Adriana Romiti

Optimal nutritional indexes in chronic liver disease.

A population of 70 patients with liver cirrhosis, most of whom were nonalcoholic, was studied. Distribution of ideal body weight and body mass index was below the median of controls, but very few patients were below the cut-off points for normalcy. Distribution of triceps skinfold and arm muscle circumference was also below the median and, in most patients, was also below the cut-off points. Serum visceral protein concentrations and anthropometric parameters each were reciprocally correlated with one another, but no correlation was observed between visceral proteins and anthropometric parameters. Serum visceral proteins appeared to correlate better with the degree of liver damage than with the degree of malnutrition. Therefore, anthropometric parameters seem preferable to serum visceral proteins for the assessment of nutritional status in patients with liver cirrhosis.

Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients.

We compared the effect of lactulose or lactitol on the fecal flora of 21 cirrhotic patients without hepatic encephalopathy. All were treated with an individualized disaccharide dose to achieve and maintain two semiliquid bowel movements per day. Stool pH and fecal flora were determined before and 10 days after stabilizing the cathartic effect. Increased counts of lactobacilli were obtained with both treatments. This increase, which was related to the decreased stool pH, was more constant with lactulose. In addition, lactitol decreased certain proteolytic bacteria such as enterococci and enterobacteria. Both total aerobic and anaerobic bacterial counts showed little quantitative variations with either treatment.

Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis

Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.

Tumors of ampulla of Vater: A case series and review of chemotherapy options

Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of gastrointestinal cancers. Compared with other biliary tract neoplasms, these tumors have a relatively favorable prognosis after surgical resection. Based on their epithelium of origin, two subtypes of ampullary carcinoma have been recently distinguished: intestinal and pancreatobiliary. This study evaluates histopathological features and outcomes of ampullary carcinoma and to compares the survival of these tumors to that of other biliary tract tumors. The chemotherapic options available for ampullary cancer are also reviewed. We analyzed data from 20 consecutive patients with ampullary carcinomas and 26 patients with other biliary tract carcinomas, observed in our Institution. Statistical analysis was performed by using either Fishers exact test or χ(2) test for categorical variables. Median time of survival was calculated and compared using the Log-Rank test. Similar distribution of demographic characteristics and stage between ampullary and other biliary tract cancers was observed. Patients with ampullary cancer underwent surgery more frequently than other biliary cancers while chemotherapy and radiotherapy were used equally. In accordance with the literature, a longer median survival was observed in the group of ampullary carcinomas.

Early Postprandial Energy Expenditure and Macronutrient Use After a Mixed Meal in Cirrhotic Patients

The effect of meal ingestion (9 kcal/kg of body weight, 53% carbohydrate, 30% fat, 17% protein, as a liquid formula) on energy expenditure and oxidation rate of carbohydrate, fat, and protein was assessed by indirect calorimetry and urinary nitrogen excretion before and for 3 hours after eating in stable cirrhotic patients and control subjects of comparable age. Postprandial modifications of substrate and hormone levels were also studied. Compared with basal values, the mean +/- SD resting energy expenditure during the first 3 hours after meal ingestion increased similarly in cirrhotic patients (+0.32 +/- 0.12 kcal/min) and control subjects (+0.31 +/- 0.08 kcal/min). Dietary induced thermogenesis was equivalent to 10% of the energy contained in the meal in both groups. Before eating, the carbohydrate oxidation rate was lower and fat oxidation higher in cirrhotic patients than in the control subjects. After eating, glucose oxidation increased whereas fat and protein oxidation rates were reduced in both groups. As a consequence the amount of fat oxidized in the postprandial period remained higher in cirrhotic patients than in the control subjects. After meal ingestion, serum glucose levels increased whereas plasma free fatty acid and glycerol levels decreased in both groups. The substrates, however, remained significantly higher in cirrhotic patients than in control subjects, despite the higher postprandial insulin increment in the patients group, thus suggesting the presence of insulin resistance. Because the postprandial glucose oxidation rate was normal, the low insulin-mediated glucose uptake observed in cirrhotic patients seems to reflect a defect in the nonoxidative disposal of the glucose ingested.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy for the biliary tract cancers: Moving toward improved survival time

BackgroundThe biliary tract carcinomas rank fifth in incidence among all gastrointestinal tumours. This group of tumours includes both cholangiocarcinoma and gallbladder carcinoma. Although surgery represents the main therapeutic option for these patients, both radiotherapy and chemotherapy could be used in a multidisciplinary approach. Several studies are currently available on the use of chemotherapy, including 5-fluorouracil, mitomycin C, methotrexate, doxorubicin and cisplatin or newer anticancer molecules, such as gemcitabine, capecitabine, oxaliplatin and irinotecan. However, the small sample size of most of these studies prevents generalization.DiscussionWe reviewed the available data on both chemotherapy and targeted therapies for biliary carcinoma. By using conventional chemotherapy, a response rate ranging from 10% to 40% has been reported. Although encouraging data emerged with the use of targeted therapies, further efforts are needed to improve treatment options for patients with biliary tract cancer.

Circulating tumor cells count predicts survival in colorectal cancer patients

Background & Aims: Respiratory complications represent an important adverse event of endoscopic procedures. We screened for respiratory complications aer endoscopic procedures using a questionnaire and followed-up patients suggestive of respiratory infection. Method: In this prospective observational, multicenter study performed in Outpatient practices of gastroenterology we investigated 15,690 patients by questionnaires administered 24 hours aer the endoscopic procedure. Results: 832 of the 15,690 patients stated at least one respiratory symptom aer the endoscopic procedure: 829 patients reported coughing (5.28%), 23 fever (0.15%) and 116 shortness of breath (SOB, 0.74%); 130 of the 832 patients showed at least two concomitant respiratory symptoms (107 coughing + SOB, 17 coughing + fever, 6 coughing + coexisting fever + SOB) and 126 patients were followed-up to assess their respiratory complaints. Twenty-nine patients (follow-up: 22.31%, whole sample: 0.18%) reported signs of clinically evident respiratory infection and 15 patients (follow-up: 11.54%; whole sample: 0.1%) received therefore antibiotic treatment. Coughing or vomiting during the endoscopic procedure resulted in a 156.12-fold increased risk of respiratory complications (95% CI: 67.44 - 361.40) and 520.87-fold increased risk of requiring antibiotic treatment (95% CI: 178.01 - 1524.05). All patients of the follow-up sample who coughed or vomited during endoscopy developed clinically evident signs of respiratory infection and required antibiotic treatment while this occurred in a signicantly lower proportion of patients without these symptoms (17.1% and 5.1%, respectively). Conclusions: We demonstrated that respiratory complications following endoscopic sedation are of comparably high incidence and we identied major predictors of aspiration pneumonia which could inuence future surveillance strategies aer endoscopic procedures.

A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

BackgroundMany emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines.MethodsA phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines.ResultsTwenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1–14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%).ConclusionThe schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.

Gastric epithelial cell proliferation in patients with liver cirrhosis

An increased risk for gastric cancer in patients with liver cirrhosis has recently been reported. This study was performed in order to determine gastric epithelial cell proliferation in cirrhotic patients and to evaluate the role of congestive gastropathy (CG) and Helicobacter pylori infection in this process. Thirty-six cirrhotic patients and 18 controls were enrolled in the study. All patients underwent endoscopy and three biopsies were performed in the antrum and three in the gastric body. The presence of H. pylori infection was assessed by a rapid urease test and histology. The antral biopsies were used for gastric cell proliferation assessment by an immunohistochemical analysis (Ki-67). There was no significant difference in epithelial cell proliferation between cirrhotics and controls. Gastric proliferation values were higher in patients with H. pylori infection compared with uninfected patients, both in cirrhotic (P = 0.003) and in control groups (P = 0.06). Among the cirrhotic group, we found a progressive increase in gastric cell proliferation values related to the degree of CG, the highest values being observed in cirrhotic patients with severe CG. Moreover, cirrhotics with both severe CG and H. pylori infection had the highest proliferation values when compared with all other subgroups. In conclusion, this study found that: (1) CG significantly affects epithelial cell proliferation in gastric mucosa in cirrhotic patients, (2) H. pylori infection plays a similar role in gastric cell proliferation in both cirrhotic and non-cirrhotic patients, and (3) CG and H. pylori could act synergistically in this process.

A metronomic schedule as salvage chemotherapy for upper gastrointestinal tract cancer

In recent years, metronomic chemotherapy, consisting of continuous administration of low doses of cytotoxic agents, has being used as rescue therapy for different tumours. The aim of this study was to retrospectively assess the efficacy and safety of low-dose metronomic, oral capecitabine in pretreated or frail patients with recurrent upper gastrointestinal tract cancer. Patients with pretreated upper gastrointestinal tract cancer or who were not candidates for standard chemotherapy because of toxicity concerns received capecitabine at 1500 mg per day continuously until disease progression or occurrence of toxicity. Forty-seven patients (25 oesophagogastric cancer, 22 pancreatobiliary cancer; 25 men, 22 women; median age 69 years, range 42–90) were included in the study. Forty-five percent of the patients had received at least two previous lines of treatment and the median number of previous treatments was 1 (range 0–5). Twelve (31.6%) patients achieved clinical benefit (one partial response, 11 stable disease), whereas nine (23.7%) patients were progression free for at least 6 months. In an exploratory analysis, there was a significant relationship between performance status and clinical benefit (hazard ratio=8.25; P=0.01). The median overall survival was 5 months. A good performance status was associated with a longer survival (hazard ratio=0.26; P<0.01). No severe toxicity or treatment-related death was reported. Metronomic capecitabine showed good safety and moderate activity in frail or pretreated patients with advanced, upper gastrointestinal tract cancer.