Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes.

AIM: The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia (A1C = 7.5-12.0%). METHODS: In an initial 12-week phase (Phase A), 492 patients were randomised 1 : 1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6 weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up-titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up-titrated to 45 mg qd RESULTS: At the end of Phase A, mean changes from baseline were -1.0% and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycaemic parameters were greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose (p = 0.03); -90.3 mg/dl vs. -69.1 mg/dl for 2-h postmeal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO. The incidence of hypoglycaemia was similarly low in both groups. Body weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p < 0.001). CONCLUSION: Improvements in glycaemic control were greater with SITA/MET vs. PIO, with weight loss vs. weight gain. Both treatments were generally well tolerated.

Ovarian cancer: lymph node metastases.

PURPOSE OF INVESTIGATION: To analyze pelvic and paraaortic lymph node involvement in epithelial ovarian cancer. METHODS: Between 1995 and 2006, 60 patients with FIGO Stages II, III, IV epithelial ovarian cancer underwent surgical treatment, including systematic pelvic and paraaortic lymphadenectomy. RESULTS: Aortic lymph node metastases were documented in 45 (75%) patients and pelvic nodal metastases in 42 (70%). The incidence of paraaortic nodal involvement was 20% (12/60) in the absence of positive pelvic nodes while the incidence of pelvic nodal involvement was 15% (9/60) in the absence of paraaortic disease; both pelvic and paraaortic lymph node involvement occurred in 55% of patients. The most frequent groups for nodal metastases are paracaval (56%), externaliliac (60%), and obturator (55%). CONCLUSION: The rate of nodal involvement is important in ovarian cancer and there is a high prevalence of both pelvic and paraaortic lymph node metastases. For this reason bilateral pelvic and paraaortic lymphadenectomy is necessary for staging and as treatment for micrometastases, also in patients with unilateral tumors.

A new uterine suture technique for postpartum hemorrhage.

At present, postpartum hemorrhage is still an important cause of maternal mortality and morbidity. When medical therapy has no success, conservative surgical procedures are applied before making a hysterectomy. Three transverse sutures are applied to the entire uterine wall both to the right and the left side of the uterus. Our technique has been applied to 4 women with postpartum hemorrhage secondary to uterine atony. Bleeding was stopped immediately by compressive sutures. The four patients had normal menstruation cycles after delivery and had new pregnancies. No woman had postoperative complications. Uterus compressive suture is an effective alternative to hysterectomy to treat postpartum hemorrhage secondary to atony. This is a simple and quick procedure that preserves fertility.

Vascular endothelial growth factor (VEGF): can we use it as prognostic factor in endometrial cancer?

AIM: The aim of the study was to investigate if VEGF levels reflect the severity of endometrial cancer and the clinic relationship between microvasal density (MVD) and concentration of VEGF in tumor. METHODS: The study was conducted on 22 patients affected by endometrial cancer who were submitted to total abdominal radical hysterectomy plus bilateral salpingo-ophorectomy. VEGF (pg/mL) and MVD values were measured on histologic specimens of endometrial cancer obtained during the surgical treatment. The means and standard deviations of estimated values were calculated and a statistical comparison was effected by student t test for not coupled data. Pearson correlation test was used to analyze the eventual correlation among VEGF and MVD values in overall patients. RESULTS: We have documented that VEGF expression and MVD change according to FIGO stage, lympho-vascular infiltration and lymph node involvement. Pearson correlation test shows a good linear positive correlation in overall patients between VEGF and MVD values. CONCLUSIONS: Results obtained show a possible use of VEGF as prognostic factor in endometrial cancer. Confirmation of these data may permit both to identify high-risk patients, who must be treated with a more aggressive treatment, and to use an angiogenic therapy in endometrial cancer.

Double laparotomy wound recurrence of endometrial carcinoma.

INTRODUCTION: Abdominal scar recurrence of endometrial carcinoma after abdominal total hysterectomy is very rare. We report a case of a 65-year-old woman who had two recurrences in the abdominal incisional scar after total hysterectomy. CASE REPORT: A 65-year-old woman underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy because of well-differentiated endometrial adenocarcinoma (Stage IIB). Thus, the patient was treated by external beam radiotherapy. She developed two recurrences in the abdominal incisional scar two and three years after total hysterectomy, respectively. Surgery plus chemotherapy and surgery plus hormonal therapy were used for treatment of the first and second scar recurrence, respectively. CONCLUSIONS: It is a very intriguing and controversial biologic question how neoplastic cells can implant and grow in an abdominal scar without other concomitant metastases. We report a review of the literature and the possible mechanism of recurrences in laparotomy wounds.

Female adnexal tumor of probable wolffian origin: clinicopathological, immunohistochemical and cytofluorimetric analyses of a 22-year-old virgin. case report.

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).

