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Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Ciliated epithelial cells have been rarely observed in urothelium lined mucosa. Only extremely rare reports in the literature have described this phenomenon and no cases have been described in other sites than the male urethra. Herein, we illustrate the finding of ciliated pseudostratified columnar cells in the renal calyx mucosa adjacent to an area of urothelial invasive carcinoma in an 82 year-old man with previous history of nephrolithiasis. The ciliated cells covered a linear extension of 0.5 cm: they were positive for keratin 7 and keratin 8/18 and negative for keratin 20. Alcian blue staining was positive in some vacuoles in the apical cytoplasm of the same cells whereas PAS (Periodic Acid-Schiff) staining was negative. GATA3 resulted negative in ciliated cells except for a layer in the basal portion of the epithelium, just above the basal membrane. The actual prevalence of ciliated epithelia in the urinary tract is not well documented and the current knowledge on the subject is limited to electron scanning microscopy studies. The significance of this phenomenon remains unknown: it could be either a developmental abnormality or more probably a metaplastic change. Associated urolithiasis, which has been described in both a previous report and in the present one, could hypothetically represent a possible trigger for this unusual cell change. However, this hypothesis needs to be confirmed through further investigation.

Background: The intraoperative insertion of a double J stent (DJS) is known to reduce urological complications and is broadly accepted in kidney transplant (KTx) patients. The magnetic ureteral DJS (mDJS) represents a valid alternative device as it can be removed without cystoscopy, using a transurethral magnet. This is of particular importance in the pediatrics, allowing us to avoid cystoscopy requiring general anesthesia (GA) in this population. To date, few data are available on the systematic use of mDJS in pediatric patients undergoing KTx., Methods: We report a retrospective analysis of 32 consecutive pediatric KTx at our center from July 2020 to December 2021., Results: Ureteral stents remained in place for a median of 35 days (range: 12-76). Non-surgical magnetic removal of the mDJS was attempted in all cases without complications. In most cases (69%), the removal procedure was performed in an outpatient clinic. In 10 cases, the mDJS was removed in the operating room under sedation before removal of the abdominal Tenckhoff catheter. All patients were clinically followed (range: 3-15 months)., Conclusions: We confirm the safety and feasibility of systematic use of mDJS in the setting of pediatric KTx. The systematic use of this device contributes to reduce the need for GA and the rate of hospital admission., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background and Objective: Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular endothelial cell cancer involving the hepatic tissue with full malignant potential. HEHE diagnosis is challenging because blood tests and radiological findings are often non-pathognomonic. Therapeutic possibilities are manifold, ranging from a simple "wait and see" to surgical approaches, up to systemic therapies with vascular endothelial growth factor (VEGF) and mechanistic target of rapamycin (mTOR) inhibitors. The standardized adoption of the surgical approaches, namely resection or transplantation, still remains unclear. Aim of this review is to clarify the role of the surgical strategies for the management of HEHE., Methods: A review of the literature was done with the intent to focus on the relevant studies exploring the role of the different surgical therapies. A search of these studies was done using the electronic database MEDLINE-PubMed., Key Content and Findings: The surgical approaches, namely resection or transplantation, represent the best option in treating well-selected patients with HEHE. Resection is indicated in the case of single lesion or oligonodular monolobar disease. Liver transplantation is indicated in the case of multifocal bilobar disease, even in the presence of resectable extrahepatic disease. The potential role of a minimally invasive approach should represent a relevant field to explore., Conclusions: The impact of surgery for the treatment of HEHE requires further studies to further clarify its relevant role. Standardized approaches are required.

