Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance.

BACKGROUND: A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. OBJECTIVE: We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. METHODS: We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). RESULTS: Metabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with milk-sensitized tolerance. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. CONCLUSIONS: By combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathologic mechanisms underlying childhood allergy and suggest potential therapeutic targets.

Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy.

BACKGROUND & AIMS: The tumour microenvironment (TME) is a crucial mediator of cancer progression and therapeutic outcome. The TME subtype correlates with patient response to immunotherapy in multiple cancers. Most previous studies have focused on the role of different cellular components in the TME associated with immunotherapy efficacy. However, the specific structure of the TME and its role in immunotherapy efficacy remain largely unknown. METHODS: We combined spatial transcriptomics with single-cell RNA-sequencing and multiplexed immunofluorescence to identify the specific spatial structures in the TME that determine the efficacy of immunotherapy in patients with hepatocellular carcinoma (HCC) receiving anti-PD-1 treatment. RESULTS: We identified a tumour immune barrier (TIB) structure, a spatial niche composed of SPP1+ macrophages and cancer-associated fibroblasts (CAFs) located near the tumour boundary, which is associated with the efficacy of immune checkpoint blockade. Furthermore, we dissected ligand‒receptor networks among malignant cells, SPP1+ macrophages, and CAFs; that is, the hypoxic microenvironment promotes SPP1 expression, and SPP1+ macrophages interact with CAFs to stimulate extracellular matrix remodelling and promote TIB structure formation, thereby limiting immune infiltration in the tumour core. Preclinically, the blockade of SPP1 or macrophage-specific deletion of Spp1 in mice led to enhanced efficacy of anti-PD-1 treatment in mouse liver cancer, accompanied by reduced CAF infiltration and increased cytotoxic T-cell infiltration. CONCLUSIONS: We identified that the TIB structure formed by the interaction of SPP1+ macrophages and CAFs is related to immunotherapy efficacy. Therefore, disruption of the TIB structure by blocking SPP1 may be considered a relevant therapeutic approach to enhance the therapeutic effect of immune checkpoint blockade in HCC. IMPACT AND IMPLICATIONS: Only a limited number of patients with hepatocellular carcinoma (HCC) benefit from tumour immunotherapy, which significantly hinders its application. Herein, we used multiomics to identify the spatial structure of the tumour immune barrier (TIB), which is formed by the interaction of SPP1+ macrophages and cancer-associated fibroblasts in the HCC microenvironment. This structure constrains immunotherapy efficacy by limiting immune cell infiltration into malignant regions. Preclinically, we revealed that blocking SPP1 or macrophage-specific deletion of Spp1 in mice could destroy the TIB structure and sensitize HCC cells to immunotherapy. These results provide the first key steps towards finding more effective therapies for HCC and have implications for physicians, scientists, and drug developers in the field of HCC.

Retroperitoneal Laparoscopic Hepatectomy for a Subcapsular Hepatocellular Carcinoma in Segment VI (Video).

