Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.

Self-expanding plastic stents for inoperable malignant strictures of the cervical esophagus.

Dysphagia and respiratory complications are the major problems in patients suffering from malignant strictures of the cervical esophagus. In inoperable cases, interventional palliation is the cornerstone of treatment. The aim of this study was to evaluate the use of self-expanding plastic stents (SEPS) in this group of patients. In a retrospective study, 23 patients suffering from various malignant obstructive diseases of the cervical esophagus, including squamous cell carcinoma (n = 10), laryngeal cancer (n = 7), lung cancer with esophageal invasion (n = 5), and metastatic breast cancer (n = 1), underwent SEPS placement, under endoscopic and fluoroscopic guidance. Tracheoesophageal fistula was documented in five patients. Technical success rate, improvement of dysphagia grade, and stent-related complications were evaluated after stent placement. Stent insertion was successfully achieved in all cases, namely in 20 patients at the first stent placement attempt and in three patients after a second attempt. Dysphagia grade was notably improved after 24 h. In two cases, major complications occurred. These were successfully treated without the need of stent extraction. Barium swallowing studies demonstrated complete sealing of all fistulas. Foreign-body sensation that gradually disappeared within the first week after stent placement was observed in eight patients. Recurrence of dysphagia occurred in three patients, due to hyperplastic tissue proliferation (n = 2) and tumor overgrowth (n = 1). Late migration of the stent was detected in one case after 67 days. SEPS placement is an effective and safe palliative treatment for malignant strictures of the cervical esophagus. Main advantages include easy retrievability and reduced rates of reinterventions.

Gemcitabine as palliative treatment in patients with unresectable pancreatic cancer previously treated with placement of a covered metal stent. A randomized controlled trial.

PURPOSE: To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL). PATIENTS AND METHODS: Forty-nine patients with unresectable PC and obstructive jaundice, previously treated with the placement of a covered metal biliary endoprosthesis, were randomized to receive gemcitabine (group A: 9 males, 7 females) or to be followed without any anticancer intervention (group B: 18 males, 15 females). Gemcitabine was administered weekly as intravenous (i.v.) 30 min infusion of 1000 mg/m2 for 3 consecutive weeks followed by 1-week rest (28-day cycle). QoL was evaluated with the QLQ-C30 questionnaire. RESULTS: 229 gemcitabine doses were administered (median doses per patient 14.3, range 7-22). No statistically significant differences were observed regarding survival (group A: median 21 weeks, range 13-33; group B: median 22 weeks, range 13-29; p=0.809). According to the average QLQ-C30 score, group B patients showed statistically significant higher values (p=0.0001). Leukopenia, neutropenia, thrombocytopenia and anemia were the most common side effects in group A (81.25, 68.75, 62.50 and 31.25%, respectively). CONCLUSION: Gemcitabine didn't show to improve survival and QoL in patients with advanced PC previously treated with a covered metallic biliary endoprosthesis due to obstructive jaundice.

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial.

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5 mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30 mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49+/-6 wk) as compared to the control group (28+/-1 wk) and to the SSTR negative group (28+/-2 wk), LR=20.39, df=2, P<0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group, respectively. CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

Experimental isolation and transplantation of hepatocytes with the use of antibody against interleukin-2 receptor (daclizumab) as immunosuppressive agent.

INTRODUCTION: Daclizumab (Dmab) is a genetically engineered humanized IgG1 monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (Tac, CD25, p55) expressed on activated human T lymphocytes. Dmab has been used in a clinical protocol of islet transplantation with satisfactory results. The aim of the present study was to evaluate the use of an antibody against the interleukin-2 receptor (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte allotransplantation (allo-Tx) in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 48 Lewis rats as recipients: four groups of 12 animals each with induction of FHF and 24 hour later hepatocyte Tx--group A: no treatment; group B: cyclosporin (20 mg/kg days 0 to 5 and 10 mg/kg days 6 to 15); group C: Dmab (0.05 mg day of Tx and 0.05 mg day 7); and group D: Dmab and cyclosporine. Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: Statistical analysis showed better survival among groups C (83%, MST = 13) and D (92%, MST = 14.25) compared to groups A (max 72, MST = 1.5) or B (50%, MST = 9). Survival in group D was better but not significantly than group C. Biochemical evaluation and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model showed the safe, effective use of Dmab.

Palliative treatment of advanced esophageal cancer with metal-covered expandable stents. A cost-effectiveness and quality of life study.