Background: Minimally invasive surgery (MIS) for hepatopancreatic and biliary (HPB) diseases has been widely used in adults, while in children, its application is limited due to its complexity. Herein, we report the experience of MIS for paediatric HPB diseases and literature review., Methods: All children (≤18 years-old) undergoing major HPB operations by MIS during January 2017-June 2020 in our institution were prospectively enrolled., Results: Out of 139 children operated on for HPB diseases with MIS, 26 (18.7%) patients (age: 11 (1-17) years-old; weight: 41.9 (10.7-75.5) kg) underwent major HPB surgery, including 11 pancreatic resections and 15 liver resections, all performed by a full-laparoscopic-technique. Four (15.3%) surgeries were electively converted to an open-technique for safer operative management. None required a blood transfusion. The median hospital admission was 6 days. Post-operatively, all patients had early mobilization and good recovery. Two (7.7%) patients experienced post-operative complications requiring radiological intervention. Oncological radical resection (R0) was achieved in all tumours, and after 2 years, all children were free of tumour recurrence., Conclusion: MIS for HPB surgery is safe and feasible in children, with less surgical trauma, short hospital-stay and better aesthetic results. An adequate learning curve in specialized centres is essential for good outcomes., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Several studies have explored the risk of graft dysfunction after liver transplantation (LT) in recent years. Conversely, risk factors for graft discard before or at procurement have poorly been investigated. The study aimed at identifying a score to predict the risk of liver-related graft discard before transplantation. Secondary aims were to test the score for prediction of biopsy-related negative features and post-LT early graft loss. A total of 4207 donors evaluated during the period January 2004-Decemeber 2018 were retrospectively analyzed. The group was split into a training set (n = 3,156; 75.0%) and a validation set (n = 1,051; 25.0%). The Donor Rejected Organ Pre-transplantation (DROP) Score was proposed: - 2.68 + (2.14 if Regional Share) + (0.03*age) + (0.04*weight)-(0.03*height) + (0.29 if diabetes) + (1.65 if anti-HCV-positive) + (0.27 if HBV core) - (0.69 if hypotension) + (0.09*creatinine) + (0.38*log10AST) + (0.34*log10ALT) + (0.06*total bilirubin). At validation, the DROP Score showed the best AUCs for the prediction of liver-related graft discard (0.82; p < 0.001) and macrovesicular steatosis ≥ 30% (0.71; p < 0.001). Patients exceeding the DROP 90th centile had the worse post-LT results (3-month graft loss: 82.8%; log-rank P = 0.024).The DROP score represents a valuable tool to predict the risk of liver function-related graft discard, steatosis, and early post-LT graft survival rates. Studies focused on the validation of this score in other geographical settings are required., (© 2022. The Author(s).)

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents an innovative surgical technique used for the treatment of large hepatic lesions at high risk for post-resection liver failure due to a small future liver remnant. The most significant amount of literature concerns the use of ALPPS for the treatment of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and colorectal liver metastases (CRLM). On the opposite, few is known about the role of ALPPS for the treatment of uncommon liver pathologies. The objective of the present study was to evaluate the current literature on this topic. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible articles published up to February 2020 were included using the MEDLINE, Scopus, and Cochrane databases. Among the 486 articles screened, 45 papers met the inclusion criteria, with 136 described cases of ALPPS for rare indications. These 136 cases were reported in 18 different countries. Only in two countries, namely Germany and Brazil, more than ten cases were observed. As for the ALPPS indications, we reported 41 (30.1%) cases of neuroendocrine tumor (NET) metastases, followed by 27 (19.9%) cases of gallbladder cancer (GBC), nine (6.6%) pediatric cases, six (4.4%) gastrointestinal stromal tumors, six (4.4%) adult cases of benign primary liver disease, four (2.9%) adult cases of malignant primary liver disease, and 43 (31.6%) adult cases of malignant secondary liver disease. According to the International ALPPS Registry data, less than 10% of the ALPPS procedures have been performed for the treatment of uncommon liver pathologies. NET and GBC are the unique pathologies with acceptable numerosity. ALPPS for NET appears to be a safe procedure, with satisfactory long-term results. On the opposite, the results observed for the treatment of GBC are poor. However, these data should be considered with caution. The rationale for treating benign pathologies with ALPPS appears to be weak. No definitive response should be given for all the other pathologies. Multicenter studies are needed with the intent to clarify the potentially beneficial effect of ALPPS for their treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn-20-355). The authors have no conflicts of interest to declare., (2021 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma., Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication., Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201; 7.438) for CCI and 5.507 (4.152; 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896; 4.115) for CCI and 2.439 (1.666; 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set., Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and doctor-patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing enbloc the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.

Background: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a new surgical technique for the resection of advanced hepatic malignancies with predicted insufficient future liver remnant. In some patients, ALPPS can be associated with an increased risk of poor outcomes. Minimally invasive surgery (MIS) has been proposed in combination with ALPPS with the intent to minimize this risk. We systematically evaluated the outcomes of MIS-ALPPS cases to compare the relative outcomes of open ALPPS versus MIS-ALPPS., Methods: A systematic review was done in accordance with the PRISMA guidelines. Search terms utilized included the following: ("ALPPS"[Title/Abstract] OR "associating liver partition and portal vein ligation for staged hepatectomy"[Title/Abstract] OR "in situ split"[Title/Abstract]) AND ("minimally invasive"[Title/Abstract] OR "laparoscopic"[Title/Abstract] OR "robotic"[Title/Abstract])., Results: Fifteen articles were identified, with a total of 27 patients reported. Colorectal metastatic disease was the most commonly observed indication for MIS-ALPPS (66.7%), followed by hepatocellular carcinoma (25.9%). Time passed from the first to the second stage ranged 7-30 days. MIS-ALPPS patients did not experience procedure failures between the first and second stages. Only four (15.4%) subjects had a grade IIIb complication. No perioperative mortality after the first or second stage was reported. Compared with open ALPPS, MIS-ALPPS demonstrated better results. Hospital stay duration ranged 8-33 days with a follow-up ranging 1-20 months., Conclusions: MIS-ALPPS appears to be safe, with potentially lower morbidities and mortalities relative to open patients. The present results should be considered with caution. A limited number of articles exist on this topic. Furthermore, selection biases exist when comparing open versus MIS-ALPPS data. Registry studies are needed to better define the outcomes of patients undergoing MIS-ALPPS.