INTRODUCTION: Hepatocellular carcinoma located in hepatic segment VI/VII or close to the adrenal gland were generally considered challenging for minimally invasive resection. For these individualized patients, this may be overcome by the novel use of a retroperitoneal laparoscopic hepatectomy; however, minimally invasive retroperitoneal liver resection is difficult to perform.1-3 This video article demonstrates a pure retroperitoneal laparoscopic hepatectomy for a subcapsular hepatocellular carcinoma. VIDEO: A 47-year-old male patient with Child-Pugh A liver cirrhosis presented with a small tumor located very close to the adrenal gland next to segment VI of the liver. An enhanced abdominal computed tomographic scan demonstrated a solitary 2.3 × 1.6 cm lesion. Considering the special location of the lesion, a pure retroperitoneal laparoscopic hepatectomy was performed after obtaining the patient's consent. The patient was positioned in the flank position. The procedure was carried out using the balloon technique for a retroperitoneoscopic approach, with the patient in the lateral kidney position. The retroperitoneal space was first accessed through a 12-mm skin incision above the anterior superior iliac spine in the mid-axillary line and was expanded by inflating a glove balloon to 900 mL. A 5 mm port below the 12th rib in the posterior axillary line and a 12 mm port below the 12th rib in the anterior axillary line were placed. Following incision of Gerota's fascia, the dissection plane between the perirenal fat and the anterior renal fascia located at the superomedial side of the kidney was explored. The retroperitoneum behind the liver was fully exposed after the upper pole of the kidney was isolated. After localization of the tumor by intraoperative ultrasonography through the retroperitoneum, the retroperitoneum was dissected directly above the tumor. We used an ultrasonic scalpel to divide the hepatic parenchyma, and a Biclamp for hemostasis. The blood vessel was clamped using titanic clips, and the specimen was extracted using a retrieval bag following resection. A drainage tube was placed after completing meticulous hemostasis. Closure of the retroperitoneum was performed using a conventional suture method. RESULTS: The total operation time was 249 min, with an estimated blood loss of 30 mL. The final histopathological diagnosis showed a 3.0 × 2.2 × 2.0 cm-sized hepatocellular carcinoma. The patient was discharged on postoperative day 6 without any complications. CONCLUSION: Lesions located in segment VI/VII or close to the adrenal gland were generally considered difficult for minimally invasive resection. Under these circumstances, a retroperitoneal laparoscopic hepatectomy might be a more suitable option as it is a safe, effective and complementary approach to standard minimally invasive technology for the resection of small hepatic tumors in these special locations of the liver.

Risk factors for pulmonary complications after laparoscopic liver resection: a multicenter retrospective analysis.

BACKGROUND: Postoperative pulmonary complications (PPCs) are among the most common complications after liver resection. Although the application of laparoscopy has reduced the incidence of PPCs, the rate of PPCs after laparoscopic liver resection (LLR) remains high and the risk factors for the same are unclear. Therefore, this study aimed to determine the risk factors for PPCs after LLR. METHODS: In this multicenter study, 296 patients underwent LLR from January 2019 to December 2020. Demographic data, pathological variables, and perioperative variables were reviewed. Univariate and multivariate analyses were performed to identify the independent risk factors for PPCs. RESULTS: Of the 296 patients, 80 (27.0%) developed PPCs. Patients with PPCs had significantly increased total costs, operation costs, length of stays, and postoperative hospital stays. Multivariate analysis identified three independent risk factors for PPCs after LLR: smoking [Odds ratio (OR): 5.413, 95% confidence intervals (CI): 2.446-11.978, P = < 0.001], location of lesion in segment 7 or 8 (OR 3.134, 95% CI 1.593-6.166, P = 0.001), duration of liver ischemia (OR 1.038, 95% CI 1.022-1.054, P < 0.001), and presence of intraoperative hypothermia (OR 3.134, 95% CI 1.593-6.166, P < 0.001). CONCLUSION: Smoking, location of lesion in segment 7 or 8, duration of liver ischemia and intraoperative hypothermia were independent risk factors for PPCs which significantly increased the length of stays and burden of healthcare costs.

Periodic Surface-Enhanced Raman Scattering-Encoded Magnetic Beads for Reliable Quantitative Surface-Enhanced Raman Scattering-Based Multiplex Bioassay.

Surface-enhanced Raman scattering (SERS)-based immunoassay on encoded beads is highly attractive with the advantages of ultrasensitivity, multiplex and high throughput. However, it was a great challenge to screen out in-focus signals of the immunoconjugated SERS nanoprobes on spherical bead conveniently. Here, periodic SERS-encoded magnetic beads (PSE-MBs) were developed through droplet optofluidic technique by using monodisperse SERS-encoded magnetic nanospheres as building blocks. The designed PSE-MBs not only exhibit huge coding capacity, but also provide the strongest and reproducible SERS coding signals as "in-focus beacons". When PSE-MBs are used as capture carriers in SERS-based immunoassay, both multiple target analytes and in-focus signals of SERS nanoprobes could be easily identified according to the collected SERS coding signals. Thus, reliable quantitative analysis of multiple target analytes could be conveniently achieved by such detection protocol. Additionally, the magnetic ingredient in PSE-MBs made the operation easily during the bioassay. The multiple advantages of PSE-MBs including large coding capacity, in-focus beacons and magnetic operation endorse them to be robust capture carriers in reliable quantitative SERS-based multiplex immunoassay.

