Lorenzo Norberto

A randomized study comparing ligation with propranolol for primary prophylaxis of variceal bleeding in candidates for liver transplantation.

Whether beta‐blockers (BB) or banding is the best therapy for primary prophylaxis of variceal bleeding is subject to debate. A randomized comparison between the 2 treatments was performed in candidates for liver transplantation (LT). A total of 62 patients with Child‐Turcotte‐Pugh B‐C cirrhosis and high risk varices received propranolol (31) or variceal banding (31). The primary endpoint was variceal bleeding. There were 2 variceal hemorrhages (6.5%) in the banding group, related to postbanding ulcers, and 3 (9.7%) in the propranolol group (P = not significant [n.s.]). Deaths and bleeding related deaths were 3 and 1 for banding and 3 and 2 for BB, respectively (P = n.s.). A total of 14 patients underwent LT in the banding group and 10 in the propranolol group (P = n.s.). Adverse events were 2 postbanding ulcer bleedings in ligated patients (1 fatal) and 5 were intolerant to propranolol (P = n.s.). Mean costs per patient were higher with banding than with propranolol treatment (4,289 ± 285 vs. 1,425 ± 460 U.S. dollars, P < 0.001). In conclusion, propranolol and banding are similarly effective in reducing the incidence of variceal bleeding in candidates for LT, but ligation can be complicated by fatal bleeding and is more expensive. Our results suggest that banding should not be utilized as primary prophylaxis in transplant candidates who can be treated with BB. Liver Transpl, 2007.

Outcome of patients receiving photodynamic therapy for early esophageal cancer

PURPOSE Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Human Gastric Juice Contains Chitinase That Can Degrade Chitin

Chitin digestion by humans has generally been questioned or denied. Only recently chitinases have been found in several human tissues and their role has been associated with defense against parasite infections and to some allergic conditions. In this pilot study we tested the gastric juices of 25 Italian subjects on the artificial substrates 4-methylumbelliferyl-β-D-N,N’,diacetylchitobiose or/and fluorescein isothiocyanate (FITC) chitin to demonstrate the presence of a chitinase activity. Since this chitinase activity was demonstrated at acidic pH, it is currently referred to acidic mammalian chitinase (AMCase). AMCase activity was present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h and from 8,881 to 1,254,782 fluorescence emission (CPS), according to the used methods. In the remaining five of 25 gastric juices, AMCase activity was almost absent in both assay methods. An allosamidine inhibition test and the measurement at different pH values confirmed that this activity was characteristic of AMCase. The absence of activity in 20% of the gastric juices may be a consequence of virtual absence of chitinous food in the Western diet.

Push-through intubation: Effective palliation in 409 patients with cancer of the esophagus and cardia

Between 1980 and 1989, 355 patients with cancer of the esophagus and 54 with cancer of the cardia underwent push-through intubation because of advanced tumor stage or medical contraindications to tumor resection. In 36 other patients (8.1%), the attempt at transtumoral intubation failed. The hospital mortality rate after intubation was 3.4%. The following complications were observed: hemorrhage in 2.0% of the patients, esophageal perforation in 4.9%, tube dislodgment in 12.7%, and tube obstruction in 4.4%. Early resumption of semisolid oral feeding was possible in 80% of the discharged patients. The actuarial 1-year survival rate was 7.7% and the median survival, 3.9 months. In conclusion, push-through intubation represents a valid therapeutic choice, which is indicated mainly for patients with a long, infiltrating, and circumferential stricture of the thoracic esophagus or cardia that is inoperable and for patients with an esophagorespiratory or esophagomediastinal fistula.

Surgical predictors of recurrence of Crohn’s disease after ileocolonic resection

Background/aimsAnastomotic recurrence after bowel resection is a major problem in Crohn’s disease (CD) surgery. The aims of this retrospective study are to assess the role of anastomotic configuration, the type of suture and the type of surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis.Materials and methodsIn this retrospective study, we enrolled 141 consecutive patients who had undergone ileocolonic resection for CD. Univariate actuarial analysis was performed according to demographic, clinical and surgical predictors. Variables that resulted to be significant at the univariate analysis were included in two multivariate Cox proportional hazards models that analyzed symptomatic and surgical recurrence, respectively.ResultsIn the long-term, handsewn side-to-side anastomosis reported a significantly lower surgical recurrence rate than stapled end-to-side (p < 0.05). At multivariate analysis, anastomosis type, surgical and intestinal complications (p < 0.01) and age at CD onset (p < 0.05) resulted to be significant predictors for re-operation for CD recurrence. Multivariate analysis showed that surgical complication was also a significant predictor of symptomatic recurrence.ConclusionsSide-to-side anastomosis configuration seems to delay re-operation and can be assumed as the standard configuration in ileocolonic anastomosis in CD. Post-operative complications and young age at disease onset might be a signal of aggressive CD that may warrant prophylactic pharmacological therapy.

Barrett's esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian Registry (EBRA).

Objective:To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barretts esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. Background:BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. Methods:In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. Results:HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2–4); median follow-up = 44.6 [IQR: 24.7–60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51–68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9–50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63–21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22–11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03–1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. Conclusions:These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments.

