Neoadjuvant and/or adjuvant chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: a systematic review and meta-analysis study protocol.

INTRODUCTION: Whether gastric cancer (GC) patients with deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) benefit from perioperative (neoadjuvant and/or adjuvant) chemotherapy is controversial. This protocol delineates the planned scope and methods for a systematic review and meta-analysis that aims to compare the efficacy of perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC patients. METHODS AND ANALYSIS: This study protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols-P guideline. PubMed, Embase, Cochrane (CENTRAL), and the Web of Science databases will be searched, supplemented by a secondary screening of relevant records. Both randomised controlled trials and non-randomised studies will be included in this study. The primary and secondary outcomes under scrutiny will be overall survival, disease-free survival and progression-free survival. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will analyse different treatment settings (eg, neoadjuvant or adjuvant or combined as perioperative chemotherapies) separately and conduct sensitivity analyses. ETHICS AND DISSEMINATION: No ethics approval is required for this systematic review and meta-analysis, as no individual patient data will be collected. The findings of our study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023494276.

Small bowel intramural hematoma caused by warfarin: case report and literature review.

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

Activation of the FOXM1/ASF1B/PRDX3 axis confers hyperproliferative and antioxidative stress reactivity to gastric cancer.

Nucleosome assembly during DNA replication is dependent on histone chaperones. Recent studies suggest that dysregulated histone chaperones contribute to cancer progression, including gastric cancer (GC). Further studies are required to explore the prognostic and therapeutic implications of histone chaperones and their mechanisms of action in GC progression. Here we identified histone chaperone ASF1B as a potential biomarker for GC proliferation and prognosis. ASF1B was significantly upregulated in GC, which was associated with poor prognosis. In vitro and in vivo experiments demonstrated that the inhibition of ASF1B suppressed the malignant characteristics of GC, while overexpression of ASF1B had the opposite effect. Mechanistically, transcription factor FOXM1 directly bound to the ASF1B-promoter region, thereby regulating its transcription. Treatment with thiostrepton, a FOXM1 inhibitor, not only suppressed ASF1B expression, but also inhibited GC progression. Furthermore, ASF1B regulated the mitochondrial protein peroxiredoxin 3 (PRDX3) transcription in a FOXM1-dependent manner. The crucial role of ASF1B-regulated PRDX3 in GC cell proliferation and oxidative stress balance was also elucidated. In summary, our study suggests that the FOXM1-ASF1B-PRDX3 axis is a potential therapeutic target for treating GC.

Univariable and multivariable Mendelian randomization study identified the key role of gut microbiota in immunotherapeutic toxicity.

BACKGROUND: In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified. METHODS: To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) for gut microbiota were retrieved from the MiBioGen consortium (18,340 participants). GWAS summary data for irAEs were gathered from an ICIs-treated cohort with 1,751 cancer patients. Various MR analysis methods, including inverse variance weighted (IVW), MR PRESSO, maximum likelihood (ML), weighted median, weighted mode, and cML-MA-BIC, were used. Furthermore, multivariable MR (MVMR) analysis was performed to account for possible influencing instrumental variables. RESULTS: Our analysis identified fourteen gut bacterial taxa that were causally associated with irAEs. Notably, Lachnospiraceae was strongly associated with an increased risk of both high-grade and all-grade irAEs, even after accounting for the effect of BMI in the MVMR analysis. Akkermansia, Verrucomicrobiaceae, and Anaerostipes were found to exert protective roles in high-grade irAEs. However, Ruminiclostridium6, Coprococcus3, Collinsella, and Eubacterium (fissicatena group) were associated with a higher risk of developing high-grade irAEs. RuminococcaceaeUCG004, and DefluviitaleaceaeUCG011 were protective against all-grade irAEs, whereas Porphyromonadaceae, Roseburia, Eubacterium (brachy group), and Peptococcus were associated with an increased risk of all-grade irAEs. CONCLUSIONS: Our analysis highlights a strong causal association between Lachnospiraceae and irAEs, along with some other gut microbial taxa. These findings provide potential modifiable targets for managing irAEs and warrant further investigation.

Uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Choosing an optimal reconstruction method is pivotal for patients with gastric cancer undergoing distal gastrectomy. The uncut Roux-en-Y reconstruction, a variant of the conventional Roux-en-Y approach (or variant of the Billroth II reconstruction), employs uncut devices to occlude the afferent loop of the jejunum. This modification is designed to mitigate postgastrectomy syndrome and enhance long-term functional outcomes. However, the comparative benefits and potential harms of this approach compared to other reconstruction techniques remain a topic of debate. OBJECTIVES: To assess the benefits and harms of uncut Roux-en-Y reconstruction after distal gastrectomy in patients with gastric cancer. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, WanFang Data, China National Knowledge Infrastructure, and clinical trial registries for published and unpublished trials up to November 2023. We also manually reviewed references from relevant systematic reviews identified by our search. We did not impose any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing uncut Roux-en-Y reconstruction versus other reconstructions after distal gastrectomy for gastric cancer. The comparison groups encompassed other reconstructions such as Billroth I, Billroth II (with or without Braun anastomosis), and Roux-en-Y reconstruction. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The critical outcomes included health-related quality of life at least six months after surgery, major postoperative complications within 30 days after surgery according to the Clavien-Dindo Classification (grades III to V), anastomotic leakage within 30 days, changes in body weight (kg) at least six months after surgery, and incidence of bile reflux, remnant gastritis, and oesophagitis at least six months after surgery. We used the GRADE approach to evaluate the certainty of the evidence. MAIN RESULTS: We identified eight trials, including 1167 participants, which contributed data to our meta-analyses. These trials were exclusively conducted in East Asian countries, predominantly in China. The studies varied in the types of uncut devices used, ranging from 2- to 6-row linear staplers to suture lines. The follow-up periods for long-term outcomes spanned from 3 months to 42 months, with most studies focusing on a 6- to 12-month range. We rated the certainty of evidence from low to very low. Uncut Roux-en-Y reconstruction versus Billroth II reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to major postoperative complications (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.24 to 4.05; I² = 0%; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; I² = 0%; 2 studies, 282 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.64, 95% CI 0.29 to 1.44; I² not applicable; RD -0.00, 95% CI -0.03 to 0.02; I² = 32%; 3 studies, 615 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, low- to very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to changes in body weight (mean difference (MD) 0.04 kg, 95% CI -0.84 to 0.92 kg; I² = 0%; 2 studies, 233 participants; low-certainty evidence), may reduce the incidence of bile reflux into the remnant stomach (RR 0.67, 95% CI 0.55 to 0.83; RD -0.29, 95% CI -0.43 to -0.16; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 7; 1 study, 141 participants; low-certainty evidence), and may have little or no effect on the incidence of remnant gastritis (RR 0.27, 95% CI 0.01 to 5.06; I2 = 78%; RD -0.15, 95% CI -0.23 to -0.07; I2 = 0%; NNTB 7, 95% CI 5 to 15; 2 studies, 265 participants; very low-certainty evidence). No studies reported on quality of life or the incidence of oesophagitis. Uncut Roux-en-Y reconstruction versus Roux-en-Y reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may make little to no difference to major postoperative complications (RR 4.74, 95% CI 0.23 to 97.08; I² not applicable; RD 0.01, 95% CI -0.02 to 0.04; I² = 0%; 2 studies, 256 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.34, 95% CI 0.05 to 2.08; I² = 0%; RD -0.02, 95% CI -0.06 to 0.02; I² = 0%; 2 studies, 213 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may increase the incidence of bile reflux into the remnant stomach (RR 10.74, 95% CI 3.52 to 32.76; RD 0.57, 95% CI 0.43 to 0.71; NNT for an additional harmful outcome (NNTH) 2, 95% CI 2 to 3; 1 study, 108 participants; very low-certainty evidence) and may make little to no difference to the incidence of remnant gastritis (RR 1.18, 95% CI 0.69 to 2.01; I² = 60%; RD 0.03, 95% CI -0.03 to 0.08; I² = 0%; 3 studies, 361 participants; very low-certainty evidence) and incidence of oesophagitis (RR 0.82, 95% CI 0.53 to 1.26; I² = 0%; RD -0.02, 95% CI -0.07 to 0.03; I² = 0%; 3 studies, 361 participants; very low-certainty evidence). We are very uncertain about these results. Data were insufficient to assess the impact on quality of life and changes in body weight. AUTHORS' CONCLUSIONS: Given the predominance of low- to very low-certainty evidence, this Cochrane review faces challenges in providing definitive clinical guidance. We found the majority of critical outcomes may be comparable between the uncut Roux-en-Y reconstruction and other methods, but we are very uncertain about most of these results. Nevertheless, it indicates that uncut Roux-en-Y reconstruction may reduce the incidence of bile reflux compared to Billroth-II reconstruction, albeit with low certainty. In contrast, compared to Roux-en-Y reconstruction, uncut Roux-en-Y may increase bile reflux incidence, based on very low-certainty evidence. To strengthen the evidence base, further rigorous and long-term trials are needed. Additionally, these studies should explore variations in surgical procedures, particularly regarding uncut devices and methods to prevent recanalisation. Future research may potentially alter the conclusions of this review.

