ABSTRACT BACKGROUND: Biliary fistula is one of the most common complications after liver resection and is associated with significant morbidity and mortality. One of the methods used to evaluate biliary fistulas is the White test, which consists of injecting a lipid emulsion into the bile duct. However, no standard technique for performing the White test has been published. AIMS: The aim of this study was to standardize the technique for performing the White test in patients undergoing hepatectomies, with and without previous cholecystectomy, and to assess the preliminary results. METHODS: Patients over 18 years of age who were submitted to open hepatectomy were included in the study. The primary outcome was the rate of biliary fistula. Secondary outcomes were the incidence of acute pancreatitis and overall morbidity, measured by the Clavien-Dindo classification. RESULTS: The standard technique for the White test was performed on 17 patients. In total, three patients had previous cholecystectomy, and two had low insertion of the cystic duct, requiring cannulation of the hepatocholedochal duct. None of the patients developed clinically significant biliary leaks. Acute pancreatitis did not occur in any patient. One patient developed pneumonia requiring mechanical ventilation (Clavien-Dindo IV). All others had minor or no complications. CONCLUSIONS: The standardized technique for performing the White test suggests an appropriate strategy to maximize the detection of intraoperative biliary leaks.

BACKGROUND:Data on the influence of donor gender on post-liver transplant outcomes is scarce and is lacking. AIMS:The aim of this study was to evaluate the prognostic factors of mortality in patients undergoing liver transplantation (LT) with a thorough evaluation of the influence of the donor variables. METHODS:All patients undergoing LT at a single center from December 2011 to December 2018 were included. The main outcome measure of the study was overall patient survival. The mortality predictors were evaluated using Cox regression. RESULTS:The study analyzed 202 patients, 118 (58.1%) being males, and the average age was 54.19±11.66 years. Post-LT survival for the entire cohort of 202 patients as assessed by the KaplanMeier method at 1, 3, 5, and 7 years was 81.6, 73.1, 67.6, and 63%, respectively. The only predictor of increased overall mortality was female donor gender [HR 1.918, 95%CI 1.150-3.201, p=0.013]. Weight and height differences between donor and recipient were not related to mortality (p=0.545 for weight and p=0.964 height). CONCLUSIONS:Female donor gender was associated with an increase in overall post-LT mortality, especially for male recipients, regardless of anthropometric parameters. For male patients receiving livers from female donors, infection was the most common cause of mortality, occurring in the first year following LT.

BACKGROUND Liver transplantation (LT) is the preferred treatment for end-stage liver diseases. Early allograft failure (EAF) can result in death or retransplantation. One of the key factors predicting EAF is the degree of graft injury, which is typically assessed by elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Aminotransferase levels exceeding 5000 U/L within 48 hours of LT are indicative of poor short-term graft survival. AIM To investigate outcomes in liver transplant recipients with peak aminotransferase levels exceeding 5000 U/L and to identify predictors of EAF. METHODS Adult patients who underwent LT from a deceased (brain-dead) donor between 2011 and 2024 at Hospital de Clínicas de Porto Alegre were screened. Patients with peak AST or ALT levels > 5000 U/L post-LT were included, excluding those with vascular thrombosis. EAF was defined as death or re-transplantation within 90 days. A receiver operating characteristic curve were generated for each EAF predictor to determine the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value were calculated for each predictor’s best cutoff, as defined by the Youden Index. Survival curves were plotted using the Kaplan-Meier method. RESULTS Between 2011 and 2024, 341 patients underwent LT. Of these, 29 (8.5%) patients had AST and/or ALT levels exceeding 5000 U/L within the first 48 hours post-LT. Four patients were excluded due to vascular thrombosis, resulting in a study cohort of 25 patients. EAF were also observed in 11 patients. One-year and five-year graft survival rates were 51.7% and 42.6%, respectively. For patients without EAF, one-year and five-year graft survivals were 92.3% and 76.2%, respectively. The key predictors of EAF included serum factor V and arterial lactate levels on postoperative day (POD) 1, with AUCs of 0.936 and 0.919, respectively. The optimal cutoff for EAF prediction were 26.2% for serum factor V and 9 mmol/L for arterial lactate. CONCLUSION Aminotransferase levels > 5000 U/L were associated with high EAF risk. However, favorable graft function indicators on POD 1 were associated with long-term survival comparable to that of general LT recipients. Serum factor V and arterial lactate levels emerged as valuable prognostic markers.

