Mark R. Conaway

Efficacy and complications of covered wallstents in malignant distal biliary obstruction

BACKGROUNDnThis study evaluated the efficacy and the complications associated with the use of the covered Wallstent in the setting of unresectable malignant biliary obstruction.nnnMETHODSnBetween March 2001 and January 2003, all patients with distal malignant biliary obstruction that required drainage were treated with a covered Wallstent. Every 2 months, the patients were evaluated clinically and biochemical tests of liver function were obtained. Data were recorded for the following variables: early complications (within 30 days of stent placement), early and late stent occlusion, duration of stent patency, need for subsequent biliary intervention, and patient survival.nnnRESULTSnA total of 88 covered Wallstents were inserted in 80 patients. Stent patency rates at 3, 6, and 12 months were 90%, 82%, and 78%, respectively. Complications included stent migration (5), stent occlusion (12), episodes of cholecystitis (3), and episodes of post-ERCP pancreatitis (5). Biliary intervention was required in 9 patients subsequent to placement of the initial covered Wallstent.nnnCONCLUSIONSnDeployment of a covered Wallstent is safe and relatively easy. It achieves biliary drainage with an acceptable risk to benefit ratio in the majority of patients with distal malignant biliary obstruction.

Ninety-Day Outcome Rates of a Prospective Cohort of Consecutive Patients With Mild Ischemic Stroke

Background and Purpose— Prior studies have shown that patients with mild ischemic stroke have substantial disability rates at hospital discharge. We sought to determine disability rates at 90 days among patients not treated with thrombolytic therapy and explore the role of early neurological worsening. Methods— We reviewed a prospective cohort of 136 consecutive patients with mild deficits (National Institutes of Health Stroke Scale score ⩽5) presenting within 24 hours of onset and no baseline disability. Baseline MRIs were performed on all subjects. Five-day MRIs were performed on a prespecified subcohort. Results— Among 136 patients, 40 (29%; 95% CI, 22%–38%) had poor outcomes (modified Rankin Scale score 2–6) at 90 days. Early worsening (4-point National Institutes of Health Stroke Scale increase; 25% versus 1%, P<0.001) and acute infarct growth (>10% on MRI–diffusion-weighted imaging; 79% versus 53%, P=0.02) from baseline to 5 days were more common among those with poor outcome. Conclusions— Patients with mild ischemic stroke have substantial rates (29%) of disability at 90 days.

Factors predictive of malignancy and Endoscopic resectability in ampullary neoplasia

OBJECTIVE:Endoscopic treatment of ampullary lesions has been well described, though it remains uncertain if specific features predict malignancy, and whether identifiable factors are associated with successful endoscopic resection of benign lesions.METHODS:Fifty-six consecutive patients undergoing endoscopic evaluation of ampullary neoplasia between March 2000 and May 2004 were included in the study. Clinical presentation, underlying medical conditions, endoscopic treatment, endoscopic ultrasound (EUS) to define extent of local involvement, pathology results, and outcome were documented. Data elements for analysis included EUS findings, lesion lifting with submucosal injection, age, gender, tumor size, and endoscopic intervention. Analyses were performed to determine the ability to predict malignancy and the ability to extirpate benign lesions.RESULTS:Thirty-one males and 25 females were included; mean age was 62 yr. Final diagnoses included 29 adenomas, 20 adenocarcinomas, 4 adenomyomas, 2 paragangliomas, and 1 neuroendocrine tumor. Thirty of 35 patients with benign lesions had extirpation with a mean of two endoscopic procedures. Complications of endoscopic resection included cholangitis (1), bleeding (2), and pancreatitis (4). The presence of malignancy was associated by multivariate analysis with the inability to obtain a cleavage plane with saline injection. Univariate analysis also identified EUS T stage as a predictor of malignancy. In benign lesions, none of the analyzed variables predicted successful endoscopic resection.CONCLUSION:In ampullary lesions, failure to achieve a cleavage plane with submucosal injection is the strongest predictor of malignancy followed by EUS T stage. Endoscopic treatment of benign ampullary neoplasia is effective; no factor was predictive of successful extirpation.

The level of carcinoembryonic antigen and the presence of mucin as predictors of cystic pancreatic mucinous neoplasia.