Midline and off-midline wound closure methods after surgical treatment for pilonidal sinus.

BACKGROUND: Pilonidal sinus disease is a common and debilitating condition. Surgical treatment remains the mainstay for managing chronic disease, with options including midline and off-midline wound closure methods. However, the optimal approach remains uncertain. Recent developments in tension-free midline techniques require further exploration. OBJECTIVES: To assess the effects of midline and off-midline wound closure methods for pilonidal sinus, and to determine the optimal off-midline flap procedures. SEARCH METHODS: In June 2022, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus EBSCO, and clinical trials registries. We also scanned the reference lists of included studies, as well as reviews, meta-analyses, and health technology reports. We applied no language, publication date, or study setting restrictions. SELECTION CRITERIA: We included parallel RCTs involving participants undergoing midline closure without flap techniques and off-midline closure for pilonidal sinus treatment. We excluded quasi-experimental studies and studies that enroled participants presenting with an abscess. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. The critical outcomes included wound healing (time to wound healing, proportion of wounds healed), recurrence rate, wound infection, wound dehiscence, time to return to work, and quality of life. We assessed biases in these outcomes utilising the Cochrane risk of bias 2 tool and appraised evidence certainty via the GRADE approach. MAIN RESULTS: We included 33 studies with 3667 analysed participants. The median or average age of the participants across the included studies ranged from 21.0 to 34.2 years, with a predominant male representation. Geographically, the trials were primarily conducted in the Middle East. We identified nine intervention comparisons. In this abstract, we focus on and present the summarised findings for the three primary comparisons. Off-midline closure versus conventional midline closure Off-midline closure probably reduces the time to wound healing (mean difference (MD) -5.23 days, 95% confidence interval (CI) -7.55 to -2.92 days; 3 studies, 300 participants; moderate-certainty evidence). However, there may be little to no difference between the two methods in the proportion of wounds healed (100% versus 88.5%, risk ratio (RR) 1.13, 95% CI 0.92 to 1.39; 2 studies, 207 participants; very low-certainty evidence). Off-midline closure probably results in lower rates of recurrence (1.5% versus 6.8%, RR 0.22, 95% CI 0.11 to 0.45; 13 studies, 1492 participants; moderate-certainty evidence) and wound infection (3.8% versus 11.7%, RR 0.32, 95% CI 0.22 to 0.49; 13 studies, 1568 participants; moderate-certainty evidence), and may lower rates of wound dehiscence (3.9% versus 8.9%, RR 0.44, 95% CI 0.27 to 0.71; 11 studies, 1389 participants; low-certainty evidence). Furthermore, off-midline closure may result in a reduced time to return to work (MD -3.72 days, 95% CI -6.11 to -1.33 days; 6 studies, 820 participants; low-certainty evidence). There were no data available for quality of life. Off-midline closure versus tension-free midline closure Off-midline closure may reduce the time to wound healing (median 