Effect of Extracerebral Contamination on Near-infrared Spectroscopy as Revealed during Organ Donation: A Prospective Observational Study in Brain-dead Organ Donors.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been utilized widely in anesthesia and intensive care to monitor regional cerebral oxygen saturation (rScO2). A normal oxygenation of extracerebral tissues may overlay and thereby mask cerebral desaturations, a phenomenon known as extracerebral contamination. The authors investigated the effect of a cessation of extracerebral tissue perfusion on rScO2 in patients with anoxic brains. METHODS: In a single-center, prospective, observational study, brain-dead adults undergoing organ donation were investigated. rScO2 was measured bifrontally using the INVOS 5100C/7100 as well as the ForeSight Elite system. To achieve an efficient conservation of organs and to prevent a redistribution of the perfusion fluid to other tissues, the aorta was clamped before organ perfusion. rScO2 was monitored until at least 40 min after aortic clamping. The primary outcome was the amount of extracerebral contamination as quantified by the absolute decrease in rScO2 after aortic clamping. Secondary outcomes were the absolute rScO2 values obtained before and after clamping. RESULTS: Twelve organ donors were included. Aortic clamping resulted in a significantly (P < 0.001) greater absolute decrease in rScO2 when comparing the INVOS (43.0 ± 9.5%) to the ForeSight (27.8 ± 7.1%) monitor. Before aortic clamping, near-normal rScO2 values were obtained by the INVOS (63.8 ± 6.2%) and the ForeSight monitor (67.7 ± 6.5%). The rScO2 significantly (P < 0.001) dropped to 20.8 ± 7.8% (INVOS) and 39.9 ± 8.1% (ForeSight) 30 min after clamping, i.e., a condition of a desaturation of both extracerebral and cerebral tissues. CONCLUSIONS: The abrupt end of extracerebral contamination, caused by aortic clamping, affected both NIRS monitors to a considerable extent. Both the INVOS and the ForeSight monitor were unable to detect severe cerebral hypoxia or anoxia under conditions of normal extracerebral oxygenation. While both NIRS monitors may guide measures to optimize arterial oxygen supply to the head, they should not be used with the intention to detect isolated cerebral desaturations.

Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

BACKGROUND & AIMS: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepatocellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma. METHODS: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein. RESULTS: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011). CONCLUSION: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.

Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.

Background and aims: Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT. Method: All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared. Results: Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group. Conclusion: Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.

Identification and characterization of a hepatic IL-13-producing ILC3-like population potentially involved in liver fibrosis.

BACKGROUND AND AIMS: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers. APPROACH AND RESULTS: A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an "unconventional" ILC3-like cell represented the major IL-13-producing liver ILC subset. IL-13 + ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1-expressing ILC precursors as the potential progenitor of hepatic IL-13 + ILC3-like cells. CONCLUSIONS: We identified a formerly undescribed subset of IL-13-producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.

Surgical site infections are independently associated with the development of postoperative acute-on-chronic liver failure in liver cirrhosis.

Acute-on-chronic liver failure (ACLF) is associated with organ failure and high short-term mortality. Bacterial infections and surgery have been reported as major precipitants for ACLF. However, detailed characterization of postoperative infections after elective surgery in patients with liver cirrhosis and their impact on the development of ACLF have not been investigated yet. A total of 235 patients with cirrhosis without ACLF and proven bacterial infections undergoing elective surgery were included. The primary end point was the development of ACLF within 28 days after surgery, and secondary end points were infection development within 28 days and 3-month ACLF-related mortality. Cox regression analysis was used for identification of risk factors associated with ACLF development, infection development, and mortality. A total of 86 patients (37%) developed ACLF within 28 days after surgery. Patients with new postoperative infections had significantly higher rates of associated ACLF episodes within 28 days (51% vs. 24%, p < 0.001) and higher 3-month mortality ( p < 0.05) than patients without postoperative infections. New infections after surgery [HR: 2.43 (1.59-3.71), p < 0.001] and organ/space surgical site infections [HR: 2.46 (1.26-4.80), p = 0.01] in particular were independent risk factors associated with ACLF development 28 days after surgery. Extensive procedures were associated with the development of new postoperative infection episodes within 28 days. Infections treated with initial appropriate empirical antibiotic strategies showed significantly improved survival. This study characterizes and identifies bacterial infections in general and organ/space surgical site infection in particular as precipitating events for the development of ACLF after elective surgery in patients with cirrhosis. Postoperative ACLF combined with infections leads to higher postoperative short-term mortality than each condition separately, especially in extensive procedures. Interdisciplinary care, early identification of postoperative ACLF and infections, and adequate, broad, and early treatment strategies are needed to improve postoperative outcome.

