Recurrent cholangitis in patients with a non-stenotic hepaticojejunostomy: incidence and risk factors.

BACKGROUND: Cholangitis is a well-known complication after hepaticojejunostomy (HJ), which is mainly caused by a stenotic anastomosis. However, the rate of cholangitis in patients with a non-stenotic (i.e. patent) HJ is unknown. We aimed to evaluate the incidence and risk factors of recurrent cholangitis in patients with a non-stenotic HJ. METHODS: This single-center retrospective cohort study included all consecutive patients who had undergone hepatobiliary or pancreatic (HPB) surgery requiring HJ (2015-2022). Primary outcome was recurrent non-stenotic cholangitis, risk factors for recurrent non-stenotic cholangitis were identified using logistic regression. RESULTS: Overall, 835 patients with a HJ were included of whom 31/698 (4.4%) patients developed recurrent cholangitis with a non-stenotic HJ during a median follow-up of 34 months (IQR 22-50) and 98/796 (12.3%) patients developed a symptomatic HJ stenosis. These 31 patients experienced 205 cholangitis episodes, median 7.0 (IQR 3.8-8.8) per patient, and 71/205 (34.6%) cholangitis episodes required hospitalization. Male sex (aOR 3.17 (95% CI: 1.34-7.49)) and benign disease (aOR 2.97, 95% CI 1.40-6.33) were identified as risk factors for recurrent cholangitis in non-stenotic HJ in both univariate and multivariable analysis. CONCLUSION: This study shows that 4% of patients developed recurrent cholangitis without an underlying HJ stenosis.

Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy : A comparison of benefits.

PURPOSE: The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). METHODS: The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V15Gy, V30Gy, V45Gy and Dmean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. RESULTS: Both IMPT and MRI-based target tailoring resulted in significant reductions in V15Gy, V30Gy, V45Gy and Dmean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V45Gy for bowel bag was >275 cm3 and >200 cm3, respectively, during standard IGART alone. CONCLUSIONS: In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity.

CD14 is associated with biliary stricture formation.

UNLABELLED: The pathogenesis of intrahepatic biliary stricture formation in patients with primary sclerosing cholangitis (PSC) or after liver transplantation (LTx) remains elusive. CD14 receptor signaling is a key mediator of the innate immune system; its common genetic variant is associated with alcoholic liver disease. PSC and LTx cohort patients and primary biliary cirrhosis (PBC) control patients were genotyped for the CD14 -260C>T (rs2569190) polymorphism, and genotypes were correlated with long-term clinical outcome. Biliary tissue, bile, and whole blood of PSC patients and healthy controls were screened for markers of the innate immune system and bacterial infection. In 121 PSC patients, the CD14 -260C>T genotype was associated with development of dominant bile duct strictures (P = 0.02). In 365 LTx patients, TT carriers (4.1%) were protected against the formation of nonanastomotic biliary strictures versus CC/CT patients (12.6%; P = 0.01). Chemokine ligand 8 (P = 0.04) and chemokine receptor 6 (P = 0.004) were up-regulated in biliary tissue of PSC patients with the TT versus the CC/CT genotype. Lipopolysaccharide whole-blood stimulation resulted in a significant change in interleukin (IL)-8 (P = 0.05) and IL-12p40 levels (P = 0.04) in healthy control subjects carrying the TT genotype. TT PSC patients were protected against Gram-negative bacterial biliary infection (TT: 0% vs. CC/CT: 22.5%; P = 0.02). Serum-soluble CD14 levels correlated with the CD14 -260C>T genotype (P = 0.02), representing an independent risk indicator of survival in PSC patients (hazard ratio, 0.40; 95% confidence interval, 0.19-0.86; P =0.01). CONCLUSIONS: The function of the innate immune response by CD14 is crucial during biliary infection and stricture formation. The benefits of CD14 signaling modification should be addressed in future studies. (Hepatology 2016;64:843-852).

Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients.

Modeling of heat and mass transfer processes for the gap-lyophilization system using the mannitol-trehalose-NaCl formulation.

Gap freezing (GF) is a new concept that was developed to reduce the primary drying time using an alternative freezing process. The purpose of this investigation was to determine the gap-tray heat transfer coefficient, Kgtr , and to investigate the effect of gap lyophilization on cycle reduction of a mannitol-trehalose-NaCl (MTN) formulation. The values of Kgtr were measured using the product temperature profiles in three different configurations: (1) shelf freezing followed by shelf drying (denoted as SF-SD), (2) GF followed by SD (denoted as GF-SD), and (3) GF followed by gap drying (denoted as GF-GD). For the lyophilization cycle using shelf drying (SF-SD), 80% of the heat transferred during primary drying was from the bottom shelf to the vial, versus 20% via radiation from the top shelf. For the lyophilization cycle using gap drying (GF-GD), only 37% of the heat transferred during primary drying was from the bottom shelf to the vial versus 63% via radiation from the top shelf. Furthermore, GF in conjunction with annealing significantly reduces the dry layer resistance of the MTN formulation, which is the opposite of what was observed with a conventional freezing cycle.