Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

MTFR2-dependent mitochondrial fission promotes HCC progression.

BACKGROUND: The role of mitochondrial dynamics, encompassing fission, fusion, and mitophagy, in cancer progression has been extensively studied. However, the specific impact of mitochondrial dynamics on hepatocellular carcinoma (HCC) is still under investigation. METHODS: In this study, mitochondrial dynamic genes were obtained from the MitoCarta 3.0 database, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Based on the expression of these dynamic genes and differentially expressed genes (DEGs), patients were stratified into two clusters. Subsequently, a prognostic model was constructed using univariate COX regression and the least absolute shrinkage and selection operator (LASSO) regression, and the prognostic signature was evaluated. We analyzed the interaction between these model genes and dynamic genes to identify hub genes and reveal mitochondrial status. Furthermore, we assessed immune infiltration, tumor mutational burden (TMB), tumor stemness indices (TSI), and the response to immune checkpoint block (ICB) therapy using the TIDE algorithm and risk scores. Additionally, transmission electron microscopy (TEM), hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) were conducted to afford detailed visualization of the morphology of the mitochondria and the expression patterns of fission-associated proteins. RESULTS: Patients in Cluster 2 exhibited heightened mitochondrial fission and had a worse prognosis. The up-regulated dynamic genes in Cluster 2 were identified as fission genes. GO/KEGG analyses reconfirmed the connection of Cluster 2 to augmented mitochondrial fission activities. Subsequently, a ten-gene prognostic signature based on the differentially expressed genes between the two clusters was generated, with all ten genes being up-regulated in the high-risk group. Moreover, the potential links between these ten signature genes and mitochondrial dynamics were explored, suggesting their involvement in mediating mitochondrial fission through interaction with MTFR2. Further investigation revealed that the high-risk group had an unfavorable prognosis, with a higher mutation frequency of TP53, increased immune checkpoint expression, a higher TIS score, and a lower TIDE score. The mitochondrial imbalance characterized by increased fission and upregulated MTFR2 and DNM1L expression was substantiated in both HCC specimens and cell lines. CONCLUSIONS: In conclusion, we developed a novel MTFR2-related prognostic signature comprising ten mitochondrial dynamics genes. These genes play crucial roles in mitochondrial fission and have the potential to serve as important predictors and therapeutic targets for HCC.

Video-Based Indocyanine Green Fluorescence Applied to Robotic Duodenum-Preserving Pancreatic Head Resection.

BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) serves as a surgical intervention for managing benign and low-grade malignant neoplasms located in the head of the pancreas. This surgical approach enables the thorough excision of pancreatic head lesions, reducing the necessity for digestive tract reconstruction and enhancing the patient's quality of life.1 Performing a minimally invasive DPPHR is a complex surgical procedure, particularly when safeguarding the bile duct and the pancreaticoduodenal arterial arch. Robotic surgery is among the latest innovations in minimally invasive surgery and is widely used in many surgical specialties. It offers advantages such as rotatable surgical instruments, muscle tremor filters and up to 10-15 times three dimensional (3D) visual field,2 and achieves high flexibility and accuracy in surgical operations. Indocyanine green (ICG) fluorescence imaging technology is also applied to provide real-time intraoperative assessment of the biliary system and blood supply, which helps maintain the biliary system's integrity.3,4 We first report the complete procedure of ICG applied to the da Vinci robotic Xi system for preserving the DPPHR. METHODS: A 48-year-old female patient was diagnosed with pancreatic duct stones, chronic pancreatitis, and pancreatogenic diabetes. Enhanced computed tomography (CT) scans revealed pancreatic head stones, pancreatic atrophy, scattered calcifications, and a dilated pancreatic duct. An attempt at endoscopic retrograde cholangiopancreatography (ERCP) treatment was abandoned during hospitalization due to unsuccessful catheterization. Following informed consent from the patient and her family, a robotic DPPHR was conducted utilizing ICG fluorescence imaging technology. Approximately 60 min before the surgery, 2 mg of ICG was injected via the peripheral vein. The individual was positioned in a reclined posture with the upper part of the bed raised to an angle of 30° and a leftward tilt of 15°. Upon entering the abdominal cavity, existing adhesions were meticulously separated and the gastrocolic ligament was opened to expose the pancreas. The lower part of the pancreas was separated and the superior mesenteric vein (SMV) was identified at the inferior boundary of the pancreatic neck. The pancreas was cut upward and the pancreatic duct was severed using scissors. Dissection of the lateral wall of the portal vein-SMV in the pancreatic head segment was performed. Meticulous dissection was carried out along the pancreatic tissue, retracting the uncinate process of the pancreas in an upward and rightward direction. During the dissection, caution was exercised to protect the anterior and posterior pancreaticoduodenal arterial arch. By using ICG fluorescence imaging, the path of the common bile duct was identified and verified. Caution was exercised to avoid injuring the bile duct. After isolating the CBD, the head and uncinate process of the pancreas was entirely excised. Under the fluorescence imaging mode, the wholeness of the CBD was scrutinized for any potential seepage of the contrast agent. Ultimately, a Roux-en-Y end-to-side pancreaticojejunostomy (duct to mucosa) was executed. RESULTS: The surgery took 265 min and the estimated blood loss was about 150 mL. Without any postoperative complications, the patient was released from the hospital 13 days following the surgery. Postoperative pathology confirmed pancreatic duct stones and chronic pancreatitis. We have successfully performed four cases of robotic DPPHR using this technique, with only one patient experiencing a postoperative complication of pulmonary embolism. All patients were discharged successfully without any further complications. CONCLUSIONS: Employing ICG fluorescence imaging in a robotic DPPHR has been demonstrated to be both secure and achievable. This technique potentially provides novel therapeutic perspectives, particularly for patients with ambiguous delineation between pancreatic and biliary ductal structures.