Novel coronavirus (SARS-CoV-2) infection in a renal transplant recipient: Case report.

An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in Wuhan, China, with cases now confirmed in multiple countries. The clinical course of patients remains to be fully characterized, clinical presentation ranges from asymptomatic infection to acute respiratory distress syndrome and acute renal failure, and no pharmacological therapies of proven efficacy yet exist. We report a case of SARS-CoV-2 infection in a renal transplant recipient with excellent outcome. This case states the importance of close monitoring of the concentration of cyclosporine in patients treated with lopinavir/ritonavir; the routine treatment of corticosteroid can be continued. This is a rare report of SARS-CoV-2 infection in a renal transplant recipient. Further data are needed to achieve better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of SARS-CoV-2 infections in solid organ transplant recipients.

Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution.

Tip-enhanced Raman scattering (TERS) is a promising optical and analytical technique for chemical imaging and sensing at single molecule resolution. In particular, TERS signals generated by a gap-mode configuration where a silver tip is coupled with a gold substrate can resolve a single-stranded DNA (ssDNA) molecule with a spatial resolution below 1 nm. To demonstrate the proof of subnanometer resolution, we show direct nucleic acid sequencing using TERS of a phage ssDNA (M13mp18). M13mp18 provides a known sequence and, through our deposition strategy, can be stretched (uncoiled) and attached to the substrate by its phosphate groups, while exposing its nucleobases to the tip. After deposition, we scan the silver tip along the ssDNA and collect TERS signals with a step of 0.5 nm, comparable to the bond length between two adjacent DNA bases. By demonstrating the real-time profiling of a ssDNA configuration and furthermore, with unique TERS signals of monomeric units of other biopolymers, we anticipate that this technique can be extended to the high-resolution imaging of various nanostructures as well as the direct sequencing of other important biopolymers including RNA, polysaccharides, and polypeptides.

Comparative clinical efficacy and safety of cortical bone trajectory screw fixation and traditional pedicle screw fixation in posterior lumbar fusion: a systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy and safety between cortical bone trajectory (CBT) and pedicle screw (PS) in posterior lumbar fusion surgery. METHODS: Five electronic databases were used to identify relevant studies comparing the clinical efficacy and safety between CBT and PS. The main outcomes were postoperative fusion rates and complication (especially in superior facet joint violations, symptomatic ASD, wound infection, dural tear, screw malposition and hematoma). The secondary results included operation time, intraoperative blood loss, length of hospital stay, incision length, ODI, VAS, JOA score, JOA recovery rate, patients' satisfaction and health-related quality of life. RESULTS: The outcomes showed that there was no significant difference in terms of fusion rate (p = 0.55), back and leg VAS score (p > 0.05), JOA score (p = 0.08) and incidence of reoperation (p = 0.07). However, CBT was superior to PS with Oswestry Disability Index (ODI) (p = 0.02), JOA recovery rate (p < 0.00001) and patients' satisfaction (p = 0.001). In addition, CBT was superior to PS with significantly lower incidence of superior facet joint violation and symptomatic ASD. However, there was no significant difference regarding wound infection (p > 0.05) and screw malposition (p > 0.05). CBT group required significant shorter operation time, less blood loss, shorter incision length and shorter length of hospital stay in comparison with PS group (p < 0.05). CONCLUSIONS: Both CBT and PS achieve similar, fusion rate and revision surgery rate. Furthermore, CBT is superior to PS with lower incidence of complications, shorter operation time, less blood loss, shorter incision length and shorter length of hospital stay. These slides can be retrieved under Electronic Supplementary Material.

The Tumorgenicity of Glioblastoma Cell Line U87MG Decreased During Serial In Vitro Passage.

Established cancer cell lines are routinely used to study cancer. Several factors such as serial passage may affect the reproducibility of experiments with cancer cell lines, but few researches focused on these changes. In the present study, different morphology and decreased tumorigenicity were observed in late passage U87MG cells. In vitro experiments further revealed that late passage U87MG cells possessed lower invasion properties than early passage, whereas no significant differences of proliferation and migration were found between early and late passage U87MG cells. In particular, we confirmed that late passage U87MG cells exhibited more epithelial phenotype with decreased PI3K/Akt pathway and TGF-ß pathway expressions at protein level. In summary, our results focused on the changes of U87MG cells during serial in vitro passage, suggested that passage-induced changes may lead to notable changes of biological characteristics and several molecular transitions in cancer cell lines, indicating the necessity to shorten experiment-span and accomplish experiments with the same or similar passage cancer cell strains.