Clinically Relevant Pancreatic Fistula after Pancreaticoduodenectomy: How We Do It.

(1) Background: This study's goals were to investigate possible risk factors for clinically relevant postoperative pancreatic fistula (POPF) grade B/C according to the updated definitions of the International Study Group of Pancreatic Surgery and to analyze possible treatment strategies; (2) Methods: Between 2017 and 2021, 200 patients were analyzed regarding the development of POPF grade B/C with an emphasis on postoperative outcome and treatment strategies; (3) Results: POPF grade B/C was observed in 39 patients (19.5%). These patients were younger, mainly male, had fewer comorbidities and showed a higher body mass index. Also, they had lower CA-19 levels, a smaller tumor size and softer pancreatic parenchyma. They experienced a worse outcome without affecting the overall mortality rate (10% vs. 6%, p = 0.481), however, this lead to a prolonged postoperative stay (28 (32-36) d vs. 20 (15-28) d, p ≤ 0.001). The majority of patients with POPF grade B/C were able to receive conservative treatment, followed by drainage placement, endoscopic vacuum-assisted therapy (EVT) and surgery. Conservative treatment resulted in a shorter length of the postoperative stay (24 (22-28) d vs. 34 (26-43) d, p = 0.012); (4) Conclusions: Patients developing POPF grade B/C had a worse outcome; however, this did not affect the overall mortality rate. The majority of the patients were able to receive conservative treatment, resulting in a shorter length of their hospital stay.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

PURPOSE: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations. METHODS: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified. RESULTS: Patients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality. CONCLUSION: With respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly.

Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ß1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

Alveolar Echinococcosis in a Patient with Presumed Autoimmune Hepatitis and Primary Sclerosing Cholangitis: An Unexpected Finding after Liver Transplantation.

Primary sclerosing cholangitis is an important reason for liver transplantation. Hepatic alveolar echinococcosis (AE) is caused by Echinococcus multilocularis and presents characteristic calcified conglomerates detected by ultrasound or computed tomography scan of the liver. Symptoms of AE only occur after a long period of infection when cholestasis or cholangitis becomes apparent. Here, we report on a patient with presumed autoimmune hepatitis and primary sclerosing cholangitis. After liver transplantation, alveolar echinococcosis was diagnosed in the liver explant.

Persisting dental foci increase the risk for bacterial infections before and after liver transplant.

BACKGROUND: Patients awaiting liver transplant are usually assessed for presence of dental foci to prevent bacterial infection post-transplant, but evidence to support dental examination and treatment is limited. We investigated if treatment of dental foci decreased bacterial infections before and after transplant. METHODS: Patients transplanted at the university hospital of Bonn were retrospectively assessed for occurrence of bacterial infections before and after transplant according to presence and treatment of dental foci. RESULTS: 35/110 patients showed good oral health, 39/110 patients received dental care and 36/110 patients did not receive dental care despite poor oral health. Patients with alcohol-associated liver disease presented with the highest rate of dental foci. Bleeding complications due to oral care occurred in five patients with poor coagulation. After transplant, the number of infections per patient was higher in patients with poor oral health (2.9) compared to patients after dental care (1.9) or with good oral health (1.8) (p = .02), with streptococcal infections being more frequent in patients with poor oral health. Before transplant, bacterial infections, in particular bacteraemia and spontaneous bacterial peritonitis, were also more common in patients with untreated dental foci. Streptococci and Staphylococci were more often detected in patients with dental foci. Dental treatment was associated with a reduction in bacterial infections. CONCLUSION: Presence of dental foci is associated with an increased risk for bacterial infections not only after but also before liver transplant. Dental treatment might be a safe and effective procedure to mitigate this risk.

