Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity.

OBJECTIVE: Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm. DESIGN: In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS. RESULTS: Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%. CONCLUSION: Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

A prognostic score for clinical success after revascularization of critical limb ischemia in hemodialysis patients.

OBJECTIVE: The revascularization of critical limb ischemia (CLI) in hemodialysis (HD) patients features poor results in terms of patient survival and limb salvage. Recent predictive models in CLI revascularization did not specifically address HD patients. The aim of this study was to define risk factors for clinical success (CS) after revascularization of CLI in HD patients and to transform findings in a prognostic score. METHODS: A retrospective study was conducted of prospectively gathered data, including consecutive HD patients treated for CLI from January 2004 to December 2012. Patients' demographics, comorbidities, CLI stage (Rutherford classification), tissue loss (Texas University Wound classification [TUWC]), and type of revascularization were assessed. End points were CS after revascularization (amputation-free and reintervention-free survival) and a prognostic score for CS based on significant risk factors (multivariable analysis). RESULTS: In the study period, 131 patients (mean age, 70.2 ± 9.9 years; male, 76.3%) with a total of 180 limbs were treated. Endovascular (52.8%), surgical (28.9%), or hybrid (10.6%) revascularization was performed in 163 (90.6%) limbs in 117 patients. The mean (± standard deviation) follow-up was 20.8 ± 21.1 months. Considering revascularized patients, CS was 47.9%, 30.8%, and 17.8% at 6, 12, and 24 months, respectively. On multivariable analysis, age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .005), coronary artery disease (CAD; HR, 1.55; 95% CI, 1.04-2.32; P = .032), and TUWC stage D (HR, 1.80; 95% CI, 1.22-2.67; P = .003) were independent negative factors. Type of revascularization had no influence on CS. The score for predicting CS was 0.026 × age (years) + 0.441 × CAD + 0.59 × TUWC stage D. CAD and TUWC stage D were 1 in the presence of disease and 0 in the absence of disease. The score has a significant discrimination power of 75.5% (P = .036), with a best cutoff value of 2.07. Patients with a CS score <2.07 would have a low risk of clinical failure, whereas patients with a CS score >2.07 would have a high risk. There were 31 (26.5%) cases of low-risk score and 86 (73.5%) cases of high-risk score. Cases with low-risk score had a CS at 1 year of 51.6% compared with 23.3% in cases with high-risk score. CONCLUSIONS: CS after revascularization in HD patients remains poor independent of the type of revascularization. A prognostic model based on age, history of CAD, and severity of CLI (TUWC stage D lesion) can estimate an individual's chances of CS and may help in the decision-making process.

Inter-operator variability and source of errors in tumour response assessment for hepatocellular carcinoma treated with sorafenib.

OBJECTIVES: To assess the inter-operator concordance and the potential sources of discordance in defining response to sorafenib in hepatocellular carcinoma (HCC). METHODS: All patients who received sorafenib between September 2008 and February 2015 were scrutinised for this retrospective study. Images were evaluated separately by three radiologists with different expertise in liver imaging (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in liver imaging), according to: response evaluation radiological criteria in solid tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria in cancer of the liver (RECICL). RESULTS: The overall response concordance between the more expert operators was good, irrespective of the criteria (RECIST 1.1, ĸ = 0.840; mRECIST, ĸ = 0.871; RECICL, ĸ = 0.819). Concordance between the less expert operator and the other colleagues was lower. The most evident discordance was in target lesion response assessment, with expert operators disagreeing mostly on lesion selection and less expert operators on lesion measurement. As a clinical correlate, overall survival was more tightly related with "progressive disease" as assessed by the expert compared to the same assessment performed by operator 3. CONCLUSIONS: Decision on whether a patient is a responder or progressor under sorafenib may vary among different operators, especially in case of a non-specifically trained radiologist. Regardless of the adopted criteria, patients should be evaluated by experienced radiologists to minimise variability in this critical instance. KEY POINTS: • Inter-operator variability in the assessment of response to sorafenib is poorly known. • The concordance between operators with expertise in liver imaging was good. • Target lesions selection was the main source of discordance between expert operators. • Concordance with non-specifically trained operator was lower, independently from the response criteria. • The non-specifically trained operator was mainly discordant in measurements of target lesions.

