Feasibility of individualized treatment for hepatitis C patients in the real world.

BACKGROUND AND AIM: Individualized treatment with a combination of peg-interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real-life clinical setting. METHODS: A total of 253 naïve patients with HCV infection who received peg-interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non-1 (HCV non-1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV-1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV-1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24-week treatment for HCV-1 patients who achieved a rapid virological response, otherwise patients received a 48-week course of treatment. Early termination of treatment at week 16 was recommended for non-responders. RESULTS: A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non-1 infection. Among the HCV-1-infected patients, 53.5% of patients who underwent standard 24-week treatment, 66.7% of patients who underwent standard 48-week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV-1 and treated by individualized therapy had a similar efficacy response compared with the standard 48-week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220-2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189-6.855, P = 0.019) or standard 48-week treatment (adjusted OR 3.733, 95% CI 1.073-12.986, P = 0.038) had significantly higher odds of SVR compared with HCV-1 patients treated by standard 24-week course. CONCLUSION: Individualized therapy is feasible in the real world, especially for patients with HCV-1 infection.

Management and patient survival in hepatocellular carcinoma: does the physician's level of experience matter?

INTRODUCTION: The prognostic determinants of hepatocellular carcinoma (HCC) depend on tumor stage, liver function reserve, and treatments offered. The clinical impact of the physician's experience on HCC management and the survival outcome is unknown. METHODS: A total of 103 patients were managed by one high-volume physician and 249 patients by seven low-volume physicians. The experience of high-volume physician in HCC management was five times more than that of low-volume physicians. Patient survival was the single end point for this study. RESULTS: Compared to the low-volume physician group, more of the patients allocated to the high-volume physician had early stage HCC on the date of diagnosis (66/103, 64.1%; vs 119/249, 47.8%; P = 0.008), and they received curative therapies including radiofrequency ablation or liver resection (66/103, 64.1% vs 54/249, 21.7%, P < 0.001), and had significantly better survival outcome (median survival of 34 months, 95% confidence interval [CI], 17.6-50.4; vs 6 months, 95% CI, 4.3-7.7; P < 0.001) with a multivariable-adjusted hazard ratio (HR) for survival of 1.94 (95%, CI, 1.31-2.87, P < 0.001). A multivariate analysis of the pretreatment prognostic factors for these two groups identified alpha-fetoprotein (AFP) level (HR, 1.42; 95% CI, 1.01-1.99; P = 0.042), ascites (HR, 1.68; 95% CI, 1.15-2.46; P = 0.007), maximum tumor diameter (HR, 1.78; 95% CI, 1.16-2.74; P = 0.009), and portal vein thrombosis (PVT) (HR, 2.17; 95% CI, 1.49-3.17; P < 0.001) as independent factors for the low-volume physician group. However, only maximum tumor diameter (HR, 4.54; 95% CI, 1.77-11.67; P < 0.001) and PVT (HR, 5.73; 95% CI, 2.30-14.22; P = 0.002) were independent factors for the high-volume physician group. CONCLUSION: The survival of HCC patients was dependent on the level of experience of the physicians who oversaw these patients.

Endoscopic mucosal resection of early esophageal carcinoma--experience of 9 cases.