Non-tumoral portal vein thrombosis (PVT) is a frequent and challenging complication in liver transplant candidates. The prevalence reaches up to 26% in patients with cirrhosis on a transplant waiting list. Its severity increases with liver disease progression and significantly impacts post-transplant outcomes. Advanced PVT increases postoperative mortality to 30%. Effective management requires a multidisciplinary approach, especially in advanced cases. Preoperative strategies emphasize anticoagulation with low molecular weight heparin, while interventional radiology, including transjugular intrahepatic portosystemic shunts, offers alternatives in some cases. Intraoperatively, management is guided by PVT classification systems, ranging from thrombectomy and portal vein reconstruction to non-physiological reconstructions in complex cases. This manuscript explores the management of PVT in liver transplantation candidates, discusses strategies to optimize outcomes, and presents our institutional protocol for addressing this high-risk condition.

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence.

Background Data on the influence donor gender on post-liver transplant outcomes is scarce / is lacking. The aim of this study was to evaluate the prognostic factors of mortality in patients undergoing liver transplantation (LT) with a thorough evaluation of the influence of the donor variables. Methods Retrospective study of all patients undergoing LT at a single center from December 2011 to December 2018. The main outcome measure of the study was overall patient survival. The mortality predictors were evaluated using Cox regression. Results Overall, 202 patients analyzed in this study, 118 (58.1%) being males, and the average age was 54.19 ± 11.66 years. Post-LT survival for the entire cohort of 202 patients as assessed by the Kaplan-Meier method at 1-, 3-, 5-, and 7 years was 81.6%, 73.1%, 67.6%, and 63%. The only predictor of increased overall mortality was female donor gender [HR = 1.918, IC95%=1.150–3.201, (p = 0.013)]. Weight and height differences between donor and recipient were not related to mortality (p = 0.545 for weight and p = 0.964 height). Conclusion Female donor gender was associated with an increase in overall post-LT mortality, especially for male recipients, regardless of anthropometric parameters. For male patients receiving livers from female donors, infection was the most common cause of mortality occurring in the first year following LT.

Introduction and Objectives Liver transplantation (LT) is the preferred treatment for early-stage HCC. Despite restrictive criteria (Milan), recurrence is high and negatively impacts on LT survival. This study aimed to evaluate risk factors and prognosis of HCC recurrence after LT. Materials and Methods Retrospective Brazilian university hospital HCC-transplanted cohort (2002 -2021). Patients transplanted for other causes, with a follow-up < 1 year or with incidental HCC at explant were excluded. Primary outcome was recurrence of HCC. Secondary outcomes were survival and time elapsed until HCC diagnosis. Tumor burden was the sum diameter of all nodules at explant. Data extraction was conducted with Excel, and statistical analysis was performed with SPSS. Results 186 patients were included (males 123 [66.1%], median age 56 years-old), 153 (82.3%) Milan-in. Locoregional waiting-list therapy was trans arterial chemoembolization (TACE), percutaneous ethanol injection (PEI) or TACE + PEI in 63 (34.2%), 58 (31.5%) and 42 (22.8%) individuals, respectively. Downstaging was achieved in 31 patients (17.8%). Explant analysis with microvascular invasion and Milan-out was detected in 31 (16.9%) and 33 (18%) individuals, respectively. HCC recurrence occurred in 22/183 patients (12%), associated with pre-LT alfa-fetoprotein (AFP) (1.881 [IQR 109-4.510] x 6 [IQR 3-39], p=0.02), Milan-out at explant (59.1% x 11.3%, p<0.0001), microvascular invasion (45.5% x 13.9%, p<0.001), and tumor burden at explant (3.9 cm [IQR 3.2-7] x 3 cm [IQR 2-4], p=0.02). Downstaging had no impact on HCC reappearance. Median recurrence time was 22 months (IQR 10.5-42.5); most frequent sites were lungs (18.2%), liver (13.6%) or multiple (36.4%). Median survival after HCC recurrence was 17 months (IQR 6.5-36). Conclusions Tumor burden, Milan-out at explant, microvascular invasion and higher pre-LT AFP levels had a negative impact on HCC recurrence. This can identify patients with higher risk of recurrence by planning screening protocols and making early diagnoses to guide effective treatment.

BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. RESULTS Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Background: Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE.

ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

PURPOSE:Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE.METHODS:All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed.RESULTS:One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82).CONCLUSION:Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.

BACKGROUND:Celiac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. METHODS:Contrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. RESULTS:305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). CONCLUSIONS:MAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population.

Abstract Purpose Although liver transplantation (LT) outcomes have improved significantly over the last decades, early post-transplant vascular complications are still associated with an elevated risk of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications and provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. Methods All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. P were divided into three groups: RI < 0.55, RI 0.55–0.85 and RI > 0.85. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared among groups. Results Three hundred and forty-four patients were included. HAT occurred in 23 patients (6.7%), of which 7 were partial and 16 were complete. Biliary complications were more common in patients with HAT (11 [47.8%]) vs. 44 [13.4%] [p < 0.001]). There was no statistically significant difference in graft survival between patients with and without HAT. Patients with RI < 0.55 on post-operative day 1 had worse graft survival compared to patients with RI 0.55–0.85 and RI > 0.85. RI on post-operative day 3 and 5 was not predictive of graft survival. Conclusions The use of DUS on liver transplant recipients in the early post-transplant period offers the possibility of early diagnosis of vascular complications. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also provides prognostic information regarding graft-survival.

