Faculty Bibliography

HYPOTHESIS/OBJECTIVE:The gene expression profiles of benign and malignant adrenocortical tumors are different. DESIGN/METHODS:Genomewide gene expression profiling and validation. SETTING/METHODS:Tertiary medical center. PATIENTS/METHODS:Eighty-five patients with benign adrenocortical tumors (n = 74) and adrenocortical carcinoma (n = 11). INTERVENTION/METHODS:Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 89 adrenocortical tissue samples (11 malignant and 78 benign). The criteria for differentially expressed genes between benign and malignant adrenocortical tumors were a false discovery rate of less than 5% and an adjusted P < .01. Genes differentially expressed by 8-fold higher or lower were validated by RT-PCR. MAIN OUTCOME MEASURES/METHODS:The diagnostic accuracy of differentially expressed genes as determined by the area under the receiver operating characteristic curve (AUC). RESULTS:We found 37 genes differentially expressed by 8-fold higher or lower. Fifteen genes were downregulated and 22 were upregulated in adrenocortical carcinoma. Of the 37 genes, 29 differentially expressed by microarray correlated with the gene expression levels by quantitative RT-PCR (P < or = .01). Of the 37 genes validated by RT-PCR, 22 were significantly differentially expressed between benign and malignant adrenocortical tumors (P < .05). Five of these 22 genes had an AUC of 0.80 or greater (the AUC for IL13RA2 was 0.90; HTR2B, 0.87; CCNB2, 0.86; RARRES2, 0.86; and SLC16A9, 0.80), indicating high diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors. CONCLUSION/CONCLUSIONS:We identified 37 genes that are dysregulated in adrenocortical carcinoma, and several of the differentially expressed genes have excellent diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors.

BACKGROUND:Reportedly, 10-15% of patients with goiters ultimately require operative intervention, and recurrences of multinodular goiter (MNG) account for up to 12% of all thyroid operations. METHODS:We performed an evidence-based review of articles published in the English language between January 1987 and October 2007 relevant to the subject. RESULTS:Medical treatment with T4 appears to be associated with a greater proportion of patients whose nodules decreased in size by more than 50% (22% vs. 10%; range = 14-39% vs. 0-20%). Recurrence rates of benign nodular goiter after total thyroidectomy were essentially nonexistent (range = 0-0.3%) compared with those after subtotal thyroidectomy (range = 2.5-42%) and more limited resections (range = 8-34%). There was no difference between total and less-than-total thyroidectomy with respect to temporary recurrent laryngeal nerve (RLN) injury (1-10% vs. 0.9-6%, respectively) or permanent RLN palsy (0-1.4%). There was, however, a significantly higher rate of transient hypocalcemia after total thyroidectomy than less extensive operations (9-35% vs. 0-18%, respectively). In relation to redo surgery, permanent hypoparathyroidism appeared to be far more common in the redo group (0-22% vs. 0-4%) Moreover; the redo group had more frequent RLN injury, both temporary (0-22% vs. 0.5-18%) and permanent (0-13% vs. 0-4%). About half the studies examined conclude that postoperative TSH suppression is effective in reducing recurrences, while the other half state that it is not. CONCLUSION/CONCLUSIONS:The definitive management and prevention of recurrence of benign nodular goiter is primarily surgical. Total thyroidectomy essentially eliminates the risk of recurrence without an accompanying increased risk of permanent hypoparathyroidism or RLN injury. Therefore, total thyroidectomy should be considered the procedure of choice for benign multinodular goiter whenever possible, especially considering that reoperations for goiter are significantly more morbid than any initial operation.

The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta1 and its downstream target genes. In this experiment, the expression of TGF-beta1, metalloproteinase (MMP)-13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelial cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis.

Only a few cases of intrahepatic splenic tissue have so far been reported in the English literature. Those cases were developed after splenic injury or a splenectomy. We report here a case of intrahepatic splenic tissue which has two distinctive features compared to previous literature. A 59-year-old female who previously had no medical history of splenic injury or splenectomy underwent hepatic resection for intrahepatic tumor mimicking hepatocellular carcinoma. However, pathologic examination revealed it as intrahepatic splenic tissue directly abutted to the normal liver tissue without a capsule. Lacking an invasive diagnostic modality, the diagnosis of intrahepatic splenic tissue without an accompanying medical history is very difficult.

