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Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons.Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC.Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥ 50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤ 5.2%; comprehensive complication index at 1 year of ≤ 33.7; grade ≥ 3 complication rates ≤ 66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n = 106) (62% vs 32%, P < 0.001).Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Objective In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT. Methods We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: =3a complications and the CCI at 1 year: Conclusion ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.

Colorectal neuroendocrine neoplasm (CRNEN), especially rectal tumours, are diagnosed with increased frequency due to the widespread use of colonoscopy, including screening examinations. It is important to constantly update and promote the principles of optimal diagnostics and treatment of these neoplasms. Based on the latest literature and arrangements made at the working meeting of the Polish Network of Neuroendocrine Tumours (June 2021), this paper includes updated and supplemented data and guidelines for the management of CRNEN originally published in Endokrynologia Polska 2017; 68: 250-260.

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczęściej pierwszą manifestacją ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies - everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.

After another meeting of experts of the Polish Network of Neuroendocrine Tumours, updated recommendations for the management of patients with gastric and duodenal neuroendocrine neoplasms, including gastrinoma, have been issued. As before, the epidemiology, pathogenesis and clinical symptoms of these neoplasms have been discussed, as well as the principles of diagnostic procedures, including biochemical and histopathological diagnostics and tumour localisation, highlighting the changes introduced in the recommendations. Updated principles of therapeutic management have also been presented, including endoscopic and surgical treatment, and the options of pharmacological and radioisotope treatment. The importance of monitoring patients with gastric and duodenal NENs, including gastrinoma, has also been emphasised.

In this paper, we present the current guidelines for the diagnostics and management of pancreatic neuroendocrine neoplasms (PanNENs) developed by Polish experts providing care for these patients in everyday clinical practice. In oncological diagnostics, in addition to biochemical tests, molecular identification with the use of NETest liquid biopsy and circulating microRNAs is gaining importance. Both anatomical and functional examinations (including new radiopharmaceuticals) are used in imaging diagnostics. Histopathological diagnosis along with immunohistochemical examination still constitute the basis for therapeutic decisions. Whenever possible, surgical procedure is the treatment of choice. Pharmacological management including biotherapy, radioisotope therapy, targeted molecular therapy and chemotherapy are important methods of systemic therapy. Treatment of PanNENs requires a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.A total of 10,172 cases were analysed. Recipient age65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p 0.05) between groups.Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.

Cold ischemia time (CIT) is one of the most significant variables affecting graft survival after liver transplantation. The aim of this study was to identify other predictors of worse graft survival depending on the duration of cold ischemia.This retrospective cohort study included data of liver transplant recipients and donors in the period from 2014 to 2019. A total of 724 patients were analyzed after excluding retransplatations and urgent operations. Using receiver operating characteristic analysis, we identified CIT value which divides into 2 clinically different subgroups with respect to 5-year graft loss. Within those 2 subgroups, we performed Cox proportional hazard analysis with time to graft loss as endpoint.The optimal cut-off point for CIT was identified as 496 minutes. Model of end-stage liver disease score, recipient body mass index, and donor sodium concentration showed no significant effect on time to graft loss in either subgroup. For 3 factors we observed a significant effect on time to graft loss in subgroup CIT ≥496 min: transfused red cell concentrate units (hazard ratio [HR] 1.05; 95% confidence interval [CI] 1.00-1.09; P = .02), transfused fresh frozen plasma units (HR 1.04; 95% CI 1.00-1.08; P = .08), and a recipient age of60 years (HR 1.81; 95% CI 1.10-2.98; P = .02).Predictive ability of well-known risk factors for worse outcomes after liver transplantation depend on the length of cold ischemia.

Background & Aims: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. Methods: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. Results: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14–24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p

To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.

