Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population­based cohort study.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn's disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions: Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance.

BACKGROUND: The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings. METHODS: Using the ULCAN portal, we noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations. RESULTS: Our study emphasized the connection between PROX1 and α-SMA in CAFs. Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship. CONCLUSION: PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition.

Dysregulated expression of slingshot protein phosphatase 1 (SSH1) disrupts circadian rhythm and WNT signaling associated to hepatocellular carcinoma pathogenesis.

Growing evidence underscores the circadian rhythm's essential function in liver stability and disease. Its disruption is progressively linked with metabolic issues, oncogene triggers, and heightened cancer susceptibility. Research points to slingshot protein phosphatase 1 (SSH1), a modulator of cofilin-1 (CFL-1), as instrumental in the reformation of the actin cytoskeleton, thereby impacting the invasiveness of various cancer types. Yet, the dynamics of SSH1's influence on liver cell stemness and circadian activity remain unclear. Through in-silico, tissue analysis, and functional assays, the study reveals a significant SSH1 expression in HCC samples, compared to non-cancerous counterparts, across six HCC platforms (AUC between 0.62 and 0.77, p < 0.01). The aberrant expression of SSH1 was correlated with poor patients' survival (HR = 1.70, p = 0.0063) and progression-free (HR = 1.477, p = 0.0187) survival rates. Targeting SSH1, either via Sennoside A or CRISPR SSH1 in Huh7 cells (Huh7-SSH1-/-) significantly suppressed cell viability, migration, invasion, colony and tumorsphere formation of the Huh7-SSH1-/- cells. Mechanistically, we showed that downregulated SSH1 expression suppressed CLOCK, BMAL1, WNT3, ß-catenin, LRP5/6, BCL2, VIM and Snail, with concomitant upregulated CFL-1/2, and CRY1 expression, indicating dysregulated circadian rhythm and WNT/ß-catenin oncogenic pathway deactivation. Treatments in reflected notable tumor size reductions in the mice treated with SenAlight (1.76-fold, p < 0.01) and SenAdark (3.79-fold, p < 0.01). The expression of SSH1, CLOCK, BMAL1 and ß-catenin proteins were significantly downregulated in the SenAlight and SenAdark mice; this was more so in the SenAdark mice. This reveals a potential treatment approach for HCC patients.

Association between nonalcoholic fatty liver disease and colorectal cancer: A population-based study.

Colorectal cancer (CRC) and nonalcoholic fatty liver disease (NAFLD) have high prevalence rates and place a considerable burden on the health-care industry. The association between both diseases is controversial. Our aim was to examine the association between NAFLD and CRC. Using data extracted from the Taiwan National Health Insurance Research Database (NHIRD) from 2000 to 2015, we enrolled 60 298 patients with NAFLD. Of these, 52,986 met the inclusion criteria. A comparison group was selected using 4-fold propensity score matching by age, sex, and year of index date. The primary outcome was the cumulative incidence of CRC in patients with NAFLD. Over a mean follow-up period of 8.5 years, 160 new cases of CRC were identified. The incidence rate of CRC was higher in the NAFLD group (12.23 per 100,000 person-years) than in the comparison cohort (6.0 per 100,000 person-years). Cox proportional hazards regression analysis revealed that the adjusted hazard ratio (HR) of CRC was 1.259 in the study group (95% confidence interval [CI]: 1.047-1.486, P = .003). Using Kaplan-Meier analysis, we ascertained that the cumulative incidence of CRC was significantly high in the NAFLD group. Patients older than 50 years, with diabetes mellitus (DM), and with chronic liver disease also exhibited a high risk of CRC. NAFLD was associated with a high risk of CRC. CRC occurs more frequently in patients with NAFLD aged between 50 and 59 years and those older than 60 years with comorbidities, including DM and chronic liver disease. Physicians should consider the subsequent risk of CRC when treating patients with NAFLD.

Negative pressure wound management in perineal wound status post abdominoperineal resection and extralevator abdominoperineal excision: a meta-analysis and trial sequential analysis.

PURPOSE: Recent evidence-based publications disclosed that negative pressure wound therapy (NPWT) may reduce the incidence rate of surgical site infection (SSI) and length of stay (LOS) compared with conventional drainage in patient status post abdominoperineal resection (APR) and extralevator abdominoperineal excision (ELAPE). METHODS: Data sources: Eligible randomized controlled trials and retrospective and prospective studies published before January 2023 were retrieved from databases (Cochrane Library, PubMed, and Embase). STUDY SELECTION: (a) The study involved patients undergoing ELAPE or APR with postoperative NPWT; (b) the study compared NWPT with conventional drainage and reported at least one outcome of interest (i.e., SSI); and (c) the study provided adequate information to calculate the effect estimated for meta-analysis. INTERVENTIONS: We calculated the odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The measure outcomes included surgical site infection(SSI) and length of stay (LOS). RESULTS: Eight articles, involving 547 patients, met the selection criteria. Compared to conventional drainage, NPWT was associated with a significantly lower SSI rate (fixed effect, OR 0.29; 95% CI 0.18-0.45; I2 = 0%) in eight studies and 547 patients. Besides, NPWT was associated with a shorter LOS (fixed effect, MD - 2.00; CI - 2.60 to - 1.39; I2 = 0%) than conventional drainage in three studies and 305 patients. In a trial sequential analysis, the cumulative number of patients in the analyses of both outcomes exceeded the required information size and surpassed the significance boundary in favor of NPWT, suggesting conclusive results. CONCLUSION: NPWT is superior to conventional drainage in both SSI rate and LOS, and the statistical power of SSI and LOS are confirmed by trial sequential analysis.

