EUS diagnosis of vascular invasion in pancreatic cancer: surgical and histologic correlates

BACKGROUND: Endoscopic ultrasound (EUS) has been compared to intraoperative surgical palpation for diagnosis of vascular invasion by pancreatic cancer. This study compares EUS with vascular resection and histologic evidence of vascular invasion in resected pancreatic masses. METHODS: All patients with solid pancreatic masses who underwent both preoperative EUS and surgery at 1 hospital over a 7 year period were identified. The relationship of pancreatic masses to adjacent vessels was prospectively assessed by EUS. EUS findings were compared to surgical and pathology gold standards. "Vascular adherence" was defined as tumor adherence requiring vascular resection during surgery, and "vascular invasion" as histologic invasion of vessel wall by tumor. RESULTS: 30 of 68 patients were resectable. Among these 30, vascular adherence was present in 8, including 18% of patients with an intact echoplane between tumor and adjacent vessels at EUS, 29% of those with loss of echoplane alone, and 50% of those with additional EUS features of vascular involvement. Vascular invasion was present in 4, including 12% of patients with an intact echoplane, 0% of those with loss of echoplane alone, and 33% of those with additional EUS features. Sensitivity, specificity, PPV, and NPV of EUS were 63%, 64%, 43% and 80% for vascular adherence and 50% 58%, 28% and 82% for vascular invasion. NPV rose to 90% for vascular adherence if only the portal confluence vessels were considered. CONCLUSIONS: EUS has poor sensitivity, specificity, and positive predictive value for diagnosis of venous involvement by pancreatic cancer.     

Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation

Oval cell activation, as part of the regenerative process after liver injury, involves considerable cell-matrix interaction. The matricellular protein, connective tissue growth factor (CTGF), has been shown to be critical for oval cell activation during liver regeneration following N-2-acetylaminofluorene/partial hepatectomy. To understand the mode of action of CTGF during this process, N-terminal CTGF was used as bait to screen a yeast two-hybrid complementary DNA library specific for regenerating livers with massive oval cell presence. Fibronectin (FN), a prominent component of hepatic extracellular matrix (ECM), was found to specifically bind to a new site on CTGF. In addition to module IV, this study showed that module I of CTGF was sufficient for binding to FN in both solid-phase in vitro binding assays and immunoprecipitation. Immunofluorescent staining revealed a dynamic ECM remodeling characterized by an FN-concentrated provisional matrix during oval cell-aided liver regeneration. Abundant CTGF protein was colocalized with FN in the provisional matrix. When expressed as recombinant proteins and immobilized on plastic surfaces, modules I and IV of CTGF were selectively adhesive to thymus cell antigen 1-positive (Thy1(+)) oval cells, stellate cells, and sinusoidal endothelial cells but not to hepatocytes. The adhesion of these two modules on Thy1(+) oval cells required heparan sulfate proteoglycan and integrin alpha(5)beta(1). Recombinant CTGF promoted an integrin alpha(5)beta(1)-dependent migration but not proliferation on Thy1(+) oval cells. CONCLUSION: Modules I and IV enabled the linkage of CTGF to FN and activated hepatic cells. Through these bindings, CTGF on the FN-concentrated provisional matrix promoted cell adhesion and migration, thereby facilitating oval cell activation.     

The influence of age on changes in health-related quality of life over three years in a cohort undergoing hemodialysis

