal endoscopy. Methods A total of 260 patients undergoing painless gastrointestinal endoscopy (gastroscope and colonoscopy) were randomly divided into P group (propofol + saline), PK1 group (propofol + esketamine 0.05 mg/kg), PK2 group (propofol + esketamine 0.1 mg/kg), and PK3 group (propofol + esketamine 0.2 mg/kg). Anesthesia was achieved by 1.5 mg/kg propofol with different doses of esketamine. Propofol consumption per minute was recorded. Hemodynamic index, pulse oxygen saturation, operative time, induction time, awakening status, orientation recovery time, adverse events, and Mini-Mental State Examination (MMSE) were also recorded during gastrointestinal endoscopy. Results Propofol consumption per minute was 11.78, 10.56, 10.14, and 9.57 (mg/min) in groups P, PK1, PK2, and PK3, respectively; compared with group P, groups PK2 and PK3 showed a decrease of 13.92% ( P = 0.021) and 18.76% ( P = 0.000), respectively. In all four groups, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), but not pulse oxygen saturation (SpO 2 ) significantly decreased ( P = 0.000) immediately after administration of induction, but there were no significant differences between the groups. The induction time of groups P, PK1, PK2, and PK3 was 68.52 ± 18.394, 64.83 ± 13.543, 62.23 ± 15.197, and 61.35 ± 14.470 s, respectively ( P = 0.041). Adverse events and psychotomimetic effects were observed but without significant differences between the groups. Conclusions The combination of 0.2 mg/kg esketamine and propofol was effective and safe in painless gastrointestinal endoscopy as evidenced by less propofol consumption per minute, shorter induction time, and lower incidence of cough and body movement relative to propofol alone. The lack of significant differences in hemodynamic results, anesthesia-related indices, adverse events, and MMSE results showed the safety to apply this combination for painless gastrointestinal endoscopy. Trial registration This study was registered with China Clinical Trial Registration on 07/11/2020 (registration website: chictr.org.cn; registration numbers: ChiCTR https://clinicaltrials.gov/ct2/show/2000039750 ).
 
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram of the study
(continued)
An overview of studies included in this systematic scoping review and their main findings
Covid-19 is a pandemic disease that is more severe and mortal in people with immunodeficiency, such as those with inflammatory bowel disease (IBD). On the other hand, no definitive treatment has been identified for it and the best way to control it is wide spread vaccination. The aim of this study was to evaluate the benefits and side effects of different vaccines in patients with IBD. Three Electronic databases [Medline (accessed from PubMed), Scopus, Science Direct, and Cochrane] were searched systematically without time limit, using MESH terms and the related keywords in English language. We focused on the research studies on the effect and side effects of Covid-19 vaccination in patients with IBD. Articles were excluded if they were not relevant, or were performed on other patients excerpt patients with IBD. Considering the titles and abstracts, unrelated studies were excluded. The full texts of the remained studies were evaluated by authors, independently. Then, the studies' findings were assessed and reported. Finally, after reading the full text of the remained articles, 15 ones included in data extraction. All included studied were research study, and most of them (12/15) had prospective design. Totally, 8/15 studies were performed in single-center settings. In 8/15 studies, patients with IBD were compared with a control group. The results were summarized the in two categories: (1) the effect of vaccination, and (2) side effects. The effect of vaccination were assessed in 13/15 studies. Side effects of Covid-19 vaccination in patients with IBD were reported in 7/15 studies. Patients with IBD can be advised that vaccination may have limited minor side effects, but it can protect them from the serious complications of Covid-19 and its resulting mortality with a high success rate. They should be also mentioned in booster doses.
 
Background Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan–Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. Results NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. Conclusions NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.
 
