Ganciclovir-Resistant CMV Colitis in a Donor-Seronegative/Recipient-Seronegative Liver Transplant Patient.

Cytomegalovirus (CMV) disease in liver transplant patients with donor-seronegative and recipient-seronegative (D-/R-) status is a rarity. Ganciclovir-resistant CMV disease in this population has not been reported in the literature. We present a 62-year-old man who underwent orthotopic liver transplant from a cadaveric donor. The patient's status was CMV D-/R-, and he had completed 90 days of valganciclovir therapy for CMV prophylaxis, yet he developed CMV disease. We highlight the danger of the liberal use of CMV prophylaxis in this subset of the liver transplant population. To our knowledge, this is the first report of ganciclovir-resistant (GanR) CMV disease in a liver transplant patient with CMV D-/R- status.

Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

OBJECTIVE: To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. METHODS: In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. RESULT: Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P<0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). CONCLUSION: Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.

Peripancreatic soft tissue involvement: independent outcome predictor in patients with resected pancreatic adenocarcinoma.

The impact of cancer involving the peripancreatic soft tissue (PST), irrespective of margin status, following a resection of pancreatic adenocarcinoma is not known. The purpose of this study is to determine such an impact on a cohort of patients. Data from 274 patients who underwent pancreatic surgery by our team between 1998 and 2012 was reviewed. Of those 119 patients who had pancreatic resection for adenocarcinoma were retrospectively analyzed. Patients were categorized into 3 groups: Group 1 = R1 resection (N = 39), Group 2 = R0 with involved PST (N = 54), and Group 3 = R0 with uninvolved PST (N = 26). Demographics, operative data, tumor characteristics and overall survival (OS) were evaluated. Operations performed were: Whipple (N = 53), pylorus sparing Whipple (N = 41), total pancreatectomy (N = 11), and other (N = 14). Median OS for Groups 1, 2, and 3 were 8.5 months, 12 months, and 69.6 months respectively (P < 0.001). Tumor size (P = 0.016), margin status (P = 0.006), grade (P = 0.001), stage (P = 0.037), PST status (P < 0.001), complications (P = 0.046), transfusion history (P = 0.003) were all predictors of survival. Cox regression analysis demonstrated that grade (HR = 3.1), PST involvement (HR = 2.7), transfusion requirement (HR = 2.6) and margin status (HR = 2.0) were the only independent predictors of mortality. PST is a novel predictor of poor outcome for patients with resected pancreatic cancer.

Genotype-phenotype correlations in recessive RYR1-related myopathies.

BACKGROUND: RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed. METHODS: In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases. RESULTS: Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore. CONCLUSIONS: These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of genotype-phenotype associations in recessive RYR1-myopathies.