BACKGROUND: Early esophageal mucosal carcinoma (M1 and M2) can be treated by ablation, or by endoscopic resection such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection. Endoscopic resection enables pathologic examination of resected specimens. We hereby report our experiences with early esophageal cancer and its endoscopically observed types, chromoendoscopy with Lugol's iodine and EMR results. METHODS: Between May 2003 and July 2007, 9 patients with early esophageal carcinoma underwent EMR. The diagnosis was made by conventional endoscopy (waiting for the relaxed phase during esophageal peristalsis) followed by chromoendoscopy using 3% Lugol's iodine to stain suspected early lesions or in high-risks patients. Miniprobe endoscopic ultrasound examinations were performed in all cases except 1. EMRs were carried out with a cap-fitted endoscope (EMRC). RESULTS: There were 6 male and 3 female patients, with a median age of 53 years (range, 44-83 years). Six of the 9 cases had a history of smoking, 5 had a history of drinking, and 4 had a history of betel nut chewing. The endoscopic pictures of the early cancers were type 0-IIa (1 case), type 0-IIb (2 cases), and type 0-IIc (6 cases). One patient had double 0-IIc lesions. Two 0-IIb cases were detected only by chromoendoscopy using Lugol's iodine staining. The median size of the lesions was 0.85 cm (range, 0.7-2.0 cm). The final pathology reports of the endoscopically resected specimens were well-differentiated squamous cell carcinoma with free vertical and lateral margins, and no vascular or lymphatic invasion. The depths of tumor invasion were mucosal layer M1 in 7 cases, M2 in 1 case, and submucosal layer SM1 in the remaining case. There were no perforation or bleeding complications. The mean follow-up period was 13.1 months (range, 4-46 months). A M2 early esophageal cancer measuring 2 cm in diameter recurred 6 months after piecemeal EMRC. No additional adjuvant therapy was given to the SM1 case owing to her old age and bedridden condition. CONCLUSION: Early esophageal cancer can be diagnosed by meticulous examination of the esophageal mucosa with conventional endoscopy, facilitated by Lugol's iodine staining, and can be treated by EMR, which is safe. Recurrence can occur after piecemeal EMR.

Autoimmune chronic pancreatitis.

BACKGROUND: Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis that is characterized by swelling of the pancreas, narrowing of the main pancreatic duct (MPD), elevation of serum gamma globulin, or immunoglobulin G or presence of autoantibody, lymphoplasmacytic infiltration and dense fibrosis on histopathology. It is responsive to steroid therapy. The incidence of AIP can reach 5-6% of chronic pancreatitis. It can present as obstructive jaundice, body weight loss, and pancreas head mass mimicking pancreatic cancer. The recognition of AIP can avoid major surgery such as pancreatic resection. METHODS: From May 2003 to July 2007, a total of 5 cases of AIP were reviewed retrospectively. The diagnosis was made on imaging study, serology, steroid response and/or histology if surgery was carried out. RESULTS: There were 2 male and 3 female patients, with a mean age of 61 (39-75) years. Atypical AIP was found in the first case and typical AIP in the remaining 4. The presenting clinical pictures were mild epigastric pain, obstructive jaundice, and loss of body weight in 4 cases, with associated autoimmune disease in 1. Diffuse or long segmental enlargement of the pancreas without peripancreatic fat infiltration was found in all patients except 1 who only had focal pancreatic head enlargement. Distal common bile duct (CBD) stricture was seen in 4 cases and the median CBD stricture length was 1.2 (0.5-2.5) cm. Multiple narrowing of the whole MPD was seen in 2 cases, focal narrowing of the MPD in 2 and long segmental narrowing of the MPD in 1. Serum immunoglobulin G tests were done in 4 cases and were elevated in all. Antinuclear antibody was positive in 3. The first case was operated on after a preoperative diagnosis of suspicious pancreatic head tumor. The subsequent 3 cases were diagnosed correctly as AIP. The last case presented with distal CBD stricture and hypoechoic lesion in the pancreas head on endoscopic ultrasound, with only borderline pancreatic enlargement on computed tomography, and he was operated on. Retrospective endoscopic retrograde pancreatogram review revealed MPD narrowing in the pancreatic body. Endoscopic retrograde brush cytology was performed and was negative for malignancy in 3 cases. Steroid therapy was given in 3 and was responsive, but there were 2 recurrences. CONCLUSION: AIP should be a differential diagnosis in distal CBD stricture and pancreatic head mass when the patient has: (1) diffuse or long segmental enlargement of the pancreas without peripancreatic fat infiltration, with multiple narrowing of the MPD without much upstream dilatation, or narrowing of the MPD not corresponding to the region of CBD stricture; and (2) abnormal immunoserologic tests.

Biliary stenting with puncturing technique using Baron aspiration needle in ulcerative papillary carcinoma.