Insoluble excretion. a Insoluble MMX tablets in the rectum. b Insoluble excretion of intact tablets. Insoluble excretion was defined as the excretion of tablets with an intact pH-responsive coating, regardless of the number and frequency of excreted tablets
Various types of insoluble excretion. a, b “Melted tablets”, where the internal MMX is excreted with only the pH-responsive coating having dissolved. c, d So-called “ghost pills”, where the contents have disappeared, and only the coating is excreted. Cases in which excreted MMX had been exposed due to part of the coating having dissolved, and those involving so-called "ghost pills", where the contents of the tablet had disappeared, and only the coating was excreted, were not counted as insoluble excretion in this study
Insoluble excretion rate according to the extent of inflammation and stool consistency
A comparison of defecation frequency and ROC curve analysis. a A comparison of defecation frequency at the start of MMX treatment. b ROC curve analysis of defecation frequency and insoluble excretion. ROC analysis in which the defecation frequency at the start of treatment was employed as the test variable indicted that a defecation frequency of ≥ 3.5 times a day exhibited sensitivity and specificity of 66.7% and 65.5%, respectively, for predicting insoluble MMX excretion
Background Multi-matrix mesalazine (MMX) is an important treatment for ulcerative colitis (UC); however, it is often excreted intact, which increases the risk of relapse. This study aimed to clarify the risk factors for insoluble MMX excretion. Methods The subjects were 102 UC patients who were newly prescribed MMX alone to induce remission. Their stools were evaluated on the Bristol Stool Form Scale (BSFS), the presence/absence of insoluble MMX excretion was investigated in interviews, and defecation frequency at the start of treatment and disease type were retrospectively investigated by examining their medical records. Results The insoluble excretion rate (IER) was 14.7%. It tended to be higher in the patients with left-sided colitis or extensive colitis, although the differences among the disease types were not significant (p = 0.053). The mean defecation frequency of the patients that reported insoluble MMX excretion was significantly higher than that of the patients that did not report it (6.27 ± 5.28 vs. 3.69 ± 3.17, p < 0.05). The IER tended to be higher among the patients with soft stools (4.5%, 21.9%, and 23.1% in those with BSFS scores of ≤ 4, 5, and ≥ 6, respectively). In ROC analysis of defecation frequency, ≥ 3.5 defecations was found to exhibit sensitivity and specificity of 66.7% and 65.5%, respectively, for predicting insoluble MMX excretion. Conclusions The likelihood of insoluble MMX excretion is influenced by defecation frequency and the extent of inflammation. It is important to keep the possibility of insoluble excretion in mind when prescribing MMX.
 
The site of Sphinkeeper™ implantation within the interspincteric space. It shows the ten prostheses around the entire circumference of the internal anal sphincter: transverse plane (panel A) and frontal plane (panel B)
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart of study selection [21, 22] (update search not presented in PRISMA)
Purpose The purpose of this systematic review is to evaluate whether self-expandable implantable vs non-self-expandable injectable bulking agents (second-line therapies) are equal/superior in terms of effectiveness (severity, quality of life [QoL]) and safety (adverse events) for faecal incontinence (FI). Methods A systematic review was conducted, and five databases were searched (Medline via Ovid, Embase, Cochrane Library, University of York Centre for Reviews and Dissemination, and International Network of Agencies for Health Technology database). In-/exclusion criteria were predefined according to the PICOS scheme. The Institute of Health Economics risk of bias (RoB) tool assessed studies' internal validity. According to the Grading of Recommendations, Assessment, Development and Evaluation approach, the strength of evidence for safety outcomes was rated. A qualitative synthesis of the evidence was used to analyse the data. Results The evidence consists of eight prospective single-arm, before-after studies (166 patients) fulfilling the inclusion criteria for assessing clinical effectiveness and safety of implantable bulking agents. FI severity statistically significantly improved in five of seven studies rated by the Cleveland Clinic FI Score and in three of five studies measured by the Vaizey score. Statistically significant improved disease-related QoL was found in one of five studies measured by the FI QoL Score and in one of two studies rated by the American Medical Systems score. Procedure-related adverse events occurred in 16 of 166 patients (i.e., intraoperative complications, anal discomfort and pain). Device-related adverse events occurred in 48 of 166 patients, including prostheses’ dislodgement and removed/extruded prostheses. Studies were judged with moderate/high RoB. The strength of evidence for safety was judged to be very low. Conclusion Implantable bulking agents might be an effective and safe minimally invasive option in FI treatment if conservative therapies fail. FI severity significantly improved, however, effects on QoL need to be explored in further studies. Due to the uncontrolled nature of the case series, comparative studies need to be awaited.
 
