Untangling biliary reconstruction in liver transplants for primary sclerosing cholangitis.

BACKGROUND: Biliary reconstruction technique during liver transplant (LT) for primary sclerosing cholangitis (PSC) remains controversial. This study aimed to evaluate the incidence of biliary complications in patients with PSC having a duct-to-duct (DD) anastomosis or Roux-en-Y hepaticojejunostomy (HJ). METHODS: A retrospective medical record review of patients with PSC undergoing LT at a single center between June 1st, 2000 and December 31st, 2022 was performed. Primary and secondary endpoints were the incidence of biliary strictures (anastomotic [BAS] and non-anastomotic strictures [NAS]) and non-stricture complications, respectively. Univariable and multivariable regression analyses were performed to identify associations with BAS formation. Patient survival was assessed using a Kaplan-Meier curve. RESULTS: From 105 transplants performed for 101 patients, 54 (51.4%) and 51 (48.5%) received DD and HJ anastomoses. Mean recipient age and follow-up was 47 ± 13 years and 98 ± 69 months. BAS was more common (48.1% vs. 27.5%, OR 2.45, 95% CI 1.09-5.54, p = 0.03) and occurred earlier (4.8 months, IQR 2.3-13.1 vs. 41.8 months, IQR 7.2-88.7, p = 0.001) in the DD than the HJ group. NAS (seen in 36.2% of transplants) had a comparable incidence (p = 0.53) in HJ (38.9%) and DD (33.3%) groups. No difference was seen between cohorts regarding time to NAS, requirement for extended biliary dilatation programs (clinically significant biliary stricture), bile leak, and graft failure. On multivariable analysis, only the anastomotic technique was associated with BAS (DD adjusted OR 3.00, 95% CI 1.19-7.56, p = 0.02). CONCLUSION: In carefully selected patients with PSC, DD anastomosis yielded similar outcomes to HJ anastomosis after liver transplantation.

Safety and effectiveness of umbilical hernia repair in patients with cirrhosis.

PURPOSE: Umbilical hernia is a common complication in patients with cirrhosis. Early studies have reported a high morbidity and mortality associated with hernia repair. The traditional approach has been to non-operatively manage umbilical hernias in patients with cirrhosis. There are emerging data suggesting that an elective repair is a preferable approach. This study examined the outcomes of umbilical hernia repair in patients with advanced liver disease and compared this with a control group of non-cirrhotic patients. METHODS: Prospective data were collected regarding the outcome of umbilical hernia repairs performed between 2004 and 2013 at the Austin Hospital, Melbourne, Australia. Outcomes at 90 days were compared between patients with and without cirrhosis. RESULTS: 79 patients with cirrhosis and 249 controls were analysed. Of the patients with cirrhosis, 9% were classified as Child-Pugh A, 61% were Child-Pugh B and 30% were Child-Pugh C. Emergency repairs for complicated hernias was undertaken in 18% of the cirrhosis population and 10% in controls (P = 0.10). Post-operative complications occurred more commonly in patients with cirrhosis (26%) compared with controls (11%) (P < 0.01). Emergency hernia repairs were associated with a higher complication rate in both patients with cirrhosis (62%) and controls (20%) (P = 0.01). There was no significant difference in the rate of hernia recurrence as assessed by clinical examination between patients with cirrhosis (2.7%) and controls (6.8%) (P = 0.17) nor in 90-day mortality between patients with cirrhosis (n = 1, 1.3%) and the controls (n = 0) (P = 0.43). CONCLUSIONS: Within the limitations of a small study cohort and therefore an underpowered study, elective surgical repair of umbilical hernias in patients with cirrhosis, including decompensated cirrhosis, may not be associated with a significant increase in mortality when compared to a control cohort. Whilst complications are higher in cirrhotic patients, there is no difference in the rate of hernia recurrence. Emergency repairs of umbilical hernias are associated with a high complication rate in cirrhotic patients.

Neurotrophin receptor expression and responsiveness by postnatal cerebral oligodendroglia.

The low affinity neurotrophin receptor (p75(NTR)) is implicated in promoting oligodendrocytic death after nerve growth factor (NGF) stimulation but NGF and neurotrophin-3 (NT-3) can also potentiate oligodendrocytic survival. We show regional variability in p75(NTR) expression within the central nervous system of the postnatal rat; expression is readily detectable by immunohistochemistry upon a subset of CNPase-positive oligodendroglia in optic nerve but not within the cerebrum. Nevertheless, oligodendroglia isolated from the cerebrum and cultured for 16 hours express p75(NTR) as well as the trkC but not the TrkA gene. Viability was not, however, influenced by exposure to either NGF or NT-3. Cells overexpressing p75(NTR) remained unresponsive to NGF but exhibited potentiated survival with NT-3, correlating with the differential expression profile of their high affinity receptors.

Leukemia inhibitory factor is an autocrine survival factor for Schwann cells.

Schwann cells play a major role in promoting nerve survival and regeneration after injury. Their activities include providing neurotrophic factors and increasing the production of extracellular matrix components and cell surface adhesion molecules to promote axon regeneration. Following nerve transection, leukemia inhibitory factor (LIF) is up-regulated by Schwann cells at the injury site. LIF receptors are also up-regulated at the nerve injury site, but their cellular localization and function have not been fully characterized. We demonstrate that Schwann cells express mRNAs for LIF and the LIF receptor components LIF receptor subunit beta and glycoprotein 130 in vitro. We also show that although LIF is not required for the genesis of Schwann cells, it can potentiate the survival of differentiated Schwann cells in the context of neuregulin support. Not only does exogenous LIF promote survival under these conditions, but addition of the soluble LIF receptor (LIF binding protein) and anti-LIF antibodies significantly reduced cell survival, suggesting that LIF exerts autocrine effects. These results suggest that Schwann cell survival following nerve injury is potentially modulated by LIF.

Chemically-tagged Mitsunobu reagents for use in solution-phase chemical library synthesis.

A general method for high-throughput product purification of Mitsunobu reactions is described. Tagged phosphine and azodicarboxylate reagents are used to synthesize individual library members in solution-phase. Workup and purification are easily accomplished by post-reaction sequestration of the tagged reagents and reagent byproducts by a complementary functionalized ion exchange resin. The reagents are utilized in a 3 step library synthesis.

An educational intervention in the surgical intensive care unit to improve ethical decisions.

BACKGROUND: The objective of this study was to determine whether an educational intervention on medical ethics offered during a surgical intensive care unit (SICU) rotation could effect meaningful change in a tertiary SICU. METHODS: A case-based education program was presented weekly to the surgical residents during their SICU rotation. Cases for study were designed to deal with specific ethical issues common to the SICU. Cases were studied with the residents in a group facilitated by a SICU attending physician and a nursing director. The effect of the course was monitored by case review and by the length of stay (LOS) assessment for patients who died in the SICU during 1990, the base year, through 1993. RESULTS: Discussions of an ethical nature occurred more regularly and earlier during these 4 years as determined by case reviews. For patients who died after being in the SICU a minimum of more than 30 days, a marked decrease occurred in the SICU LOS from 27.8 +/- 3.7 days in 1990 to 15.7 +/- 2.4 days in 1993 (p < 0.05). The number of deaths per year and the average acuity measured by the diagnosis related group score were similar during the 4 years. The LOS in the hospital for dying patients from non-SICU services remained similar during the same time frame. These changes resulted in the dying patients using 1003 SICU days in 1993, down from the 2028 days used in 1990 (p < 0.05). CONCLUSIONS: We conclude that through offering a clinical ethics program during the SICU portion of the residency training, residents increased knowledge and skill in addressing and integrating practical ethical issues into their surgical resident practice. In addition, patient care directly improved with an associated reduced SICU LOS and reduced cost.

Pseudo-chondrosarcoma: solitary osseous metastases from atypical bronchogenic carcinoma.

A patient with bronchogenic carcinoma with a solitary metastases to the femur in whom the clinical, radiologic, and pathologic setting suggested that the primary tumor was the bone lesion (chondrosarcoma) and the pulmonary lesion was a solitary metastasis is presented. This case is added to the limited literature indicating that mucin-secreting tumors metastatic to bone may simulate primary bone tumors radiographically.

[Unusual esophageal motility disorder (author's transl)]. / Nicht-klassifizierbare Motilitätsstörung des Osophagus.

A 31 year-old female initially presented with clinical features consistent with achalasia, which were relieved by the Heller procedure. Several years later manometric tracings excluded the diagnosis of achalasia, and suggested a motility disorder of the esophageal body. A long esophageal myotomy was performed and was followed by a marked improvement in symptoms and a normalization of the manometric tracing. Multiple histologic sections from the surgical specimen revealed the absence of ganglion cells, a feature not previously described in motor disorders other than achalasia. These findings suggest that classification of esophageal motility disorders on the basis of manometric and histologic findings might not be possible and that surgical treatment should be directed towards the predominant symptoms.