Anil K. Dasyam

RAS Mutations in Thyroid FNA Specimens Are Highly Predictive of Predominantly Low-Risk Follicular-Pattern Cancers

INTRODUCTION RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described. METHODS From April 2007 to April 2009, 921 consecutive patients undergoing FNA were evaluated prospectively with a panel of molecular markers. Ultrasonographic, cytological, histological, and surgical outcomes were retrospectively assessed. RESULTS Sixty-eight aspirates from 66 patients were positive for RAS mutations including 63 cytologically indeterminate (93%), 3 malignant (4%), and 2 benign (3%) specimens. Cancer was histologically confirmed in 52 of 63 aspirates (83%) including the following: 46 papillary thyroid cancers, 4 follicular thyroid cancers, 1 medullary cancer, and 1 anaplastic cancer. All 46 RAS-positive papillary thyroid cancers, including 1 metastatic cancer, had follicular variant histology papillary thyroid cancer; only 11 tumors demonstrated vascular/capsular invasion and 4 had infiltrative growth. Of 48 patients with differentiated thyroid cancer, lymph node metastasis was uncommon and bilateral cancer was present in 48%. Only 33% of malignant nodules were suspicious by preoperative ultrasonography. At a mean follow-up of 22 months, 31 of 35 differentiated thyroid cancer patients (89%) have no evidence of recurrence, 4 patients (9%) have detectable thyroglobulin, 1 patient has bone metastases, and both patients with medullary and anaplastic cancer have died. CONCLUSION Most RAS-positive thyroid cancers have indeterminate cytology, lack suspicious ultrasound features, and are histologically low-grade follicular variant histology papillary thyroid cancer. Lymph node and distant metastases are uncommon but bilateral disease is frequent. Total thyroidectomy should be considered for initial surgical management of most patients with RAS-positive FNA results. The role of prophylactic lymphadenectomy remains unclear.

Adult Bile Duct Strictures: Role of MR Imaging and MR Cholangiopancreatography in Characterization

Bile duct strictures in adults are secondary to a wide spectrum of benign and malignant pathologic conditions. Benign causes of bile duct strictures include iatrogenic causes, acute or chronic pancreatitis, choledocholithiasis, primary sclerosing cholangitis, IgG4-related sclerosing cholangitis, liver transplantation, recurrent pyogenic cholangitis, Mirizzi syndrome, acquired immunodeficiency syndrome cholangiopathy, and sphincter of Oddi dysfunction. Malignant causes include cholangiocarcinoma, pancreatic adenocarcinoma, and periampullary carcinomas. Rare causes include biliary inflammatory pseudotumor, gallbladder carcinoma, hepatocellular carcinoma, metastases to bile ducts, and extrinsic bile duct compression secondary to periportal or peripancreatic lymphadenopathy. Contrast material-enhanced magnetic resonance (MR) imaging with MR cholangiopancreatography is extremely helpful in the noninvasive evaluation of patients with obstructive jaundice, an obstructive pattern of liver function, or incidentally detected biliary duct dilatation. Some of these conditions may show characteristic findings at MR imaging-MR cholangiopancreatography that help in making a definitive diagnosis. Although endoscopic retrograde cholangiopancreatography with tissue biopsy or surgery is needed for the definitive diagnosis of many of these strictures, certain MR imaging characteristics of the narrowed segment (eg, thickened wall, long-segment involvement, asymmetry, indistinct outer margin, luminal irregularity, hyperenhancement relative to the liver parenchyma) may favor a malignant cause. Awareness of the various causes of bile duct strictures in adults and familiarity with their appearances at MR imaging-MR cholangiopancreatography are important for accurate diagnosis and optimal patient management.

Adult Renal Cystic Disease: A Genetic, Biological, and Developmental Primer

Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases.

Portosplenomesenteric Venous Thrombosis in Patients With Acute Pancreatitis Is Associated With Pancreatic Necrosis and Usually Has a Benign Course

BACKGROUND & AIMS Although there are some data on prevalence of portosplenomesenteric venous thrombosis (PSMVT) in patients with acute pancreatitis (AP), the progression of PSMVT in patients who have and have not received anticoagulants has not been studied systematically. We evaluated the prevalence and natural history of PSMVT in a well-defined cohort of individuals with AP. METHODS In a retrospective study, we analyzed data from the University of Pittsburgh Medical Center on 162 patients with a sentinel attack of AP from 2003-2010. Data were collected on patient demographics, clinical presentation, etiology, clinical course, and outcomes. One hundred twenty-two patients underwent contrast-enhanced computed tomography; the scans were reviewed to identify thromboses and/or narrowing of splanchnic veins (splenic, superior mesenteric, and portal). RESULTS PSMVT was detected in 22 patients overall (14%; 18% among patients who underwent contrast-enhanced computed tomography). Median time to detection of PSMVT was 17 days (interquartile range, 11-40 days). PSMVT formed most frequently in the splenic vein (19 of 22, 86%), followed by portal (8 of 22, 36%) and superior mesenteric (6/22, 27%) veins. Development of PSMVT was associated with presence (21 of 22, 95%), location, and extent of pancreatic necrosis. Fifty-three percent of patients (21 of 40) with necrosis developed PSMVT. Anticoagulants were administered infrequently (6 of 22, 27%) and always for indications unrelated to PSMVT. Most patients with PSMVT developed collateral veins (19 of 22, 86%), and 27% (6 of 22) were found to have varices during endoscopic evaluation, but clot resolution was infrequent (2 of 22, 9%). No patient developed complications directly related to PSMVT. CONCLUSIONS PSMVT develops in about half of patients with necrotizing AP and is rare in the absence of necrosis. Despite infrequent administration of anticoagulants, complications directly related to PSMVT are rare.

Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia

Objective DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. Design Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing. Results KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively). Conclusions In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.

Adult choledochal cysts: current update on classification, pathogenesis, and cross-sectional imaging findings

Abstract Approximately 20% of choledochal cysts (CC) present in adult patients and they are commonly associated with a high risk of complications, including malignancy. Additionally, children who underwent internal drainage procedures for CCs can develop complications during adulthood despite treatment. Concepts regarding classification and pathogenesis of the CCs have been evolving. While new subtypes are being added to the widely accepted Todani classification system, simplified classification schemes have also been proposed to guide appropriate management. The exact etiology of CCs is currently unknown. The two leading theories involve either the presence of an anomalous pancreatico-biliary junction with associated reflux of pancreatic juice into the biliary system or, more recently, some form of antenatal biliary obstruction with resulting proximal bile duct dilation. Imaging studies play an important role in the initial diagnosis, surgical planning, and long-term surveillance of CCs.

Development of nonobstructive intraarterial thrombi after injection of thrombin into pseudoaneurysms

OBJECTIVE Our objective was to describe the development of nonobstructive, localized intraarterial thrombi after percutaneous injection of thrombin into femoral pseudoaneurysms. CONCLUSION Partial extension of thrombi into the arterial lumen may occur after injection of thrombin into small pseudoaneurysms with short necks. In our experience, this is an asymptomatic and self-limited complication of the procedure.

Isolated Peripancreatic Necrosis in Acute Pancreatitis Is Infrequent and Leads to Severe Clinical Course Only When Extensive: A Prospective Study From a US Tertiary Center.

Goals: To explore the diagnostic challenges, management, and clinical outcomes of patients with isolated peripancreatic necrosis (PPN), with emphasis on the extent of involvement, and compare them to pancreatic necrosis (PN). Background: PPN, a relatively new term, has been included as a separate entity in the Revised Atlanta Classification. Study: Clinical data of recruited acute pancreatitis patients were recorded prospectively. Contrast-enhanced computed tomographic scans were reviewed by expert radiologists blinded to clinical outcomes. Results: In total, 271 of the 400 acute pancreatitis patients underwent contrast-enhanced computed tomography, of which 29 (11%) had PPN (14: limited; 15: extensive) and 124 (46%) PN (40: <30%, 16: 30% to 50%, 68: >50% of parenchyma). Patients with PPN were similar to PN in age (56 y), gender (55% male), and body mass index (29 kg/m2). Nutritional support was provided in 18 (62%) patients with PPN and 97 (78%) with PN (P=0.12). Drainage/debridement was required in 2 patients (7%) with PPN and 64 (53%) with parenchymal necrosis (P<0.001). Persistent organ failure rates did not differ significantly (34% vs. 51%, P=0.17), but hospital stay was shorter in patients with PPN (15 vs. 20 d, P=0.05). Limited PPN required no intervention and had similar persistent organ failure rates and hospitalization length with interstitial pancreatitis (both P≥0.12). Extensive PPN mainly developed in patients with persistent organ failure (60%) and rarely required drainage (2/15). Conclusions: PPN prevalence was lower than PN with a ratio of 1:4. PPN rarely required intervention. Utilizing the extent of involvement has the potential to classify PPN and PN with escalating clinical significance and guide management.

Renal Allograft Torsion: US and CT Imaging Findings of a Rare Posttransplant Complication

Vascular torsion is a rare renal transplant complication which requires prompt diagnosis and surgery to salvage allograft function. We report here a case of renal allograft torsion with interesting imaging findings on unenhanced CT and color Doppler ultrasound. A 60-year-old woman with a history of pancreas and kidney transplant presented to the emergency room with nausea, vomiting, abdominal pain, and minimal urine output. Unenhanced CT of the abdomen demonstrated an enlarged and malrotated renal allograft with moderate hydronephrosis. Color Doppler ultrasound demonstrated lack of vascularity within the allograft. The patient was taken urgently to the operating room where the renal allograft was found twisted 360 degrees around the vascular pedicle. After the allograft was detorsed, the color of the kidney returned and the Doppler signals for arterial flow improved. Intraoperative biopsy showed no evidence of infarct or acute cellular rejection. The detorsed kidney was surgically fixed in position in its upper and lower poles. Follow-up ultrasound 1 day later demonstrated normal blood flow to the renal allograft and the serum level of creatinine returned to normal.

The cystic duct knot sign: case report with description of a new ultrasound sign of gallbladder torsion

Gallbladder torsion or volvulus is a rare but potentially lethal entity. We report the imaging findings of gallbladder torsion and describe a potentially novel ultrasound sign for the preoperative diagnosis of torsion. An 87-year-old woman presented with a 4-day history of right upper quadrant pain. An initial right upper quadrant ultrasound exam demonstrated cholelithiasis and findings of acute cholecystitis which included gallbladder distension, wall thickening, trace pericholecystic fluid, and a positive sonographic Murphy’s sign. Gallbladder torsion was prospectively diagnosed on the subsequent contrast-enhanced CT scan of the abdomen based upon the abnormal transverse orientation of the gallbladder with the neck directed laterally. Ultrasound images were reviewed and a “knot”-like hyperechoic nodular appearance of the torsed cystic duct close to the gallbladder neck was clearly apparent. Prospective identification of the torsed cystic duct may prompt the ultrasound diagnosis of gallbladder torsion.