Life-Threatening Ruptured Hepatic Artery Pseudoaneurysm Post-Liver Transplant: A Case Report.

BACKGROUND: Hepatic artery pseudoaneurysm after liver transplantation is a rare condition that can lead to spontaneous bleeding, depending on its extent and location. Treatment involves endovascular and surgical approaches in addition to liver retransplantation in cases of graft failure. CASE REPORT: A 42-year-old female underwent deceased donor liver transplantation due to cryptogenic cirrhosis and schistosomiasis with an uneventful postoperative course. However, 18 days after the operation, she presented to the emergency department with abdominal pain, hypotension, and lipothymia. A computed tomography scan revealed a hepatic artery anastomotic pseudoaneurysm, and due to hemodynamic instability, emergency laparotomy was indicated. During the operation, the pseudoaneurysm was found to be ruptured, and the recipient's hepatic artery was ligated due to life-threatening bleeding. She later developed ischemic cholangiopathy and biliary complications, eventually undergoing retransplantation 7 months after the emergency operation. The patient remains well 11 months after the retransplantation. CONCLUSION: We report a rare case of life-threatening rupture of hepatic artery pseudoaneurysm, which required emergency ligation of the recipient's hepatic artery and subsequent liver retransplantation due to biliary complications.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis.

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (- 22.05 kg [- 28.86; - 15.23), total cholesterol (- 0.88 [- 1.59; - 0.17]), triglycerides (- 0.70 [- 0.82; - 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (- 4.49 [- 7.65; - 1.33]), diastolic pressure (- 2.28 [- 4.25; - 0.31]), Hb glycated (- 0.97 [- 1.31; - 0.62]), HOMA IR (- 2.94; [- 3.52; - 2.35]) and cardiovascular risk (- 0.08; [- 0.10; - 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

The Protective Effect of Nutraceuticals on Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer.

BACKGROUND: Gastric cancer (GC) is still a prevalent neoplasm around the world and its main treatment modality is surgical resection. The need for perioperative blood transfusions is frequent, and there is a long-lasting debate regarding its impact on survival. AIM: To evaluate the factors related to the risk of receiving red blood cell (RBC) transfusion and its influence on surgical and survival outcomes of patients with GC. METHODS: Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively evaluated. Clinicopathological and surgical characteristics data were collected. The patients were divided into transfusion and non-transfusion groups for analysis. RESULTS: A total of 718 patients were included, and 189 (26.3%) patients received perioperative RBC transfusion (23 intraoperatively, 133 postoperatively, and 33 in both periods). Patients in the RBC transfusions group were older (P < 0.001), and had more comorbidities (P = 0.014), American Society of Anesthesiologists classification III/IV (P < 0.001), and lower preoperative hemoglobin (P < 0.001) and albumin levels (P < 0.001). Larger tumors (P < 0.001) and advanced tumor node metastasis stage (P < 0.001) were also associated with the RBC transfusion group. The rates of postoperative complications (POC) and 30-d and 90-d mortality were significantly higher in the RBC transfusion group than in the non-transfusion group. Lower hemoglobin and albumin levels, total gastrectomy, open surgery, and the occurrence of POC were factors associated with the RBC transfusion. Survival analysis demonstrated that the RBC transfusions group had worse disease-free survival (DFS) and overall survival (OS) compared with patients who did not receive transfusion (P < 0.001 for both). In multivariate analysis, RBC transfusion, major POC, pT3/T4 category, pN+, D1 lymphadenectomy, and total gastrectomy were independent risk factors related to worse DFS and OS. CONCLUSION: Perioperative RBC transfusion is associated with worse clinical conditions and more advanced tumors. Further, it is an independent factor related to worse survival in the curative intent gastrectomy setting.

Molecular Profile of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC's molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

Cirrhosis and hernia repair in a cohort of 6352 patients in a tertiary hospital: Risk assessment and survival analysis.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P < .001) and a lower prevalence of epigastric (1.8% × 9.0%, P < .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P < .001). The survival curve showed higher mortality for emergency surgery, MELD > 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P < .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review.

INTRODUCTION: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). METHODS: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. RESULTS: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. CONCLUSION: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

COVID-19 Pandemic Impact on Liver Donation in the Largest Brazilian Transplantation Center.

BACKGROUND: COVID-19 has spread worldwide and has become a public health emergency and a pandemic of international concern. The solid organ donation system was no different. This study aimed to investigate the effect of COVID-19 on the liver transplant (LT) system in Brazilian territory. METHODS: We retrospectively reviewed all liver donor records allocated in São Paulo State, Brazil, 1 year before and 1 year during the COVID-19 pandemic. We defined the pre-COVID-19 (PRE) period as between April 2019 and April 2020 and the post-COVID-19 (POST) period as between April 2020 and April 2021. Moreover, we compared LT performed in our institution during these periods. To evaluate outcomes, we compared 30-day survival after LT. RESULTS: In the PRE period, 1452 livers were offered for donation in São Paulo State and other Brazilian territories. Of these, 592 were used in LT. In the POST period, 1314 livers were offered for donation, but only 477 were used in LT. Organ refusal was higher in the POST period (P < .05). Our center performed 127 and 156 LTs in these periods, respectively, and an increase above 20% was significant (P = .039). There was no difference in 30-day survival between the periods (87.2% vs 87.9%, P > .5, respectively). CONCLUSIONS: The COVID-19 pandemic harmed potential and allocated donors and LTs performed. However, it is possible to maintain the LT volume of a transplant center without compromising survival outcomes through preventive strategies against COVID-19 propagation.