PURPOSE: The aim of this retrospective study was to evaluate the efficacy and safety of endoscopic therapy with self-expanding metallic endoprostheses in the management of inoperable primary malignant esophageal obstruction or stenosis and the cost-effectiveness of the method. PATIENTS AND METHODS: Between 5/1997-12/2002, obstruction of the esophagus was diagnosed in 78 patients (52 males, 26 females, age range 53-102, mean 72.3 years). The etiology was squamous cell carcinoma (n=42) and adenocarcinoma of the oesophagus (n=36). In total, 89 ultraflex metal stents were introduced endoscopically. In 46 patients dilation with Savary dilators prior to stent placement was required. A cost-effective analysis was performed, comparing oesophageal stenting with laser therapy. RESULTS: Stents were placed successfully in all patients. After 48 h, all patients were able to tolerate solid or semi-solid food. During the follow-up period 8 patients developed dysphagia due to food impaction (treated successfully endoscopically). Eleven patients developed recurrent dysphagia 4-16 weeks after stenting due to tumor overgrowth and were treated with placement of a second stent. The median survival time was 18 weeks. There was no survival difference between squamous cell and adenocarcinoma of the esophagus. A similar cost was calculated for both procedures. A significant improvement in quality of life was noted in patients undergoing stenting (96% and 75% vs. 71% and 57% for the first two months). CONCLUSION: Placement of self-expanding metal stents is a safe and cost-effective treatment modality that improves the quality of life, compared with laser therapy, for patients with inoperable malignant esophageal obstruction.

Immune thrombocytopenic purpura in a patient treated with interferon alfacon-1.

Immune thrombocytopenic purpura is an acquired disorder characterized by severe thrombocytopenia and caused by one or more antiplatelet autoantibodies. We present a case of a 20-year-old woman referred to our Unit for chronic hepatitis C virus (HCV) infection. At week 28 of treatment with interferon (alfacon-1), undetectable HCV RNA and transaminase levels within normal limits, the patient presented with immune thrombocytopenic purpura, which was successfully treated with immunoglobulin and methylprednisolone. Despite the high doses and long life of corticosteroid treatment HCV RNA remained undetectable.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.

Stenting or stoma creation for patients with inoperable malignant colonic obstructions? Results of a study and cost-effectiveness analysis.

BACKGROUND: The aim of the present study was to compare the efficacy, safety, and cost of endoscopic palliative treatment with selfexpanding metallic stents with that of stoma creation in the management of inoperable malignant colonic obstructions. METHODS: A total of 30 patients with inoperable malignant partial obstruction (due to metastases, hemodynamic instability, or pulmonary instability) in the left colon arising from colorectal or ovarian cancer were included in the study. Fifteen were randomized to undergo palliative metallic colonic stent placement and 15 to undergo stoma creation. The efficacy and safety of the two methods was compared. A cost-effectiveness analysis was also performed, including the cost of postinterventional care. RESULTS: Stents were placed successfully in 14 of 15 patients. In one patient with obstruction of a tortuous rectosigmoid flexure colon, stenting was not possible; this patient was excluded from the study. During the follow-up period, a moderate, nonocclusive ingrowth of tumor into the stent lumen was observed in six patients; they were all treated with internal laser ablation. The cost-effectiveness analysis showed that although the stoma creation procedure was less expensive, the total difference in average costs for the two methods was 6.9% (132 Euros). CONCLUSIONS: Self-expanding metallic stent placement is a palliative alternative to colostomy for patients with inoperable malignant colonic strictures. This treatment option provides a better quality of life for the patient, without the psychological repercussions of a colostomy, and it appears to be cost-effective.

Large-scale expansion of CD3(+)CD56(+) lymphocytes capable of lysing autologous tumor cells with cytokine-rich supernatants.

