Development and validation of a diagnostic and prognostic model for bone metastasis of intrahepatic cholangiocarcinoma: a population-based analysis.

Background: Bone metastasis (BM) is a common site of metastasis in patients with intrahepatic cholangiocarcinoma (ICC), significantly impacting the quality of life and prognosis of affected individuals. This investigation aimed to assess the risk of BM development in ICC patients and to prognosticate for patients with ICC-associated BM (ICCBM) through the construction of two nomograms. Methods: We conducted a retrospective analysis of data from 2,651 ICC patients, including 148 cases of BM, documented in the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. Independent predictors for the occurrence of BM in ICC patients were identified via univariate and multivariate logistic regression analyses; simultaneously, independent prognostic indicators for ICCBM patients were ascertained through univariate and multivariate Cox regression analyses. The utility of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan-Meier (KM) analysis. Results: Independent risk factors for BM in ICC included sex, tumor size, lung metastasis, brain metastasis, and intrahepatic metastasis. For ICCBM patients, independent prognostic factors comprised age, chemotherapy, and radiotherapy. The prognostic nomogram exhibited C-indexes of 0.737 [95% confidential interval (CI): 0.682-0.792] for the training cohort and 0.696 (95% CI: 0.623-0.769) for the validation cohort. Calibration curves demonstrated strong concordance between predicted outcomes and observed events. The areas under the curve (AUC) for 3-, 6-, and 12-month cancer-specific survival (CSS) were 0.853, 0.781, and 0.739, respectively, in the training cohort, and 0.794, 0.822, and 0.780 in the validation cohort. DCA illustrated significant net benefits across a broad spectrum of threshold probabilities. KM analysis revealed 1-, 2-, and 3-year CSS rates of 23.91%, 7.55%, and 2.35%, respectively, with a median CSS of 6 months, underscoring the nomograms' capacity to distinctly stratify patients according to survival risk. Conclusions: The development of these nomograms offers substantial clinical utility in forecasting BM risk among ICC patients and prognosticating for those with ICCBM, thereby facilitating the formulation of more efficacious treatment modalities.

Merging Ring-Opening 1,2-Metallate Shift with Asymmetric C(sp3)-H Borylation of Aziridines.

Chiral secondary alkyl amines with a vicinal quaternary stereocenter are undoubtedly important and ubiquitous subunits in natural products and pharmaceuticals. However, their asymmetric synthesis remains a formidable challenge. Herein, we merge the ring-opening 1,2-metallate shift with iridium-catalyzed enantioselective C(sp3)-H borylation of aziridines to deliver these frameworks with high enantioselectivities. We also demonstrated the synthetic application by downstream transformations, including the total synthesis of two Amaryllidaceae alkaloids, (-)-crinane and (+)-mesmebrane.

The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator.

The progression of liver diseases, from viral hepatitis and fatty liver disease to cirrhosis and hepatocellular carcinoma (HCC), is the most representative series of pathological events in liver diseases. While serotonin (5-HT) primarily regulates brain functions such as psychology, mood, and appetite in the central nervous system (CNS), peripheral 5-HT plays a crucial role in regulating tumor development, glucose and lipid metabolism, immune function and inflammatory response related to liver diseases. These peripheral physiological processes involving 5-HT are the key mechanisms driving the development of these liver diseases. This study presents an overview of the existing literature, focusing on the role of 5-HT in HCC, cirrhosis, fatty liver disease, viral hepatitis, and liver injury. In summary, while 5-HT promotes liver regeneration, it can also contribute to the progression of chronic liver disease. These findings indicate the potential for the development and use of 5-HT-related drugs for the treatment of liver diseases, including HCC and cirrhosis.

COAP-Pd Catalyzed Asymmetric Formal [3+2] Cycloaddition for Optically Active Multistereogenic Spiro Cyclopentane-Indandiones Bearing Cyclic N-Sulfonyl Ketimine Skeletons.

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Comparison of safety and effectiveness between robotic and laparoscopic major hepatectomy: a systematic review and meta-analysis.

