Predictive value for malignancy in the finding of microcalcifications on ultrasonography of thyroid nodules

Background. The am of this study was to determine the predictive value for malignancy of microcalcifications determined by ultrasonography in thyroid nodules. Methods. One hundred seventy-seven nodules were prospectively studied by ultrasonography and compared with their fine-needle aspirative biopsy. The association between the presence and type of calcification and cytologic findings was verified through the chi-square test or likelihood ratio. Results. Thirty nodules showed calcification, of which 17 had fine calcifications, 3 had fine and gross calcifications, and 10 had only coarse calcification. Seven (41.18%) of 17 fine calcified nodules were malignant on cytology, 8 (47.06%) were benign, 1 (5,88%) was indeterminate, and 1 was suspect for malignancy. We found statistical significance between the presence of fine calcifications and malignancy (p =.001) and, in the 13 malignant nodule group, 8 (61.50%) had fine calcifications. Conclusion. This study suggests that microcalcifications were highly specific for malignancy and were present in 61% of the malignant nodules. (c) 2008 Wiley Periodicals, Inc.

Long-Term Nutritional Outcome After Gastric Bypass

Weight loss and nutritional status 5 or more years after Roux-en-Y gastric bypass was prospectively documented. The hypothesis was that even after clinical adaptation, imbalances might still occur. Seventy-five consecutive patients (age 49.3 +/- 10.6 years, 89.3% females) were recruited 83.4 +/- 14.3 months after the intervention. Weight loss and nutritional abnormalities were registered. Body mass index (BMI) was 56.5 +/- 10.0 preoperatively, 29.4 +/- 6. 2 by 24 months and 34.4 +/- 14.6 when last seen. Major current deficit occurred for magnesium (32.1% of the patients), hemoglobin (50.8%), iron (29.8%), ferritin (36.0%), zinc (40.5%), vitamin B(12) (61.8%), vitamin D(3) (60.5%), and beta-carotene (56.8%). Low preoperative measurements had already been unveiled for iron, transferrin, zinc, and vitamin B(12). Total drug consumption tended to decrease after operation, and present findings correlated with excess weight loss (EWL). Also presence of diabetes and BMI value were predictors of long-term EWL, along with biochemical profile by 2 years. Multivitamin supplementation and gastrointestinal complaints partially correlated with nutritional results. (1) Good initial weight loss with moderate late regain, anemia, and multiple nutrient deficits was the common pattern. (2) Massive weight loss, frequent vomiting, dumping syndrome, and women in reproductive age were risk factors for hemoglobin or vitamin deficits, whereas superobesity, diabetes, and use of multiple drugs were associated with EWL result. (3) Most laboratory tests became stable by 2 years and along with BMI correlated with late EWL. (4) Two-year nutritional investigation is especially recommended because of its long-term predictive value.

The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer

The aim of the present work was to assess the role of monocarboxylate transporters (MCTs), namely MCT1 and MCT4 as well as MCT/CD147 co-expression in gastric tissues and evaluate their clinico-pathological significance in gastric carcinoma. For that, we analysed the immunohistochemical expression of MCT1, MCT4 and CD147, in a large series of gastric samples, including non-neoplastic, tumour and metastatic tissues. A significant decrease in MCT4 plasma membrane expression was observed from non-neoplastic to gastric primary malignant tissues and to lymph-node metastasis and both MCT1 and MCT4 correlated with CD147. Importantly, both MCT4 and CD147 were more frequently expressed in Lauren`s intestinal-type tumours and MCT1/CD147 co-expression was associated with advanced gastric carcinoma, Lauren`s intestinal type, TNM staging and lymph-node metastasis. Our results showed that the prognostic value of CD147 was associated with MCTI co-expression in gastric cancer cells, supporting the view that CD147 plasma membrane activity is dependent on MCT co-expression. (C) 2009 Elsevier Ltd. All rights reserved.

Prospective randomized trial of EUS versus ERCP-guided common bile duct stone removal: an interim report (with video)