Simultaneous Ship Detection and Orientation Estimation in SAR Images Based on Attention Module and Angle Regression.

Ship detection and angle estimation in SAR images play an important role in marine surveillance. Previous works have detected ships first and estimated their orientations second. This is time-consuming and tedious. In order to solve the problems above, we attempt to combine these two tasks using a convolutional neural network so that ships may be detected and their orientations estimated simultaneously. The proposed method is based on the original SSD (Single Shot Detector), but using a rotatable bounding box. This method can learn and predict the class, location, and angle information of ships using only one forward computation. The generated oriented bounding box is much tighter than the traditional bounding box and is robust to background disturbances. We develop a semantic aggregation method which fuses features in a top-down way. This method can provide abundant location and semantic information, which is helpful for classification and location. We adopt the attention module for the six prediction layers. It can adaptively select meaningful features and neglect weak ones. This is helpful for detecting small ships. Multi-orientation anchors are designed with different sizes, aspect ratios, and orientations. These can consider both speed and accuracy. Angular regression is embedded into the existing bounding box regression module, and thus the angle prediction is output with the position and score, without requiring too many extra computations. The loss function with angular regression is used for optimizing the model. AAP (average angle precision) is used for evaluating the performance. The experiments on the dataset demonstrate the effectiveness of our method.

Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus.

The influenza A virus M2 proton channel (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontinued due to widespread drug resistance. Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine. The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site. Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2. Drug binding locks the protein into a well-defined conformation, and the NMR structure of the complex shows the drug bound in the homotetrameric channel, threaded between the side chains of Asn31. Unrestrained molecular dynamics simulations predicted the same binding site. This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group. The ammonium binds as a hydrate to one of three sites aligned along the central cavity that appear to be hotspots for inhibition. These sites might stabilize hydronium-like species formed as protons diffuse through the outer channel to the proton-shuttling residue His37 near the cytoplasmic end of the channel.

Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center in China.

BACKGROUND: Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma. METHODS: A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed. RESULTS: In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis. CONCLUSIONS: The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.

Can the spleen be divided into two functional parts?

Solid evidence has revealed unsuspected functions of the spleen. Asplenic or hyposplenic patients bear an increased susceptibility to overwhelming postsplenectomy infection. We, for the first time, performed the split splenic transplantation to redress hemophilia A. We also resected the middle part of the spleen completely and anatomically for the first time. Our findings illustrate that the spleen can be divided into 2 functional parts, and may shed a new light on the understanding and practice in splenic surgery.

Semantic-Preserving Surgical Video Retrieval With Phase and Behavior Coordinated Hashing.

Medical professionals rely on surgical video retrieval to discover relevant content within large numbers of videos for surgical education and knowledge transfer. However, the existing retrieval techniques often fail to obtain user-expected results since they ignore valuable semantics in surgical videos. The incorporation of rich semantics into video retrieval is challenging in terms of the hierarchical relationship modeling and coordination between coarse- and fine-grained semantics. To address these issues, this paper proposes a novel semantic-preserving surgical video retrieval (SPSVR) framework, which incorporates surgical phase and behavior semantics using a dual-level hashing module to capture their hierarchical relationship. This module preserves the semantics in binary hash codes by transforming the phase and behavior similarities into high- and low-level similarities in a shared Hamming space. The binary codes are optimized by performing a reconstruction task, a high-level similarity preservation task, and a low-level similarity preservation task, using a coordinated optimization strategy for efficient learning. A self-supervised learning scheme is adopted to capture behavior semantics from video clips so that the indexing of behaviors is unencumbered by fine-grained annotation and recognition. Experiments on four surgical video datasets for two different disciplines demonstrate the robust performance of the proposed framework. In addition, the results of the clinical validation experiments indicate the ability of the proposed method to retrieve the results expected by surgeons. The code can be found at https://github.com/trigger26/SPSVR.

Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience.

