Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in a Mouse Knockout Model.

PURPOSE: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. METHODS: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. RESULTS: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. CONCLUSION: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

Tetradentate Pt(II) complexes based on xylenylamino linked dual pyrazolate chelates for organic light emitting diodes.

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon addition of electronegative CF3 substituent on pyridinyl groups and switching to more electron deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertical arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt···Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQEmax of 15.2% and 11.2%, respectively, affirming the successfulness of the tetradentate chelating strategy.

A Hypothalamic Circuit that Modulates Feeding and Parenting Behaviors.

Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production1-5. While many neural circuits underlying feeding and parenting behaviors are well characterized6-9, it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARCAgRP neurons directly inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that governs both parenting and satiety. Selective activation of this ARCAgRP to MPOABRS3 circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.

DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice.

Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification.

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

High-performance near-infrared OLEDs maximized at 925 nm and 1022 nm through interfacial energy transfer.

Using a transfer printing technique, we imprint a layer of a designated near-infrared fluorescent dye BTP-eC9 onto a thin layer of Pt(II) complex, both of which are capable of self-assembly. Before integration, the Pt(II) complex layer gives intense deep-red phosphorescence maximized at ~740 nm, while the BTP-eC9 layer shows fluorescence at > 900 nm. Organic light emitting diodes fabricated under the imprinted bilayer architecture harvest most of Pt(II) complex phosphorescence, which undergoes triplet-to-singlet energy transfer to the BTP-eC9 dye, resulting in high-intensity hyperfluorescence at > 900 nm. As a result, devices achieve 925 nm emission with external quantum efficiencies of 2.24% (1.94 ± 0.18%) and maximum radiance of 39.97 W sr-1 m-2. Comprehensive morphology, spectroscopy and device analyses support the mechanism of interfacial energy transfer, which also is proved successful for BTPV-eC9 dye (1022 nm), making bright and far-reaching the prospective of hyperfluorescent OLEDs in the near-infrared region.

Light Induced Proton Coupled Charge Transfer Triggers Counterion Directional Translocation.

We demonstrate directed translocation of ClO4 - anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of <200 fs. Thus, it becomes possible to visualize the manifestations of light-triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.

Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse.

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Contrary to prior publications, the KO was not neonatal lethal. Thus, we phenotyped the Adam19 KO. Results: KO mice had lower body weight and shorter tibial length than wild type (WT). Dual-energy X-ray Absorptiometry indicated lower soft weight, fat weight, and bone mineral content in KO mice. In lung function analyses using flexiVent, compared to WT, Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

Extend the benchmarking indel set by manual review using the individual cell line sequencing data from the Sequencing Quality Control 2 (SEQC2) project.

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

The circular RNA circATP8B(2) regulates ROS production and antiviral immunity in Drosophila.

We identified and validated a collection of circular RNAs (circRNAs) in Drosophila melanogaster. We show that depletion of the pro-viral circRNA circATP8B(2), but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo. In addition, circATP8B(2) is enriched in the fly gut, and gut-specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase (Duox), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2)-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2)-Duox interaction is crucial for circATP8B(2)-mediated modulation of Duox activity. In addition, Gαq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2). We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production.

Plasma protein signatures of adult asthma.

BACKGROUND: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma. METHODS: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)). RESULTS: Meta-analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75-0.79 in training set; AUC = 0.72, 95% CI = 0.69-0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma-atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis. CONCLUSION: This first large-scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel.

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.

Value and reasonable choice of reoperation for recurrence of hepatocellular carcinoma after operation / 中国实用外科杂志

For recurrent hepatocellular carcinoma(HCC),hepatectomy is an active and active treatment method.Choosing appropriate cases will get good results. RecurrentHCC complies with Milan criteria,ECOG score is 0-2,andsalvage liver transplantation(SLT) can be considered. If thediameter of the tumor is less than 5 cm,single or multiplelesions are concentrated in a certain area,located at the edgeof the liver,and the liver function is good,hepatectomy should be the first choice. Laparoscopic surgery may also beconsidered in units with good equipment and accumulatedexperience. For recurrent HCC with tumor diameter > 5 cm,aslong as liver reserve function is allowed and FRLV issufficient,it should be actively strived for resection again. If ithas been proved that recurrent HCC originated from a singlecenter or combined with MVI,comprehensive treatment shouldbe rationally arranged. Besides hepatectomy,RFA,TACE,TACE + RFA and targeted drugs should be sequentiallycombined. Otherwise,the effect of hepatectomy alone is notideal. If recurrent HCC is accompanied by decompensation ofliver function,severe cirrhosis,portal hypertension,andinvasion of the main intrahepatic vascular trunk,it isrecommended to abandon reoperation and adopt other non-surgical treatment.