Congenital Cytomegalovirus Infection: Prognostic Value of Maternal DNAemia at Amniocentesis.

BACKGROUND: Human Cytomegalovirus (HCMV) is the most common cause of childhood hearing loss and can lead to neurodevelopmental delay. To date, few studies have examined the correlation between maternal viremia and congenital HCMV infection. The aim of our study was to ascertain if HCMV DNA in the peripheral blood of pregnant women with primary HCMV infection at the time of amniocentesis may have a prognostic value in terms of congenital infection and neonatal symptomatic disease. METHODS: We performed a prospective observational study of pregnant women referred to our maternal-fetal medicine division with suspected HCMV infection. Primary infection was diagnosed based on seroconversion for HCMV and/or HCMV immunoglobulin M-positive and low or moderate HCMV immunoglobulin G avidity. At the time of amniocentesis, maternal blood samples were collected and analyzed by means of real-time polymerase chain reaction to determine the presence of viral DNAemia. Fetuses and newborns were evaluated for the presence of congenital infection and symptomatic disease. RESULTS: A total of 239 pregnant women were enrolled; 32 blood samples (13.4%) were positive, and 207 (86.6%) were negative for HCMV DNA. The overall rate of transmission was 23.4%. Fifteen infected patients (26.8%) were symptomatic. Vertical transmission occurred in 14 women (43.8%) with positive and 42 (20.3%) with negative results for HCMV DNAemia (P = .006; odds ratio, 3.06; 95% confidence interval, 1.41-6.64). Symptomatic infection occurred in 6 (42.9%) infected fetuses or newborns from women with and in 9 (21.4%) from women without viral DNAemia (P = .16). CONCLUSION: Maternal viremia at amniocentesis is associated with a 3-fold greater chance of congenital infection, but it is not correlated with symptomatic disease.

Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers.

BACKGROUND: A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor. METHODS: This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath. RESULTS: The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P = .014). DISCUSSION: The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers. CONCLUSIONS: The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02102191.

Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: a randomized, double-blind, placebo-controlled trial.

Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n = 40) or the homeopathic syrup (n = 40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (p < 0.001 and p = 0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (p < 0.001); however, viscosity was significantly lower in the homeopathic group (p = 0.018). Instead, the subjective evaluation did not significantly differ between the two groups (p = 0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs.

A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination.

Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a ß-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a ß-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.

Fetal head-symphysis distance and mode of delivery in the second stage of labor.

OBJECTIVE: To evaluate whether the fetal head-symphysis distance measured by three-dimensional transperineal ultrasound during the active second stage predicts operative delivery. DESIGN: Prospective observational study. SETTING: University hospital, Bologna, Italy. POPULATION: Seventy-one nulliparous women at term in active second stage of labor. METHODS: We acquired a series of sonographic volumes at the beginning of the active second stage (T1) and every 20 min thereafter (T2, T3, T4, T5, T6) until delivery. All volumes were retrospectively analyzed and head-symphysis distance was measured for each acquisition. We compared head-symphysis distance between women with spontaneous vaginal delivery and those with operative delivery. Receiver operator characteristic curves were constructed to estimate the accuracy of head-symphysis distance in the prediction of operative delivery. Logistic regression was used to identify independent variables associated with operative delivery. MAIN OUTCOME MEASURES: Operative delivery (vacuum or cesarean). RESULTS: Of the women included, 81.7% had a spontaneous vaginal delivery and 18.3% underwent operative delivery. Women with spontaneous vaginal delivery had shorter head-symphysis distance than women in the operative delivery group at T1 (p < 0.001), T2 (p < 0.001) and T3 (p = 0.025), whereas no significant differences were recorded thereafter. Receiver operator characteristic curves revealed accuracy values of 81.0%, 87.9% and 77.6% in the prediction of operative delivery at T1, T2 and T3, respectively. At multivariate logistic regression head-symphysis distance and epidural analgesia were the only independent predictors of operative delivery among ultrasonographic, maternal and intrapartum variables. CONCLUSIONS: Ultrasonographic measurement of head-symphysis distance in the second stage of labor can be used to predict operative delivery.