Introduction: Correct surgical technique and perioperative care are two factors that can reduce the number of complications, improve treatment outcomes and shorten the length of hospital stay. The introduction of enhanced recovery protocols has changed the approach to patient care in some centers. However, there are significant differences among centers, and in some the standard of care has remained unchanged.Aim: the goal of the panel was to develop recommendations for modern perioperative care in accordance with current medical knowledge in order to reduce the number of complications associated with surgical treatment. An additional goal was to optimize and standardize perioperative care among Polish centers.Materials and methods: the development of these recommendations was based on a review of the available literature from the PubMed, Medline and Cochrane Library databases from January 1, 1985 to March 31, 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and were assessed using the Delphi method.Results and conclusions: 34 recommendations for perioperative care were presented. They cover aspects of pre-, intra- and post-operative care. Implementation of the presented rules allows to improve the results of surgical treatment.

Introduction. Hilar cholangiocarcinoma (HC) is the tumor that requires multidisciplinary approach and treatment. The 3- and 5- year survivals of HC patients treated with surgery and palliative methods were evaluated in the study. Material and methods. A study covered 368 patients treated between 2000–2014. Of them, 137 patients were categorized for surgery (RT group), and 231 for palliative treatment (PT group). The overall 3- and 5- year survivals were determined by the log rank test. Cox hazard regression model revealed the relative prognostic factors. Results. The 3- and 5- year survival rates accounted for 38% and 21% after surgery, but 13% and 0 after palliative treatment (p < 0.0001). Radical tumor resection, negative lymph nodes, and early tumor T stage were the factors conducive to survival. Conclusions. Surgery, if the radical tumor resection is possible, offers a chance for long-term survival. The positive effects of surgery treatment are lost against most of the majority of palliative patients

Background. The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. Methods. Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. Results. European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). Conclusions. An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.

Background Obesity increases and surgical weight reduction decreases the risk of atrial fibrillation (AF) and heart failure (HF). We hypothesized that surgically induced weight loss may favorably affect left atrial (LA) mechanical function measured by longitudinal strain, which has recently emerged as an independent imaging biomarker of increased AF and HF risk. Methods We retrospectively evaluated echocardiograms performed before and 12.2 ± 2.2 months after bariatric surgery in 65 patients with severe obesity (mean age 39 [36; 47] years, 72% of females) with no known cardiac disease or arrhythmia. The LA mechanical function was measured by the longitudinal strain using the semi-automatic speckle tracking method. Results After surgery, body mass index decreased from 43.72 ± 4.34 to 30.04 ± 4.33 kg/m2. We observed a significant improvement in all components of the LA strain. LA reservoir strain (LASR) and LA conduit strain (LASCD) significantly increased (35.7% vs 38.95%, p = 0.0005 and − 19.6% vs − 24.4%, p p = 0.0075). There was a significant correlation between an increase in LASR and LASCD and the improvement in parameters of left ventricular diastolic and longitudinal systolic function (increase in E’ and MAPSE). Another significant correlation was identified between the decrease in LASCT and an improvement in LA function (decrease in A’). Conclusions The left atrial mechanical function improves after bariatric surgery. It is partially explained by the beneficial effect of weight reduction on the left ventricular diastolic and longitudinal systolic function. This effect may contribute to decreased risk of AF and HF after bariatric surgery. Graphical abstract

OBJECTIVE To compare the early results of mass and layered closure of upper abdominal transverse incisions. SUMMARY OF BACKGROUND DATA Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. METHODS This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). RESULTS A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P

Nonalcoholic fatty liver disease (NAFLD) is a common liver abnormality, but its non-invasive diagnosis in patients with severe obesity remains difficult.To investigate the usefulness of the ultrasound (US) based hepatorenal index (HRI) technique, and two biomarker-based methods, including the hepatic steatosis index (HSI) and NAFLD logit score for the diagnosis of NAFLD in subjects referred for the bariatric surgery.162 subjects, 106 with NAFLD, admitted for the bariatric surgery participated in the study. Fat fraction level and the presence of NAFLD were determined using surgical liver biopsy. Each patient underwent liver US examination and blood tests to determine the HRI, HSI and NAFLD logit score.For the NAFLD diagnosis, the HRI, HSI and NAFLD logit score techniques achieved areas under the receiver operating characteristic curves of 0.879, 0.577 and 0.825, respectively. The Spearman's correlation coefficients between the liver fat fraction values and the HRI, HSI and NAFLD logit score were equal to 0.695, 0.215 and 0.595, respectively. The optimal cut-off values for the NAFLD diagnosis for the HRI, HSI and NAFLD logit score were equal to 1.12, 56.1 and 0.59, and significantly differed from the cut-off values reported for the general population in the literature.Our study confirms the usefulness of only two out of three techniques, the HRI and the NAFLD logit score for the diagnosis of NAFLD in patients with severe obesity. Methods designed for the general population require different cut-off values to achieve accurate performance in severe obesity.