Robotic Right Hepatectomy with En Bloc Caudatectomy for Bismuth IIIa Hilar Cholangiocarcinoma: A Video Demonstration of Left-Liver-First Anterior Radical Modular Orthotopic Right Hemihepatectomy.

BACKGROUND: Minimally invasive resection for perihilar cholangiocarcinoma is a complicated and technically demanding surgical procedure. Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma.1,2 Right hepatectomy with caudate lobe resection is necessary as the treatment for bismuth IIIa hilar cholangiocarcinoma.3 The left-liver-first anterior radical modular orthotopic right hemihepatectomy (LARMORH), which can simplify surgical steps and decrease procedural difficulty, may be a better choice for Bismuth IIIa hilar cholangiocarcinoma.4 However, there are no reports of this approach using robotic technique for this operation. We will provide a detailed introduction to this method through this video. METHODS: A 45-year-old female patient was diagnosed with a hilar cholangiocarcinoma. Following a 7-day percutaneous biliary drainage of the left intrahepatic bile duct and obtaining informed consent, we performed a robotic radical resection of the HCCA using the LARMORH approach. The patient was positioned supine with the entire bed elevated 20° and tilted 15° to the left. Trocars were placed in position (Fig. 1). After entering the abdominal cavity, it was explored for tumor metastasis. The surgery adopted a left approach, initially exploring the left hepatic artery and vein to further assess resectability. After confirming resectability, the right hepatic artery and gastroduodenal artery (GDA) were dissected. The common bile duct was dissected and transected at its distal end, ensuring R0 surgical margins. Lymph nodes were cleared from the foot side to the head side, confirming the metastasis to the lymph node group 13a, so we further cleared the group 16 and 9 lymph nodes.5 Subsequently, we approached the resection of the right half and the entire caudate lobe with the reverse thinking of left hepatic resection mode, preserving only the left branch of the portal vein and left hepatic artery, and dissecting the liver tissue along the resection plane of the left liver. After transection of the left hepatic duct, the activity space of the left liver was larger and the caudate lobe could be better exposed. The Spiegel lobe was lifted to the right in a "turn the page" fashion for in situ resection of the entire caudate lobe and the right half of the liver. Finally, a bilioenteric anastomosis was performed using the Roux-en-Y method. RESULTS: Robotic right hepatectomy with caudate lobectomy was successfully performed in 450 min, with an estimated blood loss of 200 ml. The histological grading was determined as T1aN1M0 (stage IIIB) on the basis of postoperative pathological biopsy results. The patient achieved a satisfactory postoperative recovery and was discharged on the 14th postoperative day without any major complications. Following the operation, the patient received capecitabine chemotherapy according to the Chinese Society of Clinical Oncology (CSCO) criteria. Since September 2022, our team has completed three radical resections for Bismuth IIIa HCCA using this technique. All patients achieved a satisfactory postoperative recovery without any further complications. CONCLUSIONS: Robotic left-liver-first anterior radical modular orthotopic right hemihepatectomy for Bismuth IIIa HCCA is both safe and feasible. This method may provide a new surgical approach for patients with type IIIA HCCA or liver diseases requiring right hemihepatectomy combined with total caudate lobectomy.

