Indocyanine green fluorescence staining based on the "hepatic pedicle first" approach during laparoscopic anatomic liver resection.

BACKGROUND: Indocyanine green (ICG) fluorescence staining is one of the most challenging procedures for laparoscopic anatomic liver resection (LALR). Here, we introduce a novel method based on the "hepatic pedicle first" approach that can improve the success rate of positive staining. METHOD: The target hepatic pedicle (even for the subsegment) was dissected through the first porta until it became visible. Five milliliters of 0.025 mg/ml ICG was injected after the target hepatic pedicle (extra-Glissonian approach) or portal vein/hepatic artery (intra-Glissonian approach) was punctured successfully using scalp acupuncture under direct vision. Then, the Glissonian pedicle or vessel was clamped immediately to prevent the intrahepatic diffusion of ICG. During the operation, a fluorescence imaging model was used repeatedly to confirm the segmental boundary. RESULTS: Finally, 24 patients underwent LALR with the "hepatic pedicle first" approach for ICG fluorescence-positive staining. In 5 patients, ICG-positive staining failed, representing a 79.17% success rate. The average staining time was 25.92 min ± 14.64 min. There were no complications associated with vessel puncture (bile leakage, hemorrhage, and thrombosis). CONCLUSION: The "hepatic pedicle first" approach is a feasible, convenient, and safe method for ICG-positive staining, with a high success rate.

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

BACKGROUND: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. METHODS: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. FINDINGS: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). INTERPRETATION: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. FUNDING: Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Evaluation of structural and molecular variation of starch granules during the gelatinization process by using the rapid Mueller matrix imaging polarimetry system.

Starch is an essential and widely distributed natural material, but its detailed conformation and thermal transition properties are not yet well understood. We present a rapid Mueller matrix imaging system to explore the structural characteristics of starch granules by using 16 measurements with different incoming and outgoing polarizations. Due to the minimum rotation of the optical elements and the self-calibration ability of this system, the full Mueller matrix images can be accurately obtained within ten-odd seconds. Both structural and molecular features of the starch granule were investigated in the static state and gelatinization process by means of multiple optical characteristics deduced from the Mueller matrix. The experimental results for the structural changes during the gelatinization were close to other nonlinear optical approaches; moreover, the crystallinity and optical rotation of the starch granule are also determined through the use of this approach.

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.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of patients with single-nodule small hepatocellular carcinoma following curative resection: a retrospective report.

BACKGROUND: Preoperative neutrophil-to-lymphocyte ratio (NLR) has been identified as a predictor for the recurrence of hepatocellular carcinoma (HCC), but the cut-off of NLR is inconsistent in various studies. Thus, we detected the prognostic value of preoperative NLR in the single-nodule small HCC (SHCC) patients using X-tile for cutpoint. METHODS: Between January 2007 and December 2010, a total of 222 single-nodule SHCC patients underwent curative resection and were examined for the prognostic roles of preoperative NLR by X-tile. RESULTS: In this study, all patients were divided into the low-NLR subgroup (NLR ≤ 2.1) and the high-NLR subgroup (NLR > 2.1) by X-tile. Preoperative NLR showed predictive value for time to recurrence (TTR) and overall survival (OS). Moreover, NLR was associated with total bilirubin, white blood cell counts, and HBsAg, respectively (P = 0.012, <0.001, and 0.011, respectively). Especially, NLR could discriminate the outcome of patients in the subgroup with alpha-fetoprotein (AFP) levels of ≤400 ng/mL. Importantly, postoperative transcatheter arterial chemoembolization (TACE) had close relationship with OS (P = 0.001) and TTR (P ≤ 0.001). CONCLUSIONS: Therefore, this study indicates that preoperative NLR, divided by X-tile for the cutpoint, is a simple prognostic marker for the patients with single-nodule SHCC after curative resection.

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.

Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial.

PURPOSE: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab in treating advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. Primary endpoints included safety and tolerability, and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Fifty-four patients were enrolled between Apr 17, 2020 and Dec 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5-45.6] and the lower bound of the 95% CI was above the pre-specified boundary of 10%. The independent review committee (IRC) assessed ORR according to modified RECIST (mRECIST) was 46.3% (95% CI, 32.6-60.4). The median progression-free survival were 8.5 months (95% CI, 5.5-11.0) and 9.8 months (95% CI, 5.6-not evaluable) assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), aspartate aminotransferase increased (33.3%), amylase increased (29.6%), platelet count decreased (27.8%), and bilirubin increased (27.8%). CONCLUSIONS: Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies of this combination regimen as a first-line treatment of advanced HCC.

The effect of fibroblast activation on vascularization in transplanted pancreatic islets.