Background/objectives: Celiac axis stenosis (CAS) represents an uncommon and typically innocuous condition. However, when a pancreatic resection is required, a high risk for upper abdominal organs ischemia is observed. In presence of collaterals, such a risk is minimized if their preservation is realized. The aim of the present study is to systematically review the literature with the intent to address the routine management of collateral arteries in the case of CAS patients requiring pancreatoduodenectomy., Methods: A systematic search was done in accordance with the PRISMA guidelines, using "celiac axis stenosis" AND "pancreatoduodenectomy" as MeSH terms. Seventy-four articles were initially screened: eventually, 30 articles were identified (n = 87)., Results: The main cause of CAS was median arcuate ligament (MAL) (n = 31; 35.6%), followed by atherosclerosis (n = 20; 23.0%). CAS was occasionally discovered during the Whipple procedure in 15 (17.2%) cases. Typically, MAL was divided during surgery (n = 24/31; 77.4%). In the great majority of cases (n = 83; 95.4%), vascular abnormalities involved the pancreatoduodenal arteries (i.e., dilatation, arcade, channels, aneurysms). Collateral arteries were typically preserved, being divided or reconstructed in only 14 (16.1%) cases, respectively. Severe ischemic complications were reported in six (6.9%) patients, 20.0% of whom were reported in patients with preoperatively unknown CAS (p-value 0.06)., Conclusions: A correct pre-operative evaluation of anatomical conditions as well as a correct surgical planning represent the paramount targets in CAS patients with arterial collaterals. Vascular flow must be always safeguarded preserving/reconstructing the collaterals or resolving the CAS, with the final intent to avoid dreadful intra- and post-operative complications., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Aim: To perform a systematic review and meta-analysis on donor-to-recipient gender mismatch as a risk factor for post-transplant graft loss., Methods: A systematic literature search was performed using PubMed, Cochrane Library database and EMBASE. The primary outcome was graft loss after liver transplantation. Odds ratios and 95% confidence intervals were calculated to compare the pooled data between groups with different donor-to-recipient gender matches. Three analyses were done considering (1) gender mismatches (F-M and M-F) vs matches (M-M and F-F); (2) Female-to-Male mismatch vs other matches; and (3) Male-to-Female mismatch vs other matches., Results: A total of 7 articles were analysed. Gender mismatch (M-F and F-M) was associated with a significant increase of graft loss respect to match (M-M and F-F) (OR: 1.30; 95%CI: 1.13-1.50; P < 0.001). When F-M mismatch was specifically investigated, it confirmed its detrimental role in terms of graft survival (OR: 1.83; 95%CI: 1.20-2.80; P = 0.005). M-F mismatch failed to present a significant role (OR: 1.09; 95%CI: 0.73-1.62; P = 0.68)., Conclusion: Gender mismatch is a risk factor for poor graft survival after liver transplantation. Female-to-male mismatch represents the worst combination. More studies are needed with the intent to better clarify the reasons for these results., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Aim: To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio (PLR) as a risk factor for post-transplant hepatocellular cancer (HCC) recurrence., Methods: A systematic literature search was performed using PubMed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria: (1) studies comparing pre-transplant low vs high PLR values; (2) studies reporting post-transplant recurrence rates; and (3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation., Results: A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases (80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation (OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I 2 statistic value., Conclusion: Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

This article is the first description of a spontaneous hepatic rupture in a young bodybuilder with a history of clenbuterol and ephedrine alkaloid use. The patient presented with a sudden mid-epigastric pain and vomiting. Hemoglobin levels decreased a few hours later and a computed tomography scan was performed which revealed a rupture of the right liver capsule and hemoperitoneum. Two attempts at transarterial embolization did not control the bleeding and a right hemihepatectomy was performed. The pathological report identified a hepatic adenoma, a capsular tear and diffuse peliosis hepatis. The patient was discharged in a good condition after eleven days. Spontaneous hepatic ruptures are rare and life-threatening and are usually described in association with tumors, connective tissue diseases and gestosis. This article is a review of the available literature with regard to this condition, with a focus on its relation to peliosis hepatis and banned substance used by body image fanatics. The present case highlights the challenging diagnosis of this potentially fatal liver complication in a healthy appearing male, the risk associated with the online trade of performance enhancing drugs and its relation with peliosis hepatis.