C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

[Surgical treatment of Crohn's disease complications. Our experience]. / La terapia chirurgica nelle complicanze della malattia di Crohn. Nostra esperienza.

Thirty-five patients with Crohn's Disease (CD) were observed: 18 have been treated with medical therapy and 17 (48.6%) underwent to surgical treatment : 1) intolerance to the medical treatment in 5.9% (1 case); 2) local complications in 94.1% (16 cases: 6 stenosis, 2 occlusions, 3 abscesses, 3 fistulas, 1 perforation with peritonitis, 1 case toxic megacolon). The operations have been 19: resective interventions 14 (bowel and/or colon resections), conservative interventions 5. The mortality was 0, the morbidity 35,29%. The incidence of the recurrences in a follow up of 5 year was 42,9%. The Authors conclude that the surgery, indicated for the treatment of complications, can be resective surgery (perforating Crohn disease: fistulas, abscess) or conservative surgery (stenosing Crohn disease: stenosis). Recently the conservative intervention are proposed in the treatment of fistulas and abscesses too, but when the inflammation is mild and in patients that underwent to extensive intestinal resection with risk of short bowel syndrome.

The impact of antibiotic resistance on the efficacy of three 7-day regimens against Helicobacter pylori.

BACKGROUND: Antibiotic resistance affects the success of anti-Helicobacter pylori therapies and varies greatly from country to country. AIM: To compare the efficacy of three short-term triple regimens in relation to H. pylori primary resistance in our region. METHODS: We enrolled 210 H. pylori-positive dyspeptic patients for this randomized, open, parallel-group study. Three arms of 70 patients each received the following 1-week regimens: (1) ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (RCM); (2) bismuth subcitrate 240 mg b.d. + amoxycillin 1000 mg b.d. + metronidazole 500 mg b.d. (BAM); (3) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (OCM). H. pylori was assessed by CLO-test and histology before and 4 weeks after therapy. Antibiotic resistance was assessed by E-test. RESULTS: On intention-to-treat analysis RCM was more effective than OCM (84% vs. 69%; P < 0.03) and BAM (84% vs. 63%; P < 0.004). MIC determination was successful in 117 out of 210 patients (55%); metronidazole resistance was present in 52 out of 117 patients (44%) and clarithromycin resistance was present in 17 out of 117 patients (14%). Excellent cure rates were achieved when strains were sensitive to both antibiotics (100% with RCM and BAM and 90% with OCM), whereas RCM was superior to OCM (P=0.009) and BAM (P=0.001) with respect to overall resistant strains (94% vs. 57% and 38%, respectively). CONCLUSIONS: One-week RCM is the best regimen to eradicate H. pylori in our geographical area. This seems to be linked to the better ability of RCM compared to OCM and BAM in overcoming the high prevalence of H. pylori resistance to both metronidazole and clarithromycin in our region.

[Detection of parvovirus B19 in patients of the Zulia State blood bank with different hematological alterations]. / Detección de parvovirus B19 en pacientes del banco de sangre del Estado Zulia con diversas alteraciones hematológicas.

PURPOSE: To assess the seroprevalence of IgG and IgM specific for parvovirus B19 (B19) and its association with aplastic crisis developing in patients with different haematological disorders. PATIENTS AND METHODS: Fifty-three serum samples were evaluated, 24 from patients with aplastic crisis and 29 from others without such crises, all of them suffering from different haematological diseases diagnosed at the University Hospital of Maracaibo and the Zulia State Blood Bank, in Venezuela; 15 samples from healthy blood donors were examined as well. Indirect immunofluorescence technique was used in the study. Lymphocyte subsets were quantified in 10 of the patients with aplastic crisis by means of cytofluorometry. Serum proteins were assessed by electrophoresis in all samples. The statistical analysis was performed according to Student's t test and chi square, by applying the statix 4.0 and SAS programmes. RESULTS: Positive IgG was found in 20 of the 24 patients with aplastic crisis (83.3%), 20 of the 29 without crisis (68.9%) and 7 of the 15 healthy controls (46.6%). Positive IgM was found only in 2 of the 24 patients with aplastic crisis (8.3%). Both the patients without aplastic crises and the control groups were negative for PB19 IgM. The average CD4 and CD8 T lymphocyte count and the CD4-CD8 index in the patients studied were 454 CD4 cells/microL, 1,006 CD8 cells/microL and 0.5%, significantly different from the control group, whose figures were 860 CD4 cells/microL, 546 CD8 cells/microL and 1.6%. The average B lymphocyte count of the patients (628 cells/microL) was higher than that of the control group (349 cells/microL). The average NK cell count in the patient was 174 cells/microL, slightly below the control group (221 cells/microL). Mild beta-globulin decrease was found in the electrophoretic study of the serum proteins of the patients, along with significant increase of the total protein and the gammaglobulin fraction with regard to the control group. CONCLUSIONS: Higher PB19 IgG seropositivity was seen in the patients with aplastic crisis with respect to the control group, suggesting wider exposition to the virus among them with regard to the healthy population. Specific PB19 IgM was detected in 2 patients with immunodeficiency and aplastic crisis. A significant decrease of the CD4 and CD8 T-lymphocyte subsets, along with decreased CD4-CD8 quotient, were found in the aplastic crisis group, and an impairment of the immune response to the viral challenge can be inferred form this. The alterations of the serum proteins, together with the increased B lymphocytes, might suggest a polyclonal activation of these cells. The absence of other known lymphotropic viruses in most of the patients studied (50) show that the alterations found here are related to recent or past B19 infection.

[Connection between the type of drainage and sepsis in thyroid surgery]. / Rapporto fra tipo di drenaggio e sepsi nella chirurgia tiroidea.