BACKGROUND: Insufficient revascularization of transplanted pancreatic islets is an important reason why the long-term effects of pancreatic islet transplantation on type I diabetes patients have been so limited. The goal of this study was to investigate the role of fibroblasts (FBs) activated by tumor cell supernatants on the vascularization of transplanted pancreatic islets. MATERIALS AND METHODS: Pancreatic islets and activated or inactivated FBs were used for subrenal capsule transplantation. Mouse melanoma cell supernatants were used to activate FBs; the tests of the purity of the pancreatic islet cells of the donor, survival rate, and function of insulin secretion were performed to ensure high-quality transplants. Mice receiving the allogeneic transplantation were given tacrolimus and sirolimus to prevent rejection. The diabetic model was induced by streptozotocin. RESULTS: Conditioned medium made of tumor cell supernatants was found to stimulate the expression of α-smooth muscle actin and vascular endothelial growth factor A to an extent notably greater than that of pancreatic islet transplantation alone or pancreatic islet transplantation combined with inactivated FBs. FBs from the recipient were associated with capillary density in the transplanted pancreatic islet most closely to that observed in isogenically transplanted pancreatic islets and the original pancreatic islet. In this way, activated FBs derived from the recipient combined with pancreatic transplantation were able to treat diabetes, and long-term survival was achieved. CONCLUSIONS: The current research sheds new light on the revascularization of transplanted pancreatic islets: activated FBs derived from the recipients, when transplanted alongside pancreatic tissue, can promote revascularization inside the transplanted pancreatic islet.

Augmenter of liver regeneration promotes hepatic regeneration depending on the integrity of Kupffer cell in rat small-for-size liver transplantation.

BACKGROUND: Augmenter of liver regeneration (ALR) can promote hepatocyte proliferation and thereby augment liver mass restoration. This study was performed to further explore the mechanism of ALR on liver regeneration in small-for-size liver transplanted rats. METHODS: Donor Sprague-Dawley rats were divided into a Kupffer cell (KC)-depleted group (pretreated with GdCl3) and KC-competent group and then further divided into two subgroups: the ALR subgroup (infused with 100 µg/kg ALR through the portal vein) and non-ALR subgroup. Only the median lobe was retained to establish the small-for-size liver transplantation model. Ten rats from each subgroup were used for the 7 d survival study. In addition, the nuclear factor κB activity, reperfusion injury, regeneration of the remnant liver, and tumor necrosis factor α and interleukin 6 expression levels were evaluated. RESULTS: ALR could accelerate graft regeneration by increasing nuclear factor κB activity to induce tumor necrosis factor α and interleukin 6 expression in the KC-competent rats, which resulted in a higher 7 d survival rate. CONCLUSIONS: ALR could enhance the hepatocellular proliferation of small-for-size liver grafts, and these effects appeared to deeply depend on the integrity of KCs.

Case report: Single-operator peroral cholangioscopy system (SpyGlass) diagnosis of an extrahepatic biliary cystadenoma (video).

Biliary cystadenoma is a type of rare liver cystic tumor. Intrahepatic biliary cystadenomas are the most common, while extrahepatic biliary cystadenomas are rarely seen. Biliary cystadenoma tends to occur in middle-aged to older women and there is a lack of specific preoperative diagnostic markers. Recent advancements in technology and the development of the SpyGlass system have led to an increased use of cholangioscopy. Herein, we report a patient in whom a space-occupying lesion was found in the bile duct by SpyGlass, and who later underwent radical surgery. The pathology report indicated that the final diagnosis was biliary cystadenoma. SpyGlass cholangioscopy may be a novel and effective diagnostic method for biliary cystadenoma.

Necroptosis-Related Prognostic Model for Pancreatic Carcinoma Reveals Its Invasion and Metastasis Potential through Hybrid EMT and Immune Escape.