Background: EUS is being increasingly utilized for the diagnosis of choledocholithiasis and microlithiasis, especially in patients with biliary colic. Simultaneously, there is also a rising interest in the use of EUS for therapeutic interventions. Objectives: Our goal was to assess the effectiveness of EUS-directed common bile duct (CBD) stone removal to compare its safety and effectiveness with ERCP-directed intervention. Design: interim results of a prospective, randomized, single-center blinded clinical trial. Setting: A single tertiary care referral center. Patients: Fifty-two patients with uncomplicated CBD stones were prospectively randomized to CBD cannulation and stone removal under EUS or ERCP guidance. Main Outcome Measurements and Interventions: Primary outcome measure was the rate of successful cannulation of the CBD. Secondary Outcome measures included Successful removal of stones and overall complication rates. Results: CBD cannulation followed by stone extraction was successful in 23 of 26 patients (88.5%) in the EUS group (1) versus 25 of 26 patients (96.2%) in the ERCP group (11) (95% CI, -27.65%, 9.88%). Overall, there were 3 complications in the EUS group and 4 complications in the ERCP group. Limitation: The current study is an interim report from a single center report and performed by a single operator. Conclusions: Our preliminary analysis indicates that Outcomes following EUS-guided CBD stone retrieval are equivalent to those following ERCP EUS-related adverse events are similar to those following ERCP. ERCP and EUS-guided stone retrieval appears to be equally effective for therapeutic interventions of the bile duct. Additional studies are required to validate these preliminary results and to determine predictors of success of EUS-guided stone removal. (Gastrointest Endosc 2009;69:238-43.)

An integrated genomic analysis of human glioblastoma Multiforme

Glioblastoma multiforme ( GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high- density oligonucleotide arrays, and performed gene expression analyses using next- generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 ( IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.

Common mental disorders during pregnancy and adverse obstetric outcomes

Methods. A prospective cohort study was conducted with 831 pregnant women from antenatal clinics in primary healthcare in Sao Paulo, Brazil. The clinical interview schedule-revised and demographic questionnaires were administered between the 20th and 30th weeks of gestation. Information on infant weight and gestational age at birth were obtained from hospital records. Univariate analyses were used to examine the association between the main exposure and main outcomes. Statistical associations were examined with chi

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C > T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C > A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C > A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.

Common mental disorders during pregnancy: prevalence and associated factors among low-income women in Sao Paulo, Brazil

To estimate the prevalence of common mental disorders (CMD) and factors associated with these disorders among pregnant women of low socio-economic status (SES) in Sao Paulo. We performed a cross-sectional study with 831 women in their 20th to 30th weeks of pregnancy, who were attending antenatal clinics in primary care in Sao Paulo, Brazil. CMD were assessed with the Clinical Interview Schedule-Revised. Crude and adjusted prevalence ratios and 95% CI were calculated to examine the association between CMD and exposure variables. The prevalence of CMD was 20.2% (95% CI 17.5 to 23.0). Age at current pregnancy and at first delivery, current obstetric complications, not having friends in the community, living in a crowded household, lower occupational status and history of previous psychiatric treatment were all independently associated with increased prevalence of CMD. CMD is highly prevalent among pregnant women of low SES seen in primary care settings in Sao Paulo. A combination of distal and proximal psychosocial factors increase the risk for CMD. Primary health care professionals need to be aware of how common CMD in such settings and properly trained to deal with CMD during pregnancy.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Lymphatic Vessel Density and VEGF-C Expression are Significantly Different Among Benign and Malignant Thyroid Lesions

Thyroid cancer is the most frequent endocrine neoplasia worldwide. The route for metastasis and loco-regional invasion preferentially occurs by lymphatic vessels. For this reason, the assessment of lymphatic vessel density (LVD) is supposed to represent both a prognostic parameter and also a potential therapeutic target. In order to evaluate the value of LVD in benign and malignant thyroid lesions, we analyzed 110 thyroidectomy specimens using D2-40, a specific marker for lymphatic vessels and vascular endothelial growth factor C (VEGF-C), the most potent molecule of lymphatic proliferation. LVD was significantly different between papillary and follicular carcinomas in total (p = 0.045) and peritumoral area (p = 0.042). Follicular adenoma and follicular carcinoma showed an important difference of intra- (p = 0.019) and peritumoral (p = 0.033) LVD. VEGF-C was more markedly expressed in malignancies than in benignant lesions (p = 0.0001). Almost all cancers with high positive VEGF-C expression also exhibited increased peritumoral LVD (p = 0.049) when compared with the benignant lesions. Indeed, the high peritumoral LVD of malignant thyroid lesions is an important finding for surgery planning and supports the practice of total thyroidectomy in malignant thyroid neoplasm`s since the lymphatic peritumoral vessels definitely are an escape path for tumor cells.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.

Extent of Pelvic Lymphadenectomy in Women With Squamous Cell Carcinoma of the Uterine Cervix: Is There Any Prognostic Value?