The descent of the fetal head is not modified by mobile epidural analgesia: a controlled sonographic study.

The aim of our study was to assess the sonographic indices of fetal head progression obtained by three-dimensional ultrasound during the second stage of labor in women with and without mobile epidural analgesia. Sonographic volume data sets were obtained with a transperineal approach every 20 min from the beginning of the active second stage until delivery. The ultrasound parameters were calculated off-line from each volume and compared between women with and without epidural analgesia. All the sonographic measurements of the fetal head descent were comparable at each time interval between the two groups. This observation suggests that mobile epidural analgesia is not likely to affect the dynamics of the second stage of labor.

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer.

OBJECTIVE: • To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI). PATIENTS AND METHODS: • We evaluated 872 pT2-4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow-up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow-up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate-specific antigen (PSA) level and the pathological stage. • The patients were stratified as having low risk (cT1a-T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b-T2c or cGs = 7 or PSA level = 10-19.9) or high risk of LNI (cT3 or cGs = 8-10 or PSA level ≥ 20). • The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs. • The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR-free survival. RESULTS: • The mean follow-up was 55.8 months. • Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1. • Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1. • In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥ 10 LNs removed had a significantly lower BCR-free survival at univariate and multivariate analysis. CONCLUSION: • In our study population, a more extensive PLND positively affects the BCR-free survival regardless of the nodal status in intermediate- and high-risk prostate cancer.

Therapeutic management and clinical outcome of autoimmune pancreatitis.

BACKGROUND: Autoimmune pancreatitis, in comparison to other benign chronic pancreatic diseases, is characterized by the possibility of curing the illness with immunosuppressant drugs. The open question is whether to differentiate autoimmune pancreatitis as a primary or secondary disease based on the presence or absence of other autoimmune diseases or whether to consider autoimmune pancreatitis a clinical and pathological systemic entity, called IgG4-related sclerosing disease, since this aspect is also very important from a therapeutic point of view. METHODS: In this paper, we reviewed the conventional therapeutic approach used to treat autoimmune pancreatitis patients and the clinical outcome related to each treatment modality. We also reviewed some aspects which are important for the correct management of autoimmune pancreatitis, such as the surgical approach, the outcome of surgically treated autoimmune pancreatitis patients, whether medical treatment is always necessary, and, finally, when medical treatment should be initiated. CONCLUSIONS: Steroids are useful in alleviating the symptoms of the acute presentation of autoimmune pancreatitis, but some questions remain open such as the dosage of steroids in the acute phase and the duration of steroid therapy; finally, it should be assessed if other immunosuppressive non-steroidal drugs may become the first-line therapy in patients with AIP without jaundice and without atrophic pancreas.

Computed Tomography Evaluation of Normal Canine Abdominal Lymph Nodes: Retrospective Study of Size and Morphology According to Body Weight and Age in 45 Dogs.

The morphological characteristics of the largest lymphatic vessels and lymph nodes of the body have been described through ultrasonography, although food and gas in the gastrointestinal tract can often have negative effects on the response of small abdominal structures. The aim of the study was to describe the size of normal abdominal lymph nodes (ALs) in dogs affected by disease, not including lymphadenomegaly or lymphadenopathy, and divided according to body weight and age. The ALs studied included the jejunal, medial iliac, portal, gastric, splenic, and pancreaticoduodenal lymph nodes. Statistical correlation considering body weight and age as continuous variables showed that all measurements of the ALs increased according to body weight changes (p < 0.01). The most reliable values were the volume measurements (p < 0.001) compared to the length, thickness, and width. Mixed results emerged from a comparison of weight categories and age; only the jejunal lymph nodes showed a significant correlation (p < 0.05). Other characteristics (shape, attenuation, and enhancement) are subsequently reported. The resulting data can be used to categorize CT measurements of normal ALs displayed based on the body weight and age of the subjects. This study aimed to propose a new parameter of normalcy that may serve as a reference for the evaluation of infectious or neoplastic events.

Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy.

