Machine learning-driven diagnostic signature provides new insights in clinical management of hypertrophic cardiomyopathy.

AIMS: In an era of evolving diagnostic possibilities, existing diagnostic systems are not fully sufficient to promptly recognize patients with early-stage hypertrophic cardiomyopathy (HCM) without symptomatic and instrumental features. Considering the sudden death of HCM, developing a novel diagnostic model to clarify the patients with early-stage HCM and the immunological characteristics can avoid misdiagnosis and attenuate disease progression. METHODS AND RESULTS: Three hundred eighty-five samples from four independent cohorts were systematically retrieved. The weighted gene co-expression network analysis, differential expression analysis (|log2(foldchange)| > 0.5 and adjusted P < 0.05), and protein-protein interaction network were sequentially performed to identify HCM-related hub genes. With a machine learning algorithm, the least absolute shrinkage and selection operator regression algorithm, a stable diagnostic model was developed. The immune-cell infiltration and biological functions of HCM were also explored to characterize its underlying pathogenic mechanisms and the immune signature. Two key modules were screened based on weighted gene co-expression network analysis. Pathogenic mechanisms relevant to extracellular matrix and immune pathways have been discovered. Twenty-seven co-regulated genes were recognized as HCM-related hub genes. Based on the least absolute shrinkage and selection operator algorithm, a stable HCM diagnostic model was constructed, which was further validated in the remaining three cohorts (n = 385). Considering the tight association between HCM and immune-related functions, we assessed the infiltrating abundance of various immune cells and stromal cells based on the xCell algorithm, and certain immune cells were significantly different between high-risk and low-risk groups. CONCLUSIONS: Our study revealed a number of hub genes and novel pathways to provide potential targets for the treatment of HCM. A stable model was developed, providing an efficient tool for the diagnosis of HCM.

A monoclonal antibody collection for C. difficile typing ?

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in adults. Various C. difficile strains circulate currently, associated with different outcomes and antibiotic resistance profiles. However, most studies still focus on the reference strain 630 that does not circulate anymore, partly due to the lack of immunological tools to study current clinically important C. difficile PCR ribotypes. The goal of this study was to generate monoclonal antibodies recognizing various epidemic ribotypes of C. difficile. To do so, we immunized mice expressing human variable antibody genes with the Low Molecular Weight (LMW) subunit of the surface layer protein SlpA from various C. difficile strains. Monoclonal antibodies purified from hybridomas bound LMW with high-affinity and whole bacteria from current C. difficile ribotypes with different cross-specificities. This first collection of anti-C. difficile mAbs represent valuable tools for basic and clinical research.

Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology.

Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.

Clinical report and genetic analysis of a Chinese patient with developmental and epileptic encephalopathy associated with novel biallelic variants in the ST3GAL3 gene.

BACKGROUND: Defects in the Golgi enzyme beta-galactoside-alpha-2,3-sialyltransferase-III (ST3Gal-III) caused by biallelic ST3GAL3 gene variants are associated with human neurodevelopmental disorders. Although ST3GAL3 gene variants have been linked to developmental and/or epileptic encephalopathy 15 (DEE15), their presence has only been reported in nine patients; however, the real frequency may be masked by insufficient screening. METHODS: Phenotypic information was collected from a male patient with severe psychomotor developmental delay and epileptic seizures, and genetic testing was done using whole exome sequencing. A molecular dynamics simulation analysis was performed to assess the potential impacts of the identified ST3GAL3 variants on the ST3Gal-III protein function, and a literature review was conducted to compare this case with previously described cases and assess disease manifestation and genetic characteristics. RESULTS: The patient inherited compound heterozygous ST3GAL3 gene variants, NM_006279.5:c.809G>A (p.Arg270Gln) and c.921dupG (p.Thr308fs*8). Neither variant had been previously reported in the general population. The p.Arg270Gln variant disrupted a hydrogen bond in the simulated ST3Gal-III protein structure. Among 25 patients with ST3GAL3 gene defects, eight ST3GAL3 gene variants were identified, and five variants had DEE signs. CONCLUSION: Patients with DEE15 may have novel ST3GAL3 gene variants, and this study may be the first clinical report of their occurrence in a Chinese patient. These variants should be considered when evaluating patients presenting with unexplained early-onset epileptic encephalopathy, severe developmental delay, and/or intellectual disability.

Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion.

OBJECTIVE: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. METHODS: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. RESULTS: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. CONCLUSIONS: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

Cellular Ligand-Receptor Perturbations Unravel MEIS2 as a Key Factor for the Aggressive Progression and Prognosis in Stage II/III Colorectal Cancer.

