Exploring prognostic and immunological characteristics of pancreatic ductal adenocarcinoma through comprehensive genomic analysis of tertiary lymphoid structures and CD8 + T-cells.

PURPOSE: Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes. METHODS: We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods. RESULTS: Overall survival differed significantly between the training and validation cohorts' low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors. CONCLUSION: The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.

Four circadian rhythm-related genes predict incidence and prognosis in hepatocellular carcinoma.

Circadian dysregulation can be involved in the development of malignant tumors, though its relationship with the progression of hepatocellular carcinoma is not yet fully understood. We identified genes related to circadian rhythms from the Cancer Genome Atlas (TCGA), measured gene expression, and conducted genomic difference analysis to construct a circadian rhythm-related signature. The resulting prognosis model proved to be an effective biomarker, as demonstrated by Kaplan-Meier survival analysis for both the training (n = 370, P = 2.687e-10) and external validation cohorts (n = 230, P = 1.45e-02). Further, we found that patients considered 'high risk', with an associated poor prognosis, displayed elevated levels of immune checkpoint genes and immune filtration. We also conducted functional enrichment, which indicated that the risk model showed a significant positive correlation with certain malignant phenotypes, including G2M checkpoint, MYC targets, and the MTORC1 signaling pathway. In summary, we identified a novel circadian rhythm-related signature allowing assessment of prognosis for hepatocellular carcinoma patients, and further can be used to predict immune infiltration sensitivity.

Changes in Gallbladder Contractile Function and its Influencing Factors After Minimally Invasive Gallbladder-Preserving Surgery for Cholecystitis With Incarcerated Gallstones.

Background: Cholecystitis with incarcerated gallstones (CIG) is a type of acute abdomen in the field of hepatobiliary surgery. Whether gallbladder-preserving surgery (GPS) can be performed to treat it, however, depends on the improvement of gallbladder contractile function. The present study aimed to investigate the changes in gallbladder contractile function and its influencing factors after minimally invasive GPS for CIG. Methods: A total of 95 patients with CIG treated in the Aerospace Center Hospital between May 2017 and May 2019 were enrolled as the study subjects. All patients received minimally invasive GPS. The patients' operation-related conditions (including stone removal success rate, duration of surgery, intraoperative blood loss, etc.), changes in gallbladder contractile function, and influencing factors of GPS were analyzed. Results: Among the 95 patients included in the study, the success rate of stone removal was 100%, the duration of surgery was 76.0 ± 26.5 min, and the intraoperative blood loss was 10.17 ± 4.43 ml. The rate of good gallbladder contractile function at one and two years after surgery was significantly higher than before surgery (P < 0.05). Age, duration of surgery, stone recurrence, and diabetes were the independent risk factors for postoperative gallbladder contractile function (P < 0.05). Conclusion: Minimally invasive GPS for patients with CIG has a good curative effect. The changes in gallbladder contractile function after the surgery are influenced by many factors.

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt.

The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression.

Lithotomy using cholangioscopy via the left hepatic duct orifice versus the common bile duct in laparoscopic treatment of left-sided hepatolithiasis: a comparative study.

OBJECTIVE: Laparoscopic hepatectomy is widely used in the surgical treatment of left-sided hepatolithiasis (LSH). Lithotomy using a cholangioscope usually is required for the treatment of concurrent right-sided hepatolithiasis or choledocholithiasis. The primary objective of this study was to evaluate the effectiveness and safety of gallstone elimination using cholangioscopy through the left hepatic duct (LHD) orifice versus the common bile duct (CBD). PATIENTS AND METHODS: Eligible LSH patients (n=41) were scheduled for laparoscopic left lateral segmentectomy or left hemihepatectomy with intraoperative biliary exploration using cholangioscopy through the LHD orifice (LHD group, n=23) or the CBD (CBD group, n=18) at the discretion of patients. Laparoscopic T-tube insertion was performed in selected patients. Patients were regularly followed up at monthly intervals or more frequently in the presence of any symptom. The primary outcome measures included overall operative time, duration of the cholangioscopy procedure, volume of blood loss, length of hospital stay, and frequency of procedure-related complications. RESULTS: The two groups were comparable in sex, age, symptoms, site of lesion, and gallstone comorbidities (P>.05). Of the 18 patients in the CBD group, 12 (66.7%) patients had a T-tube inserted in contrast to 1 (4.5%) patient in the LHD group. The two groups were comparable in cholangioscopy duration and volume of blood loss (P>.05), whereas the LHD group had a significantly shorter operative time than the CBD group (221.4 ± 58.6 minutes versus 171.2 ± 63.5 minutes; P<.05). The postoperative duration of hospitalization was significantly shorter in the LHD group than in the CBD group (7.5 ± 2.2 days versus 4.2 ± 1.9 days; P<.05). No patient showed any recurrence of gallstones or cholangitis during the follow-up period. CONCLUSIONS: As an effective and safe technique that is comparable to choledochotomy, LHD cholangioscopy is a preferred alternative to choledochotomy in the laparoscopic treatment of LSH because it offers patients shorter operative duration and length of hospitalization.

Laparoendoscopic single-site liver resection: a preliminary report of 12 cases.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery is an emerging laparoscopic procedure previously used for cholecystectomy and appendectomy. However, few studies have examined LESS liver resection, and its benefits require investigation. This study aimed to evaluate the feasibility and safety of LESS liver resection. METHODS: From December 2009 to October 2010, 12 patients were selected for LESS liver resection with institutional review board approval. The LESS technique was performed using a transumbilical TriPort or three 5-mm trocars with a 5-mm linear or flexible laparoscope. Conventional or articulating laparoscopic instruments were used to mobilize and transect the lesions. RESULTS: The LESS liver resection procedure was successfully completed for 10 patients (83.3%), with the remaining 2 patients (16.7%) undergoing conversion to conventional multiport laparoscopy. The procedures consisted of left lateral segment resection (n = 4) and partial resection (n = 8) in addition to concomitant cholecystectomy (n = 3). The mean operative time was 80.4 min (range, 35-160 min), and the mean estimated blood loss was 45 ml (range, 20-800 min). No postoperative complications were noted except for biliary leakage (200 ml/day)in one patient. The mean hospital stay was 4.3 days (range, 2-8 days). No patient required postoperative analgesia, and the pain visual analog score 48 h after surgery was 0.53 (range, 0-2). Pathology identified 10 benign and 2 malignant liver tumors with a clear margin. CONCLUSIONS: Our preliminary data show that LESS liver resection is safe and feasible for selected patients, with potential benefits that include a fast recovery, light pain, and cosmetically acceptable scarring. However, this procedure requires advanced instruments and complicated laparoscopic techniques, with a risk of intraoperative bleeding and postoperative bile leakage.