The purpose of the study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS-biopsy) performed on regions with abnormal MRI and/or MRSI for both the transition (TZ) and the peripheral (PZ) zones in patients with suspected prostate cancer with prior negative biopsy, and to analyze the relationship between MRSI and histopathological findings. MRI and MRSI were performed in 54 patients (mean age: 63.9 years, mean PSA value: 11.4 ng/mL) and the ability of MRI/MRSI-directed TRUS biopsy was evaluated. A three-point score system was used for both techniques to distinguish healthy from malignant regions. Descriptive statistics and ROC analyses were performed to evaluate the accuracy and the best cut-off in the three-point score system. Twenty-two out of 54 patients presented cancer at MRI/MRSI-directed TRUS biopsy, nine presented cancer only in PZ, eight both in PZ and TZ, and five exclusively in TZ. On a patient basis the highest accuracy was obtained by assigning malignancy on a positive finding with MRSI and MRI even though it was not significantly greater than that obtained using MRI alone (area under the ROC curve, AUC: 0.723 vs 0.676). On a regional (n = 648) basis the best accuracy was also obtained by considering positive both MRSI and MRI for PZ (0.768) and TZ (0.822). MRSI was false positive in 11.9% of the regions. Twenty-eight percent of cores with prostatitis were false positive findings on MRSI, whereas only 2.7% of benign prostatic hyperplasia was false positive. In conclusion, the accuracy of MRI/MRSI-directed biopsies in localization of prostate cancer is good in patient (0.723) and region analyses (0.768). The combination of both MRI and MRSI results makes TRUS-biopsy more accurate, particularly in the TZ (0.822) for patients with prior negative biopsies. Histopathological analysis showed that the main limitation of MRSI is the percentage of false positive findings due to prostatitis.

Venous thromboembolism and port-related thrombosis in metastatic colorectal cancer patients: a monocenter experience.

Venous thromboembolism (VTE) may occur during the natural history of neoplastic disease and is a common cause of mortality and morbidity in cancer patients. Major risk factors for VTE in cancer patients include surgery, immobilization, hospitalization, and the administration of granulopoietic and/or erythropoietic (stimulatory) agents. Chemotherapy is a supplementary independent risk factor for VTE and the use of central venous catheters (CVC) in clinical practice has increased the risk of thromboembolic events. We conducted a retrospective study to evaluate CVC-related thrombosis and the VTE rate in 145 consecutive metastatic colorectal cancer patients. We observed only 2 cases of symptomatic CVC- related thrombotic events (1.38%) and 10 cases of thromboembolic events (6.9%) in our series. Only surgery for metastases was found to be significantly related to the development of VTE, with an incidence of 16.1% vs. 4.4 in patients who did not undergo surgery (p = 0.037). In addition, a history of VTE seems to be a supplementary risk factor for CVC-related thrombosis (p = 0.055).

Evaluation of microalbuminuria in patients with erectile dysfunction.

INTRODUCTION: The recent sophisticated diagnostic procedures aimed at identifying the exact cause of erectile dysfunction (ED) are often complicated in clinical application, invasive, or highly expensive. Microalbuminuria, a test easy to perform and of low cost, is a marker of extensive endothelial dysfunction, and it has been suggested to be linked to ED. AIM: The aim of this study was to investigate the eventual role of microalbuminuria in differentiating patients with arteriogenic and non arteriogenic ED. METHODS: The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire, and patients were classified as arteriogenic (N = 29) and non-arteriogenic (N = 49) in relation to the results of echo-color-doppler examination of cavernosal arteries in basal conditions and after intracavernous injection of 10 microg prostaglandin E(1). MAIN OUTCOME MEASURES: The microalbuminuria of 78 males without the most common atheriosclerotic risks and with ED was measured. RESULTS: Microalbuminuria, defined as urinary albumin/creatinine ratio, was not significantly (P > 0.05) different between patients of the two groups. CONCLUSIONS: Our data show that in ED patients the cavernosal arteries damage, as assessed by dynamic echo-color-doppler, may be independent on or precede extensive endothelial dysfunction, and that microalbuminuria cannot be predictive of penile arteriogenic etiology.

A prospective study on radiofrequency ablation locally advanced pancreatic cancer.