14 days in off-midline closure versus 51 days in tension-free midline closure; 1 study, 116 participants; low-certainty evidence) and increase wound healing rates at three months (94.7% versus 76.4%, RR 1.24, 95% CI 1.06 to 1.46; 1 study, 115 participants; low-certainty evidence), but may result in little to no difference in rates of recurrence (5.4% versus 7.8%, RR 0.69, 95% CI 0.30 to 1.61; 6 studies, 551 participants; very low-certainty evidence), wound infection (2.8% versus 6.4%, RR 0.44, 95% CI 0.16 to 1.17; 6 studies, 559 participants; very low-certainty evidence), and wound dehiscence (2.5% versus 3.0%, RR 0.82, 95% CI 0.17 to 3.84; 3 studies, 250 participants; very low-certainty evidence) compared to tension-free midline closure. Furthermore, off-midline closure may result in longer time to return to work compared to tension-free midline closure (MD 3.00 days, 95% CI 1.52 to 4.48 days; 1 study, 60 participants; low-certainty evidence). There were no data available for quality of life. Karydakis flap versus Limberg flap Karydakis flap probably results in little to no difference in time to wound healing compared to Limberg flap (MD 0.36 days, 95% CI -1.49 to 2.22; 6 studies, 526 participants; moderate-certainty evidence). Compared to Limberg flap, Karydakis flap may result in little to no difference in the proportion of wounds healed (80.0% versus 66.7%, RR 1.20, 95% CI 0.77 to 1.86; 1 study, 30 participants; low-certainty evidence), recurrence rate (5.1% versus 4.5%, RR 1.14, 95% CI 0.61 to 2.14; 9 studies, 890 participants; low-certainty evidence), wound infection (7.9% versus 5.1%, RR 1.55, 95% CI 0.90 to 2.68; 8 studies, 869 participants; low-certainty evidence), wound dehiscence (7.4% versus 6.2%, RR 1.20, 95% CI 0.41 to 3.50; 7 studies, 776 participants; low-certainty evidence), and time to return to work (MD -0.23 days, 95% CI -5.53 to 5.08 days; 6 studies, 541 participants; low-certainty evidence). There were no data available for quality of life. AUTHORS' CONCLUSIONS: This Cochrane review examines the midline and off-midline wound closure options for pilonidal sinus, predominantly based on young adult studies. Off-midline flap procedures demonstrate there may be benefits over conventional midline closure for pilonidal sinus, with various off-midline flap techniques. When off-midline flap closures were compared to tension-free midline closure, low-certainty evidence indicated there may be improved wound healing and increased time to return to work for off-midline closure, whilst very low-certainty evidence indicated there may be no evidence of a difference in other outcomes. There may be no evidence of an advantage found amongst the off-midline techniques evaluated. The choice of either procedure is likely to be based on a clinician's preference, experience, patient characteristics, and the patients' preferences. To more accurately determine the benefits and potential harms of these closure techniques, further large-scale and meticulously-designed trials are essential. Specifically, there is a pressing need for more studies addressing the paediatric population, in addition to adult studies.

Optimal reconstruction methods after distal gastrectomy for gastric cancer: a protocol for a systematic review and network meta-analysis update.