Approximately 10-15% of stage II and 25-30% of stage III colorectal cancer (CRC) patients experience recurrence within 5 years after surgery, and existing taxonomies are insufficient to meet the needs of clinical precision treatment. Thus, robust biomarkers and precise management were urgently required to stratify stage II and III CRC and identify potential patients who will benefit from postoperative adjuvant therapy. Alongside, interactions of ligand-receptor pairs point to an emerging direction in tumor signaling with far-reaching implications for CRC, while their impact on tumor subtyping has not been elucidated. Herein, based on multiple large-sample multicenter cohorts and perturbations of the ligand-receptor interaction network, four well-characterized ligand-receptor-driven subtypes (LRDS) were established and further validated. These molecular taxonomies perform with unique heterogeneity in terms of molecular characteristics, immune and mutational landscapes, and clinical features. Specifically, MEIS2, a key LRDS4 factor, performs significant associations with proliferation, invasion, migration, and dismal prognosis of stage II/III CRC, revealing promising directions for prognostic assessment and individualized treatment of CRC patients. Overall, our study sheds novel insights into the implications of intercellular communication on stage II/III CRC from a ligand-receptor interactome perspective and revealed MEIS2 as a key factor in the aggressive progression and prognosis for stage II/III CRC.

Associations Between Life's Essential 8 and Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of CKD among US adults. METHODS AND RESULTS: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey from 2007 to 2018 and included adults aged ≥20 years. Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and CKD. Among 24 960 participants, 4437 were determined to have CKD (weighted percentage, 14.11%). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of CKD (odds ratio for each 10-point increase, 0.79 [95% CI, 0.76-0.83]), and a nonlinear dose-response relationship was observed. Similar patterns were also identified in the associations of health behavior and health factor scores with CKD. Meanwhile, higher scores for blood glucose (odds ratio, for each 10-point increase, 0.88 [95% CI, 0.87-0.90]) and blood pressure (odds ratio, for each 10-point increase, 0.92 [95% CI, 0.91-0.94]) in the LE8 component are significantly associated with a lower prevalence of CKD. The inversed association of LE8 score and CKD was significantly stronger among middle-aged, male, and coupled participants. CONCLUSIONS: LE8 was negatively associated with the prevalence of CKD in a nonlinear fashion. Promoting adherence to optimal cardiovascular health levels may be beneficial to reduce the burden of CKD.

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

A tumor-infiltrating immune cells-related pseudogenes signature based on machine-learning predicts outcomes and immunotherapy responses in ovarian cancer.

Previous researches have provided evidence for the significant involvement of pseudogenes in immune-related functions across different types of cancer. However, the mechanisms by which pseudogenes regulate immunity in ovarian cancer (OV) and their potential impact on clinical outcomes remain unclear. To address this gap in knowledge, our study utilized a novel computational framework to analyze a total of 491 samples from three public datasets. We employed a combination of 10 machine-learning algorithms to construct a signature known as the tumor-infiltrating immune cells-related pseudogenes signature (TIICPS). The TIICPS, consisting of 12 pseudogenes, demonstrated independent prognostic value for overall survival, surpassing conventional clinical traits, 62 published signatures, and TP53 and BRCA mutation status in three cohorts. Patients with low TIICPS exhibited heightened immune-related pathways, intricate genomic alterations, substantial immune infiltration, and greater potential for immunotherapy efficacy. Consequently, TIICPS holds promise as a predictive tool for prognosis and immunotherapy response in ovarian cancer.

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma.

BACKGROUND: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. METHOD: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. RESULTS: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. CONCLUSIONS: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference.

Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment.

Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular network subtypes of GC (MNG). MNG-1 displayed the best prognosis and vigorous cell cycle activity. MNG-2 was enriched by immune-hot phenotype with the potential for immunotherapy response. MNG-3 and MNG-4 were identified with epithelial-mesenchymal transition (EMT) peculiarity and worse prognosis, termed EMT subtypes. MNG-3 was characterized by low mutational burden and stromal cells and considered a replica of previous subtypes associated with poor prognosis. Notably, MNG-4 was considered a previously undefined subtype with a dismal prognosis, characterized by chromosomal instability and immune-desert microenvironment. This subtype tended to metastasize and was resistant to respond to immunotherapy. Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) were potential interventions for MNG-4.

CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown.

