Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes

OBJECTIVE: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes. DESIGN: Prospective baseline-controlled clinical trial. PATIENTS: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months. MEASUREMENTS: At entry and after treatment, lumbar bone mineral density (BMD) and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. DNA was extracted from blood and analysed for the BsmI polymorphism of the VDR gene. RESULTS: The mean percentage (% +/- SD) change from baseline in lumbar BMD was significantly higher (P < 0.01) in bb than in BB BsmI VDR genotypes (7.92 +/- 4.31 vs. 3.40 +/- 1.81). No significant difference in lumbar BMD was observed in Bb VDR patients (6.01 +/- 3.89) in comparison with other groups. The mean percentage of change in serum OC and urinary DPD-Cr levels was significantly (P < 0.01) lower in individuals with bb than in those with BB BsmI VDR genotypes (-14.34 +/- 2.87 vs.-10.39 +/- 1.43 and -9.61 +/- 5.56 vs.-4.61 +/- 2.31). No significant difference in serum OC and urinary DPD-Cr levels was observed in Bb VDR patients (-12.31 +/- 2.11 and -6.52 +/- 2.65) in comparison with other groups. CONCLUSION: The different BsmI vitamin D receptor genotypes modify the pharmacological response to alendronate treatment in postmenopausal women with osteoporosis.     

Use of accurate diagnostic criteria may increase incidence of stercoral perforation of the colon

PURPOSE: Stercoral perforation of the colon is reported to be a rare disease with poor prognosis. The aim of this study was to determine the frequency of stercoral perforation of the colon, to define diagnostic criteria for stercoral perforation of the colon, and to analyze the patient outcome in a university hospital gastrointestinal surgery unit. METHODS: From November 1993 until November 1998 all surgically treated patients with a colorectal disease were prospectively recorded in a computerized database. Diagnosis of stercoral perforation of the colon was made if 1) the colonic perforation was round or ovoid, exceeded 1 cm in diameter, and lay antimesenteric; 2) fecalomas were present within the colon, protruding through the perforation site or lying within the abdominal cavity; and 3) pressure necrosis or ulcer and chronic inflammatory reaction around the perforation site were present microscopically. Any additional colon pathology led to exclusion from the diagnosis of stercoral perforation of the colon. Using the same criteria, 81 cases in the literature were found to qualify and were further analyzed. RESULTS: In a five-year period 1,295 patients underwent colorectal interventions through laparotomy. A total of 566 (44 percent) cases were emergencies, 220 (17 percent) of these caused by colonic perforation. Seven patients had stercoral perforation of the colon. The incidence of stercoral perforation of the colon was 0.5 percent of all surgical colorectal procedures through laparotomy, 1.2 percent of all emergency colorectal procedures, and 3.2 percent of all colonic perforations. The mean age of the patients was 59 (median, 64; range, 22–85) years. All perforations were situated in the left hemicolon or upper rectum. The round or ovoid perforation had a mean diameter of 3.6 cm. Fecalomas were present in all patients and protruded from the perforation site or were found within the free abdominal cavity in three of them. Generalized stercoral peritonitis was a constant finding. Using a colonic resection without immediate restoration of continuity, an extensive intraoperative lavage, and antibiotics, there was no in-hospital mortality. Analysis of the reports in the literature revealed additionally that 28 percent of patients with stercoral perforation of the colon have multiple stercoral ulcers in the colon and that substantial mortality is encountered if only minor surgical procedures of treatment are used. CONCLUSIONS: The incidence of stercoral perforation of the colon seemed to have been underestimated. The reason for this might be the lack of defined diagnostic criteria for this disease. Low mortality is obtained by early surgical eradication of the affected part of the colon, including all stercoral ulcers, and by aggressive therapy for peritonitis.Presented in part at the meeting of the Swiss Society of Surgery, Lugano, Switzerland, June 9 to 12, 1999.     

Preoperative staging of rectal cancer by endoluminal ultrasoundvs. magnetic resonance imaging

PURPOSE: The aim of this study was to compare the value of endoluminal ultrasonography (ELUS) with magnetic resonance imaging (MRI) for preoperative staging of rectal carcinoma. METHODS: Thirty-seven consecutive patients were examined by ELUS and MRI. Imaging results were compared with pathohistologic studies. A tumor extending beyond the bowel wall was considered to be positive and one within the bowel wall was considered negative. Lymph node involvement was considered present if nodes equal to or greater than 5 mm in diameter were found in the perirectal tissue. For evaluating the differences between the two methods, the Mc Nemar test was performed. RESULTS: T-Staging was correct in 88.2 percent (30/34) of patients by ELUS and in 82.3 percent (28/34) by MRI (difference not significant). N-Staging was correct in 80 percent (20/25) by ELUS and in 60 percent (15/25) by MRI (difference of borderline significance). A comprehensive preoperative staging (T + N) was made correctly in 68 percent (17/25) by ELUS and in 48 percent only (12/25) by MRI (difference not significant). CONCLUSIONS: We suggest that ELUS and MRI must be evaluated within the framework of established parameters when treatment modalities such as preoperative radiation therapy and local or radical surgical approach must be decided.     

Spironolactone improves lung diffusion in chronic heart failure.

AIMS: To evaluate whether anti-aldosteronic treatment influences lung diffusion (DLCO) in chronic heart failure (HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLCO abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. METHODS AND RESULTS: Thirty stable chronic HF patients, with reduced DLCO (<80% of predicted), were randomly assigned to active treatment (25 mg spironolactone daily) or placebo in addition to conventional anti-failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLCO and membrane diffusing capacity (DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLCO due to an increase of DM (DLCO: 18.3+/-3.9 vs. 19.9+/-5.5 mL/min/mmHg; DM: 28.1+/-7.7 vs. 33.3+/-8.6 mL/min/mmHg) and peak oxygen consumption (peak VO2 16.8+/-1.9 vs.18.6+/-2.2 mL/min/kg). Increments of DLCO and peak VO2 were linearly related (R=0.849, P<0.001). CONCLUSION: These data show a positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti-aldosteronic drugs improve HF clinical condition and prognosis.     

Advances in pharmacotherapy for primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.

Areas covered: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.

Expert opinion: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.     

Suprasellar granular cell tumor of the neurohypophysis: surgical outcome of a very rare tumor

Purpose

Granular cell tumors of the neurohypophysis are rare, solitary lesions, mostly presenting in the adult age. They rarely grow to a sufficient size to cause mass effect related symptoms and they may be found in most cases incidentally at autopsy. Because of their rarity as of now they have been described only as case reports or included in small clinical series.

Methods

We report a series of 11 patients, who underwent surgery for granular cell tumors of the neurohypophysis between 1996 and 2013 in a single center.

Results

Mean follow-up time after treatment was 92.2 months (range 9–231 months). Mean age at surgery was 40.7 years (range 12–66 years). There were 7 males (63.6 %) and 4 females (36.4 %). Main symptoms at presentation were: hyperprolactinemia (72.7 %), visual impairment (45.5 %) and headache (36 %). Except for 2 patients, all the others underwent surgery as primary treatment at our Institution, through a transsphenoidal (54.5 %) or a transcranial approach (45.5 %). Overall- and progression-free survival times for the entire series (calculated from the time of diagnosis) were 112.9 and 100.5 months respectively. There was one case of perioperative death in a patient who had undergone repeat transcranial surgery for residual tumor.

Conclusions

Although extremely rare, granular cell tumors of the neurohypophysis have to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management. Early diagnosis, extensive tumor removal, opportune indication of adjuvant radiotherapy are the keys to manage these cases.