BACKGROUND: Radiofrequency ablation (RFA) has been suggested as a new treatment option for patients with locally advanced cancer. This study aimed to prospectively evaluate the efficacy and safety of intraoperative RFA in patients with unresectable, locally advanced, non-metastatic carcinoma of the pancreatic head. METHODS: RFA was the first step of the surgical procedure and was carried out on the mobilized pancreatic head followed by biliary by-pass and gastrojejunal-anastomosis. Intra- and post-operative morbidity and mortality, performance status, pain control, quality of life, and survival at 24 months were evaluated. RESULTS: Seven patients (3 men and 4 women; median age 66 years, range 47-80 years) were studied and 4 were eligible for treatment. The RFA procedure was carried out in 3 of the 4 patients; in one patient it was not carried out because of the upstaging of the neoplasm. In all 3 patients RFA achieved complete necrosis of the lesion. A biliary fistula developed 7 days after the procedure in one patient; all 3 patients developed ascites 8.6 days (range 7-9 days) on average after RFA. All patients died respectively, at 3, 4, and 5 months after the treatment. CONCLUSIONS: In our experience, RFA is a feasible procedure, but it presents a very high rate of postoperative complications. Moreover, pain control, life quality and survival rate are poor. The few data suggest no impact on survival.

Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: a prospective study.

OBJECTIVE: Prospectively to evaluate patients with chronic asymptomatic pancreatic hyperenzymemia in order to identify possible pancreatic and non-pancreatic diseases. MATERIAL AND METHODS: Seventy-five asymptomatic subjects with long-standing pancreatic hyperenzymemia (45 M, 30 F; mean age+/-SD 51.5+/-16.0 years, range 19-78 years, mean duration+/-SD of pancreatic hyperenzymemia 14.7+/-7.0 months, range 7-34 months) and normal ultrasonographic evaluation were included in this study. The subjects enrolled were carefully interviewed and prospectively evaluated. All patients underwent blood screening. An additional abdominal ultrasound was also carried out and, if considered necessary, other imaging and endoscopic evaluation procedures were used. RESULTS: The follow-up of the patients after enrollment in the study was 3.3+/-1.8 years (mean+/-SD). In 38 patients (50.7%), pancreatic or extrapancreatic disease was diagnosed: 20 patients had chronic pancreatitis, 1 had autoimmune chronic pancreatitis, 1 had a benign cyst of the pancreas, 2 had serous cystadenomas, 5 had an intraductal papillary mucinous tumor of the pancreas, 3 had a ductal pancreatic adenocarcinoma, 4 patients had chronic viral hepatitis, and 2 had Crohn's disease. In 37 subjects (49.3%), no pancreatic or extrapancreatic diseases were found (3 subjects had macroamylasemia, 3 had familial hyperenzymemia, 31 had chronic non-pathological pancreatic hyperenzymemia). CONCLUSIONS: Subjects having an increase of either amylase or lipase serum levels should undergo a thorough diagnostic work-up prior to establishing the existence of chronic non-pathological pancreatic hyperenzymemia.

Prevalence, distribution, and clinical characteristics of hemangiosarcoma-associated skeletal muscle metastases in 61 dogs: A whole body computed tomographic study.

BACKGROUND: Skeletal muscle metastases (SMMs) have been described sporadically in canine oncology. HYPOTHESIS/OBJECTIVES: To determine the prevalence, localization, and clinical signs of SMMs associated with hemangiosarcoma (HSA) in a population of dogs presented for whole body computed tomography (CT). ANIMALS: Dogs with a histologically confirmed HSA and a tissue core specimen or fine needle aspirate of suspected metastatic lesions were included in the study. METHODS: Retrospective study. Dogs with a final diagnosis of visceral or muscular HSA that underwent whole body CT scan were enrolled in the study. Final diagnosis of primary tumor and SMMs was reached by histology, cytology, or both. Signalment, clinical signs, localization of the primary lesion, and metastases characteristics were reviewed. RESULTS: Sixty-one dogs met the inclusion criteria. Skeletal muscle metastases were detected in 15 dogs (24.6%) and all of these dogs had also metastases in ≥1 sites. Presence of SMMs was significantly higher in males but was not significantly related to age, neuter status, breed, localization, and dimensions of the primary tumor. Nine of 15 (60.0%) dogs with SMMs showed lameness or reluctance to move whereas these signs were not recorded in any of the 42 dogs without SMMs (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Prevalence of SMMs in our population of dogs with HSA was higher in comparison to previous studies in the human and veterinary medical literature. Whole body CT is recommended for staging of dogs with HSA, because SMMs could be missed by clinical examination and traditional diagnostic imaging modalities.

Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer.

To analyze the potential diagnostic relevance of free plasma DNA (FPDNA), we enrolled 64 patients with localized prostate cancer (CaP). FPDNA was quantified by real-time polymerase chain reaction assessment of the HTERT gene in blood samples from 64 patients with CaP and 45 healthy males. Methylation of the GSTP1 gene was used to confirm the neoplastic origin of FPDNA in selected cases. The mean +/- SD levels of FPDNA were higher in patients with CaP (15.4 +/- 10.9 ng/mL) than in control subjects (5.5 +/- 3.5 ng/mL; P <.001). By using the best cutoff value, the sensitivity of the test was 80%, the specificity was 82%, the area under the receiver operating characteristic curve, 0.881. High FPDNA values were significantly associated with pathologic T3 stage (P = . 035). Methylation of the GSTP1 gene was found in 4 (25%) of 16 FPDNA samples and 15 (94%) of 16 tissue samples. Quantification of FPDNA discriminates between patients with CaP and healthy subjects and correlates with pathologic tumor stage. FPDNA is a candidate biomarker for early diagnosis and monitoring of CaP.

Salivary cortisol and cortisone responses to short-term psychological stress challenge in late adolescent and young women with different hyperandrogenic states.

Hyperandrogenic disorders have been associated with psychological distress, reduced quality of life, anxiety and depression. The hypothalamic-pituitary-adrenal (HPA) axis plays a pivotal role in the adaptive response to stressor events. Salivary cortisol (SalF) and cortisone (SalE) testing have been proven to be useful in the evaluation of HPA-axis activity. This study investigated whether SalF and SalE responses to two putative stressor levels differed between the hyperandrogenic states in late adolescent and young women, thus measuring the HPA-axis adaptive response to acute stress events. We selected 161 drug-free females aged 16-19 years from a large population previously enrolled in a cross-sectional epidemiological study. Saliva was collected in the morning before and after two putative stressor events consisting in a self-filled questionnaire (weaker stressor) and in a structured interview plus physical examination by an endocrinologist (stronger stressor). SalF and SalE, as well as blood steroids, were assessed by liquid chromatography-tandem mass spectrometry. Subjects were subdivided into different groups according to the presence of: isolated menstrual irregularities (MI, oligo-amenorrhea; n = 22), isolated hirsutism (HIR, modified Ferriman-Gallwey score ≥ 8; n = 26), isolated hyperandrogenaemia (HT, testosterone >0.438 ng/mL; n = 14), and polycystic ovary syndrome (PCOS, MI with HIR and/or HT, n = 16). The remaining 83 apparently healthy subjects were used as controls. SalF and SalE significantly decreased after the weaker stressor, following the physiologic diurnal loss, in all the groups except for isolated HIR, where they remained unchanged (P = 0.091 and P = 0.118, respectively). In contrast, SalF and SalE remained unchanged after the stronger stressor in isolated MI, isolated HT and controls, whereas SalF increased significantly in isolated HIR (P = 0.011), and SalE increased significantly both in isolated HIR (P = 0.005) and in PCOS (P = 0.011) groups. SalF percentage variation in response to the stronger stressor was positively associated with systolic blood pressure in PCOS (P = 0.018), and both SalF and SalE percentage variations were positively associated with diastolic blood pressure in the isolated HIR group (P = 0.010 and P = 0.006, respectively). In addition, in the isolated HIR group, the SalF percentage variation was negatively associated with HDL cholesterol levels (P = 0.005). Finally, SalF and SalE percentage variations were positively associated with circulating androstenedione (P = 0.031 and P = 0.011, respectively) and DHEA (P = 0.020 and P = 0.003, respectively) in the isolated HIR group. In conclusion, this study demonstrates that hirsute and PCOS adolescent and young women are characterized by HPA-axis overactivity in response to stressful stimuli, as detectable by salivary glucocorticoid measurements. These data also indicate that the higher the HPA-axis activity, the higher the adrenal androgen output and the worse the metabolic profile.