Early botulinum toxin injection reduces pain after hemorrhoidectomy: a pilot study.

BACKGROUND: Hemorrhoidectomy is the standard procedure for treating high-grade hemorrhoids. However, postoperative pain usually causes patients to delay or refuse surgical treatment. Because maximal resting pressure in the internal anal sphincter plays a major role in post-hemorrhoidectomy pain, Botulinum toxin injections have been proposed to reduce it. However, the optimal timing of Botulinum toxin injections is still unclear. The aim of the present study was to compare the effectiveness of early and intraoperative Botulinum toxin injections for postoperative pain control. METHODS: In this pilot study, we enrolled patients who had grade III or IV hemorrhoids and underwent Ferguson hemorrhoidectomy at a single tertiary care center from October 1, 2018 to November 30, 2020. The experimental group received 50 U Botulinum toxin injections to the internal anal sphincter 1 week before the operation, and the control group received injections intraoperatively. The primary endpoint was the daily maximal and resting visual analogue scale (VAS) score recorded from postoperative days 0-6. The secondary endpoints were analgesia requirements, number of bowel movements per day, healing time, and postoperative length of stay. Power of the daily resting VAS score is at least 93%, but the power of the daily maximal VAS is a little lower (71%) (calculated by G*Power 3.1.9.2). RESULTS: Sixty-two patients (male: female = 27:35; mean age = 47.6 ± 13.1 years) were randomized to the experimental group (n = 31) or control group (n = 31). The experimental group  (n = 31) showed significantly shorter postoperative hospital stay than the controls (n = 31; p = 0.019). A generalized estimating equations model revealed that the group that received Botulinum toxin  yielded a significantly lower maximal (OR 0.4, 95% CI 0.2-1.0, p = 0.041) and resting (OR 0.4, 95% CI 0.2-0.7, p < 0.001) VAS compared to controls at all time points. The Botulinum toxin group also had significantly less resting pain from postoperative days 1-5, and lower maximal subjective pain scores on postoperative days 1 (p = 0.024) and 4 (p = 0.044). Similar trends were observed on other days. CONCLUSIONS: Early Botulinum toxin injection produced shorter hospital stays, and less reported pain after hemorrhoidectomy than intraoperative injections, especially for pain at rest. TRIAL REGISTRATION: Identifier: NCT04485780 on ClinicalTrials.gov (retrospectively registered).

Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Two-Person Colonoscopy as a Training Approach to Non-sedation Colonoscopy.

BACKGROUND: Reported learning curves of colonoscopy vary from 94 to 275 cases and focus on one-person colonoscopy. Our aim was to evaluate the learning curve of two-person non-sedation colonoscopy for trainees in a single tertiary care hospital. PATIENTS AND METHODS: We conducted a retrospective study in 1264 patients who underwent diagnostic or screening colonoscopies in a single institution from August 2012 to January 2013. Most of the patients (1174/1264) did not receive sedation during the procedure. All procedures were performed under two-person control. Two third-year residents who received previous colonoscopic training via a plastic model were the trainees. RESULTS: In comparison to the performance of 5 staff members, the colonoscopic outcomes showed no significant differences in the completion rates (77.2% vs. 79.8%, P = .382), average polyp numbers (.9 ± 1.7 vs. 1.0 ± 1.8, P = .453), polyp detection rates (43.5% vs. 46.3%, P = .434), or intubation lengths (96.4 ± 29.3 vs. 96.3 ± 26.7 cm, P = .939). The total procedure times for the 2 groups were 17.2 ± 10.6 minutes (trainees) and 12.9 ± 7.8 minutes (staff) (P < .001). CONCLUSION: Trainees achieved acceptable outcomes over an 81-97 case learning curve under a two-person non-sedation colonoscopy technique, an approach with potential as a transition to single-operator colonoscopy.

Pneumatosis cystoides intestinalis in a patient with aseptic meningitis: a case report.