After portoenterostomy (PE) for biliary atresia (BA), many patients suffer progressive deterioration of liver function and ultimately require liver transplantation. We retrospectively reviewed a single center's experience with pediatric liver transplantation for BA from 1988 to 2002. Sixty-six patients underwent 69 liver transplants for BA. Forty-two (63%) patients had previously undergone Kasai PE, 11 (17%) biliary appendicoduodenostomy (BAD), and 13 (20%) had no prior biliary drainage (NBD). The BAD procedure offered only short-term biliary drainage--the mean interval between PE and transplant was more than twice that for Kasai patients than for BAD patients (132 versus 49 weeks). The transplants included 11 cadaveric partial, 27 cadaveric whole, and 31 living related transplants. Three patients required retransplant. Prior PE did not increase the incidence of major perioperative complications or unplanned reexploration. After transplant, the 1-, 5-, and 10-year actuarial graft survival rates were 87%, 86%, and 80%, respectively. The 1-, 5-, and 10-year actuarial patient survival rates were 91%, 89%, and 83%. PE remains an important bridge to transplant. In conclusion, transplantation for BA offers excellent long-term graft and patient survival.

HYPOTHESIS/OBJECTIVE:Excision of the extrahepatic portion of congenital choledochal cysts (CCs) avoids the risk of cancer. The standard classification scheme is out of date. DESIGN/METHODS:Retrospective case series and literature review. SETTING/METHODS:Tertiary care university hospital. PATIENTS/METHODS:Thirty-eight adult patients diagnosed as having CC from 1990 to 2004. MAIN OUTCOME MEASURES/METHODS:Clinical and radiographic imaging findings, operative treatment, pathologic features, and clinical outcome. RESULTS:Thirty-nine adult patients were treated for CCs (mean [SD] age at diagnosis, 31 [17] years, and mean [SD] age at surgery 37 [14] years). The primary report was abdominal pain (36 of 39 patients). Eight patients had cholangitis, 5 had jaundice, and 6 had pancreatitis. Radiographic imaging studies and operative findings showed that the abnormality predominantly involved the extrahepatic bile duct in 30 patients, the intrahepatic and extrahepatic bile ducts in 7 patients; and 2 were diverticula attached to the common bile duct. Surgical treatment in 29 (90%) of 31 patients with benign cysts (regardless of intrahepatic changes) consisted of resection of the enlarged extrahepatic bile duct and gallbladder and Roux-en-Y hepaticojejunostomy. Eight patients (21%) were initially seen with associated cancer (cholangiocarcinoma of the extrahepatic duct in 6; gallbladder cancer in 2). Seven of 8 patients had a prior diagnosis of CC but had undergone a drainage operation (3 patients), expectant treatment (3 patients), or incomplete excision (1patient). In none of the patients with cancer was surgery not curative. Nine patients had previously undergone a cystoduodenostomy and/or cystojejunostomy as children. Four of them had cancer on presentation as adults. There were no postoperative deaths. Cancer subsequently developed in no patient whose benign extrahepatic cyst was excised, regardless of the extent of enlargement of the intrahepatic bile duct. CONCLUSIONS:Congenital CCs consist principally of congenital dilation of the extrahepatic bile duct with a variable amount of intrahepatic involvement. We believe that the standard classification scheme is confusing, unsupported by evidence, misleading, and serves no purpose. The distinction between type I and type IV CCs has to be arbitrary, for the intrahepatic ducts were never completely normal. Although Caroli disease may resemble CCs morphologically, with respect to cause and clinical course, the 2 are unrelated. The other rare anomalies (gallbladderlike diverticula; choledochocele) are also unrelated to CC. Therefore, the term "congential choledochal cyst" should be exclusively reserved for congenital dilation of the extrahepatic and intrahepatic bile ducts apart from Caroli disease, and the other conditions should be referred to by their names, for example, choledochocele, and should no longer be thought of as subtypes of CC. Our data demonstrate once again a persistent tendency to recommend expectant treatment in patients without symptoms and the extreme risk of nonexcisional treatment. The entire extrahepatic biliary tree should be removed when CC is diagnosed whether or not symptoms are present. The outcome of that approach was excellent.