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.

Computed tomography radiogenomics: A potential tool for prediction of molecular subtypes in gastric stromal tumor.

BACKGROUND: Preoperative knowledge of mutational status of gastrointestinal stromal tumors (GISTs) is essential to guide the individualized precision therapy. AIM: To develop a combined model that integrates clinical and contrast-enhanced computed tomography (CE-CT) features to predict gastric GISTs with specific genetic mutations, namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions. METHODS: A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio. The models were constructed using selected clinical features, conventional CT features, and radiomics features extracted from abdominal CE-CT images. Three models were developed: ModelCT sign, modelCT sign + rad, and model CTsign + rad + clinic. The diagnostic performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis and the Delong test. RESULTS: The ROC analyses revealed that in the training cohort, the area under the curve (AUC) values for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic for predicting KIT exon 11 mutation were 0.743, 0.818, and 0.915, respectively. In the validation cohort, the AUC values for the same models were 0.670, 0.781, and 0.811, respectively. For predicting KIT exon 11 codons 557-558 deletions, the AUC values in the training cohort were 0.667, 0.842, and 0.720 for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic, respectively. In the validation cohort, the AUC values for the same models were 0.610, 0.782, and 0.795, respectively. Based on the decision curve analysis, it was determined that the modelCT sign + rad + clinic had clinical significance and utility. CONCLUSION: Our findings demonstrate that the combined modelCT sign + rad + clinic effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions. This combined model has the potential to be valuable in assessing the genotype of GISTs.

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.

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.

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.

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.

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.

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).

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.

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.

Changes in the landscape patterns of Black-necked Crane habitat and its correlation with their individual population numbers during the past 40 years in China.

The landscape pattern of the Black-necked Crane (Grus nigricollis) habitat in China changed at different spatial scales and long-term periods due to natural factors and human activities, and habitat reduction and fragmentation threatened the survival of Black-necked Cranes. The factors driving the habitat landscape pattern and individual population changes of Black-necked Cranes remain to be studied. In this paper, based on remote sensing data of land use from 1980 to 2020, the changes in landscape pattern and fragmentation of the Black-necked Crane habitat in China over 40 years were analyzed from two different spatial scales using the land cover transfer matrix and landscape index. The correlation between landscape and Black-necked Crane individual population was analyzed. The most obvious observations were as follows: (1) Although transformation between landscapes occurred to varying degrees, the area of wetlands and arable land in the breeding and the wintering areas (net) increased significantly from 1980 to 2020. (2) Habitat fragmentation existed in the breeding and the wintering area and was more obvious in the wintering area. (3) The number of individuals of Black-necked Cranes increased period by period, and habitat fragmentation did not inhibit their population growth. (4) The number of individuals of Black-necked Crane was closely related to the wetland and arable land. The increasing area of wetlands and arable and the increasing landscape shape complexity all contributed to the growth of the individual population. The results also suggested that the number of individuals of Black-necked Crane was not threatened by the expanding arable land in China, and they might benefit from arable landscapes. The conservation of Black-necked Cranes should focus on the relationship between individual Black-necked Cranes and arable landscapes, and the conservation of other waterbirds should also focus on the relationship between individual waterbirds and other landscapes.

Clinicopathological and mutational characteristics of primary double mutant gastrointestinal stromal tumor: a single center study with review of the literature.

AIMS: Primary double KIT/PDGFRA mutations are very rare in gastrointestinal stromal tumours (GISTs) but have not been comprehensively studied to date. In the present study, we investigated the clinicopathologic and genetic features of eight cases of primary double-mutant GISTs, and we reviewed the literature. METHODS AND RESULTS: The tumours occurred in six males and two females (age range 57-83 years) and involved the small intestine (n = 4), stomach (n = 2), rectum (n = 1) and retroperitoneum (n = 1). Clinical manifestations were variable, ranging from indolent (no symptoms) to aggressive disease (tumour rupture and haemorrhage). All patients underwent surgical excision, and six of them were treated with imatinib. No one experienced recurrence or other complications during the follow-up time (10 to 61 months). Histologically, all the tumours exhibited mixed cell types, accompanied by variable interstitial changes. KIT mutations were detected in all cases, and the majority of them were present in different exons (n = 5). No PDGFRA exon 12, 14 or 18 mutations were found. All the mutations were validated by next-generation sequencing, and two additional variants with comparatively low allelic fractions were identified in one case. Two of the cases had available allele distribution data, one with an in cis compound mutation and the other with an in trans compound mutation. CONCLUSION: Primary double-mutant GISTs have distinctive clinicopathologic and mutational features. Studies of more cases are necessary for a better understanding of these tumours.

The prognostic role of surgery and a nomogram to predict the survival of stage IV breast cancer patients.