Objectives: Characterization of pancreatic cysts using endoscopic ultrasound-guided fine-needle aspiration includes cytological interpretation and chemical analysis. We prospectively analyzed the contribution of carcinoembryonic antigen (CEA) and cytological identification of extracellular mucin as predictors of mucinous neoplasia and malignancy. Methods: From January 2003 to October 2005, all patients referred to the University of Virginia with cystic lesions of the pancreas underwent endoscopic ultrasound-guided fine-needle aspiration with cytological evaluation and CEA level analysis. Data were collected prospectively and confirmed by resection or tissue biopsy. Univariate and multivariate analyses were performed on the following variables with regard to their ability to predict mucinous neoplasia: age (<55 or >55 years), sex, CEA level (<300 or >300 ng/mL), and cytological appreciation of extracellular mucin (positive or negative). P values less than 0.05 were considered significant. Results: A total of 43 patients were included in this study. There were 19 men and 24 women with a mean age of 63 ± 14 years. The only complication was pancreatitis secondary to cyst leak in one patient. Multivariate analysis confirmed CEA level greater than 300 ng/mL (P= 0.007) and the identification of mucin (P < 0.001) as significant predictors. Conclusions: With pancreatic cyst fluid analysis, the strongest predictor of mucinous neoplasia is the presence of identifiable mucin, followed by a CEA level greater than 300 ng/mL. The workup of cystic lesions of the pancreas should include chemical analysis for the CEA level and cytological examination with particular attention to extracellular mucin.

PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma

Protein kinase C-related kinases are regulated by phosphatidylinositol-3-kinase and Rho family GTPases. The isoform PRK1 has been characterized in detail in prostate cancer, but not in other carcinomas. We analyzed our prior microarray data for PRK1 gene expression in 175 carcinomas and evaluated tissue microarrays for protein expression in 251 carcinomas and a comprehensive group of normal tissues. We also used immunoblotting to determine the levels and phosphoactivation status of PRK1, PRK2, and PDK1 in 12 ovarian serous carcinomas, SKOV3 cells, and 3 samples of normal ovarian surface epithelium (OSE). The highest average level of PRK1 messenger RNA was observed in ovarian serous carcinomas compared with all other carcinomas, including those of the prostate, bladder/ureter, breast, colon, stomach/esophagus, kidney, liver, pancreas, and lung (P = .05). By immunohistochemistry, PRK1 was observed in selected normal cells, including epithelium from the gynecologic tract and hematolymphoid elements. All serous ovarian and endometrial endometrioid adenocarcinomas and mesotheliomas were immunoreactive for PRK1. The findings in nonserous ovarian and most carcinomas from the prostate, breast, and pancreas were also positive but less consistently so. In comparison with OSE, the serous carcinomas typically had greater pPRK1/total PRK1 (P = .02) as well as greater pPDK/total PDK (P = .01). The relative phosphorylation status of these 2 kinases correlated within each sample. In summary, PRK1 is present in various malignancies, but especially in serous carcinomas, where the increased activation status of PRK1 and its upstream regulator, PDK, as compared with normal OSE suggests a role in ovarian cancer development or progression.

Effects of Race, Ethnicity, and Gender on Surgical Mortality in Hypoplastic Left Heart Syndrome

Information is limited regarding the effect of race, ethnicity, and gender on the outcomes of the three palliative procedures for hypoplastic left heart syndrome (HLHS). This study examined the effects of race, ethnicity, gender, type of admission, and surgical volume on in-hospital mortality associated with palliative procedures for HLHS between 1998 and 2007 using data from the University HealthSystem Consortium. According to the data, 1,949 patients underwent stage 1 palliation (S1P) with a mortality rate of 29xa0%, 1,279 patients underwent stage 2 palliations (S2P) with a mortality rate of 5.4xa0%, and 1,084 patients underwent stage 3 palliation (S3P) with a mortality rate of 4.1xa0%. The risk factors for increased mortality with S1P were black and “other” race, smaller surgical volume, and early surgical era. The only risk factors for increased mortality with S2P were black race (11xa0% mortality; odds ratio [OR], 3.19; 95xa0% confidence interval [CI] 1.69–6.02) and Hispanic ethnicity (11xa0% mortality; OR 3.30; 95xa0% CI 1.64–6.64). For S2P, no racial differences were seen in the top five surgical volume institutions, but racial differences were seen in the non-top-five surgical volume institutions. Mortality with S1P was significantly higher for patients discharged after birth (37 vs 24xa0%; pxa0=xa00.004), and blacks were more likely to be discharged after birth (12 vs 5xa0% for all other races; pxa0<xa00.001). No racial differences with S3P were observed. The risk factors for increased mortality at S1P were black and “other” race, smaller surgical volume, and early surgical era. The risk factors for increased in-hospital mortality with S2P were black race and Hispanic ethnicity.

Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways

In head and neck squamous cell carcinoma (HNSCC), resistance to single‐agent targeted therapy may be overcome by co‐targeting of compensatory signaling pathways.

PREDICTION OF 30 DAY READMISSIONS IN PATIENTS ADMITTED FOR ACUTE MYOCARDIAL INFARCTION (AMI)

Background: The Center for Medicare and Medicaid Services (CMS) and other payers are increasingly focusing on 30 day readmissions as a quality metric tied to hospital payments. Factors that predict 30-day readmission in patients admitted with acute myocardial infarctions (AMI) have not been