Clinic predictors of efficacy and adverse events of sorafenib therapy for advanced hepatocellular carcinoma patients / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinic predictors of efficacy and adverse events of sorafenib in treating with advanced hepatocellular carcinoma (HCC) patients.</p><p><b>METHODS</b>From December 2008 to October 2011, 54 patients received sorafenib for unresectable or metastatic HCC. There were 46 male and 8 female patients. The mean age was 48.7 years (ranging from 21 to 77 years). Patients received sorafenib orally 400 mg twice daily on a continuous dosing schedule with 6 weeks counting as a single cycle. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumor and toxicity grading was performed using the National Cancer Institute Common Toxicity Criteria version 3.0. The relationship between different clinic variable factors and curative effects of sorafenib was analyzed by using Cox proportion hazard regression analysis.</p><p><b>RESULTS</b>HCC was etiological related to HBV in 52 patients (96.3%). Following sorafenib therapy, 2 patients (3.7%) achieved a partial response and 24 patients (44.4%) achieved stable disease, with a disease control rate of 48.1%. The median time to progression (TTP) was 3.8 months. Multivariate analysis showed that greater Child and Eastern Cooperative Oncology Group (ECOG) grade were independent predictors of shorter TTP (HR = 1.361, 95%CI: 1.081 - 12.665, P = 0.041; HR = 1.449, 95%CI: 1.151 - 12.305, P = 0.032). The common adverse events were hand-foot syndrome (64.8%), alopecia (46.3%), and diarrhea (44.4%).</p><p><b>CONCLUSIONS</b>Single-agent sorafenib demonstrates good efficacy and acceptable tolerability in treating advanced HCC. The presents of Child class A and ECOG performance grade 0 predict better response to sorafenib in advanced HCC patients.</p>

Radiofrequency-assisted anterior approach right hepatectomy for hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of radiofrequency-assisted anterior approach right hepatectomy for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The clinic data of 12 HCC patients who underwent radiofrequency-assisted anterior approach right hepatectomy from January 2010 to July 2011 was analyzed retrospectively. Surgical techniques and treatment response were retrospectively reviewed. All the 12 patients were male, aging from 38 to 57 years with a mean of (48 ± 6) years. Ten of the 12 patients were infected with hepatitis B virus. A retrohepatic tunnel anterior to the surface of the inferior vena cava (IVC) was developed. The liver was hanged away from the IVC and radiofrequency was carried out along the Cantline's line. Scalpel was used to cut off the liver parenchyma along the middle of the ablated area until the parenchyma was fully resected. After short hepatic veins and the right hepatic vein were ligated, ligaments of right liver were fully isolated and right liver was resected. The t test was performed between 2 groups.</p><p><b>RESULTS</b>The surgical time was 165 to 295 minutes, with a mean of (230 ± 55) minutes. The bleeding was 150 to 1500 ml, with a mean of (516 ± 378) ml, which was better than those of anterior approach right hepatectomy ((1291 ± 1159) ml) and classical right hepatectomy ((2129 ± 2012) ml; t = 1.236, 3.265; P < 0.05). The postoperative hospital stay was 8 - 19 days, with a mean of (12 ± 4) days. There were no medical complications and no postoperative death. All patients were cured and discharged.</p><p><b>CONCLUSIONS</b>Radiofrequency-assisted anterior approach right hepatectomy for HCC is safe and effective and could effectively decrease intra-operative bleeding and shorten surgical time.</p>

Role of tissue factor in hepatocellular carcinoma genesis, invasion and metastasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Numerous studies indicate that tissue factor (TF), namely tissue thromboplastin, has a close relationship with malignant tumor genesis and progress. It contributes to blood coagulation as well as the regulation of cellular differentiation, the formation of blood vessels, and also tumor recurrence and metastasis. The present study aimed to detect TF expression in hepatocellular carcinoma (HCC) patients and to elucidate its association with prognosis and clinical features of the disease.</p><p><b>METHODS</b>The plasma TF levels of 50 HCC patients and 30 controls were assayed by ELISA. The expressions of TF mRNA and protein in HCC tissues, adjacent tissues and normal tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The acquired data were analyzed with related clinic-pathological documents. The patients were followed up for five years, and the relationship between TF and prognosis was analyzed.</p><p><b>RESULTS</b>The plasma TF levels were significantly increased in HCC compared to the controls (P < 0.05), presenting a close relationship with differentiation level, tumor size and hepatocirrhosis occurrence (P < 0.05). There were remarkably higher values in cases of lymphatic metastasis, extrahepatic metastasis and portal tumor thrombus (PTT) (P < 0.05) compared to non-metastasis or non-tumor thrombus, but no significant difference with different focus number or envelope (P > 0.05). The positive rates and the relative expression of TF mRNA in HCC tissue were 63.0% (17/27) and 0.567 ± 0.268, respectively, significantly higher than that in adjacent tissues or normal tissues (P < 0.05). In the patients with positive results, the relative expression intensity varied significantly with different tumor size and index of local invasion and metastasis (P < 0.05). The positive rates and the relative expression intensities of TF protein in HCC tissue were 74.1% (20/27) and 4.093 ± 1.256, respectively, significantly higher than those in adjacent tissue or normal tissue (P < 0.05). In the patients with positive results, the relative expression intensity showed significant difference in different tumor size, differentiation level, and index of local invasion and metastasis (P < 0.05).</p><p><b>CONCLUSIONS</b>The TF levels were significantly higher in plasma and tissues of HCC patients, presenting a close relationship with the index of invasion and metastasis. It indicated that TF might be related to differentiation and metastasis of HCC.</p>