The cumulative incidence of the virological response (VR) of the normal and mildly elevated alanine aminotransferase (ALT) groups. The p-value was determined using log-rank testing
Hepatitis B virus (HBV) DNA levels of patients with normal or mildly elevated alanine aminotransferase (ALT) at each time point (*p < 0.05)
The trend of hepatitis B surface antigen (HBsAg) levels in patients with normal or mildly elevated alanine aminotransferase (ALT) across the study time points
a Liver stiffness measurements before treatment and at week 48 b Liver stiffness measurements before treatment and at week 96 (***p < 0.001)
Background: There are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients. Methods: We retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks. Results: A total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively. Conclusions: HBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients.
 
Abdominal CT showing the radiological response to combined and maintenance therapy. A–C Multiple masses in the pelvic and abdominal cavities at the initial diagnosis. D–F Partial response was achieved after two cycles of combined therapy. G–I Continuous partial response during maintenance therapy with anlotinib
Histological and immunohistochemistry analysis of the intra-abdominal desmoplastic small round cell tumor. A Histological appearance (× 200 magnification). B Immunohistochemistry of CD56 (× 200 magnification). C Immunohistochemistry of DES (× 200 magnification). D Immunohistochemistry of Ki-67 (× 200 magnification)
Grade 3 treatment-related adverse events. A Hematochezia after two cycles of the combined therapy. B Hematochezia disappeared after active management
Background Intra-abdominal desmoplastic small round cell tumors (IADSRCT) are rare and aggressive neoplasia that are resistant to chemotherapy. Anlotinib is an oral multi-target tyrosine kinase inhibitor that also has anti-angiogenic and anti-proliferative properties. In this article, we report on a case showing effective and durable responses to chemotherapy combined with anlotinib in a young man with IADSRCT. Case presentation A 27-year-old man was admitted to our hospital complaining of a palpable periumbilical mass that had been present for longer than 4 months. The diagnosis of IADSRCT was confirmed by biopsy and immunohistochemistry. An extensive unresectable metastasis was found on the initial diagnosis. The patient received six cycles of chemotherapy combined with anlotinib, and maintenance therapy with anlotinib was recommended. Hematochezia, proteinuria and hypertension were observed, however, long-term maintenance therapy was well tolerated. A partial response was observed after two cycles of combined therapy and the patient was still alive with stable disease at the time of reporting. Conclusions Chemotherapy combined with anlotinib plus anlotinib maintenance showed promising efficacy and manageable toxicity in the treatment of advanced IADSRCT.
 
Background Perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare but life-threatening complications. The treatment of Type-II-periampullary perforations that develop during endoscopic sphincterotomy remains a topic of discussion. This study aimed to evaluate the usefulness of fully covered self-expanding metal stenting (FCSEMS) for treating Type-II perforations. Methods The files of all patients who underwent the ERCP procedures between January 2015 and October 2021 were retrospectively reviewed; patients with Stapher Type-II perforation were included in the current study. Patients with FCSEMS were classified into two groups: those who underwent FCSEMS and those who were conventionally followed up. Moreover, patients with FCSEMS were classified into two subgroups: those who underwent simultaneous stenting and those who underwent late stenting. Mortality, surgical intervention, percutaneous drainage, length of hospital stay, and inflammatory markers were all compared between the groups. Results Of the 9253 patients undergoing ERCP during the study period, 28 patients (0.3%) were found to have Type-II perforation. The mean age of these patients was 67.7 ± 3.9 years, and 15 patients were female. FCSEMS was performed on 19 patients, whereas 9 patients were on conventional follow-up. None of the patients developed mortality. In the conventional follow-up group, one patient required percutaneous drainage and one required surgical intervention. In contrast, none of the patients in the FCSEMS group required additional intervention. At a statistically significant level, the length of hospital stay was found to be shorter in the FCSEMS group. There was no difference in inflammatory markers between the two groups. In nine patients, FCSEMS was performed simultaneously, whereas, in ten patients, FCSEMS was performed later because they required a second intervention. These two subgroups did not differ in terms of outcomes. Conclusions FCSEMS is a safe and effective treatment modality for patients with Type-II perforation. Moreover, it can be safely used in patients whose perforations are diagnosed during the ERCP procedure and in patients whose diagnoses are made after the procedure.
 