Salidroside ameliorates acute liver transplantation rejection in rats by inhibiting neutrophil extracellular trap formation.

Acute rejection is an important factor affecting the survival of recipients after liver transplantation. Salidroside has various properties, including anti-inflammatory, antioxidant, and hepatoprotective properties. This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (1 mg/kg/d) or salidroside (10 or 20 mg/kg/d) for seven days after liver transplantation. In addition, an in vitro experiment is performed using neutrophils incubated with salidroside (1, 10, 50 or 100 µM). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, immunosorbent assays, immunofluorescence analysis, Evans blue staining, and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo. We find that Salidroside treatment reduces pathological liver damage, serum aminotransferase level, and serum levels of IL-1ß, IL-6, and TNF-α in vivo. The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway (HMGB1, TLR-4, p-ERK1/2, p-JNK, p-P38, cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, IL-1ß, TNF-α, and IL-6) are also decreased after salidroside treatment. In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway. Furthermore, salidroside combined with tacrolimus has a better effect than either of the other treatments alone. In summary, salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.

Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. METHODS: We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. RESULTS: With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The 'upregulated' ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the 'downregulated' network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. CONCLUSIONS: In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.

PIAS4, upregulated in hepatocellular carcinoma, promotes tumorigenicity and metastasis.

Protein inhibitor of activated STAT4 (PIAS4) protein has been implicated in regulating various biological activities including protein posttranslational modification, such as SUMOylation. In this study, we explored the roles of PIAS4 in hepatocellular carcinoma (HCC). We analyzed the PIAS4 expression in cancer tissues and paracancerous tissues from 38 HCC patients and its correlation with patients' prognosis. In vitro, PIAS4 was overexpressed or knockdowned in Huh-7 and HepG-2 cells. Then Cell Counting Kit-8 assay, flow cytometry, and Transwell assay were performed to assess cell viability, apoptosis, migration, and invasion, respectively. Furthermore, SUMOylation of AMPKα and NEMO mediated by PIAS4 was investigated. The results showed that the PIAS4 expression was significantly upregulated in cancer tissues and was correlated with poor prognosis in HCC patients. PIAS4 silencing blocked the SUMOylation of AMPKα and NEMO, leading to enhanced cell proliferation, migration, and invasion. In addition, inhibition of AMPKα or NEMO by siRNAs attenuated the effect of PIAS4 silencing on Huh-7 and HepG-2 cells. In summary, our findings suggest that PIAS4 promotes tumorigenicity and metastasis of HCC cells by promoting the SUMOylation of AMPKα and NEMO.

Replication Protein A 3 Is Associated with Hepatocellular Carcinoma Tumorigenesis and Poor Patient Survival.

BACKGROUND: Replication protein A (RPA) 3 is a subunit of the RPA protein complex, which functions in multiple processes of DNA metabolism. Dysregulation of RPA1 and RPA2 has been implicated in tumor progression in several cancer types. However, the function of RPA3 in hepatocellular carcinoma (HCC) tumorigenesis has not been elucidated. METHOD: In this study, we investigated the function of RPA3 in HCC development by stably knocking down its expression using short hairpin RNA (shRNA) in HepG2 cell line, followed by cell proliferation, colony formation, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumor-promoting properties of RPA3. RESULTS: Downregulation of RPA3-inhibited cell proliferation, colony formation, soft agar growth as well as invasion in HepG2 cells were observed. Stable knockdown of RPA3 significantly inhibited tumor growth in the xenograft mouse model. In addition, qRT-PCR analysis revealed that RPA3 was upregulated in human HCC tissues compared with matched noncancerous adjacent tissues (NATs). High expression of RPA3 was associated with poor overall survival and disease-free survival. CONCLUSION: Elevated expression of RPA3 promotes tumor progression in HCC cells. RPA3 is upregulated in HCC tissues and high expression of RPA3 is associated with poorer patient survival. Therefore, this protein may represent a novel therapeutic target for intervention of HCC and prognostic biomarker for patient survival.

TAZ regulates cell proliferation and epithelial-mesenchymal transition of human hepatocellular carcinoma.

