Background Overlap and pi-shaped esophagojejunostomy are common linear-stapled reconstructions after totally laparoscopic total gastrectomy (TLTG), but whether the technical time advantage of one method is accompanied by better perioperative safety remains uncertain. This study aimed to compare the two techniques in terms of operative efficiency, recovery, and anastomotic complications. Methods In an unfunded PROSPERO-registered meta-analysis (PROSPERO registration: CRD420261398884), PubMed/MEDLINE, Web of Science, Scopus, Cochrane CENTRAL, China National Knowledge Infrastructure (CNKI), and Wanfang were searched from inception through 29 July 2026 without language restriction. Randomized and non-randomized comparative studies of adults undergoing curative TLTG with overlap versus pi-shaped reconstruction were eligible. Random-effects mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Risk of bias was assessed with RoB 2 or ROBINS-I and certainty with GRADE. Results Thirteen studies (1,246 patients; one reported-randomized study and 12 retrospective cohorts) were included; 10 studies (982 patients) contributed to at least one meta-analysis. Compared with pi-shaped reconstruction, overlap required longer total operative time (8 studies, 826 patients; MD 17.37 minutes, 95% CI: 7.67 to 27.06; I-2=66.1%) and anastomosis time (8 studies, 718 patients; MD 7.61 minutes, 95% CI: 5.84 to 9.38; I-2=67.6%). No clear differences were found in anastomotic leakage (9 studies, 880 patients; RR 0.76, 95% CI: 0.41 to 1.43), stenosis/stricture (RR 0.48, 95% CI: 0.12 to 1.82), any early postoperative complication (7 studies, 671 patients; RR 0.90, 95% CI: 0.66 to 1.24), blood loss, recovery, pulmonary infection, or reflux esophagitis. Most non-randomized studies had serious risk of bias; certainty was low for anastomosis time and very low for the remaining major outcomes. Conclusions pi-shaped reconstruction may reduce operative and anastomosis times, but the available evidence does not establish superiority in safety or recovery. Technique selection should remain individualized until prospective multicenter comparisons with standardized outcomes are available.
Background As non-B non-C hepatocellular carcinoma (NBNC-HCC) becomes increasingly common in China and transarterial chemoembolization (TACE)-based combination therapy is increasingly used, whether clinical outcomes differ between hepatitis B virus (HBV)-related HCC (HBV-HCC) and NBNC-HCC remains unclear. We compared treatment response and survival outcomes between the two groups. Methods This single-center retrospective cohort included consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC treated from January 2020 to December 2024. All patients received conventional TACE plus a tyrosine kinase inhibitor (TKI) and programmed cell death protein 1 (PD-1) inhibitor as initial combination therapy. Hepatitis C virus-related HCC and HBV/HCV coinfection were excluded. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progression-free survival (PFS) was defined from the first TACE procedure to radiological progression or death, whichever occurred first, and overall survival (OS) from the first TACE procedure to death. Multivariable logistic and Cox regression analyses were performed. Results A total of 200 patients were included, comprising 144 with HBV-HCC and 56 with NBNC-HCC. The objective response rate (ORR) was 62.5% in the HBV-HCC group and 48.2% in the NBNC-HCC group. After multivariable adjustment, NBNC-HCC was associated with lower odds of objective response [adjusted odds ratio (OR) =0.436, 95% confidence interval (CI): 0.212-0.877; P=0.02]. Median PFS was 10.0 months in the HBV-HCC group and 5.6 months in the NBNC-HCC group, and NBNC-HCC was independently associated with shorter PFS [adjusted hazard ratio (HR) =1.51, 95% CI: 1.07-2.14; P=0.02]. Median OS was 24.1 and 18.8 months, respectively (log-rank P=0.03); however, after accounting for time-varying covariate effects in the extended Cox model, etiological group was not independently associated with OS (adjusted HR =1.21, 95% CI: 0.79-1.87; P=0.39). No treatment-related deaths were documented. Conclusions NBNC-HCC was associated with a lower objective response and shorter PFS than HBV-HCC after multivariable adjustment, whereas no independent association between etiological group and OS was observed. Further prospective studies with more detailed etiological and treatment characterization are warranted.
Background Over 17% of gastrointestinal (GI) malignancies involve deficient DNA damage repair (DDR) mechanisms that have poor outcomes on standard chemotherapy but are sensitive to targeted therapies like immune checkpoint inhibitors and poly (ADP-ribose) polymerase inhibitors. Lurbinectedin is an alkylating agent that demonstrated a 35.2% overall response rate (ORR) as second-line therapy in small-cell lung cancer patients who progressed on platinum-based chemotherapies. The drug inhibits DDR, promoting apoptosis in tumor cells through double-stranded DNA breaks (DSBs). Since repair-deficient tumors cannot efficiently and adequately fix these DSBs, DNA damage accumulates and results in enhanced tumor killing. Therefore, lurbinectedin's mechanism makes it suitable for use in cancers with DDR mutations. Our study evaluated the efficacy of lurbinectedin monotherapy in patients with advanced GI malignancies who harbored DDR mutations. Methods This was a prospective open-label, single-arm phase II study at a single institution. Participants were age >= 18 years, had Eastern Cooperative Oncology Group (ECOG) performance status score <= 1, and locally advanced unresectable or metastatic GI cancer with >= 1 deleterious DDR mutation. Intravenous lurbinectedin was administered at 3.2 mg/m(2 )on day 1 every 3 weeks. Hematology and chemistry labs were obtained on days 1, 8, and 15 of cycles 1 and 2, and day 1 of every subsequent cycle. Tumor markers (CA 19-9 or carcinoembryonic antigen) were collected on day 1 of each cycle. Tumor assessment via imaging occurred at least every three cycles. The primary outcome was ORR according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary outcomes included duration of response, tumor marker normalization, progression-free survival (PFS), overall survival (OS), and safety using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Results Eight participants (7 pancreatic cancer, 1 rectal cancer) with at least two prior therapy lines were enrolled and had DDR mutations in ATM (25.0%), ARID1A (62.5%), BRCA1 (25.0%), CHEK2 (12.5%), and FANC (12.5%). Median age was 63.5 years, 62.5% were female, and 87.5% were white. The ORR at 12 weeks was 0%. Median (95% confidence interval) PFS and OS were 1.2 (0.7-2.8) and 2.4 (1.2-4.1) months, respectively. The most common related adverse events (AEs) were grade 1 and 2 anorexia (50.0%) and constipation (25.0%); and grade 2 nausea (37.5%), anemia (25.0%), and fatigue (25.0%). Two patients (25.0%) experienced grade 3 and 4 neutropenia (1 each). Conclusions In this trial of individuals with advanced GI malignancies with known DDR mutations, there was no clinical benefit of lurbinectedin, as all experienced progressive disease while on the agent (NCT05229588). Interpretation of the study is limited by the small sample size, only two types of GI cancers represented, early termination, and that most participants (62.5%) only completed one dose of the drug.