The program of sDNA tests and FIT detection and evaluation
The evaluation value of CRC patients and screening of subjects. The evaluation value of CRC patients was significantly higher than those of AA, NA, healthy controls, and other cancer patients. The evaluation value of AA and NA patients were significantly higher than those in healthy controls. No significant differences were seen between AA and NA patients, other cancer patients, and healthy controls
The ROC curves for the novel evaluation with sDNA tests and FIT were analyzed to assess CRC and early CRC, and the ROC curve for CEA to assess CRC. The AUC values for the novel evaluation with sDNA tests and FIT were 0.986 (0.975–0.996) for CRC and 0.945 (0.916–0.974) for early CRC. The AUC value for CEA was 0.611 (0.521–0.702)
The ROC curves for the novel evaluation with sDNA tests and FIT were analyzed to assess NA and AA. The AUC values for the novel evaluation with sDNA tests and FIT were 0.543 (0.434–0.651) for AA and 0.547 (0.474–0.621) for NA
Correlation between the initial levels of evaluation value and stage, and the initial levels of evaluation value and pathology. A No significant differences were seen between stage I–II and III–IV. B No significant differences were seen among patients with well, moderate, and poorly differentiated adenocarcinoma. C Dynamic changes in evaluation value following surgery. The evaluation value with sDNA tests and FIT of 20 CRC patients decreased dramatically a month after resection
Background Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China. Methods Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring. Results The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (< 165) at after surgery. Discussion The novel evaluation with sDNA test and FIT has increased sensitivity for screening of CRC and AA. The novel evaluation may have potential importance as an indicator of early CRC. Additionally, the dynamic changes of the comprehensive value after surgery were correlated with CRC treatment.
 
Eligibility criteria and grouping
Study protocol. ※Baseline variables: age, sex, ECOG-PS, ASA-PS, history of acute or recurrent pancreatitis, serum total bilirubin level before ERCP, serum amylase level before ERCP, ERCP indication, and presence of SOD, cholangitis, pancreatic duct obstruction at the head of the pancreas. ^Primary outcome: presence of PEP. #Secondary outcomes: presence of PEP in cases of difficult cannulation, PEP by various ERCP procedures, PEP by the presence of pancreatic duct cannulation and pancreatography, PEP by cannulation time, moderate and severe PEP, and PEP by high-risk factors for PEP
Findings form
Background Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure in the diagnosis and treatment of biliopancreatic diseases. The most common adverse event of ERCP is post-ERCP pancreatitis (PEP), which can sometimes be severe. Our previous study suggested that injecting ice water at the end of ERCP suppressed PEP, and we decided to investigate this effect in a multicenter randomized controlled trial. Methods This study is being conducted at eight hospitals in Japan starting in April 2022. Patients undergoing ERCP will be randomized to ice water group and control group. In the ice water group, 250 ml of ice water is injected toward the papilla at the end of ERCP. The next morning, a physical examination and blood tests are performed to evaluate for the development of pancreatitis. The goal is to have 440 cases in each group. Discussion The main cause of PEP is thought to be papilla edema. Cooling the papilla, as everyone naturally does at the time of a burn, is expected to prevent its inflammation and edema. Various methods to suppress PEP have been reported, but so far none of them are reliable. The method we have devised is very simple, easy, and safe. We hope that our study will change the world's ERCP common practice. Trial registration:UMIN000047528. Registered 20 April 2022, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053209
 
