Advances in the diagnosis and treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patients immunological status, and found dramatic changes in the IGH within the patients immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones during 2-3 weeks of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34 and IGHV4-39 in COVID-19 patients were more abundant than that of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients

BackgroundThe novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. MethodsIn this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. FindingsAmong the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. InterpretationElderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. FundingNational Natural Science Foundation of China, Chinese Academy of Medical Sciences Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published up to March 15, 2020 using keywords "2019-nCoV", "SARS-CoV-2", "novel coronavirus", and COVID-19 AND "ARB", and "angiotensin II receptor blocker" for papers published in both English and Chinese. We found three papers: one from our group, published in Science China Life Science that demonstrated an elevated Angiotensin II level in blood samples from COVID-19 patients; another a perspective article in Chinese recommending ACEI and ARBs as potential remedies for SARS-CoV-2 infections; the third a retrospective study in Chinese identifying no significant difference between ACEI/ARB associated with outcomes in 112 COVID-19 patients with CVD comorbidity. The International society of Hypertension stated on March 16th, 2020: "there are no clinical data in human to show that ACE-inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected". Added value of this studyWe retrospectively reviewed different types of anti-hypertensive drugs taken by COVID-19 patients with hypertension comorbidity prior to entering the hospital. We discovered that ARB hypertensive drugs were associated with a decreased risk of severe disease in elderly (age>65) COVID-19 patients (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025), the first evidence of ARBs association to COVID-19 infections in human. We conducted a meta-analysis in the literature and found that ARB has positive effects associated with morbidity and mortality of pneumonia. Implications of all the available evidenceARB drugs are widely used in the population with hypertension. Treatments with ACEI and ARBs should be continuous according to medical guidelines. RCT trials of ARB associated with morbidity and mortality of SARS-CoV-2 infection are recommended in the future.

Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China

BackgroundSARS-CoV-2-caused coronavirus disease (COVID-19) is posing a large casualty. The features of COVID-19 patients with and without pneumonia, SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. MethodsWe collected information on clinical characteristics, exposure history, and laboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. ResultsWe characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42 (95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to conversion was 9.71 (95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared to patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/{micro}L) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 and lactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course, T lymphocytes were generally lower, neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset. ConclusionThe epidemiological features are important for COVID-19 prophylaxis. Circulating interleukin-6 and lactate are independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.

Oncolytic Activity of a Novel Influenza A Virus Carrying Granulocyte-Macrophage Colony-Stimulating Factor in Hepatocellular Carcinoma.

Oncolytic virotherapy is a promising strategy for the treatment of cancer. Influenza A virus has shown potential as an oncolytic agent. In this study, a recombinant PR8 influenza viral vector, called delNS1-GM-CSF, was generated with a partial deletion in NS and the granulocyte-macrophage colony-stimulating factor (GM-CSF) coding sequence inserted into the influenza nonstructural protein 1 gene. The morphological characteristics of delNS1-GM-CSF were examined. The delNS1-GM-CSF virus replicated well in various cell lines, including MDCK, A549, SMCC7721, and HepG2 cells. Moreover, selective cytotoxicity of the virus was observed in various hepatocellular carcinoma (HCC) cell lines, while no effect was demonstrated in the normal liver cell line LO2, as indicated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. Importantly, using a model based on the growth of HepG2 cells as a xenograft in nude mice, it was found that a reassortant delNS1-GM-CSF virus inhibited tumor growth significantly following intratumoral injection in a dose-dependent manner. Ex vivo results showed that the tumor inhibition efficacy of delNS1-GM-CSF was observed in HCC clinical samples. Taken together, these results are the first to demonstrate that influenza A viruses may have potential as oncolytic virotherapeutic agents against HCC.

Autoimmune hepatitis-related hepatocellular carcinoma: its clinical characteristics and impact on prognosis / 中华肝胆外科杂志

Objective To study the clinical features and prognostic risk factors of patients with autoimmune hepatitis-related hepatocellular carcinoma (AIH-HCC).Methods We reviewed the clinical data of 40 patients with AIH-HCC who were treated at the 302 Hospital between May 1,2008 and April 30,2013,and analyzed the clinical characteristics and prognostic risk factors of these patients.Results These patients were diagnosed to have HCC at a mean ± SD of 55.1 ± 13.5 years (range 28-76 years).The median duration from the time of confirmed cirrhosis to a diagnosis of HCC was 49.2 ± 44.5 months (range 3-194 months).The median survival of the AIH-HCC patients was 16.0 ±4.0 months (range 1-44 months),and the 1-year survival rate was 54.0％.Univariate analysis showed AFP,tumor size,tumor number were related to prognosis (P ＜ 0.05) ; while gender,age,IAIHG score,category,history of blood transfusion,alcohol-drinking and smoking did not significantly affect the patients' survival (P ＞ 0.05).Multivariate regression analysis showed AFP and tumor number were independent prognostic factors.Most of these patients received transcatheter arterial chemoembolization(TACE),however the survival rate of those patients who received hepatectomy was significantly higher than those who received TACE or accepted conservative treatment.Conclusion Liver cirrhosis in AIH is the sine qua non for HCC development,which subsequently occurs at a rate of 1.65％ per year.Patients who had AFP-negativity or a single tumor had a better prognosis.Surgical treatment prolonged survival.

