[Liver transplantation in viral and autoimmune liver diseases]. / Lebertransplantation bei viralen und autoimmunen Lebererkrankungen.

BACKGROUND: Despite substantial progress in the management of viral and autoimmune liver diseases, these entities remain relevant indications for liver transplantation. AIMS: To provide an overview of the current knowledge regarding the management of viral and autoimmune liver diseases before and after liver transplantation. MATERIALS AND METHODS: Selective literature search, including current guidelines and abstracts of key scientific meetings. RESULTS AND DISCUSSION: Viral and autoimmune liver disease can be effectively treated in most cases, which has resulted in an overall decline in liver transplantations for this indication group. However, hepatitis D infection and primary sclerosing cholangitis remain difficult-to-treat liver diseases in some patients and may progress to end-stage liver disease despite best possible management. Viral or autoimmune hepatitis can lead to fulminant liver failure requiring emergency liver transplantation. In patients who are transplanted due to viral or autoimmune liver disease, specific measures to prevent recurrence of these diseases after transplantation are mandatory. In view of effective treatment modalities for chronic hepatitis B and C, even liver grafts from donors infected with these viruses can be considered for liver transplantation under certain circumstances.

Role of PAR1 -506 deletion/insertion polymorphism in primary sclerosing cholangitis.

AIM: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra- and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin-6 (IL-6)-dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL-6/STAT3 pathway was shown to be regulated by protease-activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 -506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated. METHODS: Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (-506 Del/Ins -13 bp). Results were correlated with clinical characteristics and transplant-free survival. RESULTS: The frequency of PAR1 -506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 -506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45-2.79). Patients with PSC carrying the PAR1 -506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant-free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076). CONCLUSIONS: Our study shows that PAR1 -506 Ins is significantly more frequent in people with PSC. As PAR1 -506 Ins allele carriers tended to have a shorter transplant-free survival, PAR1 might play a role in the development and course of PSC.

Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis.

Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.

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.

Myosteatosis independently predicts transplant-free survival in patients with primary sclerosing cholangitis.

BACKGROUND: Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with liver transplantation (LT) as the only curative therapy. Some regions use body-weight-loss as standard-exception criteria for organ allocation but data on the impact of body composition on survival of patients with PSC is scarce. METHODS: Abdominal MRI of PSC patients were quantitatively analyzed for intramuscular fat fraction (IMFF) as surrogate of myosteatosis. Clinical and laboratory data were retrieved from patient records. Primary outcome was transplant-free survival (TFS). RESULTS: 116 PSC patients were included. Median age was 38 (18-71) years with 74 (64%) male patients. 15 (13%) patients had significant weigh loss. IMFF was significantly associated with survival. Multivariate regression analysis showed IMFF ≥ 15% as independent predictor for TFS (p = 0.032, HR 3.215 CI 1.104-9.366), but not significant weight loss (p = 0.618). CONCLUSION: IMFF is independently associated with TFS in patients with PSC and may identify patients with more urgent need for LT. NCT03584204.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

IL-6-Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with periductal inflammation and fibrosis. Genetic studies suggest inflammatory cytokines and IL-6-dependent activation of transcription factor STAT3 as pivotal steps in PSC pathogenesis. However, details of inflammatory regulation remain unclear. METHODS: We recruited 50 patients with PSC (36 with inflammatory bowel disease, 14 without inflammatory bowel disease), 12 patients with autoimmune hepatitis, and 36 healthy controls to measure cytokines in the serum, bile, and immune cell supernatant using bead-based immunoassays and flow cytometry and immunohistochemistry to analyze phosphorylation of STATs in immune cells. Finally, we analyzed cytokines and STAT3 phosphorylation of T cells in the presence of JAK1/2 inhibitors. RESULTS: In PSC, IL-6 specifically triggered phosphorylation of STAT3 in CD4 + T cells and lead to enhanced production of interferon (IFN) gamma and interleukin (IL)-17A. Phospho-STAT3-positive CD4 + T cells correlated with systemic inflammation (C-reactive protein serum levels). Combination of immunohistology and flow cytometry indicated that phospho-STAT3-positive cells were enriched in the peribiliary liver stroma and represented CD4 + T cells with prominent production of IFN gamma and IL-17A. JAK1/2 inhibitors blocked STAT3 phosphorylation and production of IFN gamma and IL-6, whereas IL-17A was apparently resistant to this inhibition. DISCUSSION: Our results demonstrate systemic and local activation of the IL-6/STAT3 pathway in PSC. Resistance of IL-17A to STAT3-targeted inhibition points to a more complex immune dysregulation beyond STAT3 activation.

Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort.

BACKGROUND: Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs). METHODS: This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence. RESULTS: Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months). CONCLUSIONS: Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.

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.

Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

Management of esophageal perforations in infants by endoscopic vacuum therapy: a single center case series.

