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Validity of studies suggesting preoperative chemotherapy for resectable thoracic esophageal cancer:A critical appraisal of randomized trials

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World Journal of Gastrointestinal Oncology 2020年第1期12卷 113-123页

作者： Giulia Manzini Ursula Klotz Doris Henne-Bruns Michael Kremer department of General and Visceral surgery University of UlmUlm 89081Germany department of General and Visceral surgery Hospital of AarauAarau 5000Switzerland

BACKGROUND In 2015,Kidane published a Cochrane review and meta-analysis to summarise the impact of preoperative chemotherapy versus surgery alone on survival for resectable thoracic esophageal cancer.The authors concluded that preoperative chemotherapy improved overall survival(OS).AIM The aim of this article was to assess the validity of the three most powerful studies included in the Cochrane review and the meta-analysis supporting the advantage of preoperative chemotherapy and to investigate the impact of an exclusion of these three studies on the result of the meta-analysis.METHODS OS was selected as the endpoint of interest.Among the ten included papers which analysed this endpoint,we identified the three publications with the highest weights influencing the final result.The validity of these papers was analysed using the CONSORT checklist for randomized controlled trials.We performed a new meta-analysis without the three studies to assess their impact on the general result of the original meta-analysis.RESULTS The three analysed studies revealed several inconsistencies.Inappropriate answers were found in up to one third of the items of the CONSORT checklist.Missing information about sample-size calculation and power,unclear or inadequate randomisation,and missing blinded set-up were the most common findings.When the three criticized studies were excluded in the meta-analysis,preoperative chemotherapy showed no benefit in OS.CONCLUSION The three most powerful publications in the Cochrane review show substantial deficits.After the exclusion of these studies from the meta-analysis,preoperative chemotherapy does not seem to result in an advantage in survival.We suggest a more critical appraisal regarding the validity of single studies.

关键词： Esophageal cancer Assessment of validity Meta-analysis CONSORT Overall survival

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Clinicopathological Characteristics and Prognostic Factors of Intrahepatic Biliary Cystadenocarcinoma

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Chinese Medical Journal 2015年第9期128卷 1177-1183页

作者： Ming-Yue Xu Xian-Jie Shi Tao Wan Yu-Rong gang Hong-Guang Wang Wen-Zhi Zhang Lei He Ming-Yi Chen Shao-Cheng Lyu Wen-Wen Zhang Hui-Xing Li department of Hepatobiliary surgery People@s Liberation Army General Hospital Beijing 100853 China

Background：Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma （IBCA） or suspected IBCAs,but controversy exists regarding the prognosis for IBCAs.This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures.Methods：Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included.The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma （IBC）;factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models.Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test.Results：IBCAs had a strong female predominance,and the most common presenting symptoms were abdominal pain or discomfort.Compared with IBCs,IBCAs occurred in older patients,in more male patients,and were associated statistically significant abnormal increase in alanine aminotransferase （P =0.01） and total bilirubin （P =0.04）.Mural nodules were more frequently seen with IBCAs and may associate with malignancy.It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings.Although complete resection is recommended,enucleation with negative margins also achieved good outcomes.Median overall patient survival was 76.2 months;survival at 1,3,and 5 years was 88.0％,68.7％,and 45.8％,respectively.Radical resection and noninvasive tumor type were independent prognostic factors for overall survival.Conclusions：It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings.Complete resection is recommended for curative treatment,and patients should be closely followed postoperatively,particularly those with invasive tumors.

关键词： Intrahepatic Biliary Cystadenocarcinoma Intrahepatic Biliary Cystadenoma Liver surgery Prognosis Radiologic Findings Survival

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Management of achilles tendon injury: A current concepts systematic review

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World Journal of Orthopedics 2015年第4期6卷 380-386页

作者： Vivek Gulati Matthew Jaggard Shafic Said Al-Nammari Chika Uzoigwe Pooja Gulati Nizar Ismail Charles Gibbons Chinmay Gupte department of Orthopaedic surgery Chelsea and Westminster Hospital department of Orthopaedic surgery Imperial College

Achilles tendon rupture has been on the rise over recent years due to a variety of reasons. It is a debilitating injury with a protracted and sometimes incomplete recovery. Management strategy is a controversial topic and evidence supporting a definite approach is limited. Opinion is divided between surgical repair and conservative immobilisation in conjunction with functional orthoses. A systematic search of the literature was performed. Pubmed, Medline and EmB ase databases were searched for Achilles tendon and a variety of synonymous terms. A recent wealth of reporting suggests that conservative regimens with early weight bearing or mobilisation have equivalent or improved rates of re-rupture to operative regimes. The application of dynamic ultrasound assessment of tendon gap may prove crucial in minimising re-rupture and improving outcomes. Studies employing functional assessments have found equivalent function between operative and conservative treatments. However, no specific tests in peak power, push off strength or athletic performance have been reported and whether an advantage in operative treatment exists remains undetermined.