Operative Re-Intervention following Pancreatoduodenectomy: What Has Changed over the Last Decades.

Background: To investigate changes over the last decades in the management of postoperative complications following pancreatoduodenectomy (PD) with special emphasis on reoperations, their indications, and outcomes. Methods: 409 patients who underwent PD between 2008 and 2021 were retrospectively analyzed with respect to their need for reoperations (reoperation, n = 81, 19.8% vs. no reoperation, n = 328, 80.2%). The cohort was then compared to a second cohort comprising patients who underwent PD between 1989 and 2007 (n = 285). Results: 81 patients (19.8%) underwent reoperation. The main cause of reoperation was the dehiscence of pancreatogastrostomy (22.2%). Reoperation was associated with a longer duration of the index operation, more blood loss, and more erythrocyte concentrates being transfused. Patients who underwent reoperation showed more postoperative complications and a higher mortality rate (25% vs. 2%, p < 0.001). Compared to the earlier cohort, the observed increase in reoperations did not lead to increased mortality (5% vs. 6%, p = 353). Conclusions: The main cause for reoperation has changed over the last decades and was the dehiscence of pancreatogastrostomy. Associated with a leakage of pancreatic fluid and clinically relevant PF, it remains the most devastating complication following PD. Strategies for prevention and treatment, e.g., by endoscopic vacuum-assisted-closure therapy are of utmost importance.

Predictors of Morbidity and Mortality After Colorectal Surgery in Patients With Cirrhotic Liver Disease-A Retrospective Analysis of 54 Cases at a Tertiary Care Center.

Background: Despite various existing scores that predict morbidity and mortality of patients with cirrhotic liver disease (CLD), data on specific risk stratification of patients with CLD undergoing colorectal surgery (CRS) are rare. The aim of this study was to assess in-hospital morbidity and mortality of patients with liver cirrhosis scheduled for CRS, with specific focus on possible pitfalls of surgery in this special cohort. Methods: Between 1996 and 2018, 54 patients with CLD undergoing CRS were identified and included in this study cohort. Postoperative morbidity and mortality were assessed using the Clavien/Dindo (C/D) classification as well as by type of complication. Univariate and multivariate analyses were performed to analyze the predictive factors for increased postoperative morbidity. Results: Of the patients, 37% patients died during the procedure or postoperatively. Major complications were seen in 23.1% of patients (>C/D IIIb). Patients with Child B or C cirrhosis as well as patients undergoing emergency surgery experienced significantly more major complications (p = 0.04 and p = 0.023, respectively). The most common complications were bleeding requiring blood transfusion (51.1%) and cardiocirculatory instability due to bleeding or sepsis (44.4%). In 53.7% of patients, an anastomosis was created without a protective ostomy. Anastomotic leakage occurred in 20.7% of these patients. Multivariate analysis showed that a primary anastomosis without a protective ostomy was the strongest risk factor for major complications (p = 0.042). Discussion: Morbidity and mortality after CRS in patients with CLD remains high and is not only influenced by liver function but also by surgical variables. Considering the high rate of anastomotic leakage, creating a protective or definitive ostomy must be considered with regard to the underlying pathology, the extent of CLD, and the patient's condition. Moreover, our data suggest that surgery in these most fragile patients should be performed only in experienced centers with immediate contact to hepatologists and experts in hemostasis.

