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Aims Fluorescence in situ hybridisation (FISH) increases the sensitivity for detecting pancreatobiliary tract cancer over routine cytology. In this study, diagnostic accuracy and costs of cytology and FISH in detecting cancer in patients with jaundice with biliary strictures were assessed. Methods Brushing specimens from 109 patients with jaundice were obtained during endoscopic retrograde cholangiopancreatography and examined by cytology and FISH. The specimens were considered FISH-positive for malignancy if at least five polysomic cells or 10 cells with homozygous or heterozygous 9p21/p16 deletion were detected. Definitive diagnosis of the stricture as benign or malignant relied on surgical pathology (45 cases) or clinical-radiological follow-up >18 months (64 cases). We calculated costs of cytology and FISH based on the reimbursement from the Piedmont region, Italy (respectively, €33 and €750). Results Ninety of 109 patients had evidence of malignancy (44 pancreatic carcinomas, 36 cholangiocarcinomas, 5 gallbladder carcinomas, 5 other cancers), while 19 had benign strictures. Routine cytology showed 42% sensitivity, but 100% specificity for the diagnosis of malignancy, while FISH-polysomy showed 70% sensitivity with 100% specificity and FISH-polysomy plus homozygous or heterozygous 9p21/p16 deletion showed 76% sensitivity with 100% specificity. The cost per additional correct diagnosis of cancer obtained by FISH, in comparison with cytology, was €1775 using a sequential cytological approach (ie, performing FISH only in patients with negative or indeterminate cytology). Conclusions FISH should be recommended as the second step in detecting cancer in patients with jaundice with pancreatobiliary tract strictures and cytology negative or indeterminate for malignancy.

The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial. To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors. Prospective cohort study. 3 endoscopic units and 2 blood banks in northwestern Italy. The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51,230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38,280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95,317 person-years of observation). Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction. All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test. In the endoscopy cohort, 8.3% of patients were lost to follow-up. These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

OBJECTIVES: It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients. METHODS: One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of ≥700 μg/g dry wt (men) and ≥500 μg/g dry wt (women), stratified according to HCV genotype and γ-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months. RESULTS: Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5–27.9) of group A and 16 (28.1%, 95% CI = 17.0–41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2–3, normal γ-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96–6.24, p = 0.082). Patients with hepatic iron concentration of ≤1100 μg/g dry wt had a trend toward a higher rate of virological sustained response ( p = 0.059) when submitted to treatment B. CONCLUSION: Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.

OBJECTIVES:It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients.METHODS:One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of ≥700 μg/g dry wt (men) and ≥500 μg/g dry wt (women), stratified according to HCV genotype and γ-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months.RESULTS:Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5-27.9) of group A and 16 (28.1%, 95% CI = 17.0-41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2-3, normal γ-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96-6.24, p = 0.082). Patients with hepatic iron concentration of ≤1100 μg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B.CONCLUSION:Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.

It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients. One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of ≥700 μg/g dry wt (men) and ≥500 μg/g dry wt (women), stratified according to HCV genotype and γ-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months. Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5–27.9) of group A and 16 (28.1%, 95% CI = 17.0–41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2–3, normal γ-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96–6.24, p = 0.082). Patients with hepatic iron concentration of ≤1100 μg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B. Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.

Hepatitis C virus (HCV) infection is associated with most mixed cryoglobulinemia (MC) syndromes. In this study, HCV RNA was detected in the peripheral blood mononuclear cells of 11 (73.3%) of 15 patients with MC and in 5 (71.4%) of 7 noncryoglobulinemic patients with chronic hepatitis type C. All patients with cryoglobulinemia and 3 (42.8%) of the 7 without cryoglobulinemia (P <.05) had HCV RNA in bone marrow cells. Subjects in both groups with HCV-positive bone marrow also had HCV RNA in serum. The majority of patients with MC syndromes were infected with HCV subtypes lb and 2a. Two patients with MC had different genotypes in serum and cells. Further studies are needed to determine which bone marrow cell population is preferentially infected by HCV and to determine if this phenomenon is involved in inducing the production of cryoglobulins.

Hepatitis C virus (HCV) infection is associated with most mixed cryoglobulinemia (MC) syndromes. In this study, HCV RNA was detected in the peripheral blood mononuclear cells of 11 (73.3%) of 15 patients with MC and in 5 (71.4%) of7 noncryoglobulinemic patients with chronic hepatitis type C. All patients with cryoglobulinemia and 3 (42.8%) of the 7 without cryoglobulinemia (P < .05) had HCV RNA in bone marrow cells. Subjects in both groups with HCV-positive bone marrow also had HCV RNA in serum. The majority of patients with MC syndromes were infected with HCV subtypes 1band 2a. Two patients with MC had different genotypes in serum and cells. Further studies are needed to determine which bone marrow cell population is preferentially infected by HCV and to determine if this phenomenon is involved in inducing the production of cryoglobulins.

Background The reproducibility of patient setup for radiotherapy is based on various methods including external markers, X-rays with planar or computerized image acquisition, and, more recently, surface matching imaging. We analyzed the setup reproducibility of 16 patients affected by prostate cancer who underwent conformal radiotherapy with curative intent by using a surface image registration system. Methods We analyzed the setup reproducibility of 16 patients affected by prostate cancer candidates for conformal radiotherapy by using a surface image registration system. At the initial setup, EPID images were compared with DRRs and a reference 3D surface image was obtained by the AlignRT system (Vision RT, London, UK). Surface images were acquired prior to every subsequent setup procedure. EPID acquisition was repeated when errors > 5 mm were reported. Results The mean random and systematic errors were 1.2 ± 2.3 mm and 0.3 ± 3.0 mm along the X axis, 0.0 ± 1.4 mm and 0.5 ± 2.0 mm along the Y axis, and 2.0 ± 1.8 mm and -0.7 ± 2.4 mm along the Z axis respectively. The positioning error detected by AlignRT along the 3 axes X, Y, and Z exceeded the value of 5 mm in 14.1%, 2.0%, and 5.1% measurements and the value of 3 mm in 36.9%, 13.6% and 27.8% measurements, respectively. Correlation factors calculated by linear regression between the errors measured by AlignRT and EPID ranged from 0.77 to 0.92 with a mean of 0.85 and SD of 0.13. The setup measurements by surface imaging are highly reproducible and correlate with the setup errors detected by EPID. Conclusion Surface image registration system appears to be a simple, fast, non-invasive, and reproducible method to analyze the set-up alignment in 3DCRT of prostate cancer patients.