A Single-Institution Review of Portosystemic Shunts in Children: An Ongoing Discussion

Purpose. Review the safety and long-term success with portosystemic shunts in children at a single institution. Methods. An IRB-approved, retrospective chart review of all children ages 19 and undergoing surgical portosystemic shunt from January 1990–September 2008. Results. Ten patients were identified, 8 females and 2 males, with a mean age of 15 years (range 5–19 years). Primary diagnoses were congenital hepatic fibrosis (5), hepatic vein thrombosis (2), portal vein thrombosis (2), and cystic fibrosis (1). Primary indications were repeated variceal bleeding (6), symptomatic hypersplenism (2), and significant liver dysfunction (2). Procedures performed were distal splenorenal bypass (4), side-to-side portocaval shunt (3), proximal splenorenal shunt (2), and an interposition H-graft portocaval shunt (1). There was no perioperative mortality and only minor morbidity. Seventy percent of patients had improvement of their symptoms. Eighty percent of shunts remained patent. Two were occluded at a median follow-up of 50 months (range 0.5–13.16 years). Two patients underwent subsequent liver transplantation. Two patients died at 0.5 and 12.8 years postoperatively, one from multisystem failure with cystic fibrosis and one from post-operative transplant complications. Conclusions. The need for portosystemic shunts in children is rare. However, in the era of liver transplantation, portosystemic shunts in selected patients with well-preserved liver function remains important. We conclude that portosystemic shunts are safe and efficacious in the control of variceal hemorrhage and symptoms related to hypersplenism

Adequate symptom relief justifies hepatic resection for benign disease

BACKGROUND: The purpose of this study was to evaluate the long-term results of partial liver resection for benign liver lesions. METHODS: All patients operated on for benign liver lesions from 1991 to 2002 were included. Information was retrieved from medical records, the hospital registration system and by a telephonic questionnaire. RESULTS: Twenty-eight patients with a median age of 41 years (17–71) were operated on (M/F ratio 5/23). The diagnosis was haemangioma in 8 patients, FNH in 6, HCA in 13 and angiomyolipoma in 1. Eight patients were known to have relevant co-morbidity. Median operating time was 207 minutes (45–360). The morbidity rate was 25% and no postoperative mortality was observed. Twenty-two patients (79%) had symptoms (mainly abdominal pain) prior to surgery. Twenty-five patients were reached for a questionnaire. The median follow up was 55 months (4–150). In 89% of patients preoperative symptoms had decreased or disappeared after surgery. Four patients developed late complications. CONCLUSION: Long-term follow up after liver surgery for benign liver lesions shows considerable symptom relief and patient satisfaction. In addition to a correct indication these results justify major surgery with associated morbidity and mortality

Cystic colon duplication causing intussusception in a 25-year-old man: report of a case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Colonic intussusception is a rare congenital abnormality, mostly manifesting before the age of two with abdominal pain and acute intestinal obstruction with or without bleeding. In adults it may occur idiopathically or due to an intraluminal tumor mass.</p> <p>Case presentation</p> <p>A 25-year-old man presented with an acute abdomen and severe crampy abdominal pain. The clinical picture mimicked acute appendicitis. Transabdominal ultrasound examination revealed a 5 cm circular mass in the right upper abdomen. The ensuing computed tomography suggested an intussusception in the ascending colon. Intraoperatively, no full thickness invagination was detected. Due to a hard, intraluminal tumor a standard right hemicolectomy with ileotransversostomy was performed. The histopathological analysis revealed a cystic colon duplication leading to mucosal invagination and obstruction.</p> <p>Conclusions</p> <p>In adults, colon intussusception is a rare event causing approximately 1% of all acute intestinal obstructions. Unlike its preferentially nonsurgical management in children, a bowel intussusception in adults should be operated because an organic, often malignant lesion is present in most cases.</p

Unique genomic profile of fibrolamellar hepatocellular carcinoma

BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can be treated only with surgery. We performed an integrative genomic analysis of a large series of patients with FLC to identify associated genetic factors. METHODS: By using 78 clinically annotated FLC samples, we performed whole-transcriptome (n = 58), single-nucleotide polymorphism array (n = 41), and next-generation sequencing (n = 48) analyses; we also assessed the prevalence of the DNAJB1-PRKACA fusion transcript associated with this cancer (n = 73). We performed class discovery using non-negative matrix factorization, and functional annotation using gene-set enrichment analyses, nearest template prediction, ingenuity pathway analyses, and immunohistochemistry. The genomic identification of significant targets in a cancer algorithm was used to identify chromosomal aberrations, MuTect and VarScan2 were used to identify somatic mutations, and the random survival forest was used to determine patient prognoses. Findings were validated in an independent cohort. RESULTS: Unsupervised gene expression clustering showed 3 robust molecular classes of tumors: the proliferation class (51% of samples) had altered expression of genes that regulate proliferation and mammalian target of rapamycin signaling activation; the inflammation class (26% of samples) had altered expression of genes that regulate inflammation and cytokine enriched production; and the unannotated class (23% of samples) had a gene expression signature that was not associated previously with liver tumors. Expression of genes that regulate neuroendocrine function, as well as histologic markers of cholangiocytes and hepatocytes, were detected in all 3 classes. FLCs had few copy number variations; the most frequent were focal amplification at 8q24.3 (in 12.5% of samples), and deletions at 19p13 (in 28% of samples) and 22q13.32 (in 25% of samples). The DNAJB1-PRKACA fusion transcript was detected in 79% of samples. FLC samples also contained mutations in cancer-related genes such as BRCA2 (in 4.2% of samples), which are uncommon in liver neoplasms. However, FLCs did not contain mutations most commonly detected in liver cancers. We identified an 8-gene signature that predicted survival of patients with FLC. CONCLUSIONS: In a genomic analysis of 78 FLC samples, we identified 3 classes based on gene expression profiles. FLCs contain mutations and chromosomal aberrations not previously associated with liver cancer, and almost 80% contain the DNAJB1-PRKACA fusion transcript. By using this information, we identified a gene signature that is associated with patient survival time

Adenomyoma of the Ileum Leading to Intussusception

Adenomyoma of the ileum is a rare condition. A 68-year-old Japanese man presented with nausea and distension of the abdomen. Enhanced computed tomography of his abdomen revealed wall thickening in the ileum and dilation of the proximal small intestine. Open laparotomy was performed to find the cause of the patient's small bowel obstruction, and a tumor was found in the ileum, which had resulted in intussusception. The tumor and 20 cm of the adjacent ileum were resected. The resected specimen displayed a macroscopic appearance suggestive of a submucosal tumor. Histopathological evaluation showed duct cell proliferation and bundles of smooth muscle cells from the mucosa to the serosa, leading to a diagnosis of adenomyoma. Immunohistochemical examination found that cytokeratin 7 and carbohydrate antigen 19-9 were expressed in the duct epithelia. We report a rare case of ileal adenomyoma leading to intussusception in an adult and present the immunohistochemical evaluation of the adenomyoma

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts