Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer.

BACKGROUND: Several associations between microsatellite instability (MSI) and other clinicopathological factors have been reported in gastric cancer, but the results have been ambiguous. This systematic review and meta-analysis investigated the relationship between MSI and overall survival and clinicopathological characteristics of patients with gastric cancer. METHODS: A systematic literature search of the PubMed, Cochrane and Ovid databases until 31 January 2016 was performed in accordance with the PRISMA statement. The articles were screened independently according to PICO (population, intervention, comparator, outcome) eligibility criteria. All eligible articles were evaluated independently by two reviewers for risk of bias according to the Quality In Prognosis Study tool. RESULTS: Overall, 48 studies with a total of 18 612 patients were included. MSI was found in 9·2 per cent of patients (1718 of 18 612), and was associated with female sex (odds ratio (OR) 1·57, 95 per cent c.i. 1·31 to 1·89; P < 0·001), older age (OR 1·58, 2·20 to 1·13; P < 0·001), intestinal Laurén histological type (OR 2·23, 1·94 to 2·57; P < 0·001), mid/lower gastric location (OR 0·38, 0·32 to 0·44; P < 0·001), lack of lymph node metastases (OR 0·70, 0·57 to 0·86, P < 0·001) and TNM stage I-II (OR 1·77, 1·47 to 2·13; P < 0·001). The pooled hazard ratio for overall survival of patients with MSI versus those with non-MSI gastric cancer from 21 studies was 0·69 (95 per cent c.i. 0·56 to 0·86; P < 0·001). CONCLUSION: MSI in gastric cancer was associated with good overall survival, reflected in several favourable clinicopathological tumour characteristics.

Ceftriaxone (1 g intravenously) penetration into abdominal tissues when administered as antibiotic prophylaxis during nephrectomy.

A pharmacokinetics study was conducted to determine the effects of ceftriaxone administered before nephrectomy on the occurrence of postoperative wound infection. Ceftriaxone was administered as antibiotic prophylaxis in 11 consecutive patients undergoing nephrectomy who received 1,000 mg intravenously 30 min before surgery. Simultaneous blood and tissue samples were collected at three stages of the surgical procedure: opening of the abdominal cavity, nephrectomy, and closure of the abdominal cavity. Samples of following tissues were assayed: abdominal-wall fat, perirenal fat, kidney cortex and medulla, and urine. During the different stages of surgical procedures, ceftriaxone concentrations remained higher than the MIC90 of the potential pathogens (Staphylococcus aureus, Escherichia coli, and Enterobacteriaceae). In selected patients undergoing nephrectomy and requiring antimicrobial prophylaxis such as malnourished, debilitated, diabetic or immunosuppressed patients, the use of a single dose of ceftriaxone (1,000 mg) makes it possible to offer an optimal bacterial coverage for the prevention of postoperative infection. According to our kinetic evaluation, ceftriaxone is potentially a good antibiotic for prophylaxis in urological surgery.

Gemcitabine (GEM), 5-fluorouracil (5-FU) and folinic acid (FA) in patients with different gastroenteric malignancies.

This phase II clinical trial was performed in order to evaluate the pharmacokinetics, toxicity and anti-tumor activity of a novel combination of gemcitabine (GEM), 5-fluorouracil (5-FU) and folinic acid (FA) designed on a specific translational basis. Every 4 weeks, 44 patients with various gastroenteric malignancies, 29 of whom had pancreas carcinoma, received a short intravenous (i.v.) infusion of FA (100 mg/m2) and 5-FU (400 mg/m2) on days 1-5, and GEM 1000 mg/m2 on days 1, 8 and 16. Our results suggest that, although this treatment leads to hematological and gastroenteric toxicity, it is very active in patients with pancreatic carcinoma. We therefore believe that an improved version would merit further investigation in larger scale trials.

[Antropyloric preservation in pancreatic excisions]. / La conservazione antro-pilorica nelle exeresi pancreatiche.

The authors report 11 consecutive partial or total pancreatectomies with preservation of the pylorus. They believe this technique is to be preferred because it allows a better digestion and reduces complication rate.

[Cervical esophageal perforation caused by a foreign body: a clinical case]. / Perforazione esofagea cervicale da corpo estraneo: caso clinico.

The Authors report a case of cervical esophageal perforation from foreign body. Comparing their experience with data from literature, they point out the diagnostic importance of both X-ray studies, in order to demonstrate the site of the lesion, and CT scans, to have accurate information on perilesional infective complications (abscesses). Early surgical treatment, with primary closure of perforation and adequate drainage, associated with antibiotics and enteral or total parenteral nutrition, allows good results in most cases.

Oral metronomic chemo-hormonal-therapy of metastatic breast cancer with cyclophosphamide and megestrol acetate.