Combination with vascular resection and reconstruction in resection of hilar cholangiocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the value of vascular resection and reconstruction in resection of hilar cholangiocarcinoma.</p><p><b>METHODS</b>The clinical data of 17 patients with hilar cholangiocarcinoma received resection in combination with vascular resection and reconstruction from January 2000 to September 2009 was retrospectively analyzed. Among the 17 patients, 6 underwent portal vein segmental resection and end-to-end anastomosis, 3 underwent portal vein wedge resection, 1 underwent hepatic artery ligature, 2 underwent hepatic artery segmental resection and end-to-end anastomosis, 1 underwent portal vein arterialization, 1 underwent portal vein wedge resection and hepatic artery ligature simultaneously, 2 underwent portal vein segmental resection and hepatic artery segmental resection and end-to-end anastomosis simultaneously, 1 underwent portal vein segmental resection and right hepatic artery and gastroduodenal artery end-to-end anastomosis simultaneously.</p><p><b>RESULTS</b>Four patients died and the mortality was 4/17. Three patients died of renal dysfunction followed with multiple organ dysfunction and 1 patient died of sepsis shock. Among the 13 survive patients, 6 had a smooth postoperative recover and 7 developed complications: 3 had bile leakage, 1 had respiratory failure, 1 had cholangitis due to obstruction of U tube, 1 had abdominal infection and thrombosis in portal vein system and 1 had portal vein stenosis and liver abscess. Follow-up investigation showed that the median survival time was 18 months and four patients still alive.</p><p><b>CONCLUSIONS</b>Combination of vascular resection and reconstruction in the resection of hilar cholangiocarcinoma may help to improve the resection rate but still have a high postoperative risk. The complications of renal dysfunction should be alert during the postoperative observation. The procedure of hepatic arterial reconstruction may help to reduce postoperative morbidity.</p>

Combined hepatic resection and intraoperative thermal ablation for multifocal hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of hepatic resection combined with intraoperative ablation to treat multifocal hepatocellular carcinoma.</p><p><b>METHODS</b>Clinical data of patients diagnosed with multifocal hepatocellular carcinoma and treated with hepatic resection combined with intraoperative ablation from March 1998 to September 2007 were retrospectively reviewed. Treatment response, postoperative complications and survival data were analyzed.</p><p><b>RESULTS</b>Combined treatment modalities were well tolerated except one patient dying of postoperative hepatic functional failure. The postoperative complication rate was 23.5% with a mortality rate of 6.7%. Postoperative complication included wound infection (1 case), bile leakage (1 case), subphrenic and pleural effusion (1 case), ablation-associated liver abscess (1 case), all of which were treated with non-surgical methods. The median survival time was 25.9 months. The 1, 3, 5 year survival rates were 70.6% (12/17), 23.5% (4/17), 17.6% (3/17), respectively. Three patients survived more than 5 years after surgery. Up to April 2008, 4 patients were still alive.</p><p><b>CONCLUSION</b>Hepatectomy combined with intraoperative thermal ablation provides a treatment modality for patients with multifocal hepatocellular carcinoma and may improve the prognosis.</p>

The impact of preoperative biliary drainage on surgical morbidity in hilar cholangiocarcinoma patients / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of preoperative biliary drainage on surgical morbidity in hilar cholangiocarcinoma patients underwent surgery.</p><p><b>METHODS</b>One hundred and eleven consecutive patients with hilar cholangiocarcinoma whose serum total bilirubin (TBIL) level > 85 micromol/L and underwent surgery in the period from June 1998 to August 2007 were enrolled. There were 67 male and 44 female patients, aged from 26 to 82 years old with a mean of 56 years old.</p><p><b>RESULTS</b>Fifty-five patients underwent preoperative biliary drainage with a mean of 11.4 d of drainage period (drainage group), the other (n = 56) were the non-drainage group. The preoperative TBIL level of drainage group was (154 +/- 69) micromol/L, which was significantly lower than the value of pre-drainage (256 +/- 136) micromol/L (P = 0.000) and the value of non-drainage group (268 +/- 174) micromol/L (P = 0.005). ALT and GGT levels could be lowered by preoperative biliary drainage. The postoperative complications of these two groups were comparable (36.3% vs. 28.6%, P = 0.381). Four patients in drainage group and 5 patients in non-drainage group died of liver failure. Multivariate logistic regression indicated that hepatectomy (OR = 0.284, P = 0.003) was the independent risk factor associated with postoperative morbidity. Bismuth-Corlette classification (OR = 0.211, P = 0.028) was the independent risk factor linked to postoperative mortality.</p><p><b>CONCLUSIONS</b>Preoperative biliary drainage could alleviate liver injury due to hyperbilirubin, but it could not decrease the surgical morbidity and postoperative mortality. Concomitant hepatectomy and Bismuth-Corlette classification were independent risk factors linked to surgical risks.</p>