Delayed Gastric Emptying Does Not Influence Cancer-Specific Survival after Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD). The present study investigates the influence of delayed gastric emptying on cancer-specific survival after PD. METHODS: We included 267 patients who underwent PD between 2014 and 2021. They were analyzed regarding demographic factors, pre- and perioperative characteristics, surgical complications, and long-term survival. RESULTS: Patients with a higher Charlson Comorbidity Index (CCI) or pre-existing pulmonary disease suffered significantly more from DGE. When experiencing PPH, a prolonged hospital stay, or major overall complications (Clavien-Dindo °III-V) were more common in the DGE group. Tumor size over 3 cm negatively affected survival. CONCLUSIONS: DGE has no influence on long-term survival in PDAC patients, although it prolongs hospital stay.

Obesity Does Not Influence Delayed Gastric Emptying Following Pancreatoduodenectomy.

Background: The data about obesity on postoperative outcome after pancreatoduodenectomy (PD) are inconsistent, specifically in relation to gastric motility and delayed gastric emptying (DGE). Methods: Two hundred and eleven patients were included in the study and patients were retrospectively analyzed in respect to pre-existing obesity (obese patients having a body mass index (BMI) ≥ 30 kg/m2 vs. non-obese patients having a BMI < 30 kg/m2, n = 34, 16% vs. n = 177, 84%) in relation to demographic factors, comorbidities, intraoperative characteristics, mortality and postoperative complications with special emphasis on DGE. Results: Obese patients were more likely to develop clinically relevant pancreatic fistula grade B/C (p = 0.008) and intraabdominal abscess formations (p = 0.017). However, clinically relevant DGE grade B/C did not differ (p = 0.231) and, specifically, first day of solid food intake (p = 0.195), duration of intraoperative administered nasogastric tube (NGT) (p = 0.708), rate of re-insertion of NGT (0.123), total length of NGT (p = 0.471) or the need for parenteral nutrition (p = 0.815) were equally distributed. Moreover, mortality (p = 1.000) did not differ between the two groups. Conclusions: Obese patients do not show a higher mortality rate and are not at higher risk to develop DGE. We thus show that in our study, PD is feasible in the obese patient in regard to postoperative outcome with special emphasis on DGE.

Preoperative TIPS prevents the development of postoperative acute-on-chronic liver failure in patients with high CLIF-C AD score.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Recently, the role of surgery as a precipitating event for ACLF has been characterised. However, the impact of preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement on ACLF development in patients with cirrhosis undergoing surgery has not been investigated yet. METHODS: A total of 926 patients (363 with cirrhosis undergoing surgery and 563 patients with TIPS) were screened. Forty-five patients with preoperative TIPS (TIPS group) were 1:1 propensity matched to patients without preoperative TIPS (no-TIPS group). The primary endpoint was the development of ACLF within 28 and 90 days after surgery. The secondary endpoint was 1-year mortality. Results were confirmed by a differently 1:2 matched cohort (n = 176). RESULTS: Patients in the no-TIPS group had significantly higher rates of ACLF within 28 days (29 vs. 9%; p = 0.016) and 90 days (33 vs. 13%; p = 0.020) after surgery as well as significantly higher 1-year mortality (38 vs. 18%; p = 0.023) compared with those in the TIPS group. Surgery without preoperative TIPS and Chronic Liver Failure Consortium-Acute Decompensation (CLIF-C AD) score were independent predictors for 28- and 90-day ACLF development and 1-year mortality after surgery, especially in patients undergoing visceral surgery. In the no-TIPS group, a CLIF-C AD score of >45 could be identified as cut-off for patients at risk for postoperative ACLF development benefiting from TIPS. CONCLUSIONS: This study suggests that preoperative TIPS may result in lower rates of postoperative ACLF development especially in patients undergoing visceral surgery and with a CLIF-C AD score above 45. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is a syndrome that is associated with high short-term mortality. Surgical procedures are a known precipitating event for ACLF. This study investigates the role of preoperative insertion of a transjugular intrahepatic portosystemic shunt (TIPS) on postoperative mortality and ACLF development. Patients with TIPS insertion before a surgical procedure exhibit improved postoperative survival and lower rates of postoperative ACLF, especially in patients undergoing visceral surgery and with a high CLIF-C AD prognostic score. Thus, this study suggests preoperative TIPS insertion in those high-risk patients.