Duodenal Necrosis and Nonvariceal Digestive Bleeding After Terlipressin Administration for Treatment of Hepatorenal Syndrome: a Case Report of a Novel Side Effect of a Commonly Used Drug.

BACKGROUND: Terlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge. CASE REPORT: A 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease-Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event. CONCLUSIONS: We described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients.

Hepatic Venous Outflow Obstruction in Adult Deceased Donor Liver Transplantation: Classic Piggyback Implantation Versus a Modified Technique that Widens the Ostium of the Recipient's Left and Middle Hepatic Veins.

BACKGROUND: The classic piggyback technique uses the union of the 3 hepatic veins to perform the cavo-caval anastomosis. However, due to the lateral localization of the right hepatic vein, the partial clamping of the vena cava in this technique significantly reduces the venous return to the right atrium. To avoid this, we adopted in 2015 a modified piggyback technique, in which we use the common trunk of the middle and left hepatic veins and also perform a lateral incision toward the right in the anterior wall of the vena cava in order to widen the final ostium of the cavo-caval anastomosis. The aim of the study was to analyze the incidence of hepatic venous outflow obstruction between those 2 techniques. METHODS: Retrospective study of liver transplant recipients undergoing venography for suspected hepatic venous outflow obstruction from January 2009 to June 2021. Patients undergoing transplantation with living donors or split grafts and pediatric cases were excluded from the study. RESULTS: From January 2009 to December 2014 and from January 2015 to June 2021, 587 (group 1) and 730 (group 2) deceased-donor liver transplants were performed with the classic and the modified piggyback techniques, respectively. The incidence of cases with suspected hepatic venous outflow obstruction in groups 1 and 2 were 1.87% (n = 11) and 0.95% (n = 7), respectively (P = 0,15). The number of confirmed patients with outflow blockage that required endovascular treatment during venography in groups 1 and 2 were 4 (0.68%) and 5 (0.68%), respectively (P = 0,31). CONCLUSIONS: This modified piggyback technique did not increase the incidence of hepatic venous outflow obstruction at our service.

Innovative Technique Avoiding Bleeding After Reperfusion in Living Donor Liver Transplant Using a Modified Right Lobe Graft.

BACKGROUND: Living donor liver transplant (LDLT) is a valuable therapeutic option for overcoming the deceased donor shortage. Modified right lobe graft (MRLG) keeps the middle hepatic vein (MHV) trunk with the remnant liver to improve donor safety. Hemostasis in the MHV tributary reconstruction can be tricky; surgical stitches and energy coagulation are ineffective. Fibrin glues are excellent vascular sealants but are poor in maintaining hemostasis in an active hemorrhage or preventing resection surface-related complications after liver resection. We propose applying fibrin sealant during back table graft preparation to seal the hepatic edge and MHV reconstruction to avoid bleeding after graft revascularization. METHODS: Our retrospective cohort study included all adult patients undergoing LDLT between August 2017 and December 2021. During the back table procedure, we performed the reconstruction of the inferior right hepatic vein and/or MHV tributaries from segment 5 (V5) and segment 8 (V8) using a vein harvested from a nonrelated deceased donor. Before initiating the hepatic graft implantation, we applied fibrin sealant in the resected parenchyma, especially in the V5 and V8 anastomosis, to seal the hepatic edge and hepatic vein reconstruction. RESULTS: No bleeding was identified in the hepatic edge, and blood product transfusion was unnecessary for any recipients after reperfusion. CONCLUSION: In LDLT using MRLG with MHV reconstruction, the fibrin sealant, when applied on the raw hepatic surface, and vascular reconstruction during back table graft preparation avoided bleeding after graft revascularization.

Incidence of Donor Hepatic Artery Thrombosis in Liver Grafts Recognized During Organ Procurement and Backtable: A Rare but Treacherous Pitfall In Liver Transplantation.