Gastrointestinal stromal tumors: Report of an audit and review of the literature

Gastrointestinal stromal tumors (GISTs), tumors characterized by c-KIT mutations, are the most frequent mesenchymal tumors of the digestive tract. The stomach is the most commonly involved site. Localization, size and mitotic rate are reliable predictors of survival and the two milestones of GISTs treatment are surgery and imatinib. This article is aimed to report the data of an audit, carried out on the morphological and clinical aspects of the disease and to review the present knowledge on GISTs. A total of 172 patients with GISTs (M : F=1 : 1; mean age 65 years) were recruited. The stomach was the most frequently involved site. In 50% of the cases the tumor was smaller than 5 cm, whereas major symptoms were observed in 43% of the cases. Predictors of progressive disease were present only in a small percentage of cases but the disease was in the metastatic phase in over 25% of the cases at diagnosis. Familial aggregation was rare but a consistent share of the patients (21%) had other synchronous or metachronous cancers. The most frequent mutations were in-frame deletions and point mutations of c-KIT exon 11. This report confirms in part the available data on GIST in a consecutive series of patients recruited in Italy and shows that only large collaborative multicenter studies provide data sound enough to enable making reasonable clinical and therapeutic choices, and suggests that, as a measure of secondary prevention, a diagnostic definition should be obtained in all submucosal lesions of the GI tract and that GIST patients should be screened for second tumors.

The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation.

Objectives CD40 co-stimulator seems to be implicated in the loss of tolerance against self-antigens in many autoimmune diseases. The evidence suggests that in the pathogenesis of ulcerative colitis there is an activity state against self-antigens of the gut wall and flora. The aim of this study was to analyse the expression of CD40 in ulcerative colitis, comparing it with Crohns disease and nonspecific inflammation of the colon and to determine whether there is a relationship between its expression and the activity stage of the disease. Methods The expression of CD40 in the colonic samples of 51 patients (30 ulcerative colitis, 9 Crohns disease and 12 nonspecific inflammation) was analysed by immunohistochemistry. Twenty-four patients with ulcerative colitis were scored according to clinical, endoscopic and histological classification. Results The mean percentage of CD40+ cells per field in the colonic mucosa was: ulcerative colitis 21 ± 11%, Crohns disease 24 ± 9%, nonspecific inflammation 7 ± 7%. The ulcerative colitis patients were statistically significantly different compared to the patients with nonspecific inflammation (P < 0.005), even when comparing the patients in remission (P < 0.05). The expression in Crohns disease was similar to that in ulcerative colitis. The expression of CD40 in ulcerative colitis was directly proportional to the state of activity of the disease according to the clinical (P < 0.02), endoscopic (P < 0.01) and histological (P < 0.02) criteria. Conclusions The expression of CD40 in the colonic mucosae of patients with ulcerative colitis is significantly increased and is proportional to the state of activity. The results seem to confirm the hypothesis that a loss of tolerance could be involved in the pathogenesis of this disease.

Endoscopic dilation of benign esophageal strictures in a surgical unit: a report on 95 cases.

Ninety-five patients were treated by endoscopic dilation without fluoroscopic guidance between 1997 and 2005 for benign esophageal strictures. The etiologies were: anastomotic (38), postfundoplication (13), caustic (14), peptic (11), radiation-induced (10) and others (9). The strictures were classified at every session on a 0 to 4 scale on the basis of the diet and the luminal diameter. Savary-Gillard or Through-the Scope balloon dilators were used depending on the type and the location of the stenosis. A total of 472 dilation sessions were carried out without serious complications. A normal and a semisolid diet were respectively achieved in 75% and 91%. Recurrence of dysphagia was found in 33% and 51% of the patients respectively after 2 months and 1 year. Improvement of dysphagia, the number of sessions, and recurrence were significantly better in the patients with postsurgical stenosis as compared with those affected by caustic, peptic, and radiation-induced strictures.

CHIT1 and AMCase expression in human gastric mucosa: correlation with inflammation and Helicobacter pylori infection.

Objectives In this study, we analysed the expression of chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) genes in human gastric mucosa biopsies to establish the function of the corresponding enzymes in patients with gastritis associated or not with Helicobacter pylori infection. Methods All 27 patients who took part in this study suffered from dyspeptic symptoms and postprandial pain, and sought to undergo gastroscopy. Antral and corpus biopsy specimens were taken to analyse stomach inflammation and detect H. pylori. RNA was extracted from antral gastric biopsies and expression of genes for CHIT1 and AMCase was analysed by quantitative real-time PCR. Results In human inflamed gastric mucosa, CHIT1 and AMCase genes were expressed on average at a very low level (approximately 10–5 pg), and a correlation was shown among expression of CHIT1 gene and both positivity to the H. pylori test (P = 0.016) and gastric mucosa inflammation (P = 0.026). No correlation was found among AMCase gene expression and presence of H. pylori and inflammation. Conclusion In this study, we showed the presence of CHIT1 and AMCase mRNA in gastric mucosa and the correlation with the presence of H. pylori was significant only for CHIT1 but not for AMCase expression. This study has shown for the first time that CHIT1 mRNA is present in gastric mucosa and confirms the participation of such an enzyme in the human immune response to inflammation in general, and to H. pylori infection in particular.