The transcriptional coactivator with PDZ binding motif (TAZ) has been reported to be one of the nuclear effectors of Hippo-related pathways. TAZ is expressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in hepatocellular carcinoma (HCC). In the current study, we show that TAZ regulates cellular proliferation and epithelial-mesenchymal transition (EMT) of HCC. TAZ is overexpressed in HCC tissues and cell lines and upregulation of TAZ correlates with a lower overall survival rate of HCC patients after hepatic resection. TAZ knockdown results in inhibition of cancer cell proliferation through decreases in expression of stem cell markers (OCT4, Nanog, and SOX2). Reduction in HCC cell migration and invasion is also evident through reversal of EMT by increases E-cadherin expression, decreases in N-cadherin, vimentin, Snail, and Slug expression, and suppression of MMP-2 and MMP-9 expression. In a xenograft tumorigenicity model, TAZ knockdown could effectively inhibit tumor growth and metastasis through reversal of the EMT pathway. In conclusion, TAZ is associated with the proliferation and invasiveness of HCC cells, and the TAZ gene may contribute to a novel therapeutic approach against HCC.

Conditional survival of pancreatic ductal adenocarcinoma in surgical and nonsurgical patients: a retrospective analysis report from a single institution in China.

BACKGROUND: Conditional survival (CS) could offer reliable prognostic information for patients who survived beyond a specified time since diagnosis when the impact of late effects have the greatest influence on prognosis. We aim to investigate CS for pancreatic ductal adenocarcinoma (PDAC) patients with surgery and nonsurgery. METHODS: Chinese PDAC patients between January 2002 and September 2012 were reviewed for analyses. CS rates were calculated for survivors after surgery and nonsurgery at different time points. RESULTS: Several clinicopathologic features were associated with overall survival (OS) in each subgroup including curative resection, palliative surgery, and nonsurgery. Both univariate and multivariate analyses showed that chemotherapy was a critical predictor for OS regardless of treatment status. CS rates were higher in the curative resected patients than other cases at the same time points. Importantly, stratification of 1-year CS by carcinoembryonic antigen (CEA), (carbohydrate antigen) CA19-9, and tumor stage showed lower CEA, CA19-9, and tumor stage associated with favorable 1-year CS over time (P = 0.016, 0.009 and 0.003). CONCLUSIONS: Dynamic CS estimates could be an accurate assessment for the prognosis of PDAC patients, allowing patients and clinicians to project subsequent survival based on time change.

Prognostic value of tertiary lymphoid structures in hepatocellular carcinoma: a meta-analysis and systematic review.

Background: Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC. Methods: We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR). Results: Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients. Conclusion: The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.

Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury.

Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development. Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a "camouflage cloak" to mimic the "don't eat me" mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading. Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively. Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI.

[Ornithine aspartate and naloxone combined therapy for hepatic encephalopathy affects cognitive function, prognosis, and neuropeptide levels].

OBJECTIVE: To investigate the potential effects on cognitive function, prognosis, and neuropeptide levels of patients in response to combination therapy with ornithine aspartate plus naloxone for hepatic encephalopathy. METHODS: Eighty-four consecutive patients diagnosed with hepatic encephalopathy were randomly divided into two equal groups. The control group (n = 42) received traditional medical treatment, and the research group (n = 42) received the traditional medical treatment as well as the combination therapy with ornithine aspartate plus naloxone. The supplemental treatment was comprised of daily intravenous injection of 10-15 g ornithine aspartate in 250 ml of 5% glucose plus intravenous drip of 3 mg naloxone in 100 ml of 5% glucose, and was given in 7-day cycles for one or two cycles. The cognitive function of patients was assessed by Hasegawa Intelligence Scale (HDS) and Mini-Mental State Examination (MMSE) questionnaires. The effective rate and time duration from coma to consciousness were recorded. Changes in blood ammonia level, markers of liver function, and neuropeptide levels were measured by standard biochemical assays. Intergroup differences were assessed by the Chi-squared test. RESULTS: The HDS and MMSE scores of the research group were significantly higher than those of the control group after therapy. The effective rate, time duration from coma to consciousness, blood ammonia, the liver function markers alanine aminotransferase, gamma-glutamyl-transpeptidase and total bilirubin, and the neuropeptides arginine vasopressin and beta-endorphin were remarkably improved after treatment in the research group, as compared with that in the control group. CONCLUSION: Supplementing the traditional treatment for hepatic encephalopathy with ornithine aspartate plus naloxone combination therapy provides better therapeutic outcome than traditional treatment alone.

Incidence and risk factors of postoperative acute pancreatitis after pancreaticoduodenectomy: a systematic review and meta-analysis.