Crypt fixation and chemoprevention with lithium treatment. APC = adenomatous polyposis coli tumor-suppressor gene. DKK2 = Dickkopf WNT Signaling Pathway Inhibitor 2. ISCs = intestinal stem cells. WIF1 = WNT Inhibitory Factor 1. ISCs reside at the bottom of the crypts of the epithelium of the colon where they engage in ongoing neutral competition with each other for a position in the crypt. These neutral dynamics are disturbed whenever an ISCs acquires a second mutation in the APC allele. APC-mutant ISCs have a competitive advantage by secreting Wnt antagonists (e.g. NOTUM, WIF1, DKK2) that drive the differentiation of WT ISCs, thereby resulting in mutant crypt fixation and the development of premalignant adenomas. In this study, we propose that boosting the Wnt pathway in WT ISCs using lithium diminishes this competitive advantage and prevents adenoma formation. This figure was created by using Adobe Illustrator 2022 (version 26.0.3)
NOTUM in situ hybridization (ISH) in human FAP adenomatous lesion. Fluorescent staining of human intestinal adenomas was visualized with a SP8X confocal microscope using Leica Application Suite software (version 3.5.7)
Flowchart of the study design (as of May 2, 2022). ¹Hematology: haemoglobin, thrombocytes, leukocytes. ²Chemistry: GFR, creatinine, urea, sodium, potassium, calcium and TSH (if deviating T4). ³A pregnancy test is required for participants with the female gender. ⁴Urine sample: urine osmolality and urine creatinine. This figure was created by using Adobe Illustrator 2022 (version 26.0.3)
Total adenoma burden
Background Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by germline mutations in the Adenomatous Polyposis Coli ( APC) gene, resulting in the development of numerous colorectal adenomas. As these patients have a high risk of developing colorectal cancer (CRC), guidelines suggest prophylactic colectomy during early adulthood, however, adenoma development is still observed in the remaining intestinal tract. Therefore, FAP patients would benefit from chemoprevention strategies reducing the development of adenomas. Recent work in mice reveals a chemopreventive effect of lithium on the development of adenomas by inhibiting the expansion of Apc mutated intestinal stem cells (ISCs) within the crypts of normal intestinal mucosa. Here, we aim to investigate the effect of lithium on the spread of APC mutant cells within the human intestinal epithelium. Methods This prospective phase II single arm trial has a duration of 18 months. FAP patients (18–35 years) with a genetically confirmed APC mutation who did not undergo colectomy will be treated with lithium carbonate orally achieving a serum level of 0.2–0.4 mmol/l between month 6 and 12. Colonoscopy with biopsies of normal intestinal mucosa will be performed at baseline and every six months. The primary endpoint is the effect of lithium on the spread of APC mutant cells within intestinal crypts over time by using APC specific marker NOTUM in situ hybridization. Secondary endpoints include change in adenoma burden, patient reported side effects and safety-outcomes. Total sample size is 12 patients and recruitment will take place in the Amsterdam UMC, location AMC in the Netherlands. Discussion The outcome of this study will function as a proof-of-concept for the development of novel chemoprevention approaches that interfere with the competition between normal and mutant ISCs. Trial registration : ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT05402891 (June 1, 2022) and the EU Clinical Trials Register: EuraCT 2022-000240-30 (January 1, 2022).
 
STROBE study flowchart and the number of individuals at each stage of the study. ¹We only included those treated (class 1–2) to ensure data consistency. ²Clinical stage cT2-4N0M0 or cT1-4N+M0 for the 7th American Joint Committee on Cancer staging. ³50–70 Gy in 1.8–2 Gy/fraction. ⁴Without missing information in the TCR and death registry regarding survival status, and cause of death
Kaplan–Meier unadjusted overall survival curve (in years) in the primary analysis. CCT, consolidative chemotherapy
The overlap weights adjusted overall survival curve (in years) in the primary analysis. CCT, consolidative chemotherapy
Kaplan–Meier survival curve (in years) for the PS-matched subgroup (SA-1). CCT, consolidative chemotherapy
Background The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach. Methods Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches. Results Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52–0.86, P = 0.002). The HR of IECM was 0.66 ( P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses. Conclusions We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding.
 
Top-cited authors
Claudio Tiribelli
  • Italian Liver Foundation, Trieste, Italy
Stefano Bellentani
  • Clinica Santa Chiara
Flora Masutti
  • University of Trieste
Thierry Poynard
  • Assistance Publique Hôpitaux de Paris, Sorbonne University
Mona Munteanu