Background and Objectives: Some authors states that the removal of lymph node would only contribute towards assessing the lymph node status and regional disease control, without any benefit for the patients` survival. The aim of this paper was to assess the influence of the number of surgically dissected pelvic lymph nodes (PLN) on disease-free Survival. Methods: Retrospective cohort study on 42 women presenting squamous cell carcinoma (SCC) of the uterine cervix, with metastases in PLN treated by radical surgery. The Cox model was used to identify risk factors for recurrence. The model variables were adjusted for treatment-related factors (year of treatment, surgical margins and postoperative radiotherapy). The cutoff value for classifying the lymphadenectomy as comprehensive (15 PLN or more) or non-comprehensive (<15 PLN) was determined from analysis of the ROC curve. Results: Fourteen recurrences (32.6%) were recorded: three pelvic, eight distant, two both pelvic and distant, and one at an unknown location. The following risk factors for recurrence were identified: invasion of the deep third of the cervix and number of dissected lymph nodes <15. Conclusions: Deep invasion and non-comprehensive pelvic lymphadenectomy are possible risk factors for recurrence of SCC of the uterine cervix with metastases in PLN. J. Surg. Oncol. 2009;100:252-257. (C) 2009 Wiley-Liss, Inc.

Characterization of acid-base status in maintenance hemodialysis: physicochemical approach

Acidosis is a common and deleterious aspect of maintenance dialysis. Traditionally, it is considered to be an elevated anion gap acidosis caused by the inability to excrete nonvolatile anions. Stewart`s approach made it possible to identify real determinants of the acid-base status and allowed quantification of the components of these disturbances, especially the unmeasured anions. We performed a cross-sectional study to identify and quantify each component of acidosis in hemodialysis maintenance patients. Sixty-four maintenance hemodialysis patients and 14 controls were enrolled in this study. Gasometrical and biochemical analysis were performed before the midweek dialysis session. Quantitative physicochemical analysis was carried out using the Stewart methodology. Hemodialysis patients were found to have mild acidemia (mean pH: 7.33 +/- 0.06 versus 7.41 +/- 0.05) secondary to metabolic acidosis (serum bicarbonate: 18.8 +/- 0.26 versus 25.2 +/- 0.48 mEq/l). The metabolic acidosis was due to retention of unmeasured anions (6.5 +/- 0.29 versus 3.1 +/- 0.62 mEq/l), hyperchloremia (105.1 +/- 0.5 versus 101.8 +/- 0.7 mEq/l), and hyperphosphatemia (5.90 +/- 0.19 versus 3.66 +/- 0.14 mg/dl). Compared with control values, the unmeasured anions and hyperchloremia had a similar acidifying effect (3.4 and 3.3 mEq/l), corresponding to almost 90% of the metabolic acidosis. Unmeasured anions and hyperchloremia are important components of acidosis in maintenance hemodialysis, in addition to phosphorus. Future studies to determine the etiology and consequences of hyperchloremic acidosis are warranted.

Management of Common Bile Duct Stones in Cirrhotic Patients with Coagulopathy: A Comparison of Supra-Papillary Puncture and Standard Cannulation Technique

Bleeding is not uncommon following endoscopic sphincterotomy. Supra-papillary puncture (SPP) might be safer than standard cannulation (SC) techniques in patients with coagulopathy. The aim of the study was to compare the safety and effectiveness of SPP and SC. This was a prospective case control intervention study. Decompensated cirrhotic patients with coagulopathy and choledocolithiasis underwent SC and SPP methods for biliary access. One hundred five patients (56 [53.3%] men, mean [SD] age 56 [15.8]) underwent ERCP. SC and SPP were performed in 63 and 42 patients, respectively. Biliary access was achieved in 56/63 (89%) and 40/42 (95%) of patients undergoing SC and SPP, respectively (P = 0.13; 95% CI [-0.16; 0.03]). Complications occurred in 10/63 (15.8%) patients undergoing SC and 5/42 (11.9%) SPP (P = 0.28; 95% CI [-0.17, 0.16]). Five (7.9%) and two (3.2%) episodes of post-sphincterotomy bleeding was seen in the SC and SPP groups, respectively (P = 0.36; 95% CI [-0.16, 0.05]). In contrast, three (4.8%) episodes of pancreatitis were seen in the SC and none in the SPP group (P = 0.05; 95% CI [0.001; 0.004]). A cost-effectiveness analysis demonstrated that SPP is an acceptable alternative at an ICER of US$ 5,974.92 per additional successful procedure. SPP is a safe and effective technique for the management of common bile duct stones in decompensated cirrhotic patients. Conditional to the willingness-to-pay and to the local ERCP-related costs, SPP is also a cost-effective alternative to the SC methods. SPP is associated with a lower rate of complications but larger studies to validate these findings are necessary.