Neumonía intrahospitalaria: guía clínica aplicable a Latinoamérica preparada en común por diferentes especialistas / Clinical guidelines for the treatment of nosocomial pneumonia in Latin America an interdisciplinary consensus document

No disponible

Comparative evaluation of standard criteria and CA-125 in ovarian cancers treated with platinum or paclitaxel.

PURPOSE: To assess CA-125 in defining tumor response in patients treated with paclitaxel. PATIENTS AND METHODS: We analyzed 150 women treated for epithelial ovarian carcinoma with platinum or paclitaxel. We compared the patients treated with two agents, using a precise definition of CA-125 response, determined by 50% and 75% reductions, like other authors have published. RESULTS: CA-125 criteria gave response rates very similar to the standard response rates, both for patients treated with platinum (75% vs 63%) and also for those treated with paclitaxel (40% vs 39%). Rates of false-positive prediction of response by CA-125 were also similar for patients treated with these two agents. CONCLUSION: Precise 50% or 75% CA-125 response criteria are as sensitive as standard criteria for assessing activity of therapy for the ovarian cancers treated with platinum or paclitaxel. We propose that they may be useful in defining response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer.

Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia: clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma.

OBJECTIVE: Type II mixed cryoglobulinemia (type II MC) is often characterized by features of indolent B cell lymphoma (IBCL) found on pathologic examination of bone marrow, whereas the clinical evidence does not indicate a neoplastic disorder. To better address the issue of indolent malignant versus nonmalignant bone marrow lymphoproliferation underlying type II MC, molecular analyses of B cell clonality were performed in the present study, in conjunction with clinical and pathologic characterization. METHODS: Polymerase chain reaction DNA amplification of immunoglobulin heavy chain genes was performed in bone marrow biopsy specimens obtained from 15 selected patients with type II MC, all infected with hepatitis C virus. Five of them had also developed overt B cell lymphoma (OBCL) during followup. Bone marrow features were consistent with IBCL in 9 of the 15 patients (group 1) and with reactive lymphoplasmacytosis in 6 of the 15 (group 2). RESULTS: An oligoclonal B cell expansion was detected in 6 of 9 baseline bone marrow lesions from group 1 patients (biclonal or monoclonal expansion in the remaining 3 cases), and in 6 of 6 from group 2 patients. OBCL was always monoclonal. Selected lesions were analyzed by clonospecific hybridization and by cloning and sequence analysis in patients who had developed OBCL at followup. In 4 of 5 cases, OBCL did not originate from the dominant B cell clones that were overexpanded in the putative neoplastic baseline bone marrow lesions. OBCL clones showed significant homology with rheumatoid factor database sequences. CONCLUSION: Based on the present results, as well as on evidence from previous studies of liver lesions, oligoclonal non-neoplastic B cell proliferation in the course of chronic infection-related inflammation appears to be the key feature of type II MC. Of note, molecular evidence from target tissues supports the clinical findings both at the time of type II MC diagnosis and in cases of OBCL complication. Bone marrow pathologic findings resembling those of IBCL should thus be considered in the light of clinical and molecular evidence.

Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: viral detection in gastric low-grade lymphoma associated with autoimmune disease and in chronic gastritis.

The hepatitis C virus (HCV) has been linked to B-cell lymphoproliferation and autoimmunity, and has been localized in several tissues. The clinical observation of an HCV-infected patient with Sjögren's syndrome (SS) and Helicobacter pylori (HP) positive gastric low-grade B-cell non-Hodgkin's lymphoma (NHL), which did not regress after HP eradication, led us to investigate the possible localization of HVC in the gastric microenvironment. HCV genome and antigens were searched in gastric biopsy specimens from the previously mentioned case, as well as from 9 additional HCV-infected patients (8 with chronic gastritis and 1 with gastric low-grade B-cell NHL). HCV-specific polymerase chain reaction (PCR) and immunohistochemistry procedures were used. The gastric B-cell NHL from the patient with SS was characterized by molecular analyses of B-cell clonality. HCV RNA was detected in both the gastric low-grade B-cell NHL and in 3 out of 6 gastric samples from the remaining cases. HCV antigens were detected in the residual glandular cells within the gastric B-cell NHL lesions, in glandular cells from 2 of the 3 additional gastric lesions that were HCV positive by PCR, and in 1 additional chronic gastritis sample in which HCV-RNA studies could not be performed. By molecular analyses, of immunoglobulin genes, the B-cell NHL from the patient with SS was confirmed to be a primary gastric lymphoma, subjected to ongoing antigenic stimulation and showing a significant similarity with rheumatoid factor (RF) and anti-HCV- antibody sequences. Our results show that HCV can localize in the gastric mucosa.

[Bronchiectasia in HIV-positive patients]. / Bronquiectasias en pacientes HIV positivos.