BACKGROUND: Robotic platform has been increasingly applied in major hepatectomy. However, the role or advantage of robotic approach comparing with laparoscopic approach in major hepatectomy remains controversial. This meta-analysis compares perioperative outcomes of robotic major hepatectomy (RMH) to laparoscopic major hepatectomy (LMH) for hepatic neoplasms. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Library were searched to identify comparative studies compared RMH versus LMH for hepatic neoplasms. The search timeframe was set before May 2023. Main outcomes were mortality, overall morbidities, serious complications, and conversion to open surgery. Secondary outcomes were operative time, intraoperative blood loss, blood transfusion, postoperative length of hospital stay, R0 resection, reoperation, and readmission. Studies were evaluated for quality by Cochrane risk of bias tool or Newcastle-Ottawa scale. Data were pooled as odds ratio (OR) or mean difference (MD). This study was registered at PROSPERO (CRD42023410951). RESULTS: Twelve retrospective cohort studies concerning total 1657 patients (796 RMH, 861 LMH) were included. Meta-analyses showed no significant differences in mortality (OR=1.23, 95% CI=0.50-2.98, P =0.65), overall postoperative complications (OR=0.83, 95% CI=0.65-1.06, P =0.14), operative time (MD=6.47, 95% CI=-14.72 to 27.65, P =0.55), blood transfusion (OR=0.77, 95% CI=0.55-1.08, P =0.13), R0 resection (OR=1.45, 95% CI=0.91-2.31, P =0.12), reoperation (OR=0.76, 95% CI=0.31-1.88, P =0.56), and readmission (OR=0.63, 95% CI=0.28-1.44, P =0.27) between RMH and LMH. Incidence of serious complications (OR=0.60, 95% CI=0.40-0.90, P =0.01), conversion to open surgery (OR=0.41, 95% CI=0.27-0.63, P <0.0001), blood loss (MD=-91.42, 95% CI=-142.18 to -40.66, P =0.0004), and postoperative hospital stay (MD=-0.64, 95% CI=-0.78 to -0.49, P <0.00001) were reduced for RMH versus LMH. CONCLUSIONS: RMH is associated with comparable short-term surgical outcomes and oncologic adequacy compared to LMH when performed by experienced surgeons at large centres. RMH may result in reduced major morbidities, conversion rate, blood loss, and hospital stay, but these results were volatile. Further randomized studies should address the potential advantages of RMH over LMH.

Establishment of a prognostic model based on m6A regulatory factors and stemness of hepatocellular carcinoma using RNA-seq data and scRNA-seq data.

BACKGROUND: Hepatocellular carcinoma (HCC) with high incidence and mortality is one of the most common malignant cancers worldwide. Increasing evidence has reported that N6-methyladenosine (m6A) modification has been considered as a major contribution to the occurrence and development of tumors. METHOD: In our study, we comprehensively analyzed the connection between m6A regulatory factors and cancer stem cells (CSCs) of HCC to establish a clinical tool for predicting its outcome. First, we concluded that the expression level of m6A regulatory factors was related with the stemness of hepatocellular carcinoma. Subsequently, we gained a ten hub regulatory factors that were associated with prognosis of hepatocellular carcinoma by overall survival (OS) analysis using ICGC and TCGA datasets, and these regulatory factors included YTHDF1, IGF2BP1, METTL3, IGF2BP3, HNRNPA2B1, IGF2BP2, RBM15B, HNRNPC, RBMX, and LRPPR. Next, we found that these ten hub m6A regulatory factors were highly expressed in CSCs, and CSCs related pathways were also enriched by the gene set variation analysis (GSVA). Then, correlation, consensus clustering and PCA analysis were performed to reveal potential therapeutic benefits of HCC. Moreover, univariate Cox regression (UNICOX), LASSON and multivariate Cox regression (MULTICOX) analyses were adopted to establish HCC prognosis prediction signature. RESULTS: Four regulatory factors RBM15B, LRPPRC, IGF2BP1, and IGF2BP3 were picked as valuable prognostic indicators. CONCLUSION: In summary, these ten hub regulatory factors would be useful therapeutic targets for HCC treatment, and RBM15B/LRPPRC/IGF2BP1/IGF2BP3 prognostic indicators can be used to guide therapy for HCC patients.