BACKGROUND: Distal gastrectomy (DG) is a commonly used surgical procedure for gastric cancer (GC), with three reconstruction methods available: Billroth I, Billroth II, and Roux-en-Y. In 2018, our team published a systematic review to provide guidance for clinical practice on the optimal reconstruction method after DG for GC. However, since then, new evidence from several randomized controlled trials (RCTs) has emerged, prompting us to conduct an updated systematic review and network meta-analysis to provide the latest comparative estimates of the efficacy and safety of the three reconstruction methods after DG for GC. METHOD: This systematic review and network meta-analysis update followed the PRISMA-P guidelines and will include a search of PubMed, Embase, and the Cochrane Library for RCTs comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after DG for patients with GC. Two independent reviewers will screen the titles and abstracts based on predefined eligibility criteria, and two reviewers will assess the full texts of relevant studies. The Bayesian network meta-analysis will evaluate various outcomes, including quality of life after surgery, anastomotic leakage within 30 days after surgery, operation time, intraoperative blood loss, major postoperative complications within 30 days after surgery, incidence and severity of bile reflux, and loss of body weight from baseline. ETHICS AND DISSEMINATION: The review does not require ethical approval. The findings of the review will be disseminated through publication in an academic journal, presentations at conferences, and various media outlets. INPLASY REGISTRATION NUMBER: INPLASY2021100060.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

The Global Burden of Vascular Intestinal Disorders in 204 Countries and Territories From 1990 to 2019: Global Burden of Diseases Study.

Objectives: Assess the prevalence, mortality, and disability-adjusted life years (DALYs) of vascular intestinal disorders (VID) from 1990 to 2019. Methods: This study conducted a secondary data analysis utilizing the Global Burden of Diseases Study 2019. The prevalence, mortality and DALYs of VID were analyzed by sex, age and socio-demographic index (SDI), respectively. Analyses were performed by using R software. Results: Globally, the number of prevalent VID cases increased from 100,158 (95% uncertainty interval: 89,428-114,013) in 1,990-175,740 (157,941-198,969) in 2019. However, the age-standardized rates (ASR) of VID prevalence declined from 2.47 (95% uncertainty interval: 2.24-2.76) per 100,000 population to 2.21 (1.98-2.48) per 100,000 population between 1990 and 2019. Furthermore, the ASR of mortality also decreased from 1990 to 2019. Between 1990 and 2019, the regions with high and high-middle level exhibited the highest diseases burden. Conclusion: Globally, the diseases burden associated with VID demonstrated a decline from 1990 to 2019. However, concerted efforts are still required to enhance measures to combat VID within countries categorized as high and high-middle SDI.

The necessity and safety of simultaneous cholecystectomy during gastric surgery for patients with asymptomatic cholelithiasis.

OBJECTIVES: The incidence of cholelithiasis is higher among individuals who have undergone gastric surgery. The benefits of concomitant gallbladder removal in asymptomatic gallstone patients remain uncertain. The aim was to investigate the necessity and safety of simultaneous cholecystectomy in this particular patient population. METHODS: We performed a systematic review and meta-analysis to assess the incidence of asymptomatic cholelithiasis converting to symptomatic after gastric surgery and the complication rate associated with simultaneous cholecystectomy. PubMed, Embase, and the Cochrane Library were searched for relevant articles published until 10 March 202210 March 2022. RESULTS: Patients with asymptomatic cholelithiasis after gastric surgery were at a higher risk of developing symptomatic cholelithiasis compared to those without cholelithiasis (relative risk [RR] 2.28, 95% confidence interval [CI] 1.23-4.25) and those with unknown gallbladder conditions (RR 2.70, 95% CI 1.54-4.73). Additionally, patients who underwent simultaneous cholecystectomy did not face a higher risk of complications compared to those who only underwent gastric surgery (RR 0.86, 95% CI 0.48-1.53). CONCLUSIONS: Simultaneous cholecystectomy is both necessary and safe for patients with asymptomatic cholelithiasis undergoing gastric surgery. It is crucial to assess the gallbladder's condition before gastric surgery, and if the gallbladder status is unknown, simultaneous cholecystectomy should be avoided.

Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study.

