Navigating reflux disease after achalasia treatments:Balancing risks and benefits

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia.Alongside its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved.In this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after POEM.POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure.Certain patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them.This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis

Non-cirrhotic non-malignant portal vein thrombosis(NCPVT)is an uncommon condition characterised by thrombosis of the portal vein,with or without extension into other mesenteric veins,in the absence of cirrhosis or intra-abdominal malignancy.Complications can include intestinal infarction,variceal bleeding and portal biliopathy.In this article,we address current concepts in the management of NCPVT including identification of risk factors,classification and treatment,and review the latest evidence on medical and interventional management options.

Tendoscopic Surgery for Peroneal Tendons Instability: A Literature Review

Introduction: There has been a surge in the use of tendoscopic surgery for treating peroneal tendons instability. The novelty of this approach demanded a literature review of its indications, limitations, and clinical outcomes. Aim: a literature review of the clinical studies reporting on tendoscopic peroneal tendon stabilisation surgery along with its outcomes and complications. Methods: We carried out a comprehensive review of the literature up until September 2022 with an extensive search of the MEDLINE, Embase and Cochrane library databases. Results: Initial search resulted in 66 articles. Four duplicate articles were removed. Further 30 articles were excluded after title and abstract screening. Eight studies satisfied the inclusion criteria and were included in this review. Articles were analysed for outcomes and complications. Conclusion: The tendoscopic technique for peroneal tendon instability is an effective and safe surgical technique with very low failure rate. Levels of Evidence: Level IV.

Role of routine lymph node dissection alongside resection ofintrahepatic cholangiocarcinoma: Systematic review and metaanalysis

BACKGROUND The global incidence of intrahepatic cholangiocarcinoma(ICCA)is soaring.Due to often delayed presentation,only a narrow spectrum of the disease is usually surgically resectable.To more accurately stage the disease,reduce recurrence,and improve overall survival,surgical teams are increasingly performing intraoperative lymph node dissection(LND)as well.This procedure has its associated morbidity,while there is no consensus or formal guidelines on its role in this setting.Hence,there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA.AIM To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA.METHODS We performed a systematic literature search using Pubmed,Medline,Embase,and the Cochrane Library,for all studies involving LND,ICCA,and surgical resection using several keywords,Medical Subject Headings(MeSH)tags,and appropriate synonyms.All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included,while single-arm case series,studies with insufficient data,and duplicates were excluded.We included all English-language studies from the different academic databases up till early December 2022.The primary outcome measures were set for overall survival(OS)and disease-free survival(DFS).RESULTS This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA,of whom 6424(56.3%)underwent hepatectomy with LND while the remainder underwent hepatectomy only.In patients who underwent LND,on average,27.7%of the resected lymph nodes were positive for metastatic disease.Overall,the results showed that performing LND did not significantly improve OS or DFS.However,the effect of LND on OS showed a degree of variability by geographical region,in Eastern and Western countries.As LND is increasingly being performed,further time-based analysis was undertaken to identify time-dependent changes in the role of LND.An increasing adoption of LND was not associated with improved OS.Furthermore,no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either.CONCLUSION LND might aid in staging,prognosticating,and deciding further management of resected ICCA,but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.

Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy:A systematic scoping review

BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.

Robotic surgery for rectal cancer: A systematic review of current practice

AIM: To give a comprehensive review of current litera-ture on robotic rectal cancer surgery.METHODS: A systematic review of current literature via PubMed and Embase search engines was per-formed to identify relevant articles from january 2007 to november 2013. The keywords used were: "robotic surgery", "surgical robotics", "laparoscopic computer-assisted surgery", "colectomy" and "rectal resection". RESULTS: After the initial screen of 380 articles, 20 pa-pers were selected for review. A total of 1062 patients(male 64.0%) with a mean age of 61.1 years and body mass index of 24.9 kg/m2 were included in the review.Out of 1062 robotic-assisted operations, 831(78.2%) anterior and low anterior resections, 132(12.4%) in-tersphincteric resection with coloanal anastomosis, 98(9.3%) abdominoperineal resections and 1(0.1%) Hart-mann's operation were included in the review. Robotic rectal surgery was associated with longer operative time but with comparable oncological results and anastomotic leak rate when compared with laparoscopic rectal surgery. CONCLUSION: Robotic colorectal surgery has con-tinued to evolve to its current state with promising re-sults; feasible surgical option with low conversion rate and comparable short-term oncological results. The challenges faced with robotic surgery are for more high quality studies to justify its cost.