Identification of a cuproptosis and copper metabolism gene-related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma.

Background: The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear. Methods: Based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed. Results: We constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks. Conclusions: We constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy.

Autophagy in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is a major complication of liver resection or liver transplantation that can seriously affect patient's prognosis. There is currently no definitive and effective treatment strategy for HIRI. Autophagy is an intracellular self-digestion pathway initiated to remove damaged organelles and proteins, which maintains cell survival, differentiation, and homeostasis. Recent studies have shown that autophagy is involved in the regulation of HIRI. Numerous drugs and treatments can change the outcome of HIRI by controlling the pathways of autophagy. This review mainly discusses the occurrence and development of autophagy, the selection of experimental models for HIRI, and the specific regulatory pathways of autophagy in HIRI. Autophagy has considerable potential in the treatment of HIRI.

COAP/Pd-Catalyzed Linear Asymmetric Allylic Alkylation for Optically Active 3,3-Disubstituted Oxindole Derivatives with a Four-Carbon Amino Side Chain.

An asymmetric linear selective allylic alkylation of vinylaziridines with 3-aryl oxindoles has been developed by using a chiral oxamide-phosphine (COAP-Bn-OMe-p)/palladium complex in methanol, which furnished a wide variety of 3,3-disubstituted oxindole derivatives in good yields with excellent regio- and enantioselectivities.

Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgeries, such as hepatectomy and liver transplantation. In recent years, several non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as factors involved in the pathological progression of HIRI. In this review, we summarized the latest research on lncRNAs, miRNAs and the lncRNA-miRNA regulatory networks in HIRI. DATA SOURCES: The PubMed and Web of Science databases were searched for articles published up to December 2021 using the following keywords: "hepatic ischemia-reperfusion injury", "lncRNA", "long non-coding RNA", "miRNA" and "microRNA". The bibliography of the selected articles was manually screened to identify additional studies. RESULTS: The mechanism of HIRI is complex, and involves multiple lncRNAs and miRNAs. The roles of lncRNAs such as AK139328, CCAT1, MALAT1, TUG1 and NEAT1 have been established in HIRI. In addition, numerous miRNAs are associated with apoptosis, autophagy, oxidative stress and cellular inflammation that accompany HIRI pathogenesis. Based on the literature, we conclude that four lncRNA-miRNA regulatory networks mediate the pathological progression of HIRI. Furthermore, the expression levels of some lncRNAs and miRNAs undergo significant changes during the progression of HIRI, and thus are potential prognostic markers and therapeutic targets. CONCLUSIONS: Complex lncRNA-miRNA-mRNA networks regulate HIRI progression through mutual activation and antagonism. It is necessary to screen for more HIRI-associated lncRNAs and miRNAs in order to identify novel therapeutic targets.

Development of a web-based calculator to predict three-month mortality among patients with bone metastases from cancer of unknown primary: An internally and externally validated study using machine-learning techniques.

Background: Individualized therapeutic strategies can be carried out under the guidance of expected lifespan, hence survival prediction is important. Nonetheless, reliable survival estimation in individuals with bone metastases from cancer of unknown primary (CUP) is still scarce. The objective of the study is to construct a model as well as a web-based calculator to predict three-month mortality among bone metastasis patients with CUP using machine learning-based techniques. Methods: This study enrolled 1010 patients from a large oncological database, the Surveillance, Epidemiology, and End Results (SEER) database, in the United States between 2010 and 2018. The entire patient population was classified into two cohorts at random: a training cohort (n=600, 60%) and a validation cohort (410, 40%). Patients from the validation cohort were used to validate models after they had been developed using the four machine learning approaches of random forest, gradient boosting machine, decision tree, and eXGBoosting machine on patients from the training cohort. In addition, 101 patients from two large teaching hospital were served as an external validation cohort. To evaluate each model's ability to predict the outcome, prediction measures such as area under the receiver operating characteristic (AUROC) curves, accuracy, and Youden index were generated. The study's risk stratification was done using the best cut-off value. The Streamlit software was used to establish a web-based calculator. Results: The three-month mortality was 72.38% (731/1010) in the entire cohort. The multivariate analysis revealed that older age (P=0.031), lung metastasis (P=0.012), and liver metastasis (P=0.008) were risk contributors for three-month mortality, while radiation (P=0.002) and chemotherapy (P<0.001) were protective factors. The random forest model showed the highest area under curve (AUC) value (0.796, 95% CI: 0.746-0.847), the second-highest precision (0.876) and accuracy (0.778), and the highest Youden index (1.486), in comparison to the other three machine learning approaches. The AUC value was 0.748 (95% CI: 0.653-0.843) and the accuracy was 0.745, according to the external validation cohort. Based on the random forest model, a web calculator was established: https://starxueshu-codeok-main-8jv2ws.streamlitapp.com/. When compared to patients in the low-risk groups, patients in the high-risk groups had a 1.99 times higher chance of dying within three months in the internal validation cohort and a 2.37 times higher chance in the external validation cohort (Both P<0.001). Conclusions: The random forest model has promising performance with favorable discrimination and calibration. This study suggests a web-based calculator based on the random forest model to estimate the three-month mortality among bone metastases from CUP, and it may be a helpful tool to direct clinical decision-making, inform patients about their prognosis, and facilitate therapeutic communication between patients and physicians.

