Use of double wire-guided technique and transpancreatic papillary septotomy in difficult ERCP: 4-year experience.

Background and aims: Post-ERCP complications increase with repeated attempts at cannulation. We evaluated several advanced biliary cannulation techniques applied when the standard approach fails. Methods: In total, 1873 consecutive patients underwent ERCP at our institution during the period 2010 - 2014. Guidewire-assisted (GA) cannulation with no contrast injection until deep biliary cannulation was considered the standard technique. Advanced techniques used were double wire-guided (DWG) cannulation, transpancreatic papillary septotomy (TPS), and needle-knife sphincterotomy (NKS). When GA cannulation failed, DWG cannulation was usually attempted first if the pancreatic duct (PD) wire was in place; if that failed, TPS or NKS was performed. Alternatively, TPS or NKS were performed alone. A prophylactic pancreatic stent was placed with repeated PD cannulation or PD contrast injection. During the last 2 years of review, indomethacin suppositories were given post-procedure to all patients who underwent advanced techniques. Results: The overall biliary cannulation success rate was 97 % (1823/1873). Advanced techniques were used in 12 % of ERCPs (230/1873), with 87 % (200/230) success rate. DWG was used alone or in combination with other techniques in 58 % (134/230) of advanced cases, with 68 % (91/134) success rate. Biliary cannulation was achieved in 96 % (91/95) of procedures when DWG was used alone, 76 % (26/34) with TPS alone, 80 % (37/46) for NKS alone, and 84 % (46/55) with multiple techniques. The overall rate of post-ERCP pancreatitis was 0.4 %, with all patients treated conservatively. Conclusion: In our experience at an urban tertiary care center, use of advanced techniques in difficult ERCP improved the overall success rate of biliary cannulation after standard technique failure without a significant increase in complication rate.

Troxis necrosis, a novel mechanism for drug-induced hepatitis secondary to immunomodulatory therapy.

OBJECTIVES: A case of drug-induced hepatitis mediated by troxis necrosis, a form of autoimmune hepatitis, is described. METHODS: Clinical data, light and electron microscopy of an ultrasound-guided core needle liver biopsy specimen, were examined to investigate the cause of transaminitis in a 26year old male patient on Cellcept and Plaquenil for the treatment of lupus erythematosus. A systematic PUBMED review of troxis necrosis as the underlying mechanism for drug-induced hepatitis was performed. RESULTS: Liver function tests (LFTs) were significant for elevated AST (305) and ALT (174); the autoimmune workup was significant for anti-ANA positivity and α-SMA negativity. On light microscopy, the liver biopsy shows focal areas of lymphocytic infiltrates surrounding and forming immunologic synapses with lobular hepatocytes, indicating lobular hepatitis of autoimmune nature. Electron microscopy confirmed the presence of immunologic synapses. Upon cessation of the offending medications, the LFTs returned to baseline with no further intervention. Literature search yielded 7 previously reported cases of drug-induced hepatitis mediated by troxis necrosis. CONCLUSION: Troxis necrosis is a novel mechanism for drug-induced hepatitis, including immunomodulatory medications including a monoclonal anti-TWEAK antibody and Cellcept and Plaquenil, two widely used immunosuppression/anti-rejection medications.

Access to primary care is associated with better autoimmune hepatitis outcomes in an urban county hospital.

BACKGROUND: Autoimmune hepatitis causes chronic hepatitis and often leads to cirrhosis and death without treatment. We wanted to see if having access to primary care or insurance prior to diagnosis is associated with better outcomes for patients in an urban, public hospital with mostly socioeconomically disadvantaged Hispanic patients. METHODS: We did a retrospective study at our institution. Kaplan Meier survival analysis was done looking at transplant-free overall survival for patients diagnosed at our institution. The log-rank test was done to compare survival between patients with and without prior access to primary care, and between patients with and without insurance at diagnosis. RESULTS: Overall 5- and 10-year transplant-free overall survival was 91% (95% CI, 83-100%) and 75% (95% CI, 50-99%), respectively. Patients with primary care prior to diagnosis had significantly better transplant-free overall survival than those without (log rank test p = 0.019). Patients with primary care also had better clinical markers at diagnosis. Having insurance at diagnosis was not associated with better outcomes. CONCLUSIONS: Outcomes of autoimmune hepatitis are poor in our setting but access to primary care prior to diagnosis was associated with better outcomes. This is likely due to the important role that primary care plays in detecting disease and initiating treatment earlier. With the expansion of access to healthcare that the Affordable Care Act provides, future patients are likely to do better with even rare diseases like autoimmune hepatitis.

[Ca2+]i-independent contractile force generation by rat hepatic stellate cells in response to endothelin-1.

The contractile force generated by hepatic stellate cells in response to endothelin-1 contributes to sinusoidal blood flow regulation and hepatic fibrosis. This study's aim was to directly test the widely held view that changes in cytosolic Ca2+ concentration ([Ca2+]i) mediate stellate cell force generation. Contractile force generation by primary cultures of rat hepatic stellate cells grown in three-dimensional collagen gels was directly and quantitatively measured using a force transducer. Stellate cell [Ca2+]i, myosin activation, and migration were quantified using standard techniques. [Ca2+]i was modulated using ionomycin, BAPTA, KCl, and removal of extracellular Ca2+. Removal of extracellular Ca2+ did not alter endothelin-1-stimulated force development or [Ca2+]i. Ionomycin, a Ca2+ ionophore, triggered an increase in [Ca2+]i that was three times greater than that stimulated by endothelin-1, but only induced 16% of the force and 38% of the myosin regulatory light chain (MLC) phosphorylation induced by endothelin-1. Physiological increases in [Ca2+]i induced by hyperkalemia had no effect on contractile force. Loading BAPTA, a Ca2+ chelator, in stellate cells completely blocked endothelin-1-induced increases in [Ca2+]i but had no effect on endothelin-1-stimulated force generation or MLC phosphorylation. In contrast, Y-27632, a selective rho-associated kinase inhibitor, inhibited endothelin-1-stimulated force generation by at least 70% and MLC phosphorylation by at least 80%. Taken together, these observations indicate that changes in [Ca2+]i are neither necessary nor sufficient for contractile force generation by rat stellate cells. Our results challenge the current model of contractile regulation in hepatic stellate cells and have important implications for our understanding of hepatic pathophysiology.

Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight.

To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.