Endoscopic-ultrasound-guided biliary drainage with placement of electrocautery-enhanced lumen-apposing metal stent for palliation of malignant biliary obstruction: Updated meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced (ECE) delivery of lumen-apposing metal stent (LAMS) is gradually being recognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography (ERCP) failure. However, most of the studies that have assessed its efficacy and safety were small and heterogeneous. Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence. AIM: To update the efficacy and safety of ECE-LAMS for treatment of biliary obstruction after ERCP failure. METHODS: We searched PubMed, EMBASE, and Scopus databases from the inception of the ECE technique to May 13, 2022. Primary outcome measure was pooled technical success rate, and secondary outcomes were pooled rates of clinical success, reintervention, and adverse events. Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R software (version 4.1.3). RESULTS: Fourteen eligible studies involving 620 participants were ultimately included. The pooled rate of technical success was 96.7%, and clinical success was 91.0%. Adverse events were reported in 17.5% of patients. Overall reintervention rate was 7.3%. Subgroup analyses showed results were generally consistent. CONCLUSION: ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible. The consistency of results across most subgroups suggested that this is a generalizable approach.

Autoimmune regulator (Aire) deficiency results in reduced memory CD8+ T cells after Listeria monocytogenes infection in a murine model.

Homozygous mutations in the autoimmune regulator (AIRE) gene that cripple thymic negative selection of autoreactive T cells result in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). However, how AIRE regulates the T-cell response against foreign pathogens is not well understood. Here, we observed comparable primary CD8+ T cells but a markedly reduced memory T-cell population and protective function in Aire-/- mice compared with wild-type after infection with a strain of recombinant Listeria monocytogenes. In adoptive transfer models, exogenous congenic CD8+ T cells transferred into Aire-/- mice also showed a reduction in the memory T-cell population, indicating an important role for extrathymic Aire-expressing cells in shaping or sustaining memory T cells. Moreover, using a bone marrow chimeric model, we found that Aire expressed in radioresistant cells plays an important role in maintaining the memory phenotype. These results provide important insights into the role of extrathymic Aire in the T-cell response to infection.

Minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (VARTD) in the management of infected walled-off pancreatic necrosis with deep extension: initial experience from a prospective single-arm study.

BACKGROUND: The currently preferred minimally invasive approaches have substantially improved outcomes of infected walled-off pancreatic necrosis (iWON). However, iWON with deep extension (iWONde) still poses a tricky challenge for sufficient necrosis evacuation by one stand-alone approach, often requiring repeated interventions. The aim of this study was to assess the effectiveness and safety of a minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (hereafter called VARTD) in the management of iWONde. METHODS: Patients who had developed an iWONde were recruited to receive the VARTD in this prospective single-arm study. The primary efficacy endpoint was clinical improvement up to day 28 after the VARTD, defined as a ≥ 75% reduction in size of necrotic collection (in any axis) on CT and clinical resolution of sepsis or organ dysfunction. The primary safety endpoint was a composite of major complications or death during follow-up. Six-month postdischarge follow-up was available. RESULTS: Between July 18, 2018, and November 12, 2020, we screened 95 patients with necrotizing pancreatitis; of these, 21 iWONde patients (mean [SD] age, 42.9 [11.7] years; 10 [48%] women) were finally enrolled. The primary efficacy endpoint was achieved by most participants (14/21, 67%). No participants required repeated interventions. The primary safety endpoint occurred in six patients (29%). Except one in-hospital death attributable to repeated intra-abdominal hemorrhage, others were discharged without any major complication. CONCLUSIONS: The VARTD approach appears to have a reasonable efficacy with acceptable complication rates and thus might be an option for improving clinical management of iWONde. TRIAL REGISTRATION: This study is registered with Chinese Clinical Trial Registry (chictr.org.cn number, ChiCTR1800016950).

Preoperative endoscopic transpapillary stenting: A solution to preventing and/or treating postsurgical external pancreatic fistula and infection in patients with infected necrotizing pancreatitis.

Currently, open surgical necrosectomy is only performed when the step-up approach fails in patients with necrotizing pancreatitis. As a common complication after surgery, external pancreatic fistula often leads to a long hospital stay and increased expenditure. Current therapeutic strategies include conservative management; however, unresponsive patients with pancreatic leaks will frequently require interventions. Existing evidence indicates that endoscopic transpapillary stenting can shorten the duration of external pancreatic fistula; however, the length of conservative treatment in the early stage cannot be avoided. Therefore, endoscopic transpapillary stenting cannot play a decisive role in the treatment and prevention of postsurgical external pancreatic fistula. The authors propose that endoscopic transpapillary stenting before surgery, however, can be used to prevent and treat postsurgical external pancreatic fistula and complications caused by the prolonged maintenance of the drainage tube for abscesses, including retrograde infection, through its physiological drainage effect. This hypothesis has important clinical implications for the accelerated postoperative recovery of patients with necrotizing pancreatitis.

Diagnosis and treatment pattern among rural and urban breast cancer patients in Southwest China from 2005 to 2009.

The incidence of all cancers in China is generally higher in urban areas; however, the mortality risk for affected patients is considerably higher in rural areas. We present a subanalysis investigating the differences in patient and disease characteristics, treatment patterns, and outcomes between rural and urban patients who were diagnosed with breast cancer at West China Hospital between 2005-2009. Baseline patient and disease characteristics were recorded, and patients were followed up for a minimum of 3 years, or until death. For this subanalysis, patients were stratified by their residential status (rural or urban). Of the 2252 patients in the cohort, 76.3% were from urban areas and 22.1% were from rural areas. Significant differences were observed in the prevalence of luminal A and human epidermal growth factor receptor 2-positive breast cancers among rural and urban patients. Estrogen receptor (ER)-positive patients were less likely to receive anti-ER therapy if they were from rural areas compared with urban areas; the use of aromatase inhibitors was also significantly lower for rural patients than urban patients. Univariate, multivariate, and Kaplan-Meier analyses all demonstrated that overall survival and progression-free survival were significantly lower for rural patients than urban patients.

Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients.

BACKGROUND: The prevalence of BRCA1/2 variants in Chinese breast cancer patients varies among studies. Germline or somatic BRCA1/2 mutations are associated with sensitivity to poly(ADP-ribose) polymerase-1 inhibitors and DNA-damaging agents. We aimed to investigate the distribution of both somatic and germline BRCA1/2 variants in unselected Chinese breast cancer patients, and explore their roles in tumor phenotype and disease prognosis. METHODS: 507 breast cancer patients, unselected for family history of breast cancer or age at diagnosis, were prospectively enrolled from West China Hospital between Feb. 2008 and Feb. 2014. BRCA1/2 variants in the exons/flanking regions were detected in fresh-frozen tumors using next-generation sequencing and confirmed by independent methods. Germline/somatic status was validated by Sanger sequencing in paired blood/normal tissue. RESULTS: BRCA1/2 pathogenic or likely pathogenic (P/LP) variants were detected in 50 patients (9.9%), including 40 germline carriers (18 in BRCA1, 22 in BRCA2), 9 patients with somatic variants (3 in BRCA1, 6 in BRCA2), and 1 patient with concurrent germline/somatic variants in BRCA2. The triple-negative (21.4%) and Luminal B (9.7%) subtypes had higher rates of BRCA1/2 variants. In patients with disease stage 0~II, presence of a germline or somatic BRCA1 P/LP variant increased the risk of relapse as compared to non-carriers [univariate hazard ratio (HR): 3.70, P = 0.04]. Germline BRCA1 P/LP variants, which were associated with aggressive tumor phenotypes, predicted worse disease-free survival in the subgroup of stage 0~II (HR: 4.52, P = 0.02) and N0 (HR: 5.4, P = 0.04) compared to non-carriers. CONCLUSION: A high frequency of germline and somatic BRCA1/2 P/LP variants was detected in unselected Chinese breast cancer patients. Luminal B subtype should be considered as a high-risk population of BRCA1/2 mutation, in addition to triple-negative breast cancer. BRCA1 status was associated with aggressive tumor phenotype and worse disease progression in early stage breast cancer patients.

Treatment and survival patterns of Chinese patients diagnosed with breast cancer between 2005 and 2009 in Southwest China: An observational, population-based cohort study.

Breast cancer is a significant health issue both globally and within China. Here, we present epidemiological data for female patients diagnosed with breast cancer and treated at West China Hospital, Sichuan University, between 2005 and 2009. Patients who were diagnosed with breast cancer between 2005 and 2009 were enrolled. Data cut-off in this analysis was October 2013, allowing a minimum of 3 years' follow-up, or follow-up until death. Data were collected and subject to statistical analyses to assess relationships between patient and cancer characteristics, treatment patterns and long-term outcomes. A total of 2252 women with breast cancer were included in the analyses. Luminal B was the most common subtype of breast cancer and human epidermal growth factor 2 (HER2)-positive (nonluminal) was the least common. Most patients had early-stage disease (stage ≤IIIa) at diagnosis. Patients with luminal A appeared to have the best overall survival (OS), compared with other subtypes. Hormone-receptor positivity was associated with improved prognosis, compared with negativity (OS hazard ratio [HR] 0.5). Late-stage compared with early-stage disease at diagnosis was associated with much poorer OS across all patients and tumor subtypes. Clear differences were apparent between breast cancer subtypes and the response to treatment. The interaction of breast cancer subtypes, treatments and disease stage is complex. One of the most important factors for improved prognosis is diagnosis and treatment at an early-stage of disease. With breast cancer becoming an increasingly important health concern, this highlights the importance of establishing systems and protocols to identify and treat patients with breast cancer as early as possible.

[Survival of Patients with Metastatic Recurrent Triple-negative Breast Cancer].

OBJECTIVES: To determine factors associated with the survival of patients with metastatic recurrent triple-negative breast cancer (mrTNBC). METHODS: Initial metastatic recurrent (during or after therapy) patients with triple-negative breast cancer (TNBC) confirmed by post-operate pathology in the West China Hospital of Sichuan University were followed up. The accumulative survival rates after recurrence were calculated using Kaplan-Meier method and differences were tested using log-rank tests. Cox proportional hazards regression analyses were performed to identify independent predictors of survival rates. RESULTS: A total of 142 patients were included in this study. They were followed up on average 41.9 months (range: 5.1-189.5 months), and had median post-recurrence survival time of 22.0 months.Tumor diameter, lymph node status, TNM stage, disease-free interval (DFI), numbers of recurrent lesions, brain metastasis, liver metastasis and the rapeutic patterns were associated with the survival of patients. The Cox proportional hazards regression model identified multi-lesions recurrence ( P=0.004), DFI≤12 months ( P=0.010), brain metastasis ( P=0.037) and single-modal therapy (SMT) ( P<0.001) as independent risk predictors of post-recurrence survival. In the patients with local recurrence, multi-modal therapy (MMT) had 53.0%post-recurrence 3-year survival rate compared with 11.4% of SMT ( P=0.024). Similar results were also found in the patients with distant metastases (post-recurrence 3-year survival rate 58.1% for MMT versus 29.3% for SMT, P=0.003). CONCLUSIONS: Multi-lesions recurrence, short DFI and brain metastasis are independent risk predictors, while MMT is a protective factor for the survival of patients with mrTNBC.