Machine learning approaches for prediction of early death among lung cancer patients with bone metastases using routine clinical characteristics: An analysis of 19,887 patients.

Purpose: Bone is one of the most common sites for the spread of malignant tumors. Patients with bone metastases whose prognosis was shorter than 3 months (early death) were considered as surgical contraindications. However, the information currently available in the literature limits our capacity to assess the risk likelihood of 3 month mortality. As a result, the study's objective is to create an accurate prediction model utilizing machine-learning techniques to predict 3 month mortality specifically among lung cancer patients with bone metastases according to easily available clinical data. Methods: This study enrolled 19,887 lung cancer patients with bone metastases between 2010 and 2018 from a large oncologic database in the United States. According to a ratio of 8:2, the entire patient cohort was randomly assigned to a training (n = 15881, 80%) and validation (n = 4,006, 20%) group. In the training group, prediction models were trained and optimized using six approaches, including logistic regression, XGBoosting machine, random forest, neural network, gradient boosting machine, and decision tree. There were 13 metrics, including the Brier score, calibration slope, intercept-in-large, area under the curve (AUC), and sensitivity, used to assess the model's prediction performance in the validation group. In each metric, the best prediction effectiveness was assigned six points, while the worst was given one point. The model with the highest sum score of the 13 measures was optimal. The model's explainability was performed using the local interpretable model-agnostic explanation (LIME) according to the optimal model. Predictor importance was assessed using H2O automatic machine learning. Risk stratification was also evaluated based on the optimal threshold. Results: Among all recruited patients, the 3 month mortality was 48.5%. Twelve variables, including age, primary site, histology, race, sex, tumor (T) stage, node (N) stage, brain metastasis, liver metastasis, cancer-directed surgery, radiation, and chemotherapy, were significantly associated with 3 month mortality based on multivariate analysis, and these variables were included for developing prediction models. With the highest sum score of all the measurements, the gradient boosting machine approach outperformed all the other models (62 points), followed by the XGBooting machine approach (59 points) and logistic regression (53). The area under the curve (AUC) was 0.820 (95% confident interval [CI]: 0.807-0.833), 0.820 (95% CI: 0.807-0.833), and 0.815 (95% CI: 0.801-0.828), respectively, calibration slope was 0.97, 0.95, and 0.96, respectively, and accuracy was all 0.772. Explainability of models was conducted to rank the predictors and visualize their contributions to an individual's mortality outcome. The top four important predictors in the population according to H2O automatic machine learning were chemotherapy, followed by liver metastasis, radiation, and brain metastasis. Compared to patients in the low-risk group, patients in the high-risk group were more than three times the odds of dying within 3 months (P < 0.001). Conclusions: Using machine learning techniques, this study offers a number of models, and the optimal model is found after thoroughly assessing and contrasting the prediction performance of each model. The optimal model can be a pragmatic risk prediction tool and is capable of identifying lung cancer patients with bone metastases who are at high risk for 3 month mortality, informing risk counseling, and aiding clinical treatment decision-making. It is better advised for patients in the high-risk group to have radiotherapy alone, the best supportive care, or minimally invasive procedures like cementoplasty.