Background: Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported. Objectives: To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence. Design: Retrospective study. Methods: A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used. Results: The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2-27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% versus 66.7%, p = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% versus 91.8%, p = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% versus 64.8%, p = 0.004; 97.9% versus 89.5%, p = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7-18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1-2 AEs. Conclusion: Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.

Comparison of the outcomes of patients with HCC with or without donafenib after radical resection to better understand the efficacy and safety of postoperative adjuvant donafenib Why was this study done? Donafenib is the only new-generation targeted drug developed in the past 14 years that has demonstrated superior efficacy and increased safety in the first-line treatment of HCC. We aimed to explore whether postoperative adjuvant donafenib can improve the prognosis of patients with HCC at high-risk of recurrence. What did the researchers do? Medical data of patients with HCC at high-risk of recurrence who underwent radical resection at two medical centers between April 2021 and October 2022 were collected to compare long-term outcomes of patients treated with and without donafenib and explore the safety of adjuvant donafenib treatment. What did the researchers find? A total of 196 patients with HCC at high-risk of recurrence, including 49 who received adjuvant donafenib treatment and 147 who did not, were analyzed. At a median follow-up of 21.8 months, it was observed that adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and compliance profiles. What do the findings mean? The study provides real-world clinical empirical data on adjuvant donafenib treatment for patients with HCC at high-risk of recurrence, and these results may provide new directions for adjuvant treatment of HCC.

Diagnosis and Treatment of Hepatic Hematoma After Liver Transplantation in a Timely Manner.

OBJECTIVE: Hematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT. METHODS: Among 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT. The clinical outcomes of various treatment modalities for these three cases were analyzed. RESULTS: Three out of 131 (2.3%) LT recipients developed graft hematoma. Patient 1 developed a spontaneous intrahepatic hematoma, without evident predisposing factors, while patient 2 developed an intrahepatic hematoma following endoscopic retrograde cholangiopancreatography (ERCP). The third case that is extrahepatic hematoma was speculated to be a result of minor hepatic parenchymal injury stemming from compressive and volume-reducing manipulation of a large graft, or secondary to focal ischemic necrosis of the liver. Our management protocol was summarized as follows: (1). Immediate ultrasound and CT, particularly enhanced CT; (2). Puncture and percutaneous drainage (PD) of the hematoma; (3). Arterial embolization if the origin could be identified as a ruptured vessel; (4). Surgical evacuation of the hematoma in the presence of bile leakage, to avoid a compartment respectably secondary infection. All three patients responded favorably to treatment and remained alive to date. CONCLUSION: Prompt diagnosis and sequential individualized management can successfully deal with intra-/extrahepatic graft hematoma after LT. Our results underscored that an individualized management considering potential future complications into account.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients.

BACKGROUND: The combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT. METHODS: This retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV. RESULTS: Only 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA-positive patients remained at a lower level than that of HBV-DNA-negative patients. CONCLUSIONS: Entecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.

Downregulating hypoxia-inducible factor-2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma.

The hypoxic microenvironment inside solid tumors, including hepatocellular carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The recently identified hypoxia-inducible factor (HIF)-2 executes the hypoxia response. Its expression feature and transcriptional targets indicate a possible dominance of HIF-2 in regulating genes in HCC. The aim of the present study was to determine whether transfection of siRNA targeting HIF-2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF-2 siRNA into human HCC cells downregulated the expression of HIF-2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α, and cyclin D1, but had little effect on the expression of HIF-1α, fms-related tyrosine kinase-1 (Flt-1), the glucose transporter (GLUT)-1, and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF expression. Furthermore, HIF-2 siRNA inhibited proliferation, induced cell cycle arrest at the G(0)/G(1) phase, and acted synergistically with doxorubicin to inhibit the growth of human HCC cells in vitro. Transfection of HIF-2 siRNA also downregulated tumoral expression of HIF-2α, VEGF, TGF-α, and cyclin D1 in vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2 tumors established in immunodeficient mice by inhibiting cell proliferation, tumor angiogenesis and microvessel perfusion. The results of the present study suggest that targeting HIF-2α with siRNA warrants investigation as a potential strategy to enhance the efficacy of doxorubicin in the treatment of HCC.