Explore the vast range of titles available.

Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation. Livers from 10-week old leptin-deficient obese (ob/ob, n = 9) and lean C57 mice (n = 9) were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity. Ob/ob and lean mice livers showed severe (>60%) macrovesicular and mild (<30%) microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP) levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers. Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in steatotic donor livers.

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.

Background Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Treatment options include liver resection, tumor ablation, and liver transplantation. Methods We report the results of all patients undergoing partial hepatectomy for HCC with curative intent from a center where all major treatment modalities were available. Results A series of 53 patients were identified, of whom 72% had underlying liver disease, mostly chronic hepatitis B infection. Altogether, 57% of patients underwent major resections, of whom 43% had histologically proven cirrhosis. Postoperative morbidity and mortality occurred in 41.5% and 7.5%, respectively. After a median follow‐up of 34 months, the survival probabilities at 1, 3, and 5 years were 74.1%, 54.1%, and 42.6%, respectively. A total of 47% developed recurrent disease over the study period with a median disease‐free survival of 13.8 months. The probabilities of recurrence at 1, 3, and 5 years were 35.2%, 49.4%, and 55.9%, respectively. Among those who developed recurrence, 76% died, with a median time to death from the time the recurrence was diagnosed of 7.8 months. There was a good association between the CLIP score and survival following liver resection. Multivariate analysis showed that only tumor recurrence and the presence of cirrhosis was a significant determinant of the risk of tumor‐related death. Conclusion These findings confirm that with careful patient selection liver resection for HCC can achieve good long‐term patient survival and acceptable risks.

Evaluates the outcome for patients listed for liver transplantation (LT) with a pre-transplant diagnosis of hepatocellular carcinoma (HCC). Notes that time spent on the waiting list exposes patients to the risk of tumour progression prior to transplantation. Considers patients with 1 to 3 tumours, up to 5cm in diameter, and no vascular invasion or extra-hepatic disease on imaging, eligible for LT. Analyses outcomes for patients by intention to treat from the time of listing. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Obituary. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

When patients with hypogammaglobulinemia are encountered, a vigorous search should be undertaken for secondary treatable causes. Here we describe the first case of a patient with severe asymptomatic hypogammaglobulinemia where the underlying cause was undiagnosed celiac disease. A strict gluten free diet resulted in resolution of her mild long-standing abdominal symptoms and correction of her hypogammaglobulinemia. There was corresponding improvement in her duodenal histology and normalisation of her celiac serology. Protein losing enteropathy was unlikely to have been the mechanism of her profound hypogammaglobulinemia, as her albumin was within the normal range and she had a normal fecal alpha 1 antitrypsin level. Application of the Ameratunga et al. (2013) diagnostic criteria was helpful in confirming this patient did not have Common Variable Immunodeficiency Disorder (CVID). Celiac disease must now be considered in the differential diagnosis of severe hypogammaglobulinemia. There should be a low threshold for undertaking celiac serology in patients with hypogammaglobulinemia, even if they have minimal symptoms attributable to gut disease.

This report describes a case of malignant granular cell tumour arising in the mediastinum, detailing the investigations undertaken to reach this rare diagnosis. A 63-year-old man was referred from the Pacific Islands for investigation of a 8cm mediastinal mass extending into the left pleura and associated with pleural nodules and pleural effusion. Needle aspiration via bronchoscopy yielded insufficient material for cytological interpretation and needle biopsy showed normal respiratory epithelium. CT-guided FNA revealed scattered large polygonal to spindle cells with granular cytoplasm and indistinct borders. The needle core biopsy yielded scanty cells with abundant granular cytoplasm, oval and regular nuclei which were moderately positive for CD68, vimentin and S100 and negative for CKMNF116, CK5/6, CK7, CK20, TTF-1, chromogranin and synaptophysin. In view of the benign morphology, these cells were interpreted to be histiocytes. The incisional biopsy revealed cords and trabeculae of cells identical to the CT samples. These cells were polygonal with abundant granular cytoplasm. Some cells showed large eosinophilic cytoplasmic globules not seen in the FNA sample. The tumour was however, heterogeneous in appearance with some areas exhibiting criteria of malignancy: necrosis, vesicular nuclei with large nucleoli, high nuclear-to-cytoplasmic ratio and nuclei pleomorphism. In addition, p53 expression in 10% of tumour nuclei, a high Ki67 proliferative rate (>10%), the deep seated location and extension of the tumour into adjacent organs favoured a diagnosis of malignancy.

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Analysis of gene mutation, copy number and RNA expression of 57 sporadic pNETs showed that pNET genomes are dominated by aneuploidy. Remarkably, ~25% of pNETs had genomes characterized by recurrent loss of heterozygosity (LoH) of the same 10 chromosomes, accompanied by bi-allelic MEN1 inactivation, and these cases had generally poor clinical outcome. Another ~25% of all pNETs had chromosome 11 LoH and bi-allelic MEN1 inactivation, lacking the recurrent LoH pattern these had universally good clinical outcome. Some level of aneuploidy was common, and overall ~80% of pNETs had LoH of 1 chromosome. This aneuploidy led to changes in RNA expression at the level of whole chromosomes and allowed pathogenic germline variants (e.g. ATM) to be expressed unopposed, inactivating downstream tumor suppressor pathways. Some pNETs appear to utilise VHL gene methylation or mutation to activate pseudo-hypoxia. Contrary to expectation neither tumor morphology within well-differentiated pNETs nor single gene mutation had significant associations with clinical outcome, nor did expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. MEN1 was the only statistically significant recurrently mutated driver gene in pNETs. Only one pNET had clearly oncogenic and actionable SNVs (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two distinct patterns of aneuploidy described here, associated with markedly poor and good clinical outcome respectively, define a novel oncogenic mechanism and the first route to genomic precision oncology for this tumor type.

Summarises the transplant-related activity of the New Zealand Liver Transplant Unit over the first four years. Examines records of all patients assessed for liver transplantation between 1 Dec 1997 and 30 Dec 2001. Records listing criteria, demographics, waiting time, transplant-hospitalisation details and long-term outcome for those who underwent liver transplantation. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Liver transplantation (LT) is potentially curative for early hepatocellular carcinoma (HCC) but time spent on the waiting list exposes patients to the risk of tumour progression prior to transplantation. We prospectively evaluated the outcome for New Zealand patients listed for LT with a pre-transplant diagnosis of HCC. Patients with 1 to 3 tumours, up to 5 cm in diameter, and no vascular invasion or extra-hepatic disease on imaging, were considered eligible for LT. The results were analysed by intention to treat from the time of listing. Fifty-nine patients were listed with a pre-transplant diagnosis of HCC between February 1998 and June 2004. Ten (17%) were de-listed before LT because of tumour progression, and 9 of 45 (20%) who underwent LT have experienced tumour recurrence up to 59 months post-transplant. For patients listed with a diagnosis of HCC, 5-year actuarial survival was 56.1% from the time of listing. For those listed and transplanted with a diagnosis of HCC, 5-year actuarial survival from the time of transplant was 63.5%. This is significantly worse than the 89.8% 5-year survival for patients transplanted without HCC over the same period (p=0.018) and this difference was entirely due to tumour recurrence. 37% of patients listed according to our criteria were either de-listed due to tumour progression or experienced recurrence after LT. Based on this experience strategies aimed at preventing waiting list drop out have been adopted, however expansion of tumour-related selection criteria cannot be recommended without a concomitant increase in donor organ availability.