INTRODUCTION: Donor hepatic artery thrombosis (dHAT) identified during liver procurement and backtable is a rare and little-reported event that can make liver transplants unfeasible. METHODS: This is a retrospective study of dHAT identified during liver grafts procurements or backtable procedures. All grafts were recovered from brain-dead donors. The demographic characteristics of the donors and the incidence of dHAT were analyzed. The data were also compared to a cohort of donors without dHAT. RESULTS: There was a total of 486 donors during the study period. The incidence of dHAT was 1.85% (n = 9). The diagnosis of dHAT was made during procurement in 5 cases (55.5%) and during the backtable in 4 (44.4%). Most donors were female (n = 5), with an average BMI of 28.14 ± 6.9 kg/m2, hypertensive (n = 5), and with stroke as cause of brain death (n = 8). The most prevalent site of dHAT was a left hepatic artery originating from the left gastric artery (n = 4). Of the 9 cases reported, 2 livers were used for transplantation, and 7 were discarded. Comparing those cases to a cohort of 260 donors without dHAT, we found a higher incidence of anatomic variations in the hepatic artery (P = .01) and of stroke as cause of brain death (P = .05). CONCLUSION: The occurrence of dHAT before liver procurement is a rare event, however it may become a treacherous pitfall if the diagnosis is late. Grafts with anatomic variations recovered from women with brain death due to stroke and with past history of hypertension seem to be at a higher risk of presenting dHAT.

Pancreas Transplantation in a Single Center: Risk Factors Associated With Pancreatic Allograft Thrombosis.

BACKGROUND: Pancreas transplantation remains a challenging procedure for small and medium-sized transplants teams, despite improvements in graft survival. Data regarding the impact of the procurement team's experience on the outcomes of pancreas transplant are lacking. The objective of this study was to evaluate risk factors that lead to pancreatic allograft thrombosis, especially the experience of the pancreas procurement team. METHODS: A retrospective study of 137 patients who underwent pancreas transplantation between March 2005 and May 2017 was conducted. Donor's and recipient characteristics were evaluated as well as their relationship to pancreatic allograft thrombosis. Cases were divided according to the number of pancreas procurements previously done by the procurement surgeon: group 1 (30 to 40 retrievals) and group 2 (≥40 retrievals). RESULTS: Simultaneous pancreas-kidney transplants accounted for 89.8% of cases (n = 123). Surgeons from group 2 performed 62.8% (n = 86) of the procurements. The graft was removed in 19 cases (13.8%) due to thrombosis. In univariate analysis, lower experience of the retrieval team was associated with allograft loss (P = .04). In multivariate analysis, donor intensive care unit time ≥5 days (P = .03) and lower experience of the procurement team were associated with increased risk of pancreatic allograft thrombosis (P = .02), whereas recipient's age from 30 to 40 years (P = .018) or ≥40 years (P = .02) was found as a protective factor. CONCLUSIONS: Pancreatic allograft thrombosis remains an important cause of graft loss in pancreas transplantation. Recipient's age, prolonged donor intensive care unit time, and lower experience of the procurement team directly influence pancreatic allograft thrombosis.

Model for establishing a new liver transplantation center through mentorship from a university with transplantation expertise.

BACKGROUND: Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted. MATERIAL AND METHODS: The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on. RESULTS: The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship. CONCLUSION: The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved.

Current aspects of renal dysfunction after liver transplantation.

The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.

Attitude and knowledge of medical students toward donation after circulatory death.

OBJECTIVE: A survey among medical students in a Brazilian public university was performed to investigate the acceptance of organ donation in Brazil, particularly donation after circulatory death (DCD). METHODS: A questionnaire including 26 objectives and Likert scale questions was validated and sent to all medical students of our institution. The answers were analyzed considering the whole set of individuals as well as by dividing the medical students into two groups: less graduated students and more graduated students. RESULTS: From 1050 students, 103 spontaneous answers (9.8%) were retrieved after 3 weeks. A total of 89.3% agreed totally with deceased donor organ donation and 8.7% agreed partially. However, only 50.5% of the students agreed totally and 31.1% agreed partially to living donation. Students revealed that 82.6% know the concept of brain death. On the other hand, 71.8% of them declared not knowing the concept of planned withdrawal of life-sustaining therapy, mainly cardiorespiratory support. A total of 85.4% of students agreed totally with donation after brain death and 11.7% agreed partially. However, when questioned about donation in awaiting circulatory death after a planned withdrawal of life-sustaining therapy, only 18.4% agreed totally and 32% agreed partially. Both groups of less and more graduated students showed similar results. CONCLUSIONS: Our study found a clear lack of information and consequently in acceptance of DCD. Education in the field of end-of-life management may improve not only the acceptance of DCD donation but also the whole understanding of planned withdrawal of life-sustaining therapy.

The Development of Feeding and Eating Disorders after Bariatric Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients in the postoperative period following bariatric surgery are at risk of developing eating disorders. This study aims to analyze the relation between bariatric surgery and the development and recurrence of eating disorders. MATERIAL AND METHODS: A literature review was carried out on 15 November 2020. Fourteen studies that met the eligibility criteria were included for qualitative synthesis, and 7 studies for meta-analysis. RESULTS: The prevalence of eating disorders in the postoperative period was 7.83%, based on the 7 studies in the meta-analysis. Binge eating disorder alone was 3.81%, which was the most significant factor, and addressed in 6 of these studies. CONCLUSION: The investigated studies have significant methodological limitations in assessing the relation between bariatric surgery and eating disorders, since they mostly present data on prevalence. PROSPERO CRD42019135614.