OBJECTIVES: To assess the extent to which persons aged 70 and older undergoing hemodialysis (HD) had greater changes in health‐related quality of life (HRQOL) over 3 years than younger patients undergoing HD. DESIGN: Longitudinal. SETTING: The Hemodialysis Study (HEMO Study) was a randomized, clinical trial of the effects of HD dose and membrane flux on mortality and morbidity in patients undergoing chronic dialysis. PARTICIPANTS: Secondary analysis of the HEMO Study. MEASUREMENTS: Participants completed the Index of Well‐Being (IWB) and the Kidney Disease Quality of Life—Long Form (KDQOL‐LF), which also includes the Medical Outcomes Study 36‐item Short Form Questionnaire (SF‐36) annually. Changes in subjects those aged 70 and older were compared with changes in subjects aged 55 to 69 and 18 to 54. RESULTS: At baseline, 1,813 (98%) of HEMO participants completed HRQOL surveys. Their mean age was 58, 56% were female, 64% were black, and mean duration of dialysis was 3.8 years. In subjects with HRQOL data at the first three annual assessments, there were no substantial mean declines in the SF‐36 Physical or Mental Component Summary scales over 3 years. In models incorporating effects of attrition, the differences in average change over 3 years between patients undergoing HD aged 70 and older and the younger cohorts were small in magnitude. There were high rates of adverse HRQOL events in all age groups and significantly higher composite event rates of death or clinically significant decline in HRQOL over 3 years was found in subjects aged 70 and older. CONCLUSION: Although HRQOL was impaired in the population undergoing HD, HRQOL scores at baseline reflect a better‐preserved multidimensional quality of life in respondents in the HEMO Study aged 70 and older than in younger patients undergoing HD. There was no substantial relationship between age and average decline in HRQOL score over 3 years in participants in the HEMO Study.     

Genetic counseling and interpretation of genetic tests in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer

PURPOSE: Genetic counseling and interpreting genetic test results can be complex. Moreover, without knowing the limitations of the methods used and the lifetime probability of developing cancer in individuals who carry a gene that predisposes to cancer, misinterpretation may lead to false assurance. The purpose of this review is to discuss how genetic counseling will benefit patients and their family, the genetic tests available for hereditary colorectal cancer syndromes, and the interpretation of results. METHODS: Current literature was reviewed and our clinical and research experiences were incorporated. RESULTS: This review serves as a guide to enable various health care providers to better counsel patients in their quest for advice on prevention, early detection, and surveillance for colorectal cancer. Notable topics of discussion are who should undergo genetic counseling and consider testing and how the interpretation of test results can be misleading; for example, understanding the difference between a no mutation detectedvs. a negative test result. CONCLUSIONS: Genetic counseling is of paramount importance for patients to fully understand the limitations of genetic testing and will aid in the management of patients who are susceptible to colorectal cancer.     

Occlusion of the coronary sinus ostium: a danger for cavopulmonary anastomosis.

Coronary sinus (CS) ostial obstruction decompressing through a left superior vena cava is a rare finding and presents unique risks to patients requiring a Glenn anastomosis for single-ventricle palliation. Preoperative diagnosis is imperative in order to avoid inadvertent ligation or coil occlusion. We report three cases with single-ventricle physiology and CS obstruction identified at cardiac catheterization. Balloon occlusion angiography proved valuable in making the diagnosis.     

Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant

Treatment options for persons with leukemia relapsing after allogeneic transplantation are limited. We analyzed the outcome of 279 patients with acute and chronic leukemia, who relapsed after HLA-identical sibling transplantation and received a second allogeneic transplant. The influence of potential risk factors on treatment-related mortality (TRM), relapse, treatment failure (relapse or death) and overall survival after second transplantation were assessed using proportional-hazards regression. The cumulative incidences (95% confidence interval) of relapse and TRM at 5 years were 42 (36-48)% and 30 (24-36)%, respectively. The 5-year probabilities of both overall and leukemia-free survival were 28 (23-34)%. In multivariate analyses, risks of treatment failure and mortality were lower in younger patients (< or =20 years) and patients who relapsed after 6 months from first transplantation. Risks of relapse were lower in patients who relapsed after 6 months from first transplantation and in complete remission prior to second transplantation. Risks of relapse were higher after reduced-intensity conditioning regimens. Any potential advantage of using a different matched related donor for a second transplantation is not supported by these data. Although age, disease status and conditioning regimen are important, duration of remission after first transplantation appear to be the most important determinant of outcome.     