Liver transplantation for alcoholic liver disease

Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease.Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft.There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores.Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up.There is conflicting evidence to support a fixed period of pretransplant abstinence,although most units do follow this.Alcoholic hepatitis(AH) continues to be a contraindication for transplantation,however there is a need for further research in this f ield as a subset of patients with AH who do not respond to medical treatment,have high early mortality and could benefit from transplantation.One year,3-year,and 5-year survival post-transplant is similar for both ALD and non-ALD recipients.The incidence of post-transplant rejection and retransplantation is also similar to other recipients.ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation.ALD patients are more prone to develop de-novo malignancy;this is attributed to the long term effect of alcohol,tobacco combined with immunosuppression.Post-transplant surveillance is important to detect early relapse to alcoholism,presence of de-novo malignancy and treat the same adequately.

Colorectal cancer and pollution

The incidence of colorectal carcinoma is increasing in young patients, in contrast to the well established wisdom that it is exclusively diagnosed in patients older than 40 years. In this survey, we examined all possible risk factors, and we recommend a number of measures for early detection in young patients who are at risk of developing this malignant tumor.

Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer

Hepatocellular carcinoma(HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.

Acute kidney injury and post-reperfusion syndrome in liver transplantation

In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRSinduced AKI, avoiding confounding factors, we have limited our study to "acute kidney injury AND DCD AND liver transplantation". Accordingly, three out of five studies were selected for our purpose.

Trends on gastrointestinal bleeding and mortality:Where are we standing?

Bleeding from the gastrointestinal tract and its management are associated with significant morbidity and mortality.The predisposing factors that led to the occurrence of these hemorrhagic instances are largely linked to the life style of the affected persons.Designing a new strategy aimed at educating the publics and improving their awareness of the problem could effectively help in eradicating this problem with no associated risks and in bringing the mortality rates down to almost zero.

Epidemiology and inflammatory bowel diseases

The role of alcohol in causing or aggravating the pathogenesis of inflammatory bowel disease is unclear.For finding a conclusive answer for this valuable question we conducted this review.Only two studies were identified that successfully fulfilled our inclusive criteria.Usual consumption of alcohol reduced the risk compared with less frequent use(odds ratio = 0.57,95%CI:0.37-0.86).Light alcoholic drinking has protective effects against development of ulcerative colitis.But this inverse association disappeared when smoking was included.

No difference in mortality among ALPPS,two-staged hepatectomy,and portal vein embolization/ligation:A systematic review by updated traditional and network meta-analyses

Background:There is an ongoing debate on the feasibility,safety,and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)technique.The aim of this study was to compare ALPPS,two-staged hepatectomy(TSH),and portal vein embolization(PVE)/ligation(PVL)using updated traditional meta-analysis and network meta-analysis(NMA).Data sources:Electronic databases were used in a systematic literature search.Updated traditional metaanalysis and NMA were performed and compared.Mortality and major morbidity were selected as primary outcomes.Results:Nineteen studies including 1200 patients were selected from the pool of 436 studies.Of these patients,315(31%)and 702(69%)underwent ALPPS and portal vein occlusion(PVO),respectively.Ninetyday mortality based on updated traditional meta-analysis,subgroup analysis of the randomized controlled trials(RCTs),and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE,PVL,and TSH cohorts.Moreover,analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts.The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters,time to operation,definitive hepatectomy,and R0 margins rates compared with the PVO cohort.In contrast,1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort.Conclusions:This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches.Furthermore,two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

Role of early transjugular intrahepatic portosystemic stent-shunt in acute variceal bleeding:An update of the evidence and future directions

Variceal bleeding is a serious complication of cirrhosis and portal hypertension.Despite the improvement in management of acute variceal bleed(AVB),it still carries significant mortality.Portal pressure is the main driver of variceal bleeding and also a main predictor of decompensation.Reduction in portal pressure has been the mainstay of management of variceal bleeding.Transjugular intrahepatic porto-systemic stent shunt(TIPSS)is a very effective modality in reducing the portal hypertension and thereby,controlling portal hypertensive bleeding.However,its use in refractory bleeding(rescue/salvage TIPSS)is still associated with high mortality.“Early”use of TIPSS as a“pre-emptive strategy”in patients with AVB at high risk of failure of treatment has shown to be superior to standard treatment in several studies.While patients with Child C cirrhosis(up to 13 points)clearly benefit from early-TIPSS strategy,it’s role in less severe liver disease(Child B)and more severe disease(Child C>13 points)remains less clear.Moreover,standard of care has improved in the last decade leading to improved 1-year survival in high-risk patients with AVB as compared to earlier“early”TIPSS studies.Lastly in the real world,only a minority of patients with AVB fulfil the stringent criteria for early TIPSS.Therefore,there is unmet need to explore role of early TIPSS in management of AVB in well-designed prospective studies. In this review, we have appraised the role of early TIPSS, patient selection anddiscussed future directions in the management of patients with AVB.

Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

Computed tomography pulmonary angiography using a 20% reduction in contrast medium dose delivered in a multiphasic injection

AIM To evaluate the feasibility of reducing the dose of iodinated contrast agent in computed tomography pulmonary angiography(CTPA). METHODS One hundred and twenty-seven patients clinically suspected of having pulmonary embolism underwent spiral CTPA, out of whom fifty-seven received 75 mL and the remaining seventy a lower dose of 60 mL of contrast agent. Both doses were administered in a multiphasic injection. A minimum opacification threshold of 250 Hounsfield units(HU) in the main pulmonary artery is used for assessing the technical adequacy of the scans. RESULTS Mean opacification was found to be positively correlated to patient age(Pearson's correlation 0.4255, P < 0.0001) and independent of gender(male:female, 425.6 vs 450.4,P = 0.34). When age is accounted for, the study and control groups did not differ significantly in their mean opacification in the main(436.8 vs 437.9, P = 0.48),left(416.6 vs 419.8, P = 0.45) or the right pulmonary arteries(417.3 vs 423.5, P = 0.40). The number of sub-optimally opacified scans(the mean opacification in the main pulmonary artery < 250 HU) did not differ significantly between the study and control groups(7 vs 10).CONCLUSION A lower dose of iodine contrast at 60 mL can be feasibly used in CTPA without resulting in a higher number of sub-optimally opacified scans.

Is iron overload in alcohol-related cirrhosis mediated by hepcidin?

In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation.We demonstrate a reciprocal relation-ship between serum or urinary hepcidin and serum ferritin,which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin.The ferritin level falls with increasing hepcidin production after transplantation.Neither inflammatory indices(IL6)nor erythropoietin appear to be related to hepcidin expression in this case.We suggest that inappropriately low hepcidin production by the cirrhotic liver may contribute substantially to elevated tissue iron stores in cirrhosis and speculate that hepcidin replacement in these patients may be of therapeutic benefi t in the future.

Inflammatory bowel disease-related colorectal cancer:Past,present and future perspectives

Inflammatory bowel disease-related colorectal cancer(IBD-CRC)is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients.IBD is often associated with diet and lifestyle-related gut microbial dysbiosis,the interaction of genetic and environmental factors,leading to chronic gut inflammation.According to the“common ground hypothesis”,microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC.Among the many underlying factors known to increase the risk of IBD-CRC,perhaps the most important factor is chronic persistent inflammation.The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability.Multiple pathways have been identified,regulated by many positive and negative factors involved in the development of cancer,which in this case follows the‘inflammation-dysplasia-carcinoma’sequence.Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC,among which colonoscopic surveillance is the most widely accepted and implemented modality,forming part of many national and international guidelines.However,the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons—cost-benefit to health systems,resource requirements,and also because of studies showing conflicting long-term data.Our review provides a comprehensive overview of past,present,and future perspectives of IBD-CRC.We explore and analyse evidence from studies over decades and current best practices followed globally.In the future directions section,we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.

Recurrence and survival following microwave, radiofrequency ablation, and hepatic resection of colorectal liver metastases: A systematic review and network meta-analysis

Background: Gold standard for colorectal liver metastases(CRLM) remains hepatic resection(HR). However, patients with severe comorbidities, unresectable or deep-situated resectable CRLM are candidates for ablation. The aim of the study was to compare recurrence rate and survival benefit of the microwave ablation(MWA), radiofrequency ablation(RFA) and HR by conducting the first network meta-analysis. Data sources: Systematic search of the literature was conducted in the electronic databases. Both updated traditional and network meta-analyses were conducted and the results were compared between them. Results: HR cohort demonstrated significantly less local recurrence rate and better 3-and 5-year diseasefree(DFS) and overall survival(OS) compared to MWA and RFA cohorts. HR cohort included significantly younger patients and with significantly lower preoperative carcinoembryonic antigen(CEA) by 10.28 ng/m L compared to RFA cohort. Subgroup analysis of local recurrence and OS of solitary and ≤3 cm CRLMs did not demonstrate any discrepancies when compared with the whole sample. Conclusions: For resectable CRLM the treatment of choice still remains HR. MWA and RFA can be used as a single or adjunct treatment in patients with unresectable CRLM and/or prohibitive comorbidities.

Understanding of chemoprophylaxis and concordance in inflammatory bowel disease

AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5 point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixtyfour percent of patients claimed full concordance with chemoprophylaxis for maintenance of remission. Eightyfour percent of patients considered daily concordance during remission to be very important. Seventy-five percent stated they understood the reasons for taking the drugs. However, only 50% of the patients were aware of any link of their condition to bowel cancer. Seventy-nine percent of patients felt their concordance and understanding would be improved if they were informed of the chemoprophylactic potential of the medication.