Liver transplantation for hepatocellular carcinoma within the Milan criteria versus the University of California San Francisco criteria: a comparative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Currently, liver transplantation (LT) for HCC is the only hope for cure from the tumor and from end-stage liver disease (ESLD). The organ pool shortage in deceased donor LT and the donor-related ethical concerns in living-donor LT necessitate the use of rigorous criteria for LT for HCC. In this respect, two main criteria for LT for HCC were implemented with good outcome, namely, the Milan and the University of California San Francisco criteria. Comparison of the outcome of LT for HCC using either of the two criteria has seldom been reported in the literature. PATIENTS AND METHODS: Eighty-eight patients underwent LT between August 2003 and end of July 2013 for the presence of pathologically proven pure HCC lesions at our institution. Cases of pediatric LT or liver retransplantation were excluded from this study. Cases with mixed HCC and cholangiocarcinoma were excluded from this study. RESULTS: Eighty-eight patients underwent LT between August 2003 and July 2013 for the presence of pathologically proven pure HCC lesions at our institution. The mean follow-up duration was 45±30.9 months. HCC recurrence was related significantly to the presence of vascular invasion and degree of differentiation of HCC lesion (P value of 0.0001 and 0.001, respectively). CONCLUSION: Patient and tumor free survival did not differ significantly between patients within Milan or University of California San Francisco criteria or beyond both criteria. Vascular invasion and poor differentiation are still the most influential factors for post-transplant long-term outcomes in HCC patients.

Misdiagnosed or Incidentally Detected Hepatocellular Carcinoma in Explanted Livers: Lessons Learned.

BACKGROUND: Misdiagnosed or incidentally detected hepatocellular carcinoma (HCC) in liver explant is an undesirable surprise that might pose a medical challenge in the post-transplant setting. MATERIAL AND METHODS: From May 2001 to the end of December 2013, 463 and 137 liver transplants for adult and pediatric patients, respectively, were performed at our center. Ten cases were found to have misdiagnosed or incidental malignant lesions on pathological examination of the explant. RESULTS: We considered 105 patients for LT because of presence of HCC; 102 patients were accurately diagnosed by pretransplant imaging and the other 3 patients were misdiagnosed as HCC and then found to have mixed HCC-cholangiocarcinoma (CC) (2.9% misdiagnosis rate). Seven more patients were found to have i-HCC in explanted livers. Therefore, 109 patients were transplanted for presence of HCC (6.5% of them diagnosed incidentally). The overall rate of incidental HCC (i-HCC) among all liver explants was 1.2%. In the adult group no subjects had HCC recurrence, while only 1 subject had HCC recurrence in the pediatric group. All mixed HCC-CC lesions were found in adult patients. Two patients died from recurrence of cholangiocarcinoma after liver transplant. The other patient is still surviving with no recurrence at 13-month follow-up. CONCLUSIONS: Misdiagnosed or incidental malignancy is a rare but reported finding following liver transplantation. Their preoperative suspicion is quite challenging. A thorough explant pathology study is needed to diagnose this condition. It is evident that the outcome of this undesirable finding was judged mainly by tumor biology.

Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature.

Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to mutations in PHKA1, PHKA2, or PHKB and PHKG2 genes resulting in the deficiency of phosphorylase kinase. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. The majority of cases of GSD IX are attributed to defects in PHKA2 which usually cause a mild disease. We report three patients with PHKG2-related GSD IX presenting with significant hepatic involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping resolved a dilemma about an erroneously normal phosphorylase kinase activity in patient 1. The novel mutation found in all the three patients (p.G220E) affects the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that patients with PHKG2 mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. Therefore, defect in PHKG2 should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis.

Genetic diagnosis in consanguineous families with kidney disease by homozygosity mapping coupled with whole-exome sequencing.

BACKGROUND: Accurate diagnosis of the primary cause of an individual's kidney disease can be essential for proper management. Some kidney diseases have overlapping histopathologic features despite being caused by defects in different genes. In this report, we describe 2 consanguineous Saudi Arabian families in which individuals presented with kidney failure and mixed clinical and histologic features initially believed to be consistent with focal segmental glomerulosclerosis. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We studied members of 2 apparently unrelated families from Saudi Arabia with kidney disease. MEASUREMENTS: Whole-genome single-nucleotide polymorphism analysis followed by targeted isolation and sequencing of exons using genomic DNA samples from affected members of these families, followed by additional focused genotyping and sequence analysis. RESULTS: The 2 apparently unrelated families shared a region of homozygosity on chromosome 2q13. Exome sequence from affected individuals lacked sequence reads from the NPHP1 gene, which is located within this homozygous region. Additional polymerase chain reaction-based genotyping confirmed that affected individuals had NPHP1 deletions, rather than defects in a known focal segmental glomerulosclerosis-associated gene. LIMITATIONS: The methods used here may not result in a clear genetic diagnosis in many cases of apparent familial kidney disease. CONCLUSIONS: This analysis shows the power of new high-throughput genotyping and sequencing technologies to aid in the rapid genetic diagnosis of individuals with an inherited form of kidney disease. We believe it is likely that such tools may become useful clinical genetic tools and alter the manner in which diagnoses are made in nephrology.

Renal failure associated with APECED and terminal 4q deletion: evidence of autoimmune nephropathy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes' response to Candida albicans at 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH. AIRE full gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.