Purpose Treatment response following transarterial chemoembolization (TACE) is frequently evaluated with Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm, but its association with patients’ outcomes is not supported in the literature. The purpose of this study was to provide such data. Methods A retrospective analysis of 99 TACE patients with stage A/B hepatocellular carcinoma according to Barcelona-Clinic Liver Cancer staging system was performed. Two radiologists assessed LR-TR, while a third radiologist re-assessed divergent results. Overall survival (OS) and time to disease progression (TTP) were the primary endpoints of the study, while the Cox proportional hazard model was used for outcome analyses. Results Interobserver agreement was substantial between the two readers with κ = 0.69 (95% CI 0.58–0.81). The median OS in viable, equivocal, and non-viable groups were 27, 27, and 73 months, respectively (p p = 0.97), while equivocal response remained statistically significant (HR 3.52. [95% CI 1.27–9.71], p = 0.015). No significant association was noted when viable and equivocal groups were analyzed in aggregate (HR 1.03 [95% CI 0.4–2.4], p = 0.96). The median TTP did not differ between non-viable and viable groups (23 vs 18 months, respectively; p = 0.98). None of the analyzed predictors was associated with TTP. Conclusion Initial LR-TR response was not an independent predictor for OS nor TTP. The preliminary results suggest the necessity for more aggressive management of equivocal patients.

Perioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

Background Orthotopic liver transplantation (LT) is a technically complex surgical procedure associated with a major risk of hemodynamic instability and metabolic derangement, especially in patients with coexisting renal dysfunction. Some centers have applied intraoperative renal replacement therapy (ioRRT) to support patients with preoperative renal failure and prevent critical complications. Although there is a strong theoretical rationale for this treatment, there remains a paucity of definite data demonstrating its benefits. Methods This was a retrospective observational study of all adult patients undergoing intraoperative dialysis in our center from January 2010 till December 2016. Results The study group consisted of 88 patients with a mean MELD score of 31.4. Six patients underwent simultaneous liver and kidney transplantation. Forty-four (50%) recipients were admitted to the intensive care unit before transplantation, and 19 (21.6%) needed mechanical ventilation. Twenty-eight (31.8%) of the procedures were retransplantations, and 40 (45.4%) patients had been undergoing renal replacement therapy before LT. The mean preoperative serum creatinine was 2.82 ± 1.13 mg/dL. The majority of patients (54.5%) was operated on using the veno-venous bypass technique. The mean arterial blood pH and potassium levels after reperfusion were 7.2 ± 0.12 and 4.04 ± 0.95 mmol/L, respectively. Postreperfusion syndrome (PRS) occurred in 11 (13.9%) patients in whom dialysis started at least 15 minutes before reperfusion. Dialysis circuit clotting occurred in 9.1% of cases. There were no other adverse events of ioRRT. Conclusion Our data suggests that intraoperative dialysis in severely ill patients with a high MELD score is safe and effective. Lower than expected PRS occurrence needs to be confirmed in a study with a control group.