Drainage in thyroid surgery, although still controversial, is used at our service routinely, as it guarantees the output of serum, sometimes abundant after thyroidectomy, and allows the immediate check of hemorrhage. It is nevertheless known that the presence of drainage can favour the occurrence of infection of the surgical bed. Through a randomized trial, we tested the incidence of sepsis after thyroidectomy, using in one group a double open Silastic drain and in another group a double aspirative drain. We registered 3 cases of wound infection and 4 cases of seroma in the group treated with open drainage versus one case of wound infection and 2 cases of seroma in the group treated with aspirative drainage. Such difference, although evident, did not result significant. Nevertheless, it is our opinion to conclude that the aspirative draining system guarantees a better sterility of the surgical wound, and therefore a lower incidence of wound complications.

[The role of drainage and antibiotic prophylaxis in thyroid surgery]. / Il ruolo del drenaggio e della profilassi antibiotica in chirurgia tiroidea.

BACKGROUND: It is our habit to employ an open drainage after thyroid surgery in our department. We have also found a large number of surgical infections in these patients (5.8% vs 2.5). Aim of the study is to evaluate prospectively if contamination happens during surgical procedure or in a later time according to the presence of the open drainage. METHODS: From October 1995 to November 1996, 113 patients who underwent a subtotal thyroidectomy were randomized into two groups: group A with antibiotic prophylaxis (57 patients) and group B without it (56 patients). RESULTS: One case (1.7%) of sepsis among 57 patients of group A and 2 cases (3.4%) among 56 patients of group B were observed. CONCLUSIONS: No statistical difference was found between the two groups despite antibiotic prophylaxis covering surgical procedure. It is personal opinion that sepsis arose after surgical procedure, due to the presence of the open drainage.

[Comparison of colorectal mechanical suture techniques]. / Tecniche di sutura meccanica colo-rettale a confronto.

UNLABELLED: Objective of this study is to establish which kind of stapled anastomosis is the most reliable in rectal surgery. 67 patients randomly assigned to three groups underwent low anterior resection of the rectum with end-to-end, side-to-end or double stapling anastomosis. Main outcome measures were incidence of leakage at the intraoperative check of the suture, postoperative leakage, stenosis, mortality, mean post-operative stay. Side-to-end anastomosis were followed by 4 intra-operative (19%) and one post-operative (4.7%) leakages with one case of mortality (4.7%). Four intra-operative (18.2%) and 5 post-operative (22.7%) leakages, 3 stenosis (13.6%) and one case of mortality (4.5%) were observed after double-stapling procedures. No intra- or post-operative anastomotic complications were seen after end-to-end anastomosis. Mean post-operative stay was 20, 31 and 13 days for the three methods respectively. CONCLUSIONS: In this series of colo-rectal anastomoses, the end-to-end stapling technique appears to be safer and more reliable than others.

Surveillance after colorectal cancer surgery.

Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.

[Hypertriglyceridemia following treatment with interferon alpha in essential thrombocythemia]. / Hipertrigliceridemia posterior a terapia con interferon alfa en trombocitemia esencial.

A case of essential thrombocytemia treated with alpha interferon is reported, with hematological remission, but as a side effect hypertriglyceridemia is relevant. It was normalized when alpha interferon was stopped. This is the first case of essential thrombocythemia in Venezuela treated with biological modifiers, with hematological remission, but with hypertriglyceridemia as side effect.

Carcinoembryonic antigen (CEA) in serum and bile of colorectal cancer patients with or without detectable liver metastases.

It has been suggested that bile CEA levels could represent a sensitive index for the detection of occult liver metastases in colorectal cancer (CRC) patients. We measured serum and gallbladder bile CEA concentrations in a control group, in a group of patients with benign disease of the biliary tree, and in patients with CRC at different stages. Neoplastic patients without evidence of liver metastases at the time of laparotomy, but with elevated biliary CEA levels, were selected for a follow-up study. Our results indicate that (a) bile CEA levels are falsely increased in several benign biliary diseases; (b) CRC patients with detectable liver metastases have elevated biliary CEA levels; (c) high biliary CEA levels do not represent a predictive parameter for the presence of occult liver metastases in CRC patients.

[CD10(CALLA)-negative acute lymphoblastic leukemia. A group with a bad prognosis]. / Leucemia linfoblástica aguda CD10 (CALLA) negativo. Grupo de mal pronóstico.

The results of 188 patients with acute lymphoblastic leukemia, studied between 1985 and 1990, showed that 8 cases were CD10 negative, Dr, and CD19 positive. These findings indicate cell dedifferentiation and poor prognosis. The patients age ranged from 2 to 30 years, with a mean of 11 years. The male/female ratio was 5/3. Lymph node enlargement and splenomegaly were found in the 8 patients. With the exception of one patient in whom leucopenia was present, the white cell counts were always higher than 30,000/dl. The karyotype was studied in four cases, and all of them were hyperdiploid. This is the first report in Venezuela of cases with acute lymphoblastic leukemia - CD 10 negative.

[Caloric substrates in postoperative parenteral nutrition]. / I substrati calorici nella nutrizione parenterale postoperatoria.

The paper describes the carbohydrate, lipidic and nitrogen metabolism of the postoperative period which is subdivided into an early and a late phase. Since the metabolism of caloric substrates in the early postoperative period is a stress metabolism with glucose intolerance and wide protein catabolism, the authors emphasise that an insufficient caloric intake is worse than the fasting state and suggest that alternative caloric sources, such as branched chain amino acids, fatty acids and, even, ketonic bodies, should be used.