ABSTRACT BACKGROUND: Morbidity of liver resections is related to intraoperative bleeding and postoperative biliary fistulas. The Endo-GIA stapler (EG) in liver resections is well established, but its cost is high, limiting its use. The linear cutting stapler (LCS) is a lower cost device. AIMS: To report open liver resections, using LCS for transection of the liver parenchyma and en bloc stapling of vessels and bile ducts. METHODS: Ten patients were included in the study. Four patients with severe abdominal pain had benign liver tumors (three adenomas and one focal nodular hyperplasia). Among the remaining six patients, four underwent liver resection for the treatment of colorectal liver metastases, three of which had undergone preoperative chemotherapy. The other two cases were one patient with metastasis from a testicular teratoma and the other with metastasis from a gastrointestinal neuroectodermal tumor. RESULTS: The average length of stay was five days (range 4–7 days). Of the seven patients who underwent resections of segments II/III, two presented postoperative complications: one developed a seroma and the other a collection of abdominal fluid who underwent percutaneous drainage, antibiotic therapy, and blood transfusion. Furthermore, the three patients who underwent major resections had postoperative complications: two developed anemia and received blood transfusions and one had biloma and underwent percutaneous drainage and antibiotic therapy. CONCLUSIONS: The use of the linear stapler in hepatectomies was efficient and at lower costs, making it suitable for use whenever EG is not available. The size of the LCS stapler shaft is more suitable for en bloc transection of the left lateral segment of the liver, which is thinner than the right one. Further studies are needed to evaluate the safety of LCS for large liver resections and resections of tumors located in the right hepatic lobe.

Objective: This study aimed to estimate the performance of single-phase-enhanced computed tomography and ultrasonography examinations in the preoperative evaluation of solid abdominal tumors and their relationship with relevant adjacent structures in children. Methods: This retrospective study included 50 pediatric patients with malignant solid abdominal tumors treated with surgical resection between 2009-2017. Preoperative computed tomography and ultrasonography were compared to operative findings (gold standard) in the diagnosis of invasion or encasement of adjacent structures. Accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated. Results: Renal (20.4%) and neuroblastic (19.4%) tumors were the most common. Complete surgi-cal resection with negative margins was achieved in 44 (88%) patients. The comparison between single-phase-enhanced computed tomography and ultrasonography findings showed the follow-ing results: sensitivity = 90.3% vs 86.6%, specificity = 86.8% vs 94.6%, negative predictive value = 95.3% vs 94.4%, positive predictive value = 75.3% vs 86.9%, and accuracy = 87.9% vs 92.2%. The correlation (kappa index) between computed tomography and ultrasonography examinations was 0.72 (p < 0.001). In 14% (7/50) of the patients, the invasion of adjacent struc-tures was diagnosed by ultrasonography but not by computed tomography (1 patient had 2 invaded structures). Conclusion: Ultrasonography can be considered a complementary method to single-phase -enhanced computed tomography in the preoperative evaluation of children with an abdominal tumor. The present study showed that ultrasonography and single-phase-enhanced computed tomography each possess a high accuracy in the preoperative planning of resection of solid abdominal tumors in children. Thus, it seems that the combination of both imaging methods would be enough for the evaluation of most abdominal tumors in the pediatric population. (c) 2022 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda.

Background: Although liver transplantation (LT) outcomes have improved significantly over the last decades, early post-transplant vascular complications, such as hepatic arterial thrombosis (HAT), are still associated with an elevated risk of graft failure. Doppler Ultrasound (DUS) is a non-invasive, semi-quantitative method capable of detecting vascular abnormalities by estimating the resistance to arterial blood flow, quantified through the Resistive Index (RI). In order to detect early acute HAT, DUS is performed on the first post-transplant week. The aim of this study was to evaluate the association of RI parameters of DUS performed on the first post-transplant week with graft survival of transplanted livers.

Mucosal melanoma (MM) is an aggressive tumor originating from melanocytes located in the respiratory, gastrointestinal, and urogenital tract with clinical and pathologic characteristics distinct from cutaneous melanoma. In addition, MMs have a unique biology that contributes to delayed diagnosis and, therefore an adverse prognosis. The factors all contribute to a treatment paradigm unique from its more studied cutaneous brethren. Due to the rarity of this disease, well-established protocols for the treatment of this pathology have yet to be established. The use of immune checkpoint inhibitors patterned after cutaneous melanoma has become the de facto primary therapeutic approach; however, cytotoxic strategies and pathway-targeted therapies have a defined role in treatment. Judicious use of these approaches can give rise to durable unmaintained disease responses.