Disputes in devascularization for the treatment of portal hypertension / 中华消化外科杂志

A common pathophysiological changes caused by liver cirrhosis indudes damage of liver function and portal hypertension,and upper gastrointestinal hemorrhage caused by portal hypertension is the main cause of death in patients with liver cirrhosis.Therefore,the main purpose of portal hypertension treatment should be prevention and control of esophagus and fundus of stomach variceal bleeding.However,upper gastrointestinal bleeding can not be completely cured no matter by medication or endoscopic treatment,devascularization or shunt.Although liver transplantation is the best treatment method for portal hypertension,the application of liver transplantation is limited by the source of donor and medical condition.Devascularization is effective to treat upper gastrointestinal hemorrhage caused by portal hypertension,while disputes exist on the surgical indications,timing and procedure selection.

Surgical treatment for type Ⅳ hilar cholangiocarcinoma / 中国普通外科杂志

Objective To explore the surgical management in patients with Bismuth Ⅳ hilar cholangiocarcinoma.Methods Retrospective study was used to analyze the clinical data with operative and pathologic diagnosis of Bismuth Ⅳ hilar cholangiocarcinoma in the recent five years.Results Of the 22 patients,there were 13 males and 9 females,with M∶F=1.4∶1.In the group of non-liver transplantation(NLTX),5 cases(31.3%) underwent resection(radical resection in 2 cases;palliative resection in 3 cases),and 11 cases had nonresectional internal or external drainage.In the liver transplantation group(LTX),the resection rate was 100 %(6/6).Five LTX cases survived for 28,19,17,12 and 9 months respectively,and one died from chronic rejection in 11 months after operation.In the NLTX group,the 1-and 2-yr survival rate was 32.1 % and 0% respectively.The 1-and 2-yr survival rate of LTX was 80.0 %(4/5)and 50.0 %(1/2)respectively.There was significant difference between the two groups in average survival rate(P=0.041).Conclusions Aggressive surgical treatment should be adopted for Bismuth Ⅳ hilar cholangiocarcinoma,and radical resection is crucial to enhance survival rate.LTX is a good choice for the patients with unresectable Bismuth Ⅳ hilar cholangiocarcinoma and the prognosis is satisfactory.

Diagnosis and treatment of pulmonary infection after liver transplant:a report of 34 cases / 中国普通外科杂志

Objective To explore the prevention and treatment of early pulmonary infection after liver(transplant).Methods A retrospective analysis was carried out on the clinical data of 34 cases suffered from post-transplant pulmonary infection among 62 cases of liver transplant.Results Among the 34 cases,27 cases recovered and 7 cases died.The sputum of 27 cases was cultured positive for bacteria and fungus(including) Gram-negative bacteria(51.9%),Gram-positive bacteria(29.6%) and fungus(18.5%),cytomegalovirus 1 case,EB virus in 1 case,and pathogens unknown in 5 cases.Conclusions (Gram-negative) bacteria are the main pathogens of pulmonary infection after liver transplant.The critical stage of pulmonary infection is the first week after operation.The perioperative management of respiratory tract and rational use of antibiotics are important for prevention and treatment of post-transplant pulmonary infection.

Hand-assisted laparoscopic hepatectomy combined with splenectomy:A report of 3 cases / 中国微创外科杂志

Objective To study the feasibility and safety of hand-assisted laparoscopic hepatectomy combined with splenectomy. Methods Hand-assisted laparoscopic hepatectomy combined with splenectomy was performed in 3 patients. A midline epigastric or right subcostal incision was made for hand-assisted port. The attachments of the spleen were dissected with a harmonic scalpel and the pedicle of the spleen was severed with the Endo-GIA. The transection of the liver was conducted using the harmonic scalpel dissection and nonabsorbable polymer clipping. The cut surface of the liver was closed by interrupted sutures. Results The operation was successfully completed in all the 3 patients. The surgical time was 130 min, 115 min, and 145 min, and the blood loss was 350 ml, 50 ml, and 150 ml, respectively. No serious postoperative complications occurred. The postoperative hospital stay was 9, 7, and 11 days, respectively. Follow-up observations for 6, 23, and 5 months showed no recurrence. Conclusions Hand-assisted laparoscopic hepatectomy combined with splenectomy is feasible and safe in selected patients .