BACKGROUND: Endoscopic vacuum therapy (EVT) has become a standard treatment method for esophageal perforations in adults. However, experience with EVT in infants is scarce. In this retrospective case series, we report on four very young infants who were successfully treated with EVT for esophageal perforations of different etiology. METHODS: Four infants were diagnosed with esophageal perforations on day 7, 32, 35 and 159 of life, respectively. The youngest one was prematurely born in the 31st week of pregnancy weighing 980 g only. Three infants had perforations due to foreign body insertion (nasogastric tube or pulling through of percutaneous endoscopic gastrostomy (PEG) tube through the esophagus). One child had an anastomotic dehiscence after Foker's surgery for atresia. In three children EVT was applied as first-line therapy for perforation, in one child EVT was a rescue therapy due to persisting leakage after surgical closure involving thoracotomy. Depending on the esophageal diameter, either an open-pore drainage film or polyurethane sponge was attached to a single-lumen 8 Fr suction catheter, endoscopically (or fluoroscopically by wire-guidance) placed into the esophagus (intraluminal EVT) and supplied with continuous negative pressure (ranging between 75 and 150 mmHg). The EVT system was exchanged twice per week. RESULTS: Complete closure of the perforation/leakage could be achieved in all four infants (100%) after 22 days of continuous EVT (median value; range 7-39) and 4.5 EVT exchanges (median value; range 1-12). No serious adverse events occurred. CONCLUSIONS: EVT is an effective and safe addition to our therapeutic armamentarium in the management of esophageal perforations irrespective of its etiology. Here we prove the feasibility of EVT even in very young infants. The use of an extra thin vacuum open-pore drainage film is helpful to cope with the small esophageal diameter. EVT settings and exchange rates similar to those known from adult treatment were used.

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.

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.

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.

Management of post-operative pancreatic fistulas following Longmire-Traverso pylorus-preserving pancreatoduodenectomy by endoscopic vacuum-assisted closure therapy.

BACKGROUND: Pylorus-preserving pancreatoduodenectomy (PPPD) with pancreatogastrostomy is a standard surgical procedure for pancreatic head tumors, duodenal tumors and distal cholangiocarcinomas. Post-operative pancreatic fistulas (POPF) are a major complication causing relevant morbidity and mortality. Endoscopic vacuum therapy (EVT) has become a widely used method for the treatment of intestinal perforations and leakages. Here we report on a pilot single center series of 8 POPF cases specifically caused by dehiscences of the pancreatogastric anastomosis (PGD), successfully managed by EVT. METHODS: We included all patients with PGD after PPPD, who were treated with EVT between 07/2017 and 08/2020. For EVT a vacuum drainage film (EVT film) or open-pore polyurethane foam sponge (EVT sponge) was fixed to a 14Fr or 16Fr suction catheter and placed endoscopically within the PGD for intracavitary EVT with continuous suction between - 100 and - 150 mmHg. The EVT film/sponge was exchanged twice per week. EVT was discontinued when the PGD was sufficiently healed. RESULTS: PGD closure was achieved in 7 of 8 patients after a mean EVT time of 16 days (range 8-38) and 3 EVT film/sponge exchanges (range 1-9). One patient died on day 18 after PPPD from acute hemorrhagic shock, unlikely related to EVT, before effectiveness of EVT could be fully achieved. There were no adverse events directly attributable to EVT. CONCLUSIONS: EVT could be an effective and safe addition to our therapeutic armamentarium in the management of POPF with PGD. Unless prospective comparative studies are available, EVT as minimally invasive therapeutic alternative should be considered individually by an interdisciplinary team involving endoscopists, surgeons and radiologists.

A Combined TLR7/TLR9/GATA3 Score Can Predict Prognosis in Biliary Tract Cancer.

Biliary tract cancer (BTC) refers to a heterogenous group of epithelial malignancies arising along the biliary tree. The highly aggressive nature combined with its silent presentation contribute to the dismal prognosis of this tumor. Tumor-infiltrating immune cells (TIICs) are frequently present in BTC and there is growing evidence regarding their role as therapeutic targets. In this study, we analyzed the immune cell infiltration in BTC and developed a promising immune signature score to predict prognosis in BTC. Immunohistochemistry (IHC) was carried out on tissue microarray sections from 45 patients with resectable cholangiocarcinoma for the detection of 6-sulfoLacNAc+ monocytes (slanMo), BDCA-2+ plasmacytoid dendritic cells (pDC), CD8+ or CD4+T-lymphocytes, CD103+ cells, GATA3+ cells, Toll-like receptor (TLR) 3, 7 and 9-expressing cells as well as programmed cell death protein 1 and programmed cell death ligand 1 positive cells. Data from the IHC staining were analyzed and correlated with clinicopathological and survival data. High expression of TLR7, TLR9, and GATA3 was associated with improved overall survival (OS, Log-rank p < 0.05). In addition, TLR9 was associated with better disease-free survival (Log-rank p < 0.05). In the multivariate Cox proportional-hazards model for OS, the TLR/TLR9/GATA3 score was found to be an independent prognostic factor for OS ("Score 2" vs. "Score 0": HR 11.17 95% CI 2.27-54.95, p < 0.01).

Ruxolitinib for treatment of polycythemia vera and myelofibrosis in patients after liver transplantation.

Although ruxolitinib contributes to immunomodulation and can lead to severe infections, it seems a feasible treatment strategy for patients with polycythemia vera and myelofibrosis after liver transplantation.