Clinical applications of circulating tumor cells in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor and ranked as the fourth cause of cancer-related mortality. The poor clinical prognosis is due to an advanced stage and resistance to systemic treatment. There are no obvious clinical symptoms in the early stage and the early diagnosis rate remains low. Novel effective biomarkers are important for early diagnosis and tumor surveillance to improve the survival of HCC patients. Circulating tumor cells (CTCs) are cancer cells shed from primary or metastatic tumor and extravasate into the blood system. The number of CTCs is closely related to the metastasis of various solid tumors. CTCs escape from blood vessels and settle in target organs, then form micro-metastasis. Epithelial-mesenchymal transformation (EMT) plays a crucial role in distant metastasis, which confers strong invasiveness to CTCs. The fact that CTCs can provide complete cellular biological information, which allows CTCs to be one of the most promising liquid biopsy targets. Recent studies have shown that CTCs are good candidates for early diagnosis, prognosis evaluation of metastasis or recurrence, and even a potential therapeutic target in patients with HCC. It is a new indicator for clinical application in the future. In this review, we introduce the enrichment methods and mechanisms of CTCs, and focus on clinical application in patients with HCC.

A rare case with multiple arterial variations of the liver complicated laparoscopic pancreaticoduodenectomy.

BACKGROUND: Hepatic arterial variations were fully elaborated in anatomical monographs. Here, we aimed to present a rare case with multiple arterial variations of the liver complicated laparoscopic pancreaticoduodenectomy. CASE PRESENTATION: We report a 67-year-old woman with a periampullary tumor underwent laparoscopic pancreaticoduodenectomy. Intraoperatively, the aberrant right hepatic artery derived from the gastroduodenal artery (GDA) was observed and had accidentally sacrificed due to untimely ligature of GDA. Three-dimensional reconstruction based on preoperative contrast-enhanced CT performed to better study the anatomy. It demonstrated a replaced right hepatic artery branched from the GDA and supplied right liver lobe. Meanwhile, the middle hepatic artery derived from the common hepatic artery and supplied hepatic segment IV. Additionally, the replaced left hepatic artery emerged from the left gastric artery and fed into left liver lobe. CONCLUSIONS: The origination and course of hepatic arterial anatomy should be thoroughly assessed in planning and performing hepatopancreatobiliary surgeries. Reconstruction images of contrast-enhanced CT are helpful to visualize the vascular variations and its spatial relation with adjacent structures.

Laparoscopic versus open pancreaticoduodenectomy for pancreatic and periampullary tumor: A meta-analysis of randomized controlled trials and non-randomized comparative studies.

Objective: This meta-analysis compares the perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) to those of open pancreaticoduodenectomy (OPD) for pancreatic and periampullary tumors. Background: LPD has been increasingly applied in the treatment of pancreatic and periampullary tumors. However, the perioperative outcomes of LPD versus OPD are still controversial. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs) and non-randomized comparative trials (NRCTs) comparing LPD versus OPD for pancreatic and periampullary tumors. The main outcomes were mortality, morbidity, serious complications, and hospital stay. The secondary outcomes were operative time, blood loss, transfusion, postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), bile leak (BL), delayed gastric emptying (DGE), lymph nodes harvested, R0 resection, reoperation, and readmission. RCTs were evaluated by the Cochrane risk-of-bias tool. NRCTs were assessed using a modified tool from the Methodological Index for Non-randomized Studies. Data were pooled as odds ratio (OR) or mean difference (MD). This study was registered at PROSPERO (CRD42022338832). Results: Four RCTs and 35 NRCTs concerning a total of 40,230 patients (4,262 LPD and 35,968 OPD) were included. Meta-analyses showed no significant differences in mortality (OR 0.91, p = 0.35), serious complications (OR 0.97, p = 0.74), POPF (OR 0.93, p = 0.29), PPH (OR 1.10, p = 0.42), BL (OR 1.28, p = 0.22), harvested lymph nodes (MD 0.66, p = 0.09), reoperation (OR 1.10, p = 0.41), and readmission (OR 0.95, p = 0.46) between LPD and OPD. Operative time was significantly longer for LPD (MD 85.59 min, p < 0.00001), whereas overall morbidity (OR 0.80, p < 0.00001), hospital stay (MD -2.32 days, p < 0.00001), blood loss (MD -173.84 ml, p < 0.00001), transfusion (OR 0.62, p = 0.0002), and DGE (OR 0.78, p = 0.002) were reduced for LPD. The R0 rate was higher for LPD (OR 1.25, p = 0.001). Conclusions: LPD is associated with non-inferior short-term surgical outcomes and oncologic adequacy compared to OPD when performed by experienced surgeons at large centers. LPD may result in reduced overall morbidity, blood loss, transfusion, and DGE, but longer operative time. Further RCTs should address the potential advantages of LPD over OPD. Systematic review registration: PROSPERO, identifier CRD42022338832.