Between July 1995 and July 1997 we diagnosed bronchiectasis confirmed by CT scan chest in 25 (18 men and 7 women) out of 295 hospitalised patients with HIV infection who suffered from lower respiratory infection. Median age at time of diagnosis of bronchiectasis was 32 years old. The patients were mostly intravenous drug addicts. In all cases a previous pulmonary infection was revealed (Pneumocystis carinii pneumonia, tuberculosis, recurrent pneumonia) with impairment of immune status (CD4 media = 64.8 mm3). Presence of persistent or intermittent cough with purulent sputum, repeated low respiratory infection and abnormal chest radiograph were correlated to bronchiectasis by chest CT scan. We conclude, that there is a significant occurrence of bronchiectasis in patients with HIV infections and pulmonary disease, thus increasing morbidity and mortality in these patients and being the cause of repeated hospitalisations due to bacterial respiratory infections.

Bronquiectasias en pacientes HIV positivos. / [Bronchiectasia in HIV-positive patients]

Between July 1995 and July 1997 we diagnosed bronchiectasis confirmed by CT scan chest in 25 (18 men and 7 women) out of 295 hospitalised patients with HIV infection who suffered from lower respiratory infection. Median age at time of diagnosis of bronchiectasis was 32 years old. The patients were mostly intravenous drug addicts. In all cases a previous pulmonary infection was revealed (Pneumocystis carinii pneumonia, tuberculosis, recurrent pneumonia) with impairment of immune status (CD4 media = 64.8 mm3). Presence of persistent or intermittent cough with purulent sputum, repeated low respiratory infection and abnormal chest radiograph were correlated to bronchiectasis by chest CT scan. We conclude, that there is a significant occurrence of bronchiectasis in patients with HIV infections and pulmonary disease, thus increasing morbidity and mortality in these patients and being the cause of repeated hospitalisations due to bacterial respiratory infections.

Hepatic lymphoid aggregates in chronic hepatitis C and mixed cryoglobulinemia.

We have examined the clinical (virological and immunological), histological and immunohistochemical features of liver lymphoid nodules in hepatitis C virus-positive (HCV+)/mixed cryoglobulinemia (type II and III) and chronic hepatitis C. The clinical features of liver disease were found to be similar in all patients. In all these groups, liver lymphoid nodules were observed to a similar extent, being more frequent in earlier phases of liver disease and less in more advanced stages. These data were confirmed by studies in serial biopsy samples taken from individual patients with type II mixed cryoglobulinemia; the loss of lymphoid nodules with progression to more advanced histological stages of disease in these patients was accompanied by a decrease of the serum levels of cryoglobulins (although not statistically significant). By immunohistochemical analysis, the liver lymphoid nodules contained predominantly B cells with a CD5+/bcl2+/Ki67- phenotype, which were always polyclonal in type III mixed cryoglobulinemia and chronic hepatitis C, and monoclonal in type II mixed cryoglobulinemia. These immunological features were consistent with an active role of the immune system in HCV-associated liver necro-inflammation. Only in type II mixed cryoglobulinemia was there a clonal restriction of B cells. The immunological profile (autoantibodies) and viral genotypes were examined in some patients, but no significant correlation with clinical and immunohistochemical findings was found; however, the prevalence of genotype 2a was significantly higher in type II mixed cryoglobulinemia than in type III and chronic hepatitis without cryoglobulinemia.

[Lipid metabolic disorders in obesity: their epidemiology, physiopathology and clinico-therapeutic implications]. / Le turbe del metabolismo lipidico nell'obesità: epidemiologia, fisiopatologia ed implicazioni clinico-terapeutiche.

The centralization of body fat, particularly in abdominal or visceral depots, is associated with qualitative and quantitative lipid abnormalities. Examples of these qualitative alterations include changes in low density lipoprotein composition, namely an increased number of small or dense low density lipoprotein particles, which seem to be prone to increased lipid oxidation. Oxidative modification of low density lipoproteins is involved in atherosclerotic development of the arterial wall. Alterations of lipid composition often arise in a context of insulin resistance with hyperinsulinism. Genetic features, such as apolipoprotein E polymorphism, also play a significant role in lipoprotein metabolism. The principle treatment of obesity and associated dyslipidemia is to reduce energy intake through diet. Moderate exercise is effective, especially in patients with insulin resistance. Drug therapy is considered primarily for patients who refuse to make behavioral changes.

Idiopathic CD4+ lymphocytopenia and systemic vasculitis.

The syndrome defined as "idiopathic CD4 lymphocytopenia' (ICL) is a rare disease of unknown aetiology, often associated with severe depression of immune defences and the occurrence of opportunistic infections. A case is reported wherein a severe immunodeficiency syndrome with persistent idiopathic CD4+ lymphopenia developed in a woman suffering from systemic microscopic polyarteritis; no signs of HIV 1/2 or HTLV I/II infection were evident. The patient died of widespread opportunistic infections. The association of ICL with vasculitis has never been reported until now. A link between the two diseases cannot be ruled out.