A 60 year-old man with obstructive jaundice due to an ulcerative papillary carcinoma underwent endoscopic retrograde cholangiopancreatography. Owing to the totally destroyed papilla of Vater, access to the biliary tract was impossible. Instead of needle knife fistulotomy, puncturing with an 18-G aspiration needle on the supra-papillary bulge followed by biliary stenting was performed successfully. To our knowledge, this technique has not been reported before in the English literature and probably can have fewer complications of bleeding and perforations produced by needle knife fistulotomy.

Hemoclip treatment for post-endoscopic sphincterotomy bleeding.

BACKGROUND: The incidence of bleeding after endoscopic sphincterotomy (EST) ranges from 2%-12.1%. Endoscopic treatments include injection and thermal therapy, which can have recurrent bleeding and potential complications of chemical and thermal injuries. There is only 1 case report of post-EST bleeding managed by hemoclipping in the literature. Treatment of post-EST bleeding with hemoclip is reported in this study. METHODS: From March 1999 to May 2003, a retrospective analysis of 162 cases of EST was made. Nine cases (5.5%) of post EST bleeding, 7 male and 2 female patients, with a mean age of 58 +/- 16 (37-82) years, were treated with hemoclipping. Four cases of recurrent bleeding were treated with secondary clipping when previous local epinephrine injection was ineffective, and the remaining 5 cases were managed with primary hemoclipping. RESULTS: Six cases were of major bleeding; 3 needed blood transfusion (mean: 7.3 units: 6-8 units) and 3 had a reduction of hemoglobin > 2 g/dL but without blood transfusion. The location of bleeder was 5 on the left side, 2 on the right side and 1 in both flaps of post-EST papilla. The median clips used were 2 (1-7), and the median missed clips were 0.5 (0-3). The success rate hemostasis was 88.8%, including 4 recurrent major bleeding after previous local epinephrine injection. Some technical difficulties were encountered. The failed case that underwent operation was due to total inability to get a visual field because of massive bleeding. There were no complications related to hemoclipping. CONCLUSIONS: Hemoclipping can be an alternative method for hemostasis in post-EST bleeding.

Role of endoscopic ultrasound-guided fine-needle aspiration in lung and mediastinal lesions.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was initially introduced for diagnosing gastrointestinal and pancreatic lesions, and later on for lung and mediastinal lesions. It can provide tissue diagnosis of lung cancer where bronchoscopy is non-diagnostic. It is a minimally invasive method for lymph node (N) and metastasis (M) staging of non-small cell lung cancer, and is helpful for tissue proof of mediastinal mass with unknown origin. Few data on this topic have been reported from Eastern countries. We report our experience of using EUS-FNA for tissue proof of lung and mediastinal lesions. METHODS: This was a retrospective analysis of prospectively collected data of 20 cases, with 21 EUS-FNAs of lung and mediastinal lesions (1 EUS-FNA performed on left adrenal gland) for tissue diagnosis and staging. With patients' informed written consent and fasting for 8 hours, EUS-FNA was performed with a linear echoendoscope using a 22- or 5-gauge needle and a syringe with 10-20 mL negative pressure. The cytology smear was fixed with 98% alcohol, while cell-block and tissue were sent for histology. There was no onsite cytopathologist. EUS-guided Tru-Cut biopsy was performed in 1 case. Malignancy was proven by FNA biopsy results, mediastinoscopy when performed, or by clinical course and follow-up. RESULTS: Of the 20 cases, 19 were male and 1 was female; mean age was 63.9 ± 12.6 years. Median tumor size was 2.6 cm (range, 1.8-5.0 cm), and median number of punctures was 3 (range, 2-7). Eighteen EUS-FNA punctures were performed at the mediastinum, and 2 directly on lung mass. The size of the left adrenal metastasis for extramediastinal EUS-FNA was 1.2 cm. Of the 16 EUS-FNA-positive cases, 12 were for tissue diagnosis, 3 were for both tissue diagnosis and staging (N2 and M1 staging), and 1 was for N2 staging. EUS-FNA provided a tissue diagnosis in 14 cases where bronchoscopy was negative. In 16 positive EUS-FNAs, all except 1 had adequate tissue for FNA biopsy. The sensitivity, specificity, and diagnostic accuracy of EUS-FNA were 84.2%, 100%, and 85%, respectively. CONCLUSION: EUS-FNA can diagnose lung cancer by confirmation of mediastinal lymph node metastasis, by direct puncture of lung tumor close to the esophagus. It is useful for lymph node (N) stations 5, 7, 8 and metastasis (M) staging in non-small cell lung cancer, and for the diagnosis of mediastinal mass of unknown etiology.

Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy.

BACKGROUND AND AIM: Elevated serum alpha-fetoprotein (AFP) levels are noted in patients with chronic hepatitis C (CHC) without hepatocellular carcinoma (HCC). The change in AFP levels after treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) combination therapy is still unknown. The aim of this study was to investigate the predictors of elevated serum AFP in patients with CHC, and its change after Peg-IFN/RBV therapy. METHODS: A total of 123 patients, intended to receive pegylated interferon alfa-2a plus ribavirin therapy, were enrolled. Eighty-three patients had complete treatment and received follow up for and additional 24 weeks. The factors that may affect the elevation of pretreatment AFP and the normalization of post-treatment AFP were determined. RESULTS: The mean AFP level was 18.5 +/- 63.0 ng/mL (range, 1.3-676.0 ng/mL); 41 (33.3%) of the 123 patients had elevated serum AFP (more than 10 ng/mL) at baseline. A multivariate logistic regression analysis disclosed that older age (odds ratio [OR], 1.093; 95% confidence interval [CI], 1.015-1.177; P = 0.018), more advanced METAVIR fibrosis stage (OR, 5.237; 95% CI, 1.244-22.037; P = 0.024), a higher aspartate aminotransferase (AST) level (IU/L) (OR, 1.020; 95% CI, 1.008-1.033; P = 0.001), and lower platelet count (x10(9)/L, OR, 0.985; 95% CI, 0.968-0.994; P = 0.003) were independent determinants of pretreatment AFP elevation. After treatment, 72 of 83 (86.7%) cases were found to have normal post-treatment AFP levels (<10 ng/mL) at the end of follow up (EOF). Post-treatment negativity of the chronic hepatitis C virus (HCV)-RNA (OR, 10.014; 95% CI, 1.000-100.329; P = 0.050) and the post-treatment platelet count (x10(9)/L) (OR, 1.025; 95% CI, 1.001-1.050; P = 0.040) were associated with normal AFP at EOF. AFP progressively decreased with significant differences starting from the 12th week after treatment to the end of treatment, and was lowest at the EOF date for the sustained viral response (SVR) group. On the contrary, the non-SVR group did not have an AFP change during and after treatment. CONCLUSION: Older age, low platelet count, higher AST levels, and advanced fibrosis predisposed chronic hepatitis C patients without HCC to have elevated serum AFP levels. After Peg-IFN/RBV combination therapy, a higher platelet count and HCV viral eradication were determinants of normal AFP at EOF. Serial AFP levels decreased after treatment, presenting in a time-dependent manner, specifically for the SVR group.

Guidewire technique for endoscopic transpapillary procurement of bile duct biopsy specimens without endoscopic sphincterotomy.

BACKGROUND: Endoscopic sphincterotomy may be required when endoscopic transpapillary bile duct biopsy specimens are needed for tissue diagnosis. However, endoscopic sphincterotomy has potential complications. A guidewire technique for obtaining transpapillary biopsy specimens without endoscopic sphincterotomy was evaluated. METHODS: A total of 13 patients (11 men, 2 women; mean age 67.5 years) with biliary stricture or obstruction underwent endoscopic retrograde cholangiography. A guidewire was then inserted across the stricture or obstruction and into an intrahepatic duct. Alongside the guidewire, the biopsy forceps (1.5 mm diameter) was introduced into the papillary orifice with the duodenoscope extremely close to the papilla. OBSERVATIONS: Tissue was obtained in 92.3% of the cases for histopathologic evaluation without difficulty or complication. The single failure occurred in a patient who had undergone a partial gastrectomy with Billroth I anastomosis. CONCLUSIONS: The guidewire technique for endoscopic transpapillary procurement of biopsy specimens of the bile duct obviates the need for endoscopic sphincterotomy.