关键词： Orthopaedic surgery Achilles tendon injury Sports injury Tendon rupture Conservative management

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Targeting RAS phosphorylation in cancer therapy:Mechanisms and modulators

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3433-3446页

作者： Yuran Qiu Yuanhao Wang Zongtao Chai Duan Ni Xinyi Li Jun Pu Jie Chen Jian Zhang Shaoyong Lu Chuan Lv Mingfei Ji department of Urology Changzheng HospitalNaval Military Medical UniversityShanghai 200003China department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China department of Hepatic surgery VI Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China department of Cardiology Renji HospitalShanghai Jiao Tong UniversitySchool of MedicineShanghai 200120China department of Plastic surgery Changhai HospitalNaval Military Medical UniversityShanghai 200438China

RAS,a member of the small GTPase family,functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state.RAS gain-of-function mutations are one of the leading causes in human oncogenesis,accounting for w19%of the global cancer burden.As a well-recognized target in malignancy,RAS has been intensively studied in the past decades.Despite the sustained efforts,many failures occurred in the earlier exploration and resulted in an‘undruggable’feature of RAS proteins.Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins.Therefore,the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties.A better understanding of RAS phosphorylation can contribute to future therapeutic strategies.In this review,we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways.Importantly,the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

关键词： RAS Phosphorylation Undruggable Protein kinases Allostery

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Timing of surgical repair of bile duct injuries after laparoscopic cholecystectomy: A systematic review

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World Journal of Hepatology 2022年第2期14卷 442-455页

作者： Patryk Kambakamba Sinead Cremen Beat Möckli Michael Linecker department of HPB and Transplant surgery St.Vincent’s University Hospital DublinDublin d04 T6F4Ireland department of surgery Cantonal Hospital GlarusGlarus 8750Switzerland department of Visceral and Transplantation surgery University of Geneva HospitalsGeneva 1205Switzerland department of surgery and Transplantation University Medical Center Schleswig HolsteinKiel 24105Germany

BACKGROUND The surgical management of bile duct injuries(BDIs)after laparoscopic cholecystectomy(LC)is challenging and the optimal timing of surgery remains unclear.The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature.AIM To assess timing of surgical repair of BDI and postoperative complications.METHODS The MEDLINE,EMBASE,and The Cochrane Library databases were systematically screened up to August 2021.Risk of bias was assessed via the Newcastle Ottawa scale.The primary outcomes of this review included the timing of BDI repair and postoperative complications.RESULTS A total of 439 abstracts were screened,and 24 studies were included with 15609 patients included in this review.Of the 5229 BDIs reported,4934(94%)were classified as major injury.Timing of bile duct repair was immediate(14%,n=705),early(28%,n=1367),delayed(28%,n=1367),or late(26%,n=1286).Standardization of definition for timing of repair was remarkably poor among studies.Definitions for immediate repair ranged from24 h to>12 wk after LC)and late repair(>6 wk after LC)showed a broad overlap.CONCLUSION The lack of standardization among studies precludes any conclusive recommendation on optimal timing of BDI repair after LC.This finding indicates an urgent need for a standardized reporting system of BDI repair.

关键词： Bile duct injury Major bile duct injury Laparoscopic cholecystectomy Surgical repair Immediate repair Early repair Delayed repair Late repair Biliary reconstruction Standardization of bile duct injury repair reporting

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A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release

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World Journal of Gastroenterology 2012年第21期18卷 2727-2729页

作者： Giovanni Di Nardo Salvatore Oliva Marina Aloi Federica Ferrari Simone Frediani Adriana Marcheggiano Salvatore Cucchiara department of pediatrics Pediatric Gastroenterology and Liver Unit Sapienza University of Rome00161 Rome Italy department of Medical Science Sapienza University of Rome00161 Rome Italy

pediatric Menetrier's disease (MD) is an uncommon, acute, self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy. Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission. Diagnosis often requires fullthickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy. We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR). To the best of our knowledge, this is the first pediatric MD case successfully treated with octreotide LAR. Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy.