Impact of regular additional endobiliary radiofrequency ablation on survival of patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.

Prognosis of patients with advanced extrahepatic cholangiocarcinoma (eCCA) is poor. The current standard first-line treatment is systemic chemotherapy (CT) with gemcitabine and a platinum derivate. Additionally, endobiliary radiofrequency ablation (eRFA) can be applied to treat biliary obstructions. This study aimed to evaluate the additional benefit of scheduled regular eRFA in a real-life patient cohort with advanced extrahepatic cholangiocarcinoma under standard systemic CT. All patients with irresectable eCCA treated at University Hospital Bonn between 2010 and 2020 were eligible for inclusion. Patients were stratified according to treatment: standard CT (n = 26) vs. combination of eRFA with standard CT (n = 40). Overall survival (OS), progression free survival (PFS), feasibility and toxicity were retrospectively analyzed using univariate and multivariate approaches. Combined eRFA and CT resulted in significantly longer median OS (17.3 vs. 8.6 months, p = 0.004) and PFS (12.9 vs. 5.7 months, p = 0.045) compared to the CT only group. While groups did not differ regarding age, sex, tumor stage and chemotherapy treatment regimen, mean MELD was even higher (10.1 vs. 6.7, p = 0.015) in the eRFA + CT group. The survival benefit of concomitant eRFA was more evident in the subgroup with locally advanced tumors. Severe hematological toxicities (CTCAE grades 3 - 5) did not differ significantly between the groups. However, therapy-related cholangitis occurred more often in the combined treatment group (p = 0.031). Combination of eRFA and systemic CT was feasible, well-tolerated and could significantly prolong survival compared to standard CT alone. Thus, eRFA should be considered during therapeutic decision making in advanced eCCA.

Model for end-stage liver disease underestimates mortality of patients with acute-on-chronic liver failure waiting for liver transplantation.

BACKGROUND AND AIMS: Patients with acute-on-chronic liver failure (ACLF) show excess mortality in MELD-Na based organ allocation for liver transplantation (LT). Whether MELD-based allocation in the Eurotransplant region similarly underprioritizes ACLF patients is unknown. METHODS: 428 patients listed for LT from 01/2010 to 02/2021 at a tertiary center in Germany were screened and 209 patients included as derivation (n = 123) and validation cohort (n = 86). Competing risk analysis for waitlist mortality and LT as competing events was performed. RESULTS: 90-day waitlist mortality for patients with MELD < and ≥ 25 at baseline was 9% vs. 33%, respectively (p = 0.009). Competing risk analysis shows significantly higher 90-day waitlist mortality in patients listed with ACLF compared to those without ACLF (p = 0.021) in the low MELD stratum. Probability of LT was similar between the two groups (p = 0.91). In the high MELD group, 90-day waitlist mortality and rates of LT were not significantly different between patients with and without ACLF (31% vs. 20%, p = 0.55 and 59% vs. 60%, p = 0.72, respectively). Post-transplant survival was similar between patients with and without ACLF. This result was confirmed in the validation cohort. CONCLUSION: MELD-based organ allocation in the Eurotransplant region underestimates waitlist mortality in patients with ACLF in lower MELD ranges.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

First Line and Second Line Chemotherapy in Advanced Cholangiocarcinoma and Impact of Dose Reduction of Chemotherapy: A Retrospective Analysis.

OBJECTIVE: Prognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma. MATERIALS AND METHODS: This is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation. RESULTS: Fifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC. CONCLUSION: In our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.