BACKGROUND: Glioblastoma (GBM) is a type of highly malignant brain tumor that is known for its significant intratumoral heterogeneity, meaning that there can be a high degree of variability within the tumor tissue. Despite the identification of several subtypes of GBM in recent years, there remains to explore a classification based on genes related to proliferation and growth. METHODS: The growth-related genes of GBM were identified by CRISPR-Cas9 and univariate Cox regression analysis. The expression of these genes in the Cancer Genome Atlas cohort (TCGA) was used to construct growth-related genes subtypes (GGSs) via consensus clustering. Validation of this subtyping was performed using the nearest template prediction (NTP) algorithm in two independent Gene Expression Omnibus (GEO) cohorts and the ZZ cohort. Additionally, copy number variations, biological functions, and potential drugs were analyzed for each of the different subtypes separately. RESULTS: Our research established multicenter-validated GGSs. GGS1 exhibits the poorest prognosis, with the highest frequency of chr 7 gain & chr 10 loss, and the lowest frequency of chr 19 & 20 co-gain. Additionally, GGS1 displays the highest expression of EGFR. Furthermore, it is significantly enriched in metabolic, stemness, proliferation, and signaling pathways. Besides we showed that Foretinib may be a potential therapeutic agent for GGS1, the worst prognostic subtype, through data screening and in vitro experiments. GGS2 has a moderate prognosis, with a slightly higher proportion of chr 7 gain & chr 10 loss, and the highest proportion of chr 19 & 20 co-gain. The prognosis of GGS3 is the best, with the least chr 7 gain & 10 loss and EGFR expression. CONCLUSIONS: These results enhance our understanding of the heterogeneity of GBM and offer insights for stratified management and precise treatment of GBM patients.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Multi-center validation of an immune-related lncRNA signature for predicting survival and immune status of patients with renal cell carcinoma: an integrating machine learning-derived study.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been reported to play an important role in tumor immune modification. Nonetheless, the clinical implication of immune-associated lncRNAs in renal cell carcinoma (RCC) remains to be further explored. METHODS: 76 combinations of machine learning algorithms were integrated to develop and validate a machine learning-derived immune-related lncRNA signature (MDILS) in five independent cohorts (n = 801). We collected 28 published signatures and collated clinical variables for comparison with MDILS to verify its efficacy. Subsequently, molecular mechanisms, immune status, mutation landscape, and pharmacological profile were further investigated in different stratified patients. RESULTS: Patients with high MDILS displayed worse overall survival than those with low MDILS. The MDILS could independently predict overall survival and convey robust performance across five cohorts. MDILS has a significantly better performance compared with traditional clinical variables and 28 published signatures. Patients with low MDILS exhibited more abundant immune infiltration and higher potency of immunotherapeutic response, while patients with high MDILS might be more sensitive to multiple chemotherapeutic drugs (e.g., sunitinib and axitinib). CONCLUSION: MDILS is a robust and promising tool to facilitate clinical decision-making and precision treatment of RCC.

Genome-scale CRISPR-Cas9 screening stratifies pancreatic cancer with distinct outcomes and immunotherapeutic efficacy.

Pancreatic cancer (PC) was featured by dramatic heterogeneity and dismal outcomes. An ideal classification strategy capable of achieving risk stratification and individualized treatment is urgently needed to significantly improve prognosis. In this study, using the 105 prognostic cancer essential genes identified by genome-scale CRISPR-Cas9 screening and univariate Cox analysis, we established and verified three heterogeneous subtypes via non-negative matrix factorization (NMF) and nearest template prediction (NTP) algorithms in the TCGA-PAAD cohort (176 samples) and four multi-center cohorts (233 samples), respectively. Among them, C1 with the worst prognosis was enriched in immune-related pathways, possessed superior infiltration abundance of immune cells and immune checkpoint molecules expression, and might be most sensitive to immunotherapy. C3, owing a moderate prognosis, might be featured by proliferative biological function, and despite its highest immunogenicity, the defects in antigen processing and presentation ability coupled with barren immune environment render it ineffective for immunotherapy, while it had potential sensitivity to paclitaxel and methotrexate. Besides, C2 harbored the best prognosis and was characterized by metabolism-related functions. These results could deepen our understanding of PC molecular heterogeneity and provide a trustworthy reference for prognostic stratification management and precision medicine in clinical practice.

Contribution of the IGCR1 regulatory element and the 3'Igh CTCF-binding elements to regulation of Igh V(D)J recombination.

Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from VH, D, and JH gene segments located in separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination from a JH-based recombination center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound RAG presents Ds for joining to JHs to form a DJH-RC. Igh has a provocative number and organization of CTCF-binding elements (CBEs) that can impede loop extrusion. Thus, Igh has two divergently oriented CBEs (CBE1 and CBE2) in the IGCR1 element between the VH and D/JH domains, over 100 CBEs across the VH domain convergent to CBE1, and 10 clustered 3'Igh-CBEs convergent to CBE2 and VH CBEs. IGCR1 CBEs segregate D/JH and VH domains by impeding loop extrusion-mediated RAG-scanning. Downregulation of WAPL, a cohesin unloader, in progenitor-B cells neutralizes CBEs, allowing DJH-RC-bound RAG to scan the VH domain and perform VH-to-DJH rearrangements. To elucidate potential roles of IGCR1-based CBEs and 3'Igh-CBEs in regulating RAG-scanning and elucidate the mechanism of the ordered transition from D-to-JH to VH-to-DJH recombination, we tested effects of inverting and/or deleting IGCR1 or 3'Igh-CBEs in mice and/or progenitor-B cell lines. These studies revealed that normal IGCR1 CBE orientation augments RAG-scanning impediment activity and suggest that 3'Igh-CBEs reinforce ability of the RC to function as a dynamic loop extrusion impediment to promote optimal RAG scanning activity. Finally, our findings indicate that ordered V(D)J recombination can be explained by a gradual WAPL downregulation mechanism in progenitor-B cells as opposed to a strict developmental switch.

Laparoscopic endoscopic cooperative surgery for the duodenal neuroendocrine tumor: a single-center case series (How I Do It).

BACKGROUND: Duodenal neuroendocrine tumors (D-NETs) are uncommon. The surgical treatment for D-NETs was in debate. Laparoscopic and endoscopic cooperative surgery (LECS) is a promising approach for treating gastrointestinal tumors. The study aimed to evaluate the feasibility and safety of LECS for D-NETs. Meanwhile, the authors described the details of the LECS technique. METHODS: All patients diagnosed with D-NETs underwent LECS between September 2018 and April 2022 were retrospectively reviewed. The endoscopic procedures were performed with endoscopic full-thickness resection. The defect was manually closed under the surveillance of the laparoscopy. RESULTS: A total of seven patients were enrolled, including three men and four women. The median age was 58 years (ranging from 39-65). Four tumors were located in the bulb and three in the second portion. All cases were diagnosed as NET with grade G1. The tumor depth was pT1 in two cases and pT2 in five cases. The median specimen size and the tumor size were 22 mm (ranging from 10-30) and 8.0 mm (ranging from 2.3-13.0), respectively. En-bloc resection and curative resection rates are 100 and 85.7%, respectively. There were no severe complications. Until 1 June 2022, there was no recurrence. The median follow-up was 9.5 months (range, 1.4-45.1). CONCLUSIONS: LECS with endoscopic full-thickness resection is a reliable surgical procedure. The minimally invasive advantages of LECS enable more individualized treatment options for a specific group. Limited by the length of observation, the long-term performance of LECS for D-NETs requires additional investigation.

Exploration of the lymphadenectomy strategy for elderly pancreatic ductal adenocarcinoma patients undergoing curative-intent resection.

There has been a long-standing controversy regarding the number of lymph nodes (LNs) examined intraoperatively for accurate lymphatic staging and significantly better survival of patients with pancreatic ductal adenocarcinoma (PDAC), and no consensus has been reached for the elderly with the age of over 75 years. Given these, the present study aims to investigate the appropriate number of examined lymph nodes (ELNs) for elderly patients mentioned above. In this study, population-based data on 20,125 patients in 2000 to 2019 from the Surveillance, Epidemiology, and End Results database were reviewed retrospectively. The eighth edition staging system of the American Joint Committee on Cancer (AJCC) was applied. Propensity score matching (PSM) was performed to reduce the effects of multiple biases. By using binomial probability law and maximally selected rank statistics, the minimum number of ELN (MNELN) for accurate nodal involvement assessment and optimal ELN number for significantly better survival were calculated, respectively. In addition, Kaplan-Meier curves and Cox proportional hazard regression models were constructed for further survival analysis. As a result, 6623 patients were enrolled in total in the study. Elderly patients had fewer lymph node metastases and a smaller lymph node ratio (LNR) (all P<0.05). However, poorer overall survival (OS) and cancer-specific survival (CSS) of elderly patients were observed in each pN stage (all P<0.05), except for CSS in N2. The proportions of N2 and N0 stages increased and decreased respectively with increasing number of ELN significantly. MNELN for accurate nodal assessment was 19 according to binomial probability law, and the optimal ELN number for significantly better survival was 17. Additionally, the number of ELN (<17 or ≥17) was also considered a strong prognostic predictor for elderly PDAC patients (≥75 years) in the Cox proportional hazard regression model (Overall survival: hazard ratio [HR]=0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001; Cancer-specific survival: HR=0.75, 95% CI: 0.66-0.85, P<0.001). In conclusion, extended lymphadenectomy is suitable for elderly PDAC patients undergoing curative-intent surgery owing to an accurate assessment of nodal status and improved long-term prognosis. However, a random, prospective clinical trial is warranted before the recommendation of extended lymphadenectomy for the elderly.