Background: Since numerous retrospective studies and prospective trials have shown divergent results, whether the surgical excision of the primary tumor results in survival benefits for de novo stage IV breast cancer patients is inconclusive. Consequently, we need a prediction model of prognosis, judge the efficiency of breast surgery, and identify the advanced breast cancer patients who would benefit from surgery. Methods: We analyzed the data of 2,747 metastatic breast cancer patients (the surgery group) and 4,508 patients (the non-surgery group) from the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2015. Propensity score matching (PSM) was used to attain a balance between the covariates of both groups. We then assessed the potential risk factors for the breast cancer-specific survival (BCSS) of patients in the non-surgery group by Cox regression and constructed a nomogram to predict BCSS. All the patients were classified into different risk groups based on the median risk score obtained from the nomogram. The hazard ratios of BCSS and overall survival (OS) of patients in the two groups were calculated. Results: After PSM, 2,288 patients severally in the two groups (the surgery group and the non-surgery group) were enrolled in the study. A nomogram incorporating 13 potential risk factors (i.e., age, race, cohabitation status, income, tumor grade, histotype, tumor size, lymph node status, molecular subtype, metastasis to brain, liver, lung, and chemotherapy) was constructed using the data of patients in the non-surgery group. The C statistics for the internal (patients in the non-surgery group) and external (patients in the surgery group) validation of the nomogram were 0.70 [95% confidence interval (CI), 0.69-0.71] and 0.73 (95% CI, 0.72-0.74), respectively. In the low-risk group, patients in the surgery group had lower risks of breast cancer-specific mortality (BCSM) (hazard ratio =0.53; 95% CI, 0.47-0.59; P for interaction =0.014) and overall mortality (OM) (hazard ratio =0.52; 95% CI, 0.46-0.58; P for interaction =0.002) than those in the non-surgery group. Conclusions: Breast surgery might improve the survival of metastatic breast cancer patients in the low-risk group. The established nomogram could provide a reference for clinicians in enabling personalized treatment among advanced breast cancer patients.

Identification of Endoplasmic Reticulum Stress-Related Subtypes, Infiltration Analysis of Tumor Microenvironment, and Construction of a Prognostic Model in Colorectal Cancer.

Recently, endoplasmic reticulum (ER) stress has been shown to influence tumor progression and immune cell function in the tumor microenvironment (TME). However, the underlying role of ER stress-related gene patterns in colorectal cancer (CRC) development remains unclear. We analyzed the ER stress-related gene patterns in 884 patients with CRC from the Gene Expression Omnibus database and evaluated the cell-infiltrating patterns in the TME. Two ER stress-related patterns were identified in patients with CRC that had distinct cell-infiltrating patterns in the TME and clinical characteristics. A risk score and nomogram based on 14 screened prognosis-correlated genes was built and validated to predict patient survival. Patients with a higher risk score were shown to have an unfavorable prognosis, and the risk score was associated with cell infiltration and drug sensitivity. Furthermore, spatial transcriptomics data were utilized to explore ER stress-related gene patterns in CRC tissues, and it was shown that ER stress phenotype involves in the formation of the immunosuppressive TME. This study demonstrated that ER stress-related gene patterns play a role in influencing the TME and predicting prognosis. These analyses of ER stress in the TME of CRC might deepen our understanding of CRC progression and immune escape and provide novel insights into therapeutic strategies.

The KDM6A-SPARCL1 axis blocks metastasis and regulates the tumour microenvironment of gastrointestinal stromal tumours by inhibiting the nuclear translocation of p65.

BACKGROUND: It is urgent to explore the pathogenic mechanism of gastrointestinal stromal tumours (GISTs). KDM6A, a histone demethylase, can activate gene transcription and has not been reported in GISTs. SPARCL1 may serve as a metastasis marker in GIST, but the molecular mechanism remains to be further explored. This study aimed to explore the biological function and molecular mechanism of KDM6A and SPARCL1 in GIST. METHODS: CCK-8, live cell count, colony formation, wound-healing and Transwell migration and invasion assays were employed to detect the cell proliferation, migration and invasion. A xenograft model and hepatic metastasis model were used to assess the role of KDM6A and SPARCL1 in vivo. RESULTS: KDM6A inhibited the proliferation, migration and invasion of GIST cells. Mechanistically, KDM6A promotes the transcription of SPARCL1 by demethylating histone H3 lysine trimethylation and consequently leads to the inactivation of p65. SPARCL1 affected the metastasis of GIST cells in a mesenchymal-epithelial transition- and matrix-metalloproteinase-dependent manner. SPARCL1 knockdown promoted angiogenesis, M2 polarisation and macrophage recruitment by inhibiting the phosphorylation of p65. Moreover, KDM6A and SPARCL1 inhibited hepatic metastasis and macrophage infiltration in vivo. CONCLUSIONS: Our findings establish the critical role of the KDM6A-SPARCL1-p65 axis in restraining the malignancy of GIST.

Open and minimally invasive surgery for gastrointestinal stromal tumours: a systematic review and network meta-analysis protocol.

INTRODUCTION: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive system, and complete resection is the only way to provide a radical cure for resectable GISTs. Open surgery and minimally invasive approaches, including laparoscopy, robotic surgery and endoscopy, consist of the mainstream GIST resection. However, there is still a lack of evidence regarding which surgical outcomes and long-term prognosis would be better. Thus, we are planning to conduct a network meta-analysis and systematic review aiming to determine the comparative effectiveness among laparotomy, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery in GISTs. METHOD AND ANALYSIS: PubMed, EMBASE, the Cochrane Library and Web of Science will be searched for published studies to identify the proper literature comparing open resection, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery for resecting GISTs from inception to February 2021. Randomised controlled trials (RCTs) and non-randomised studies comparing at least two different interventions for GIST resection will be included. RCTs and non-randomised studies will be synthesised and analysed separately. Bayesian network meta-analysis will be performed to compare the surgical outcomes and long-term prognosis among the resection methods above. The included studies will be divided into several subgroups according to tumour location and size for further analysis. Sensitivity analysis will be performed to identify and explain heterogeneity to make our results robust. Meta-regression will serve as a supplementary method if data are available. The quality of evidence will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: No ethical approval is required for this network meta-analysis, as it is based on already published data. The findings of the review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021237892.