Utility of Tokyo Guidelines 2018 in early laparoscopic cholecystectomy for mild and moderate acute calculus cholecystitis: A retrospective cohort study.

Background: Tokyo Guidelines 2018 (TG18) proposed laparoscopic cholecystectomy (LC) for acute calculus cholecystitis (ACC) irrespective of the duration of symptoms. This retrospective study assessed the impact of utility of TG18 in early LC for ACC. Methods: From 2018 to 2020, 66 patients with mild (grade I) and moderate (grade II) ACC who underwent early surgery were studied. Subgroup analyses were based on timing of surgery and operation time. Results: A total of 32 and 34 patients were operated within and beyond 7 days since ACC onset. More patients with grade II ACC were in the beyond 7 days group (P < 0.05). More patients with enlarged gallbladder were in the within 7 days group (P < 0.05). The duration of symptoms to admission, symptoms to LC, and operation time were longer in the beyond 7 days group (P < 0.05). There were no significant differences regarding intraoperative blood loss, conversion to bail-out procedures, complication rate, hospital stay, and cost between the two groups (P > 0.05). Longer operation time was significantly associated with duration of symptoms to admission, symptoms to LC, and conversion to laparoscopic subtotal cholecystectomy (LSC) (P < 0.05). Conclusion: In a subset of carefully selected patients, applying TG18 in early LC for mild and moderate ACC results in acceptable clinical outcomes. Standardized safe steps and conversion to LSC in difficult cases are important.

One-stage versus two-stage management for acute cholecystitis associated with common bile duct stones: a retrospective cohort study.

BACKGROUND: Both one-stage [laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE)] and two-stage [endoscopic retrograde cholangiopancreatography (ERCP) followed by sequential LC] approaches are effective treatment for concomitant common bile duct (CBD) stones and gallstone. Although many studies compared one-stage with two-stage surgical approach for cholecysto-choledocholithiasis, there are very few studies compared the two management strategies for acute cholecystitis (AC) associated with CBD stones. METHODS: Between January 2014 and December 2019, patients with concomitant AC and CBD stones proposed to early surgery were retrospectively studied. The patients were scheduled to undergo either the one-stage [LCBDE and LC (LCBDE+LC) were undertaken at the same operation] or two-stage [preoperative ERCP for CBD stone clearance was followed by LC 1-3 days later (pre-ERCP+LC)] procedure. The success rate of complete stone clearance, procedure-related complication, hospital stay, hospitalization charges and later biliary complications were compared between the two groups. RESULTS: Sixty patients were included in the study, 28 in the one-stage group and 32 in the two-stage group. There was no significant difference in the success rate of complete stone clearance (96.4% vs. 93.8%, P = 1.000), complication rate (10.7% vs. 9.4%, P = 1.000), incidence of pancreatitis (0 vs. 6.3%, P = 0.494) or length of hospital stay (12 ± 5 vs. 11 ± 4 days, P = 0.393) between the two groups. CONCLUSION: For patients with concomitant AC and choledocholithiasis proposed to early surgery, both the one-stage (LCBDE+LC) and two-stage (pre-ERCP+LC) approaches were acceptable and broadly comparable in achieving clearance of CBD stones.