Background: Postoperative acute pancreatitis (POAP) is a specific complication after pancreatectomy. The acute inflammatory response of the residual pancreas may affect the healing of pancreatoenteric anastomoses, leading to postoperative pancreatic fistulas (POPFs), abdominal infections, and even progressive systemic reactions, conditions that negatively affect patients' prognoses and can cause death. However, to the best of our knowledge, no systematic reviews or meta-analytic studies have assessed the incidence and risk factors of POAP after pancreaticoduodenectomy (PD). Method: We searched PubMed, Web of Science, Embase, and Cochrane Library databases for relevant literature describing the outcomes of POAP after PD until November 25, 2022, and we used the Newcastle-Ottawa Scale to assess the quality of the studies. Next, we pooled the incidence of POAP and the odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors using a random-effect meta-analysis. I2 tests were used to assess heterogeneity between the studies. Results: We analyzed data from 7,164 patients after PD from 23 articles that met the inclusion criteria for this study. The subgroup results of the meta-analysis by different POAP diagnostic criteria showed that the incidences of POAP were 15% (95% CI, 5-38) in the International Study Group for Pancreatic Surgery group, 51% (95% CI, 42-60) in the Connor group, 7% (95% CI, 2-24) in the Atlanta group, and 5% (95% CI, 2-14) in the unclear group. Being a woman [OR (1.37, 95% CI, 1.06-1.77)] or having a soft pancreatic texture [OR (2.56, 95% CI, 1.70-3.86)] were risk factors of POAP after PD. Conclusion: The results showed that POAP was common after PD, and its incidence varied widely according to different definitions. Large-scale reports are still needed, and surgeons should remain aware of this complication. Systematic Review Registration: identifier: CRD42022375124.

Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy.

Background: During clinical practice, routine blood tests are commonly performed following pancreaticoduodenectomy (PD). However, the relationship between blood cell counts, inflammation-related indices, and postoperative complications remains unclear. Method: We conducted a retrospective study, including patients who underwent PD from October 2018 to July 2023 at the First Hospital of Chongqing Medical University, and compared baseline characteristics and clinical outcomes among different groups. Neutrophil count (NC), platelet count (PLT), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) were derived from postoperative blood test results. We investigated the association between these indicators and outcomes using multivariable logistic regression and restricted cubic spline analysis. The predictive performance of these indicators was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Result: A total of 232 patients were included in this study. Multivariate logistic regression and restricted cubic spline analysis showed that all indicators, except for PLT, were associated with clinical postoperative pancreatic fistula (POPF). SII, NLR, and NC were linked to surgical site infection (SSI), while SII, NLR, and PLR were correlated with CD3 complication. PLT levels were related to postoperative hemorrhage. SII (AUC: 0.729), NLR (AUC: 0.713), and NC (AUC: 0.706) effectively predicted clinical POPF. Conclusion: In patients undergoing PD, postoperative inflammation-related indices and blood cell counts are associated with various complications. NLR and PLT can serve as primary indicators post-surgery for monitoring complications.

Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.

Importance: The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. Objective: To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Interventions: Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. Main Outcomes and Measures: The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Results: Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Conclusions and Relevance: Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03785743.

A reinforced suture method for stapled gastrointestinal anastomosis to reduce gastrointestinal hemorrhage during Whipple operation in laparoscopy.

PURPOSE: Laparoscopy is being increasingly accepted for pancreaticoduodenectomy. Stapled anastomosis (SA) is used extensively to facilitate laparoscopic pancreaticoduodenectomy (LPD); however, the incidence of anastomotic bleeding after stapled gastrointestinal anastomosis is still high. METHODS: One hundred and thirty-nine patients who underwent LPD using Whipple method were enrolled in our study. We performed the SA with our reinforced method (n = 68, R method) and without the method (n = 71, NR method). We compared the clinical characteristics and anastomosis methods of patients with or without gastrointestinal-anastomotic hemorrhage (GAH), and operative parameters were also compared between the anastomotic methods. RESULTS: Of the 139 patients undergoing LPD, 15 of them developed GAH. The clinical characteristics of patients with or without GAH were not significantly different except in the anastomotic method (P < 0.001). In the univariate logistic regression analyses, only the anastomotic method was associated with GAH. Furthermore, patients with the NR method had significantly higher incidences of GAH (P < 0.001) and Clavien-Dindo grade ≥ III complications (P < 0.001). CONCLUSION: Our retrospective analysis showed that the SA performed with reinforced method might be a reform of SA without the reinforcement, as indicated by the lower incidence of GAH. However, further research is necessary to evaluate the utility of this reinforced method.