BACKGROUND: Observational studies suggested that inflammatory bowel disease (IBD) (i.e., Crohn's disease [CD] and ulcerative colitis [UC]) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) and ischemic stroke. However, it is still unclear whether the observed associations causally exist. Thus, we aim to examine the potential effect of IBD, CD, and UC on the risk of CAD and ischemic stroke, using a two-sample Mendelian randomization (MR) study. METHODS: Genetic instruments for IBD, CD, and UC were retrieved from the latest published genome-wide association studies (GWASs) of European ancestry. GWAS summary data for instrument-outcome associations were gathered from four independent resources: CARDIoGRAMplusC4D Consortium, MEGASTROKE consortium, FinnGen, and UK Biobank. The inverse variance weighted (IVW) method and multiple pleiotropy-robust approaches were conducted and, subsequently, combined in a fixed-effect meta-analysis. Moreover, multivariable MR (MVMR) analysis was conducted to adjust for potential influencing instrumental variables. RESULTS: The IVW method revealed no causal effect of IBD on the risk of CAD (overall IBD on CAD: OR 1.003, 95%CI 0.982 to 1.025; CD on CAD: OR 0.997, 95%CI 0.978 to 1.016; UC on CAD: OR 0.986, 95%CI 0.963 to 1.010) or the risk of ischemic stroke (overall IBD on ischemic stroke: OR 0.994, 95%CI 0.970 to 1.018; CD on ischemic stroke: OR 0.996, 95%CI 0.979 to 1.014; UC on ischemic stroke: OR 0.999, 95%CI 0.978 to 1.020). The results of the meta-analysis and MVMR remained consistent. CONCLUSION: Our MR analysis does not support a causal effect of IBD on CAD and ischemic stroke, and previous results from observational studies might be biased through uncontrolled confoundings (such as IBD-specific medications and detection bias, etc.) that warrant further research.

Local excision and radical excision for rectal gastrointestinal stromal tumors: a meta-analysis protocol.

Background: To date, several studies have compared the surgical and oncological outcomes of local excision (LE) and radical excision (RE) for rectal gastrointestinal stromal tumors (GISTs), but some have limited numbers of small series. This protocol outlines the planned scope and methods for a systematic review and meta-analysis that will compare the surgical and oncological outcomes of LE and RE in patients with rectal GISTs. Methods: This protocol is presented in accordance with the PRISMA-P guideline. PubMed, Embase, Web of Science, Cochrane Library and Wanfang database will be systematically searched. Furthermore, reference lists of all included articles will be screened manually to add other eligible studies. We will include randomized controlled trials (RCTs) and non-randomized studies (NRS) in this study. The primary outcomes evaluated will be R0 resection rate and disease-free survival, while the secondary outcomes will contain overall survival, length of stay, tumor rupture rate and complications. Two reviewers will independently screen and select studies, extract data from the included studies, and assess the risk of bias of the included studies. Preplanned subgroup analyses and sensitivity analyses are detailed within this protocol. The strength of the body of evidence will be assessed using GRADE. Discussion: This review and meta-analysis will provide a comprehensive evaluation of the current evidence concerning the application of LE and RE in patients with rectal GISTs. The findings from this review will serve as a foundation for future research and emphasize the implications for clinical practice. Systematic review registration: PROSPERO (CRD42017078338), https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=387409, PROSPERO CRD42017078338.

Methodological quality of radiomic-based prognostic studies in gastric cancer: a cross-sectional study.

Background: Machine learning radiomics models are increasingly being used to predict gastric cancer prognoses. However, the methodological quality of these models has not been evaluated. Therefore, this study aimed to evaluate the methodological quality of radiomics studies in predicting the prognosis of gastric cancer, summarize their methodological characteristics and performance. Methods: The PubMed and Embase databases were searched for radiomics studies used to predict the prognosis of gastric cancer published in last 5 years. The characteristics of the studies and the performance of the models were extracted from the eligible full texts. The methodological quality, reporting completeness and risk of bias of the included studies were evaluated using the RQS, TRIPOD and PROBAST. The discrimination ability scores of the models were also compared. Results: Out of 283 identified records, 22 studies met the inclusion criteria. The study endpoints included survival time, treatment response, and recurrence, with reported discriminations ranging between 0.610 and 0.878 in the validation dataset. The mean overall RQS value was 15.32 ± 3.20 (range: 9 to 21). The mean adhered items of the 35 item of TRIPOD checklist was 20.45 ± 1.83. The PROBAST showed all included studies were at high risk of bias. Conclusion: The current methodological quality of gastric cancer radiomics studies is insufficient. Large and reasonable sample, prospective, multicenter and rigorously designed studies are required to improve the quality of radiomics models for gastric cancer prediction. Study registration: This protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/ja52b).