High-resolution melting analysis for detection of MYH9 mutations

May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FTNS) and Epstein (EPS) syndromes are rare autosomal dominant disorders with giant platelets and thrombocytopenia. Other manifestations of these disorders are combinations of the presence of granulocyte inclusions and deafness, cataracts and renal failure. Currently, MHA, SBS, FTNS and EPS are considered to be distinct clinical manifestation of a single illness caused by mutations of the MYH9 gene encoding the heavy chain of non-muscle myosin IIA (NMMHC-IIA). As the MYH9 gene has a high number of exons, it takes much time and material to use this method for the detection of MYH9 mutations. Recently, a new method has been introduced for scanning DNA mutations without the need for direct sequencing: high-resolution melting analysis (HRMA). Mutation detection with HRMA relies on the intercalation of the specific dye (LC Green plus) in double-strand DNA and fluorescence monitoring of PCR product melting profiles. In our study, we optimized the conditions and used HRMA for rapid screening of mutations in all MYH9 exons in seven affected individuals from four unrelated families with suspected MYH9 disorders. Samples identified by HRMA as positive for the mutation were analysed by direct sequencing. HRMA saved us over 85% of redundant sequencing.     

Morphologic Parameters of Normal Swallowing Events Using Single-Shot Fast Spin Echo Dynamic MRI

This study was designed to determine visible and measurable morphological parameters in normal swallowing using dynamic MRI with single-shot fast spin echo (SSFSE), as a preliminary study in view of noninvasive MRI swallowing evaluation in patients with dysphagia. Seven healthy volunteers aged 24–40 underwent dynamic MRI with SSFSE, with a 1.5-T unit, using a head and neck antenna. Patients repeated dry swallow, water swallow, marshmallow swallow, cake swallow, and cookie chewing for a total of five series, with 15 acquisitions per series at a rate of 700 ms per acquisition. A checklist of swallowing events and anatomic landmarks was used to determine which anatomic landmarks are always visible, which phases or swallowing movements are always visible, and which landmarks can be used to measure oral and pharyngeal motion in swallowing. The oral preparatory, oral, and oropharyngeal phases of deglutition were visible in all cases. No aspiration, reflux, or abnormal residue was observed. Spatial resolution allowed for anatomical measurements of laryngeal elevation, oropharyngeal diameter, and tongue base and velum displacement in all cases. SSFSE dynamic MRI is pertinent for evaluation of the anatomical and physiological characteristics of swallow. The temporal parameters, however, cannot be studied using this technique. Motion artifacts preclude its use in the study of mastication. It remains complementary to videofluoroscopy and other techniques in swallow evaluation.     

The relationship among previous antimicrobial use,antimicrobial resistance,and treatment outcomes for Helicobacter pylori infections

The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown.     

Musculoskeletal manifestations of endocrine disorders

PURPOSE OF REVIEW: Much of our education about endocrine disorders focuses on their diagnosis and treatment. Although the musculoskeletal manifestations of endocrine disorders are well documented, they are often overlooked. This review will discuss new developments regarding those rheumatic manifestations. RECENT FINDINGS: Diabetic research is investigating connective tissue alterations in hand syndromes. A recent review elucidated the natural history of diabetic muscle infarction. Research has identified factors that stimulate osteoblast activity in diffuse idiopathic skeletal hyperostosis and bone loss in diabetics. Accumulating evidence documents thyroid disease coexisting with connective tissue disorders. Reports document cases of vasculitis occurring after propylthiouracil treatment. Finally, data clarifies the effects of thyroid dysfunction, hyperparathyroidism, acromegaly and hypercortisolism on bone. SUMMARY: Current research mainly relates to the effects of endocrine disorders on bone. As we advance our understanding of mechanisms that lead to rheumatic disorders in endocrine disease, we will improve our ability to treat them.