BACKGROUND: Although pneumatosis cystoides intestinalis (PCI) is observed in patients who are on corticosteroid treatment, most patients have underlying diseases requiring long-term corticosteroid treatment. Herein, we present a rare case of a patient with aseptic meningitis who had PCI of the ascending colon while receiving betamethasone treatment. CASE PRESENTATION: A 46-year-old man was sent to our institution due to disturbance in consciousness and general weakness. Brain computed tomography (CT) scan showed multiple hyperdense lesions over the bilateral hemisphere at the white-gray matter junction. Empiric antibiotic treatment with vancomycin and ceftriaxone was prescribed. Due to acute generalized exanthematous pustulosis (AGEP), we ordered betamethasone and diphenhydramine. Two days later, the patient had bloating and abdominal tenderness. Moreover, contrast-enhanced abdominal CT scan revealed PCI of the ascending colon. Since ischemic bowel disease was suspected, laparoscopy and colonoscopy were carried out. However, no abnormal mucosa or mass lesion was noted. Then, tachycardia, hypotension, and change in consciousness along with loss of brainstem reflex and increased intracranial pressure were noted. After further treatment, the patient's condition worsened, and he eventually died. CONCLUSION: As the outcomes of PCI range from benign to life-threatening, an accurate diagnosis must be made to prevent unnecessary abdominal surgeries. Benign PCI in a patient without PCI correlated to underlying diseases, but received short-term corticosteroid treatment should be considered.

Transarterial chemoembolization for intrahepatic multiple recurrent HCC after liver resection or transplantation.

BACKGROUND: Transarterial chemoembolization (TACE) can reduce tumor progression and help achieve good locoregional effect in hepatocellular carcinoma (HCC) patients with intrahepatic multiple recurrence (IHMR) after liver resection (LR). The effect of TACE on HCC patients with IHMR after liver transplantation (LT) remains unclear. The purpose of this study was to investigate the effect of TACE on IHMR after LR or LT. MATERIAL AND METHODS: This hospital-based retrospective study included 968 and 180 HCC patients who had undergone LR or LT, respectively, in the past decade. Parameters included clinical characteristics, alpha-fetoprotein level, Child classification, tumor stage at first treatment, tumor size at recurrence, and recurrence and survival status. The groups were compared using the t test or chi-square test, and univariate and multivariate analyses were performed. Survival and recurrence were analyzed by the Kaplan-Meier method. Differences were significant at P<0.05. RESULTS: During follow-up, 112 patients had IHMR: 101 after LR and 11 after LT. Age, sex distribution, and HCV infection rate differed significantly between the LR and LR groups. All patients in the LT group who had recurrent HCC died within 3 years. The risk factors for death from tumor recurrence included a larger tumor size at recurrence, poor Child classification at recurrence, hyperbilirubinemia, hypoalbuminemia, and no TACE treatment. In Cox regression analysis, only vessel invasion, Child class C, and no TACE treatment were independent risk factors for death from tumor recurrence. CONCLUSIONS: TACE is beneficial for treating IHMR in patients after LR or LT.

Using an external soft tissue expander before autologous fat grafting for non-irradiated breast reconstruction.

Autologous fat grafting is a method that has been used for breast augmentation since last century. This case report presents a woman with non-irradiated breast requested autologous fat grafting after modified radical mastectomy for breast cancer. An external soft tissue expander was used before fat grafting. This innovative technique showed benefits for the patient, with tight skin after the operation.

Multiple episodes of arterial thrombosis in a young man with protein C deficiency: a case report.

A 23-year-old young adult, who had no previous illness, suffered from anterior wall acute myocardial infarction, right renal infarction and occlusion of the left distal brachial artery, popliteal artery, and tibioperoneal trunk artery within six months. He had a habit of smoking but denied a history of drug abuse. Protein C deficiency was diagnosed via the examination of a hypercoagulable panel. The investigation of the hypercoagulable state is essential in young adults with an unusual presentation of artery occlusion.

Perforated acute appendicitis resulting from appendiceal villous adenoma presenting with small bowel obstruction: a case report.

BACKGROUND: A villous adenoma is an extremely rare benign tumour in the appendix, in contrast to other benign appendiceal lesions. The clinical features are usually asymptomatic. Acute appendicitis is the most common complication with the lesion obstructing the orifice of the appendiceal lumen. Thus, a villous adenoma is usually found during surgical intervention for acute appendicitis. Mechanical obstruction induced by acute perforated appendicitis has been previously reported. Acute appendicitis caused by a villous adenoma presenting with acute intestinal obstruction has not been previously reported. CASE PRESENTATION: A 78-year-old woman presented to our Emergency Department with diffuse abdominal pain and tenderness. The abdominal plain film and computed tomography revealed an intestinal obstruction. After surgical intervention, the ruptured appendix was shown to be associated with intestinal obstruction. The post-operative pathologic diagnosis was an appendiceal villous adenoma. CONCLUSIONS: This is the first report describing an appendiceal villous adenoma, which is an occasional cause of perforated acute appendicitis, presenting as a complete intestinal obstruction. We emphasize that in elderly patients without a surgical history, the occult cause of complete intestinal obstruction must be determined. If an appendiceal tumour is diagnosed, an intra-operative frozen section is suggested prior to selecting a suitable method of surgical intervention.