Case Report: Giant abdominal hemangioma originating from the liver.

Background: Hepatic hemangioma is among the most common benign liver lesions. However, giant pedunculated hepatic hemangiomas are exceptionally rare and associated with additional risks, such as torsion. Case presentation: We present the case of a 63-year-old female patient who presented with abdominal distension and pain. Barium meal examination and gastroscopy revealed a large, smooth-surfaced submucosal bulge located at the fundus of the stomach. Subsequent MRI examination identified a mass measuring approximately 6.4 x 7 cm in the left upper abdomen. Surgical intervention was planned for mass removal. However, intraoperative exploration revealed the origin of the mass to be the liver, and subsequent histopathological examination confirmed it as a hemangioma. Conclusion: We systematically summarized the characteristics of our case along with 31 previously reported cases. Giant pedunculated hepatic hemangiomas typically occur in the left lobe of the liver. Due to their atypical presentation, a combination of imaging methods such as ultrasound, CT, and/or MRI is essential for accurate diagnosis. Furthermore, surgical intervention is recommended due to the potential risks of bleeding, rupture, and torsion.

Case Report: Systemic treatment for breast and vulvar metastases from resected rectal signet ring cell carcinoma.

Background: Breast and vulvar metastases from rectal signet ring cell carcinoma (SRCC) represent a rare and obscure clinical entity associated with poor survival. Managing patients with metastatic rectal SRCC is extremely challenging due to the absence of high-quality evidence. Case presentation: A 26-year-old woman presented with progressively worsening anal pain, constipation, and hematochezia for approximately two years. Following the diagnosis of locally advanced rectal cancer (cT3N0-1M0), she received neoadjuvant chemotherapy with modified FOLFOX6 regimen and underwent laparoscopic abdominoperineal resection. Metastases to the breast and vulva developed during postoperative chemotherapy. Genetic testing revealed RAS/BRAF wild-type and microsatellite instability (MSI)-low status. Though sequential administration of irinotecan plus tegafur and tegafur plus raltitrexed-based chemotherapy in combination with bevacizumab, the disease progressed rapidly. Sadly, the patient passed away 15 months after initial diagnosis due to rapidly progressive disease. Conclusion: Rectal SRCC is associated with younger on-set, aggressive behaviors, and worse survival outcomes. Due to poor cohesiveness, SRCC tends to develop metastases. A patient's medical history and immunohistochemical staining (such as CK20, CK7, and CDX-2) can aid in identifying the tumor origin of breast and vulvar metastases. Mutations and signaling pathways predominant in the tumorigenesis of SRCC remains unveiled. There is poor effect of conventional chemotherapies, targeted and immunotherapies for colorectal adenocarcinoma on SRCC, so novel therapies are needed to treat this patient population.

Laparoscopic versus ultrasound-guided transversus abdominis plane block for postoperative pain management in minimally invasive colorectal surgery: a meta-analysis protocol.