Necroptosis, pro-inflammatory programmed necrosis, has been reported to exert momentous roles in pancreatic cancer (PC). Herein, the objective of this study is to construct a necroptosis-related prognostic model for detecting pancreatic cancer. In this study, the intersection between necroptosis-related genes and differentially expressed genes (DEGs) of pancreatic ductal adenocarcinoma (PDAC) was obtained based on GeneCards database, GEO database (GSE28735 and GSE15471), and verified using The Cancer Genome Atlas (TCGA). Next, a prognostic model with Cox and LASSO regression analysis, and divided the patients into high-risk and low-risk groups. Subsequently, the Kaplan-Meier (KM) survival curve and the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of overall survival (OS) of PC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential biofunction and possible mechanical pathways. The EMTome database and an immune analysis were applied to further explore underlying mechanism. Finally, clinical samples of PDAC patients were utilized to verify the expression of model genes via immunohistochemistry (IHC), and the normal human pancreatic ductal cell line, hTERT-HPNE as well as human pancreatic ductal carcinoma cell lines, PANC-1 and PL45, were used to identify the levels of model genes by Western blot (WB) and immunofluorescence (IF) in vitro. The results showed that 13 necroptosis-related DEGs (NRDEGs) were screened based on GEO database, and finally four of five prognostic genes, including KRT7, KRT19, IGF2BP3, CXCL5, were further identified by TCGA to successfully construct a prognostic model. Univariate and multivariate Cox analysis ultimately confirmed that this prognostic model has independent prognostic significance, KM curve suggested that the OS of low-risk group was longer than high-risk group, and the area under receiver (AUC) of ROC for 1, 3, 5 years was 0.733, 0.749 and 0.667, respectively. A GO analysis illustrated that model genes may participate in cell-cell junction, cadherin binding, cell adhesion molecule binding, and neutrophil migration and chemotaxis, while KEGG showed involvement in PI3K-Akt signaling pathway, ECMreceptor interaction, IL-17 signaling pathway, TNF signaling pathway, etc. Moreover, our results showed KRT7 and KRT19 were closely related to EMT markers, and EMTome database manifested that KRT7 and KRT19 are highly expressed in both primary and metastatic pancreatic cancer, declaring that model genes promoted invasion and metastasis potential through EMT. In addition, four model genes were positively correlated with Th2, which has been reported to take part in promoting immune escape, while model genes except CXCL5 were negatively correlated with TFH cells, indicating that model genes may participate in immunity. Additionally, IHC results showed that model genes were higher expressed in PC tissues than that in adjacent tumor tissues, and WB and IF also suggested that model genes were more highly expressed in PANC-1 and PL45 than in hTERT-HPNE. Tracing of a necroptosis-related prognostic model for pancreatic carcinoma reveals its invasion and metastasis potential through EMT and immunity. The construction of this model and the possible mechanism of necroptosis in PDAC was preliminarily explored to provide reliable new biomarkers for the early diagnosis, treatment, and prognosis for pancreatic cancer patients.

The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

Background: The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. Methods: This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Results: Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). Conclusions: In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

Impact of simultaneous splenectomy and orthotopic liver transplantation in patients with end-stage liver diseases and splenic hyperfunction.

BACKGROUND: Whether splenectomy can be performed simultaneously during liver transplantation in patients with end-stage liver diseases complicated by hypersplenism remains controversial. This study aimed to compare the impact of simultaneous splenectomy on high- and low-risk liver transplant patients with end-stage liver diseases and severe hypersplenism. METHODS: Forty-two patients with end-stage liver diseases complicated by severe hypersplenism who had undergone orthotopic liver transplantation were enrolled in this study. Splenectomy was performed in 19 of the patients. The 42 patients were grouped according to the risk of liver diseases and operations they received. Patients were considered to be at high-risk if they had at least one of the following conditions: preoperative prothrombin time >5 seconds, portal vein thrombosis, and severe perisplenitis. High-risk patients who had undergone splenectomy were classified into group A, whereas high-risk patients who had not undergone splenectomy were classified into group B. Low-risk patients who had undergone splenectomy were classified into group C, and low-risk patients who had spleen preservation were classified into group D. Operative time, intraoperative blood loss, postoperative bleeding, pulmonary infection, perioperative mortality, and postoperative platelet recovery were analyzed. RESULTS: Operative time and intraoperative blood loss were greater in group A than in groups B-D (P<0.01), but there was no significant difference between groups C and D (P>0.05). In group A, 3 patients had postoperative bleeding, 5 had pulmonary infection, and 2 had perioperative mortality, which was higher than any other group, but postoperative bleeding, pulmonary infection, and perioperative mortality were similar to those in groups C and D. In patients undergoing simultaneous splenectomy, platelet counts recovered within 6 months after surgery. Thrombocytopenia was sustained in 3 of the 23 patients who did not undergo simultaneous splenectomy. CONCLUSION: Splenectomy should be avoided during orthotopic liver transplantation in high-risk patients, but this procedure does not increase the operative risk in low-risk patients and may be a valuable method to ensure good postoperative platelet recovery.

Second endoscopic retrograde cholangiopancreatography after failure of initial biliary cannulation: A single institution retrospective experience.