Metronomic chemotherapy is an anticancer strategy which uses conventional cytotoxic drugs administered at very low dose in close intervals. We have designed a phase II trial to investigate the safety and antitumor activity of the newest metronomic chemo-hormonal-therapy with daily cyclophosphamide and twice daily megestrol acetate (mCM regimen) in patients with metastatic pretreated breast cancer.Twenty-nine pretreated post-menopausal patients with multiple metastatic sites were enrolled. four patients had a triple negative status, nineteen a positive hormonal ER and PgR status, and three ERB-B2 over-expression. Patients received treatment with cyclophosphamide (50 mg/daily day 1-21/q28) and fractionated megestrol acetate (80 mg twice a day). The overall objective response rate was 31.0%, disease control rate 41.3%, mean time to tumor progression 7.4 months (CI 95%, 3.8-10.88, range 1-48 months) and mean overall survival 13.4 months (CI 95%, 7.24-17.18, range 1-53 months). The mCM regimen was active and well tolerated.

Giant Sigmoid Diverticulum: A Rare Presentation of a Common Pathology.

Although colonic diverticulum is a common disease, affecting about 35% of patients above the age of 60, giant sigmoid diverticulum is an uncommon variant of which only relatively few cases have been described in the literature. We report on our experience with a patient affected by giant sigmoid diverticulum who was treated with diverticulectomy. Resection of the diverticulum is a safe surgical procedure, provided that the colon section close to the lesion presents no sign of flogosis or diverticula; in addition, recurrences are not reported after 6-year follow-up.

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation.

We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m(-2)) and etoposide (100 mg m(-2)) on days 1-3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours.

Validation of diagnostic procedures on stratified populations: application on the quantification of thallium myocardial perfusion scintigraphy.

In this report we present a method for the quantitative description of the degree of deviation from the norm of 201thallium single photon emission tomographic (SPECT) data. Validation is obtained from the frequency of "positive" outcomes in subgroup of patients in whom the prevalence of coronary artery disease, for the group as a whole, is known, even if individual patient outcomes are not verified. This approach overcomes the bias associated with nonrandomized clinical studies, in which the likelihood that a more invasive but definitive procedure (coronary arteriogram) will be performed is influenced by the result of the outcome of the procedure under study.

Proliferative response of human marginal gingiva to phlogistic process and titanium implant.

In order to detect proliferative processes in human marginal gingiva in pathological conditions and after externalization of titanium implants, we have attempted BrdU incorporation after "in vitro" incubation of tissue fragments. In comparison with healthy controls, immunocytochemical detection of samples from patients affected by hypertrophic gengivitis shows a good number of proliferating cells in the basal layer of the epithelium, while only in one case can positiveness be detected after externalization of titanium implants. Since after reduction of inflammation by hygienic treatment a low number of proliferating cells can be observed only in the regions where pathological alterations are also present, we suggest that the increase in tissue proliferation may be closely dependent on the intensity of the inflammatory process. All these data demonstrate that in vitro BrdU incubation of tissue fragments represents a suitable method to evaluate cell proliferation in human tissue.

Cell kinetics of vocal fold epithelium in rats.

In order to investigate the kinetics of vocal fold epithelium a bromodeoxyuridine-anti bromodeoxyuridine method has been applied in vivo at both light and electron microscopy level. This method is able to define the length of both epithelium turnover and cell-cycle in basal elements, as well as the existence of a higher proliferation rate during night time in comparison with day time. Moreover distinct labeling patterns observed in incorporating cells allow us to define the precise localization in S-phase of cycling elements.

Concentrations of ceftriaxone (1,000 milligrams intravenously) in abdominal tissues during open prostatectomy.

Ceftriaxone concentrations in abdominal tissues were evaluated at different stages of open prostatectomy. Ceftriaxone was administered as antibiotic prophylaxis, and 15 consecutive patients were given a single dose of ceftriaxone (1,000 mg intravenously in 1 min) 30 min before surgery. Ceftriaxone concentrations in tissue were determined at three stages of the surgical procedure; upon the opening of the abdominal cavity, during the prostatectomy, and upon the closure of the abdominal cavity. Samples of the following tissues or sample were assayed: epiploic and abdominal-wall fat; Retzius' space, bladder, and prostate tissue; and urine. During the different stages of the surgical procedure, for all patients, and in the different tested tissues, ceftriaxone concentrations greater than or equal to the cutoff point (4 micrograms/g of tissue) were measured. The highest concentrations were obtained in the bladder (43 +/- 18 micrograms/g) and in the prostate (35 +/- 18 micrograms/g). In fatty tissues, concentrations were between 13 +/- 5 and 22 +/- 8 micrograms/g. All patients (15 of 15) had ceftriaxone levels in tissue greater than the MICs for the potential pathogens (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis). In conclusion, during open prostatectomy and after the use of a single dose of ceftriaxone (1,000 mg), high antibiotic levels were obtained throughout the surgical procedure in the tissues potentially involved in postoperative infection.