Background Selected patients with unresectable perihilar cholangiocarcinoma (p-CCA) are now considered as candidates for liver transplant, provided they fulfill a strict perioperative treatment and staging protocol. The aim of this study was to examine the outcomes of patients after liver transplant with incidental p-CCA found in the liver explants. Methods A cohort of 10 patients with incidental p-CCA after liver transplant in the period between 1994 and 2019 was included in this retrospective analysis. All patients with this diagnosis were scheduled for transplant because of primary sclerosing cholangitis. The primary and secondary endpoints comprised patient’s death and tumor recurrence, respectively, assessed over a 5-year postoperative period. Results Patient median age was 35 years (range, 32-42 years). Median size of the tumor was 3.0 cm (range, 2.5-4.0 cm). Five patients (50%) had metastases to local lymph nodes. Overall survival was 100%, 37.5%, and 18.8% after the first, third, and fifth postoperative year, respectively, with median survival of 21 months. Patient age (P = .827), R1 resection status (P = .144), tumor diameter (P = .432), and presence of lymph node metastases (P = .663) were not significantly associated with overall survival. Recurrence-free survival was 60.0% after the first postoperative year and 22.5% after the third and fifth postoperative years, with median recurrence-free survival of 13.6 months. No significant predictors of tumor recurrence were found. Conclusions Incidental p-CCA in patients with primary sclerosing cholangitis undergoing liver transplant is associated with universally very high risk of postoperative tumor recurrence and short expected survival.

Purpose Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [68Ga]Ga-PSMA-11 in HCC and its impact on patient management. Methods Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [68Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. Results No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [68Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUVmax) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [68Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. Conclusion [68Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1normal " (N = 129), T cell-mediated rejection (TCMR) "R2TCMR " (N = 37), early injury "R3injury " (N = 61), and fibrosis "R4late " (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR , R3injury , and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.

Background Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. Methods Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. Results Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. Conclusions EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

Background: Bile duct injury complicates patients’ lives, despite the subsequent repair. Repairing the injury must restore continuity of the bile tree and bring the patient into a state of cure referred to as “patency”. Actuarial primary or actuarial secondary patency rates, depending on whether the patient underwent primary or secondary repair of injury, are proposed to be a proper metric in evaluating outcomes. This study was undertaken to assess outcomes of 669 patients with bile duct injuries Strasberg D and E type referred to the department from public surgical wards between 1990 and 2020. In 442 patients, no attempt was made to repair prior to a referral, and in 227 an attempt to repair was made which failed. Methods: Observations were summarized on December 31st, 2020. The retrospective analysis included: primary patency attained (Grade A result), secondary patency attained (Grade C result), patency loss, and actuarial patency rates of the bile tree at 2, 5, and 10 years. Results: Twenty-five (3.7%) patients died after repair surgery. Actuarial patency rates at 2, 5, and 10 years of follow-up were 93%, 88%, and 74% or 86%, 75%, and 55% in patients attaining Grade A and Grade C outcomes, respectively (p < 0.001). Conclusion: Bile duct injury stands out as a surgical challenge, requiring specialized management at a referral center. Improper proceeding after an injury is the factor leading to faster loss of anastomotic patency.

Continuous progress in the diagnostics and treatment of neuroendocrine neoplasms (NENs), the emerging results of new clinical trials, and the new guidelines issued by medical societies have prompted experts from the Polish Network of Neuroendocrine Tumours to update the 2017 recommendations regarding the management of neuroendocrine neoplasms. This article presents the general recommendations for the management of NENs, resulting from the findings of the experts participating in the Fourth Round Table Conference, entitled "Polish Guidelines for the Diagnostics and Treatment of Neuroendocrine Neoplasms of the gastrointestinal tract, Żelechów, June 2021". Drawing from the extensive experience of centres treating these cancers, we hope that we have managed to formulate the optimal method of treating patients with NENs, applying the latest reports and achievements in the field of medicine, which can be effectively implemented in our country. The respective parts of this work present the approach to the management of: NENs of the stomach and duodenum (including gastrinoma), pancreas, small intestine, and appendix, as well as large intestine.

Early liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival.This retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival.The cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P.001).The early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.