Treatment of hepatolithiasis by laparoscopically assisted hepatectomy without T-tube drainage / 中国微创外科杂志

Objective To study the feasibility and safety of laparoscopically assisted hepatectomy without choledochotomy and T-tube drainage for the treatment of hepatolithiasis.Methods The study included 11 patients with hepatolithiasis in the left intrahepatic duct.Of the 11 patients,8 patients were complicated with choledocholith and 5 patients with cholecystolithiasis.After laparoscopically assisted left hepatectomy,extrahepatic bile duct stone removal and right hepatic duct exploration were carried out under video-assisted choledochoscopy through the left hepatic duct,without choledochotomy and T-tube drainage.Results The operation was successfully accomplished in all the 11 patients.Liver procedures included laparoscopically assisted left lateral lobectomy in 5 patients and left hemihepatectomy in 6 patients.The mean operation time was 128 min(range,110~150 min),and the mean blood loss was 95 ml(range,50~150 ml).No serious postoperative complications occurred.The mean postoperative hospital stay was 7 d(range,5~10 d).The 11 patients were followed for a mean of 7.6 months(range,2~16 months).The curative effects were classified as excellent in 10 patients and good in 1.No residual or recurrent stones were noted.Conclusions Laparoscopically asisted hepatectomy without T-tube drainage for the treatment of hepatolithiasis is feasible and safe for selected patients.This procedure offers advantages of simplicity of performance,short operation time,and fewer complications,being a worthwhile minimally invasive alternative.

A comparative study of hand-assisted laparoscopic versus open hepatectomy for liver cancer / 中国普通外科杂志

Objective To study the feasibility and invasiveness of hand-assisted laparoscopic hepatectomy(HALH) for liver cancer.Methods Forty patients undergoing hepatectomy for liver cancer were randomly divided into HALH group and open hepatectomy(OH) group.Data of patients of two groups,Which included operating time,intraoperative blood loss,length of incision,postoperative flatus time,hospital stay,complications and C-reactive protein(CRP) were compared.Results The mean intraoperative blood loss,length of incision,postoperative flatus time,hospital stay and CRP in HALH group were significantly less than that in OH group;but there was no significant difference in operating time,or complication and recurrence rate.Conclusions HALH for liver cancer is less traumatic,and achieves faster patient recovery.It is feasible and safe in selected patients.

Hand-assisted laparoscopic modified Sugiura procedure for portal hypertension: a report of 10 cases / 中国普通外科杂志

Objective To study the feasibility and safety of hand-assisted laparoscopic modified Sugiura procedure for portal hypertension. Methods Ten patients with cirrhotic portal hypertension and splenomegaly underwent hand-assisted laparoscopic modified Sugiura procedure. Results The operation was successful in all 10 patients. Mean surgical time was 189.5 minutes, Mean blood loss was 141 ml. There was no mortality nor serious postoperative complications. The mean postoperative hospital stay was 10. 5 days. Conclusions Hand-assisted laparoscopic modified Sugiura procedure is feasible and safe. It helps to reduce operative difficulty and control intraoperative bleeding for patients with portal hypertension.

Apoptosis in the acute rejection of Hamster-to-Rat liver transplantation / 中国普通外科杂志

Objective To study the occurrence of apoptosis in acute rejection of hamster-to-rat liver transplantation and the molecular mechanism. Methods On the basis of establishment of hamster-to-rat orthotopic liver transplantation, the apoptosis in xenograft were observed by histology and in situ end-lebelling of fragmented DNA;the expression of Fas-L and TGF-?1 were observed by Immunohistochemistry. Rseults In acute rejection of liver xenograft, the apoptosis of hepatocyte was detectable, meanwhile, the expression of Fas-L and TGF-?1 were found. The more severe apoptosis, the more severe acute rejection , and the more expression of Fas-L and TGF-?1 . Conclusions Apoptosis as a mechanism of cell death exists in the acute rejection of liver xenograft, and it is closely related to the expression of TGF-?1 and Fas-L.

Hepatic resection for huge primary liver carcinoma / 中国普通外科杂志

Objective To evaluate the safety and feasibility of hepatic resection for huge primary liver carcinoma (PLC). Methods 216 cases of huge PLCs(mean diameter of 14.2cm) were resected. The hepatectomies were performed under intermittent occlusion of hepatic inflow. Results All 216 cases were successfully resected. The mean time of occlusion of hepatic inflow was 19min, the mean blood loss was 743 ml. No serious complications occurred, and only seven patients died of hepatic failure and upper gastrointestinal haemorrhage postoperatively in this series. Conclusions Although resection of huge PLC is quite difficult, but if suitable surgical techique and perioperative management are adopted ,it is safe and feasible .

The clinical value of modified laparoscopic lithotomy of common bile duct / 中国普通外科杂志

Objective To discuss the clinical value of modified laparoscopic lithotomy of common bile duct.Methods Clinical data of 78 patients over the age of 60 with gallstone and choledocholithiasis who underwent modified laparoscopic lithotomy of common bile duct in the past four years were analysed.Results All operations were successful.T-tubes were withdrawn 4 weeks after operation.Of the 78 cases,77 cases hat no complications and only one case had a small incision infection.All patients recovered without complications after with drawal of T-tube.Conclusions Modified laparoscopic lithotomy of common bile duct can allow incision and suture of common bile duct and placement of T-tube under direct vision,and achieves excellent therapeatic results in the treatment of common duct stones,especially in elderly patients who cannot tolerate a long period of pneumoperitoneum.