Totally Intracorporeal Robot-Assisted Bilateral Ileal Ureter Replacement for the Treatment of Ureteral Strictures using Kangduo Surgical Robot 2000 Plus

ABSTRACT Purpose: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. Materials and Methods: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. Results: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. Conclusions: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.

Development and validation of a relatively accurate gastric cancer high-risk group screening scoring system in urban residents.

PURPOSE: Our study aimed to develop a relatively accurate gastric cancer (GC) screening score system for urban residents and to validate the screening efficacy. METHODS: The present study included a derivation cohort (n = 3406) and a validation cohort (n = 868) of urban residents. Applying the full-stack engineering intelligent system platform of Hualian Health Big Data of Shandong University, the clinical physical examination data of subjects were collected. Univariate and multivariate analyses were used to identify risk factors for GC, and subsequently, an optimal prediction rule was established to create three distinct scoring systems. RESULTS: In the GC-risk scoring system I, age, plateletocrit (PCT), carcinoembryonic antigen (CEA), glucose, albumin, creatinine were independent risk factors of GC, with scores ranging from 0 to 28 and optimal cut-off was 15.5. The second scoring system consisted of age, PCT, RDW-CV, CEA, glucose, albumin, and creatinine, with scores ranging from 0 to 31. The optimal cut-off point was determined to be 15.5. The scoring system III comprise of age, sex, PCT, RDW CV, CEA, glucose, with scores ranging from 0 to 21 and optimal cut-off was 10.5. All three scoring systems demonstrated excellent discrimination for GC, achieving an AUC of 0.884, 0.89, and 0.876, respectively. In external validation, the AUC values were 0.654, 0.658, and 0.714. Notably, the GC-risk scoring system III exhibited the highest screening efficiency. CONCLUSIONS: Urban residents benefited from the effective and verified GC-risk scoring systems, which demonstrated excellent performance in identifying individuals with an elevated risk of GC.

Long-Term Enlargement of the Neo-Aortic Root and Aortic Arch Following Arch Reconstruction in Hypoplastic Left Heart Syndrome.

BACKGROUND: Long-term enlargement of the aortic arch after aortic arch reconstruction (AAR) in hypoplastic left heart syndrome (HLHS) is not well described. METHODS: Aortic arch measurements for 50 patients with HLHS who achieved Fontan completion were converted to Pediatric Heart Network z-scores. Dimensions were assessed using linear mixed models and differences among time points were evaluated with F-tests. Sub-analysis was conducted comparing Norwood (n=36) vs hybrid (n=14) strategies. RESULTS: Median time to last imaging was 6.4 (IQR, 3.5-11.3) years. Prior to intervention, the main pulmonary artery was dilated whereas the ascending aorta (AA), transverse arch (TA), and isthmus (ISTH) were hypoplastic. With AAR, there were expected increases in all arch z-scores. The aortic arch continued to dilate after AAR reaching peak values at 7 months [Neo-Aortic Complex (NAC): z= 6.9 (5.6-8.0)] or 12 months following stage I [AAo: z=6.1 (2.9-8.3); TA: z=4.7 (3.0-5.9)]. Following peak values, there was a gradual decline in z-scores with most components still at least mildly dilated at 16 years [NAC: z=3.2 (3.1-3.9), AAo: z=3.9 (3.3-4.2); TA: z=3.1 (2.5-3.7)] with abrupt calibre change at ISTH: z= -0.8 (-1.1- -0.3)]. Norwood and hybrid strategies showed similar enlargement profiles after 7 months of age. CONCLUSIONS: Neo-aortic root and aortic arch in HLHS are enlarged early after AAR and continue to enlarge out of proportion to normal controls until 12 months of age, with gradual decline in enlargement up to adolescence. Further work should focus on modifiable surgical factors which may prove important to optimize arch growth and geometry.

Comparative study on the efficacy of low-dose and full-dose BCG bladder perfusion therapy.

BACKGROUND: Full-dose BCG bladder perfusion therapy is effective, but there are serious side effects. Whether a low dose of BCG can reduce the side effects of treatment while maintaining its efficacy is still inconclusive. OBJECTIVE: To compare the efficacy of low-dose and full-dose BCG bladder perfusion therapy and to provide reference for individual treatment of bladder cancer. METHODS: All relevant literature published in PubMed, Web of Science, and Embrase databases up to April 2024 was searched. The results and shortcomings of the existing literature are analyzed, the cognitive gaps between different studies are pointed out, and suggestions are made for future research. RESULTS: A total of 32 pieces of literature were included. Twelve studies found that the efficacy of full-dose BCG perfusion was significantly better than that of low-dose BCG perfusion, and 20 studies found no statistical difference between low-dose and full-dose BCG perfusion CONCLUSION: Although there is no significant difference in the efficacy of full-dose and low-dose BCG in bladder perfusion, the trend indicates that the efficacy of full-dose BCG is still the most accurate. In cases where BCG resources are scarce or patients are intolerant, low-dose BCG bladder perfusion therapy may be an alternative to full-dose BCG bladder perfusion therapy. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Improvement effect of compound Ento-PB on oxazolone-induced ulcerative colitis in rats.

PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.

Investigation of TMEM41A's function in breast cancer prognosis and its connection to immune cell infiltration.

BACKGROUND: Globally, breast cancer is the most common type of malignant tumor. It has been demonstrated that TMEM41A is abnormally expressed in a number of cancers and is linked to a dismal prognosis. TMEM41A's involvement in breast cancer remains unknown, though. METHODS: Data from databases such as TCGA were used in this study. Expression differences were compared using non-parametric tests. Cox regression analysis was employed, and analyses such as Nomogram were used to assess the significance of TMEM41A in predicting the prognosis of breast cancer. Lastly, it was looked into how immune cell infiltration in breast cancer is related to TMEM41A expression levels. RESULTS: The results suggest that TMEM41A is overexpressed in breast cancer and correlates with poor prognosis (P = 0.01), particularly in early-stage and ductal A breast cancer (P < 0.01). Breast cancer patients' expression of TMEM41A was found to be an independent risk factor (HR = 1.132, 95% CI 1.036-1.237) by multifactorial Cox regression analysis. The Nomogram prediction model's c-index was 0.736 (95% CI 0.684-0.787). The results of GSEA biofunctional enrichment analysis included the B cell receptor signaling pathway (P < 0.05). Ultimately, there was a significant correlation (P < 0.05) between TMEM41A expression in breast cancer and an infiltration of twenty immune cells. CONCLUSIONS: Breast cancer tissues overexpress TMEM41A, which is linked to immune cell infiltration and prognosis (particularly in early stage and luminal A breast cancer). Overexpression of TMEM41A is anticipated to serve as a novel prognostic indicator and therapeutic target for breast cancer.

Integrative analysis of transcriptome and metabolome reveals how ethylene increases natural rubber yield in Hevea brasiliensis.

Hevea brasiliensis is an important cash crop with the product named natural rubber (NR) for markets. Ethylene (ET) is the most effective yield stimulant in NR production but the molecular mechanism remains incomplete. Here, latex properties analysis, transcriptome analysis, and metabolic profiling were performed to investigate the mechanism of NR yield increase in four consecutive tappings after ET stimulation. The results revealed that sucrose and inorganic phosphate content correlated positively with dry-rubber yield and were induced upon ET stimulation. Stimulation with ET also led to significant changes in gene expression and metabolite content. Genes involved in phytohormone biosynthesis and general signal transduction as well as 51 transcription factors potentially involved in the ET response were also identified. Additionally, KEGG annotation of differentially accumulated metabolites suggested that metabolites involved in secondary metabolites, amino-acid biosynthesis, ABC transporters, and galactose metabolism were accumulated in response to ET. Integrative analysis of the data collected by transcriptomics and metabolomics identified those differentially expressed genes and differentially accumulated metabolites are mainly involved in amino-acid biosynthesis and carbohydrate metabolism. Correlation analysis of genes and metabolites showed a strong correlation between amino-acid biosynthesis during ET stimulation. These findings provide new insights into the molecular mechanism underlying the ET-induced increase in rubber yield and further our understanding of the regulatory mechanism of ethylene signaling in rubber biosynthesis.

Effect of smoking on the recurrence and progression of non-muscle-invasive bladder cancer.

BACKGROUND: It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue. OBJECTIVE: To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients. METHODS: A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research. RESULTS: A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients. CONCLUSIONS: Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Identification and functional characteristics of CHD1L gene variants implicated in human Müllerian duct anomalies.

BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders that present as a series of abnormalities within the reproductive tracts of females. Genetic factors are linked to MDAs and recent advancements in whole-exome sequencing (WES) provide innovative perspectives in this field. However, relevant mechanism has only been investigated in a restricted manner without clear elucidation of respective observations. METHODS: Our previous study reported that 2 of 12 patients with MDAs harbored the CHD1L variant c.348-1G>C. Subsequently, an additional 85 MDAs patients were recruited. Variants in CHD1L were screened through the in-house database of WES performed in the cohort and two cases were identified. One presented with partial septate uterus with left renal agenesis and the other with complete septate uterus, duplicated cervices and longitudinal vaginal septum. The pathogenicity of the discovered variants was further assessed by molecular dynamics simulation and various functional assays. RESULTS: Ultimately, two novel heterozygous CHD1L variants, including a missense variant c.956G>A (p.R319Q) and a nonsense variant c.1831C>T (p.R611*) were observed. The variants were absent in 100 controls. Altogether, the contribution yield of CHD1L to MDAs was calculated as 4.12% (4/97). All three variants were assessed as pathogenic through various functional analysis. The splice-site variant c.348-1G>C resulted in a 11 bp sequence skipping in exon 4 of CHD1L and led to nonsense mediated decay of its transcripts. Unlike WT CHD1L, the truncated R611* protein mislocalized to the cytoplasm, abolish the ability of CHD1L to promote cell migration and failed to interact with PARP1 owing to the loss of macro domain. The R319Q variant exhibited conformational disparities and showed abnormal protein recruitment behavior through laser microirradiation comparing with the WT CHD1L. All these variants impaired the CHD1L function in DNA damage repair, thus participating in MDAs. CONCLUSIONS: The current study not only expands the mutational spectrum of CHD1L in MDAs but determines three variants as pathogenic according to ACMG guidelines with reliable functional evidence. Additionally, the impairment in DNA damage repair is an underlying mechanism involved in MDAs.

Totally Intracorporeal Robot-Assisted Bilateral Ileal Ureter Replacement for the Treat-ment of Ureteral Strictures using Kangduo Surgical Robot 2000 Plus.

PURPOSE: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. MATERIALS AND METHODS: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. RESULTS: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. CONCLUSIONS: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.

Impact of Silicon Carbide Coating and Nanotube Diameter on the Antibacterial Properties of Nanostructured Titanium Surfaces.

This study aimed to comprehensively assess the influence of the nanotube diameter and the presence of a silicon carbide (SiC) coating on microbial proliferation on nanostructured titanium surfaces. An experiment used 72 anodized titanium sheets with varying nanotube diameters of 50 and 100 nm. These sheets were divided into four groups: non-coated 50 nm titanium nanotubes, SiC-coated 50 nm titanium nanotubes, non-coated 100 nm titanium nanotubes, and SiC-coated 100 nm titanium nanotubes, totaling 36 samples per group. P. gingivalis and T. denticola reference strains were used to evaluate microbial proliferation. Samples were assessed over 3 and 7 days using fluorescence microscopy with a live/dead viability kit and scanning electron microscopy (SEM). At the 3-day time point, fluorescence and SEM images revealed a lower density of microorganisms in the 50 nm samples than in the 100 nm samples. However, there was a consistently low density of T. denticola across all the groups. Fluorescence images indicated that most bacteria were viable at this time. By the 7th day, there was a decrease in the microorganism density, except for T. denticola in the non-coated samples. Additionally, more dead bacteria were detected at this later time point. These findings suggest that the titanium nanotube diameter and the presence of the SiC coating influenced bacterial proliferation. The results hinted at a potential antibacterial effect on the 50 nm diameter and the coated surfaces. These insights contribute valuable knowledge to dental implantology, paving the way for developing innovative strategies to enhance the antimicrobial properties of dental implant materials and mitigate peri-implant infections.

Novel genetic variants in the NLRP3 inflammasome-related PANX1 and APP genes predict survival of patients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear. METHODS: We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations. RESULTS: We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425. CONCLUSIONS: These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies.

Amorphophallus campanulatus tuber extract protects diabetic nephropathy in streptozotocin-induced diabetic nephropathy rat model by regulating oxidative stress and TNF-α inflammatory pathway.

PURPOSE: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. METHODS: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. RESULTS: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. CONCLUSIONS: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.

The battle within: cell death by phagocytosis in cancer.

The process by which living cells are phagocytosed and digested to death is called cell death by phagocytosis, a term that has just recently been generalized and redefined. It is characterized by the phagocytosis of living cells and the cessation of cell death by phagocytosis. Phagocytosis of dead cells is a widely discussed issue in cancer, cell death by phagocytosis can stimulate phagocytosis and stimulate adaptive immunity in tumors, and at the same time, do not-eat-me signaling is an important site for cancer cells to evade recognition by phagocytes. Therefore, we discuss in this review cell death by phagocytosis occurring in cancer tissues and emphasize the difference between this new concept and the phagocytosis of dead tumor cells. Immediately thereafter, we describe the mechanisms by which cell death by phagocytosis occurs and how tumors escape phagocytosis. Finally, we summarize the potential clinical uses of cell death by phagocytosis in tumor therapy and strive to provide ideas for tumor therapy.

Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

Correlation between exosomal PD-L1 and prognosis in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: The predictive role of exosomal programmed cell death ligand l (exoPD-L1) in prognosis has been studied extensively; however, there is still no consensus. METHODS: Three databases, including EMBASE, PubMed, and Web of Science, were searched through January 4, 2024. The pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to identify the relationship between circulating exoPD-L1 and prognosis. RESULTS: 15 studies with 1091 patients with cancer were included in this statistical analysis. High exoPD-L1 level was correlated with shorter progression-free survival (PFS) (HR = 2.58, 95% CI: 1.75-3.81) and overall survival (OS) (HR = 1.61, 95% CI: 1.32-1.98). Meanwhile, we found that dynamic upregulation of circulating exoPD-L1 in the early stages of immunotherapy was a favorable factor for prognosis (PFS: HR = 0.34, 95% CI: 0.23-0.51; OS: HR = 0.21, 95% CI: 0.13-0.26). CONCLUSION: Circulating exoPD-L1 may be a valuable prognostic indicator for patients with cancer and monitoring its changes in the early stages of immunotherapy might be used to predict tumor response and clinical outcome. This conclusion may not apply to superficial tumors.

Investigating the impact of the inflammatory immune microenvironment and steroids or COX-2 inhibitors usage on immunotherapy in advanced esophageal squamous cell carcinoma (ESCC): a propensity score matched analysis.

PURPOSE: The research aimed to evaluate the connection between pre-treatment inflammatory biomarkers and clinical results in advanced esophageal squamous cell carcinoma (ESCC) receiving immune checkpoint inhibitors. MATERIALS AND METHODS: Between 2019 and 2022, we analyzed 354 individuals diagnosed with metastatic ESCC who underwent immunotherapy. The study sought to evaluate the impact of specific inflammatory biomarkers (Neutrophil/Lymphocyte Ratio (NLR), C-reactive protein to albumin ratio (CRP/ALB) and Glasgow Prognostic Score (GPS), Cyclooxygenase-2 (COX-2) inhibitors or steroids usage on the effectiveness and survival outcomes of immunotherapy in advanced ESCC. The research utilized Kaplan‒Meier and Cox regression models alongside propensity score matching for analysis. RESULTS: The findings revealed that elevated pre-treatment NLR (11.0 vs. 14.6 months, p = 0.021) and CRP/ALB (11.4 vs. 14.6 months, p = 0.022) levels were significantly associated with poorer overall survival (OS) outcomes, while the use of steroids did not show a significant difference in OS (15.5 vs. 15.4 months, p = 0.685) between groups. Similarly, no notable disparity in OS was observed between patients treated withCOX-2 inhibitors and those who were not (13.8 vs. 11.0 months, p = 0.054). CONCLUSION: Lower levels of NLR and CRP/ALB prior to treatment were linked to better effectiveness and OS in immunotherapy for advanced ESCC. The study did not identify a significant relationship between OS in patients with esophageal cancer and the use of either steroids or COX-2 inhibitors.

Development of machine learning-based personalized predictive models for risk evaluation of hepatocellular carcinoma in hepatitis B virus-related cirrhosis patients with low levels of serum alpha-fetoprotein.

INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

Laparoscopic gastrectomy versus open gastrectomy for gastric cancer in patients among octogenarians: a meta-analysis.

PURPOSE: Currently, there is no consensus regarding whether super-elderly (aged > 80 years) patients are suitable candidates for laparoscopic surgery. This study aimed to analyse the short-term outcomes and oncological prognosis of laparoscopic gastrectomy in super-elderly patients with gastric cancer (GC). METHODS: Following PRISMA and AMSTAR-2 guidelines, we searched the Web of Science, Embase, Cochrane Library, and Pubmed databases from inception until May 2024 and performed a meta-analysis. All published studies exploring the surgical outcomes and oncological prognosis of laparoscopic versus open gastrectomy in super-elderly patients with GC were reviewed. Statistical analyses were performed using RevMan 5.3. RESULTS: A total of 1,085 studies were retrieved, eight of which were included in the meta-analysis, comprising 807 patients > 80 years of age with GC. The meta-analysis showed that compared with open gastrectomy, patients with GC > 80 years old who underwent laparoscopic gastrectomy had a longer operative time (weighted mean difference [WMD] = 30.48, p < 0.001), less intraoperative blood loss (WMD = -166.96, P < 0.001), shorter postoperative exhaust time (WMD =-0.83, p < 0.001), shorter length of stay (WMD = -0.78, p < 0.001), fewer overall complications (Odds ratio [OR] = 0.54, p = 0.003), higher 5-year overall survival rate (OR = 1.66, p = 0.03) and disease-specific survival rate (OR = 3.23, p < 0.001). Furthermore, laparoscopic gastrectomy did not significantly affect the number of lymph node dissections, the rate of D2 radical gastrectomy, major postoperative complications, or postoperative pneumonia. CONCLUSIONS: Compared to open gastrectomy, patients with GC aged > 80 years who underwent laparoscopic gastrectomy may have better short-term outcomes. Age should not be a contraindication for minimally invasive surgery.