Introduction: Transversus abdominis plane block (TAPB) is now commonly administered for postoperative pain control and reduced opioid consumption in patients undergoing major colorectal surgeries, such as colorectal cancer, diverticular disease, and inflammatory bowel disease resection. However, there remain several controversies about the effectiveness and safety of laparoscopic TAPB compared to ultrasound-guided TAPB. Therefore, the aim of this study is to integrate both direct and indirect comparisons to identify a more effective and safer TAPB approach. Materials and methods: Systematic electronic literature surveillance will be performed in the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for eligible studies through July 31, 2023. The Cochrane Risk of Bias version 2 (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tools will be applied to scrutinize the methodological quality of the selected studies. The primary outcomes will include (1) opioid consumption at 24 hours postoperatively and (2) pain scores at 24 hours postoperatively both at rest and at coughing and movement according to the numerical rating scale (NRS). Additionally, the probability of TAPB-related adverse events, overall postoperative 30-day complications, postoperative 30-day ileus, postoperative 30-day surgical site infection, postoperative 7-day nausea and vomiting, and length of stay will be analyzed as secondary outcome measures. The findings will be assessed for robustness through subgroup analyses and sensitivity analyses. Data analyses will be performed using RevMan 5.4.1 and Stata 17.0. P value of less than 0.05 will be defined as statistically significant. The certainty of evidence will be examined via the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group approach. Ethics and dissemination: Owing to the nature of the secondary analysis of existing data, no ethical approval will be required. Our meta-analysis will summarize all the available evidence for the effectiveness and safety of TAPB approaches for minimally invasive colorectal surgery. High-quality peer-reviewed publications and presentations at international conferences will facilitate disseminating the results of this study, which are expected to inform future clinical trials and help anesthesiologists and surgeons determine the optimal tailored clinical practice for perioperative pain management. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281720, identifier (CRD42021281720).

A Phase I Study of Gemcitabine/Nab-Paclitaxel/S-1 Chemotherapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. METHODS: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients` body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. RESULTS: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. CONCLUSION: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]).

Case report: A mesocolic lymphangioma in a 14-year-old child resected by laparoscopic surgery.

Introduction: Cystic lymphangioma is a benign malformation tumor of the lymphatic system. Its location is variable, and mesocolic localization remains extremely rare. Case presentation: We report a case of right mesocolon giant cystic lymphangioma in a previously healthy 14-year-old boy who was successfully managed through a minimally invasive laparoscopic excision. The patient presented with 8 months of dull abdominal pain, sporadic, located on the peri-umbilicus, exacerbated for a month. An abdominal computed tomography (CT) revealed a large, multiseptated cystic mass on the right mesocolon. Right mesocolic excision using a laparoscope was performed on this patient. He was discharged on the fifth day without complications. Recurrence was not detected in three months of follow-up. Conclusion: Cystic lymphangiomas in the mesocolon are rare benign neoplasms that pose diagnostic challenges. Complete resection is the optimal option for diagnostic confirmation and recurrence prevention. Laparoscopic surgery is feasible for children with mesocolic lymphangioma.

Histone Chaperones and Digestive Cancer: A Review of the Literature.

BACKGROUND: The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis of patients with these tumors is to identify early diagnostic markers or novel therapeutic targets. There is accumulating evidence connecting histone chaperones to the pathogenesis of digestive cancer. Histone chaperones are now broadly defined as a class of proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated that multiple histone chaperones are aberrantly expressed and have distinct roles in digestive cancers. OBJECTIVE: The purpose of this review is to present the current evidence regarding the role of histone chaperones in digestive cancer, particularly their mechanism in the development and progression of esophageal, gastric, liver, pancreatic, and colorectal cancers. In addition, the prognostic significance of particular histone chaperones in patients with digestive cancer is discussed. METHODS: According to PRISMA guidelines, we searched the PubMed, Embase, and MEDLINE databases to identify studies on histone chaperones and digestive cancer from inception until June 2022. RESULTS: A total of 104 studies involving 21 histone chaperones were retrieved. CONCLUSIONS: This review confirms the roles and mechanisms of selected histone chaperones in digestive cancer and suggests their significance as potential prognostic biomarkers and therapeutic targets. However, due to their non-specificity, more research on histone chaperones should be conducted in the future to elucidate novel strategies of histone chaperones for prognosis and treatment of digestive cancer.