We have developed culture conditions for the efficient expansion of cytotoxic effector cells from peripheral blood mononuclear cells (PBMC) by the timed addition of cytokine-rich supernatants collected from allogeneic PBMC cultures stimulated with anti-CD3 monoclonal antibody (mAb) (allogeneic CD3 supernatants; ACD3S). These cytotoxic effectors belonged primarily to CD56(+) natural killer (NK) cells, and the cell subset with the greatest cytotoxic activity was an otherwise rare population of CD3(+)CD56(+) cells (NKT cells) that expand dramatically under these conditions. CD3(+)CD56(+) cytotoxic effectors were generated from the PBMC of 16 patients with several types of cancer. The CD3(+)CD56(+) cell subset expanded significantly and efficiently lysed NK- as well as lymphokine-activated killer (LAK)-sensitive targets. More importantly, ACD3S-activated CD3(+)CD56(+) cells were capable of efficiently lysing autologous tumor cells including metastatic colorectal, ovarian, breast, lung and pancreatic tumor cells as well as melanoma cells. ACD3S-expanded CD3(+)CD56(+) cells exhibited increased levels of cytoplasmic interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (IFN-gamma) and perforin. CD3(+)CD56(+) cell-mediated cytotoxicity was not restricted by major histocompatibility complex (MHC) gene products, since it was not blocked by anti-MHC class I mAb but was highly inhibited in the presence of CD2- and CD18-specific mAb. These data suggest that CD3(+)CD56(+) cells expanded under the presence of ACD3S may be utilized in clinical protocols for cancer immunotherapy.

Treatment of malignant colonic obstructions with metal stents and laser.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and safety of combined endoscopic therapy with self-expanding metallic endoprostheses and laser application in the management of malignant colonic obstruction. METHODOLOGY: Between March 1998 and September 2000, obstruction of the distal colon was diagnosed in a total of 11 patients (6 M, 5 F, age range: 67-87 years, mean: 73). The site of obstruction was located in the rectosigmoid colon (n = 6), in the sigmoid colon (n = 4) and in the descending colon (n = 1). The etiology of stenosis was colorectal adenocarcinoma (n = 8), ovarian cancer (n = 2) and infiltrating bladder carcinoma (n = 1). In all patients the tumor was considered non-resectable. Six patients had confirmed metastases, one refused colostomy and 4 were unable to undergo surgery. After radiological visualization of the proximal extent of the stricture, the stenosis was dilated with Savary-like (10 patients) and pneumatic balloon dilators (1 patient-descending colon). RESULTS: Stents were placed successfully in 10 patients. Prostheses migration distal to lesion, into the sigmoid colon, was observed in one patient (bladder cancer). A mild autoresolved bleeding was observed in 8 patients. Five patients remained free of clinical colonic obstruction until their death, which occurred 6-16 weeks (mean: 10) after stent placement. A moderate non-occlusive ingrowth of tumor into the stent lumen was documented in the other 5 cases. These patients were treated with introspective application of Diomed laser in a total of 16 sessions (4120-12,476 Joules each session, mean: 6258, power 10-14 W, interval between 2 sessions 6 weeks) and died of progressive disease without clinical signs and endoscopic findings of reobstruction 22-56 weeks (mean: 32) after stent placement. CONCLUSIONS: Metallic stent placement is an adequate palliative and cost-effective option, effective and save, in advanced colonic obstruction due to non-resectable tumors. It circumvents the need for colostomy and allows the patient a better quality of life. Delayed stent occlusion with tumor ingrowth requires a regular follow-up and can be treated with introspective laser ablation.

Colorectal polyp detection with virtual colonoscopy (computed tomographic colonography); the reliability of the method.

BACKGROUND/AIMS: The aim of this study was to compare the reliability of virtual colonoscopy with conventional colonoscopy in detection of colorectal polyps. METHODOLOGY: Between November 1997 and February 2000, 23 patients (14 males, 9 females) aged 43-86 years (mean: 63) with colorectal polyps who underwent colonoscopy in our endoscopy unit, were referred for virtual colonoscopy. The colon was distended with an enema tube for rectal insufflation and subsequently was scanned by helical CT (Toshiba X-vision) using the following parameters: KV 120, mAs 200, table feed 5 mm/sec, slice thickness 5 mm and reconstruction intervals 2.5 mm. Using SPARC Station 20, virtual colonoscopy was generated. RESULTS: A total of 30 polyps (19 with diameter 8-15 mm and 11 larger than 15 mm) were detected with conventional colonoscopy. Virtual colonoscopy visualized 27 polyps (17 with diameter 8-15 mm and 10 with diameter > 15 mm). CONCLUSIONS: Virtual colonoscopy is a non-invasive, well-tolerated, safe technique and can be useful for detection of colorectal polyps. Weaknesses of the method are the inability to detect small lesions and to perform biopsies.

Primary melanoma of the oesophagus treated endoscopically. A case report.

Primary melanoma is a rare neoplasm of the oesophagus, with dismal outcome in most cases. We report a case of primary melanoma of the oesophagus treated endoscopically, as coexisting illness prohibited surgical resection of the tumour. A review of the literature is made.