关键词：治疗蛋白儿童肽发行代理细胞增生病毒感染

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Changing landscape of hepatitis C virus-positive donors

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World Journal of Hepatology 2017年第20期9卷 905-906页

作者： Catherine E Kling Ajit P Limaye Lena Sibulesky Division of Transplant surgery Department of Surgery University of Washington Division of Allergy and Infectious Disease Department of Medicine University of Washington

With the introduction of the new highly effective antiviral therapies, there has been a dramatic increase in the use of the hepatitis C virus(HCV)-positive livers in HCV-positive recipients. In the majority of studies, HCV positivity was defined as a donor testing HCV Ab positive. In 2015, all Organ Procurement Organizations were mandated to perform and report HCV Nucleic Acid Amplification Testing(NAT) results on all deceased and living donors. Studies are not yet available on how organs are being utilized based on NAT status and whether NAT status affects recipient outcomes. Further studies are needed to maximize the use of these organs.

关键词： Heptitis C organ utilization Hepatitis C virus aviremic Liver transplantation Hepatitis C positive recipients

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Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9

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Bone Research 2015年第3期3卷 140-151页

作者： Anat Kohn Timothy P Rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton department of Orthopaedics and Rehabilitation The Center for Musculoskeletal Research University of Rochester Medical Center department of Biomedical Genetics University of Rochester Medical Center department of Biology University of Rochester department of Orthopaedic surgery Duke Orthopaedic Cellular Developmental and Genome Laboratories Duke University School of Medicine department of Orthopaedic surgery Washington University School of Medicine

RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（Prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（Prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.

关键词： Figure Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9 NICD SOX

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Prophylaxis against hepatitis B virus recurrence after liver transplantation: A registry study

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World Journal of Gastroenterology 2015年第2期21卷 584-592页

作者： Shu Shen Li Jiang Guang-Qin Xiao Lu-Nan Yan Jia-Yin Yang Tian-Fu Wen Bo Li Wen-Tao Wang Ming-Qing Xu Yong-Gang Wei Liver Transplantation Center Department of Liver SurgeryWest China Hospital of Sichuan University

AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin(HBIG) in combination with different nucleos(t)ide analogues.METHODS: A total of 5333 hepatitis B surface antigenpositive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular(im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus(HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A(n = 4684): im HBIG plus lamivudine; group B(n = 491): im HBIG plus entecavir; group C(n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid(HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses.RESULTS: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B(86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P < 0.001) and C(86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P < 0.001). The 1-, 3-and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B(1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttranspla

关键词： Viral hepatitis Recurrence Hepatitis B immunoglobu

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World Journal of Clinical Cases 2022年第24期10卷 8490-8505页

作者： Shi-Hao Guan Xin-Yu Wang Ping Shang Qian-Cheng Du Ming-Zhi Li Xiao Xing Bin Yan department of General surgery The Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China department of General surgery Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China department of General surgery Zhongshan-xuhui HospitalFudan UniversityShanghai 200030China

BACKGROUND Pyroptosis is an inflammatory form of programmed cell death,which has been shown to be related to the prognosis of many tumors.However,its role in gastric cancer(GC)is not fully understood.AIM To evaluate the expression of pyroptosis-related genes in GC and its correlation with prognosis.METHODS We constructed prognostic multigene markers of differentially expressed genes associated with pyroptosis by least absolute contraction and selection operator Cox regression.The risk model was analyzed by Kaplan-Meier curve,two-sided log-rank test and functional enrichment analysis.RESULTS Sixty-three pyroptosis-related genes were differentially expressed in tumor tissues and adjacent nontumor tissues.Based on these differentially expressed genes,5 gene signature were constructed and all GC patients were classified into two risk groups.Kaplan-Meier survival curve showed that the overall survival(OS)of patients in the high-risk group was significantly lower than that of the low-risk group.Multivariate Cox regression analyses showed that the risk score was an independent risk factor for OS.Receiver operating characteristic curve analysis confirmed the predictive ability of the model.External validation indicated increased OS in the low-risk group.The immune function and immune cell scores of the high-risk group were generally higher than those of the low-risk group.CONCLUSION Pyroptosis-related genes play a significant role in tumor immune microenvironment.This novel model,which contains 5 pyroptosis-related genes,is an independent predicting factor for OS in GC patients,and may help to evaluate the prognosis of GC.

关键词： Gastric cancer Pyroptosis Gene signature Overall survival

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