Endoscopic retrograde cholangiopancreatography (ERCP) is not always successful when difficult biliary cannulation occurs. A second ERCP seems to be a worthwhile option following initial failure cannulation; however, relevant data are limited. Thus, the aim of the present study was to determine the outcomes of repeating ERCP in patients in whom the first biliary cannulation with or without precut sphincterotomy failed. It retrospectively analyzed 4,136 patients who underwent an initial biliary access between June 2016 and September 2020. Data from our databases were analyzed. Efficacy was based on the cannulation rate of the second ERCP and safety was assessed in terms of adverse events. Of 94 patients, 56 (59.6%) underwent a second ERCP and the success rate in biliary cannulation was 83.9% (47 of 56). The median operative time in the second ERCP was shorter than that in the initial procedure (47 vs. 65 min, P<0.001). A total of 5 patients (8.9%) suffered from mild ERCP-associated complications following the second ERCP. Compared with patients that did not undergo a second ERCP, patients that underwent a second ERCP had a lower 30-day mortality rate (13.2 vs. 1.8%, P=0.038). In addition, by univariate and multivariate analysis, it was observed that normal preoperative serum bilirubin levels and an interval time of <3 days were correlated with the cannulation failure of a second ERCP (OR=9.211, P=0.019, OR=6.765, P=0.041, respectively). A second ERCP following failure of an initial biliary cannulation appears to be safe and effective. For most clinically stable patients with an unsuccessful initial ERCP, a second ERCP after 2-4 days may be an optimal strategy. Preoperative normal serum bilirubin levels may be a risk factor that can be used for predicting cannulation failure of a second ERCP procedure.

Lipocalin2 as a useful biomarker for risk stratification in patients with acute cholangitis: A single-center prospective and observational study.

BACKGROUND: Lipocalin2 (LCN2) is being increasingly used to diagnose and predict severe bacterial infection. We aimed to evaluate the predictive value of serum lipocalin 2 for severity grading of acute cholangitis (AC) on patient admission. METHODS: A total of 108 patients were enrolled in this study. Blood samples were obtained at admission. Receiver operating characteristic (ROC) curves were built to assess the abilities of LCN2 levels to predict moderate/severe (vs. mild) or severe (vs. mild/moderate) AC with traditional markers of inflammation such as white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR). The correlations among the key research indicators were determined using spearman's test. Multivariate analysis was conducted to identify the risk factors for severe AC. RESULTS: The levels of LCN2 on admission increased significantly with the severity of AC. By analysis of ROC curve of biomarkers for differentiating patients with moderate to severe AC (versus mild AC), the AUC for LCN2 (0.925) was significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 262.2 ng/mL, with a sensitivity of 90.8% and specificity of 81.4%. In addition, the AUC for LCN2 (0.912) for severe acute cholangitis was also significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 325.7 ng/mL. The sensitivity and specificity were 86.1% and 83.3%, respectively. Furthermore, LCN2 the closest relationships were found between LCN2 and PCT (r = 0.8054, P < 0.001) through Spearman's test. Multivariate analysis showed that LCN2 was the only risk factor predicting severe AC (P < 0.05). CONCLUSION: Serum LCN2 concentration on patient admission could better predict severe acute cholangitis than WBC, CRP, PCT and NLR. Serum LCN2 may become a potential biomarker in the risk stratification of acute cholangitis and in indicating the time of biliary drainage.

Comparison of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (l-RAMPS) provides a new surgical approach for patients with pancreatic cancers of the body and tail. However, whether it can achieve comparable outcomes to the open RAMPS (o-RAMPS) remains an issue. METHODS: To evaluate the safety and effectiveness of l-RAMPS, the studies in the databases of Medline, Embase, and the Cochrane Library published before September 13, 2021 were searched and a meta-analysis was performed using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. The perioperative and oncological outcomes were analyzed. RESULTS: Five retrospective cohorts involving 189 patients were included for final pooled analysis. There were no significant differences in the patients' operation time, intra-abdominal bleeding rate, intra-abdominal infection rate, mild morbidity (Clavien-Dindo classification = 1), moderate to severe morbidity (Clavien-Dindo classification ≥2), overall morbidity, wound infection rate, pancreatic fistula rate, delayed gastric emptying rate, reoperation rate, length of hospital stay, postoperative mortality, R0 resection rate, and 2-year overall survival between the 2 approaches. Besides, l-RAMPS was associated with less blood loss (mean difference (MD) = -232.69, 95% confidence interval (CI) = -316.93 to -148.46, P < 0.00001) and shorter days until oral feeding (MD = -0.79, 95% CI = -1.35 to -0.22, P = 0.006). However, the pooled analysis also indicated a significantly fewer lymph nodes dissected (MD = -3.01, 95% CI = -5.59 to -0.43, P = 0.02) in l-RAMPS approach. CONCLUSIONS: Although l-RAMPS provides similar outcomes associated with benefits of minimal invasiveness compared to o-RAMPS, it harvested significantly fewer lymph nodes which might have potentially negative influence on the patients' long-term survival. L-RAMPS is still in the infancy stage and further investigation is needed to verify its feasibility.