Simultaneous liver and kidney transplants (SLKT) represent 1.1% of all liver transplants in Poland. Patients undergoing SLKT experience a longer operation time and concurrent kidney dysfunction may aggravate metabolic derangement associated with the procedure. The benefits of intraoperative dialysis (ioHD) in these patients have not been determined.A retrospective observational study of all adult patients undergoing SLKT in our center from January 2009 till December 2016.Study group consisted of 10 patients with End-Stage Kidney Disease (0.9% of all liver transplants): 6 patients treated with ioHD during SLKT (group 1) and 4 patients managed conservatively (group 2). All recipients were on chronic dialysis. The mean calculated Model for End-Stage Liver Disease score was 21 ± 0.9 in group 1 and 30 ± 9.5 in group 2 (P = .009). The mean preoperative serum potassium was 4.7 ± 0,6 mmol/L in group 1 and 3.97 ± 1,02 in group 2. Intraoperative serum potassium levels were comparable between the groups, but the maximum lactate and minimum bicarbonate levels were significantly worse in group 2. Postreperfusion syndrome occurred in no patient. Dialysis circuit clotting occurred in 50% of ioHD. Six patients (2 in group 1) required renal replacement therapy after SLKT; no patient was on dialysis on discharge. Three patients died within 1 year after surgery (2 in group 2).No patient developed intraoperative hyperkalemia or postreperfusion syndrome. We observed a high frequency of circuit system clotting during ioHD. Clinical benefits of intraoperative hemodialysis during SLKT need to be determined in a larger study.

This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival.This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss.The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P.001 and 2.23; 95% CI 1.55-3.19; P.001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was ≥1030 and ≥3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P.001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P.001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P = .924 and P = .629, respectively).Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.

Early allograft dysfunction (EAD) had been established as a useful tool to asses graft and patient survival after liver transplant. We wanted to evaluate effect of EAD components on early graft survival.This retrospective study included 264 patients with EAD after liver transplant in the period between 2015 and 2019. The patients with retransplants were excluded from analyses. The EAD was determined with Olthoff criteria. The logistic regression model was used for analyses. The 90-day graft survival was set as a primary outcome measure.The main indications for transplant in the analyzed group were hepatitis C virus infection (53 patients, 20.1%), hepatitis B infection (22, 8.3%), primary sclerosing cholangitis (28, 10.1%), and alcoholic liver disease (62, 23.5%), with a median model for end-stage liver disease score of 13.5 points. The 90-day graft loss occurred in 51 patients (19.3%). Each of the components used in EAD diagnosis was found to be correlated with 90-day graft loss. The bilirubin concentration on day 7 (odds ratio [OR], 3.1; 95% CI, 1.4-6.7; P.001), international normalized ratio on day 7 (OR, 179; 95% CI, 39-815; P.001), and the natural logarithm of alanine aminotransferase (OR, 3.1; 95% CI, 1.6-6.4) and aspartate aminotransferase (OR, 1.4; 95% CI, 0.4-4.9) predicted 90-day graft loss.In patients with EAD, international normalized ratio ≥ 1.6 on day 7 was the strongest predictor of early graft-loss among all EAD components.

According to the 'multiple-hit' hypothesis, several factors can act simultaneously in nonalcoholic fatty liver disease (NAFLD) progression. Increased nitro-oxidative (nitroso-oxidative) stress may be considered one of the main contributors involved in the development and risk of NAFLD progression to nonalcoholic steatohepatitis (NASH) characterized by inflammation and fibrosis. Moreover, it has been repeatedly postulated that mitochondrial abnormalities are closely related to the development and progression of liver steatosis and NAFLD pathogenesis. However, it is difficult to determine with certainty whether mitochondrial dysfunction or oxidative stress are primary events or a simple consequence of NAFLD development. On the one hand, increasing lipid accumulation in hepatocytes could cause a wide range of effects from mild to severe mitochondrial damage with a negative impact on cell fate. This can start the cascade of events, including an increase of cellular reactive nitrogen species (RNS) and reactive oxygen species (ROS) production that promotes disease progression from simple steatosis to more severe NAFLD stages. On the other hand, progressing mitochondrial bioenergetic catastrophe and oxidative stress manifestation could be considered accompanying events in the vast spectrum of abnormalities observed during the transition from NAFL to NASH and cirrhosis. This review updates our current understanding of NAFLD pathogenesis and clarifies whether mitochondrial dysfunction and ROS/RNS are culprits or bystanders of NAFLD progression.