Characteristics of gut microbiota in anastomotic leakage patients in cold zones post-colorectal cancer surgery: A high-throughput sequencing and propensity-score matching study

Objective:The study aimed to explore the association between gut microbiota and anastomotic leakage(AL)after surgery in colorectal cancer(CRC)patients from a frigid zone,based on high-throughput sequencing.Methods:A total of 98 CRC patients admitted to the Second Affiliated Hospital of Harbin Medical University from July 2018 to February 2019,who met the inclusion criteria,were included.Among these,10 patients were diagnosed as AL.After propensity-score matching of baseline characteristics,10 patients from the anastomotic leakage group(AG)and 10 patients from the normal group(NG)were finally included in this study.Fecal samples were collected,and total DNA was extracted for high-throughput sequencing and bioinformatic analysis.Results:Alpha diversity analysis showed no significant difference between the two groups,while beta diversity analysis revealed significant differences in principal components.Differential microbiota were classified as Proteobacteria at the phylum level(P=0.021).At the genus level,the abundances of Streptococcus(P=0.045),Citrobacter(P=0.008)and Klebsiella(P=0.002)were significantly different between the two groups.LEfSe analysis indicated that these genera contributed most to the differences between the groups.Conclusion:The characteristics of the gut microbiota in the AG and NG were significantly different,and these differences might be associated with AL in CRC patients from frigid zones.

Current approaches to the management of jejunal variceal bleeding at the site of hepaticojejunostomy after pancreaticoduodenectomy

Jejunal variceal bleeding at the site of hepaticojejunostomy after pancre-aticoduodenectomy due to portal hypertension caused by extrahepatic portal vein obstruction is a life-threatening complication and is very difficult to treat.Pharma-cotherapy,endoscopic methods,transcatheter embolization of veins supplying the jejunal afferent loop,portal venous stenting,and surgical procedures can be used for the treatment of jejunal variceal bleeding.Nevertheless,the optimal mana-gement strategy has not yet been established,which is due to the lack of ran-domized controlled trials involving a large cohort of patients necessary for their development.

Comparison of da Vinci 5 with previous versions of da Vinci and Sina:A review

Robotic systems have become popular in modern surgical procedures.The option of telesurgery has effectively addressed geographic limitations.These systems are offered by numerous companies worldwide.In this review article,we discuss four models of robotic systems to determine their advantages:the Sina flex system from Iran and the da Vinci Xi,SP,and 5 systems from the USA.We compared aspects such as architecture,instruments,visualizations,clinical use,and costs.Our findings suggest that the da Vinci robot,which was introduced earlier than the Sina system,utilizes proprietary and limited-use EndoWrist instruments with diameters ranging from 8 to 12 mm and features advanced imaging capabilities,including three-dimensional optical,tomographic,and fluorescence imaging.It is well established and widely utilized in various surgical procedures.Conversely,the Sina flex system employs single-use 5 mm instruments and is equipped with two-dimensional optical imaging as a standard,with optional three-dimensional and fluorescence imaging upgrades available.Despite its affordability,the Sina flex system is relatively new and has not yet been clinically tested.Additionally,the Sina flex system is more user-friendly.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt(TIPS)technique,which have made it one of the main methods for the treatment of portal hypertension complications worldwide.Innovative ideas,subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice.At the moment,the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents.The transition from bare metal stents to extended polytetrafluoroethylene–covered stent grafts made it possible to significantly prevent shunt dysfunction.However,the question of its preferred diameter,which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy,remains relevant.Currently,hepatic encephalopathy is one of the most common complications of TIPS,significantly affecting its effectiveness and prognosis.Careful selection of patients based on cognitive indicators,nutritional status,assessment of liver function,etc.,will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results.Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications.At the same time,there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis

Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mm Hg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development.

Current approaches to the management of patients with cirrhotic ascites

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords:“liver cirrhosis,”“portal hypertension,”“ascites,”“pathogenesis,”“diagnostics,” and “treatment.” Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.

Hepatic hydrothorax:An update and review of the literature

This review considers the modern concepts of pathogenesis,diagnostic methods,and treatment principles of hepatic hydrothorax(HH).HH is the excessive(>500 mL)accumulation of transudate in the pleural cavity in patients with decompensated liver cirrhosis but without cardiopulmonary and pleural diseases.It causes respiratory failure which aggravates the clinical course of liver cirrhosis,and the emergence of spontaneous bacterial pleural empyema may be the cause of death.The information was collected from the PubM ed database,the Google Scholar retrieval system,the Cochrane reviews,and the reference lists from relevant publications for 1994-2016 using the keywords:"liver cirrhosis","portal hypertension","hepatic hydrothorax","pathogenesis","diagnostics",and"treatment".To limit the scope of this review,only articles dealing with uncomplicated hydrothorax in patients with liver cirrhosis were included.The analysis of the data showed that despite the progress of modern hepatology,the presence of HH is associated with poor prognosis and high mortality.Most patients suffering from it are candidates for orthotopic liver transplantation.In routine clinical practice,stratification of the risk for an adverse outcome and the subsequent determination of individual therapeutic strategies may be the keys to the successful management of the patient’s condition.The development of pathogenetic pharmacotherapy and optimization of minimally invasive treatment will improve the quality of life and increase the survival rate among patients with HH.

Mechanisms of adaptation of the hepatic vasculature to the deteriorating conditions of blood circulation in liver cirrhosis

Pub Med, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: "Liver cirrhosis", "Endothelial dysfunction", "Sinusoidal remodeling", "Intrahepatic angiogenesis" and "Pathogenesis of portal hypertension". Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis. It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes, sinusoidal remodeling and capillarization, as well as development of the collateral microcirculation. In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation, they contribute to progression of disease and development of serious complications, in particular, related to portal hypertension.Pub Med,EMBASE,Orphanet,MIDLINE,Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015.Relevant articles were selected by using the following terms:"Liver cirrhosis","Endothelial dysfunction","Sinusoidal remodeling","Intrahepatic angiogenesis"and"Pathogenesis of portal hypertension".Then the reference lists of identified articles were searched for other relevant publications as well.Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules,the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis.It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes,sinusoidal remodeling and capillarization,as well as development of the collateral microcirculation.In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation,they contribute to progression of disease and development of serious complications,in particular,related to portal hypertension.

Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis

Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.

Restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension

In recent years, defined progress has been made in understanding the mechanisms of hemodynamic disturbances occurring in liver cirrhosis, which are based on portal hypertension. In addition to pathophysiological disorders related to endothelial dysfunction, it was revealed: There is the restructuring of the vasculature, which includes vascular remodeling and angiogenesis. In spite of the fact that these changes are the compensatory-adaptive response to the deteriorating conditions of blood circulation, taken together, they contribute to the development and progression of portal hypertension causing severe complications such as bleeding from esophageal varices. Disruption of systemic and organ hemodynamics and the formation of portosystemic collaterals in portal hypertension commence with neovascularization and splanchnic vasodilation due to the hypoxia of the small intestine mucosa. In this regard, the goal of comprehensive treatment may be to influence on the chemokines, proinflammatory cytokines, and angiogenic factors(vascular endothelial growth factor, placental growth factor, platelet-derived growth factor and others) that lead to the development of these disorders. This review is to describe the mechanisms of restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension. Development of pathogenetic methods, which allow correcting portal hypertension, will improve the efficiency of conservative therapy aimed at prevention and treatment of its inherent complications.

Therapeutic possibilities of gut microbiota modulation in acute decompensation of liver cirrhosis

The formation of liver cirrhosis(LC) is an unfavorable event in the natural history of chronic liver diseases and with the development of portal hypertension and/or impaired liver function can cause a fatal outcome. Decompensation of LC is considered the most important stratification variable for the risk of death. It is currently postulated that decompensation of LC occurs through an acute(including acute-on-chronic liver failure) and non-acute pathway. Acute decompensation of LC is accompanied by the development of life-threatening complications, characterized by an unfavorable prognosis and high mortality.Progress in understanding the underlying molecular mechanisms has led to the search for new interventions, drugs, and biological substances that can affect key links in the pathogenesis of acute decompensation in LC, for example the impaired gut-liver axis and associated systemic inflammation. Given that particular alterations in the composition and function of gut microbiota play a crucial role here, the study of the therapeutic possibilities of its modulation has emerged as one of the top concerns in modern hepatology. This review summarized the investigations that describe the theoretical foundations and therapeutic potential of gut microbiota modulation in acute decompensation of LC. Despite the encouraging preliminary data, the majority of the suggested strategies have only been tested in animal models or in preliminary clinical trials;additional multicenter randomized controlled trials must demonstrate their efficacy in larger patient populations.

Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension(PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The Pub Med database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: "liver cirrhosis", "portal hypertension", "pathogenesis", "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studie donly in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.

Left atrial appendage aneurysm: A case report

BACKGROUND An aneurysm of the left atrial appendage is one of the rare but potentially hazardous heart defects.The risk of lethal complications grows with its size.To date,about 150 cases of this defect have been described in the literature.We present a case of left atrial appendage aneurysm with the deformation of the mitral valve and the left main coronary and circumflex artery,which required mitral valve annuloplasty and bifurcation stenting.CASE SUMMARY A 58-year-old man presented to our hospital complaining of shortness of breath,general weakness,dizziness during physical exertion,and fatigue.Based on the results of echocardiography,an aneurysm of the left atrium was suspected.A free-breathing real-time cine magnetic resonance imaging with electrocardiograph synchronization confirmed the diagnosis of left atrial appendage aneurysm.The patient underwent an aneurysmectomy via a median sternotomy with cardiopulmonary bypass.Intraoperative transesophageal echocardiography revealed relative mitral insufficiency that was corrected with an annuloplasty ring.Intraoperative coronary angiogram showed impaired blood flow in the left main coronary and circumflex artery and 60%stenosis.For this reason,bifurcation stenting was performed.The patient had an uneventful postoperative clinical course and was discharged from the hospital on the 10th day in a satisfactory condition.CONCLUSION Left atrial appendage aneurysm is a rare and dangerous heart pathology that requires surgery to prevent related complications.

Risk score for predicting abdominal complications after coronary artery bypass grafting

BACKGROUND Although early abdominal complications after coronary artery bypass grafting(CABG)with cardiopulmonary bypass(CPB)are rare,the associated mortality remains high.AIM To develop a risk score for the prediction of early abdominal complications after CABG with CPB.METHODS This retrospective study was performed in the Federal State Budgetary Establishment“Federal Center of Cardiovascular Surgery”of the Ministry of Health of Russia(the city of Chelyabinsk)and included data of 6586 patients who underwent CABG with CPB during 2011-2017.The risk factors taken for evaluation were compared between patients with early abdominal complications(n=73)and without them(n=6513).We identified the most important risk factors and their influence on the development of early abdominal complications after CABG with CPB.RESULTS Gender and the presence of postinfarction cardiosclerosis,chronic kidney disease,or diabetes in the anamnesis did not affect the occurrence of abdominal complications.The leading risk factors of the early abdominal complications after CABG with CPB were multifocal atherosclerosis,extracorporeal membrane oxygenation,intra-aortic balloon pump,atrial fibrillation,perioperative myocardial infarction,and the need for resternotomy in the postoperative period.The average value of the predicted probability was 0.087±0.015 in patients with early abdominal complications after CABG with CPB and 0.0094±0.0003 in patients without these complications.The percentage of correct classification turned out to be 98.9%.After calculating a score for each of the leading risk factors,we counted a total score for each particular patient.The highest risk was noted in patients with a total score of 7 or more.CONCLUSION The developed score predicts the risk of early abdominal complications after CABG with CPB and makes it possible to stratify patients by risk groups.

Difficult procedures,better outcomes

Despite the initial skepticism and challenges,minimally invasive liver surgery especially laparoscopic liver resections(LLR),has become a first-choice surgical treatment for various liver tumors in many specialized centers worldwide(1-3).It is a safe alternative to open surgery thanks to advantages such as reduced blood loss and complication rates,shorter hospital stay,and better quality of life(4-7).However,laparoscopy requires relatively long learning,and complex procedures are limited to high-volume expert centers(8).