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Purpose: Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer., Methods: We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m(2) (day 1 and 8) and oxaliplatin 100 mg/m(2) (day 1), every 3 weeks., Results: Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4-25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1-6.5, 95% CI) and median overall survival was 8.3 months (5.8-10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%)., Conclusions: The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs.

Objective: The aim of this study was to determine reliable predictive biomarkers for patients with metastatic renal cell carcinomas (RCCs) who had received cytokine therapy., Methods: Tissue specimens were obtained from 62 patients with metastatic RCCs between 1995 and 2006. Paraffin wax embedded tissues were immunostained for carbonic anhydrase IX (CAIX), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF)., Results: Fifty-two specimens (84%) were assessed as clear cell type, with 5, 3, and 2 tumors showing sarcomatoid, papillary, and undifferentiated features, respectively. With a median 54 months of follow-up, 15/18 responding patients (83%) exhibited high CAIX staining compared with only 24/44 (55%) nonresponding patients (odds ratio, OR, 4.1; 95% confidence interval, CI 1.1-16.5, P = 0.04). There was a positive correlation between maximal COX-2 intensity and response for cytokine therapy (Spearman test P = 0.001; rho = 0.408). Corrected calcium level < or = 10 mg/dl (hazard ratio, HR, 0.1; 95% CI 0.15-0.28; P < 0.001), normal hemoglobin level (HR 0.30; 95% CI 0.15-0.50; P = 0.001), and COX-2 expression > or = 50% (HR 0.33; 95% CI 0.15-0.70; P = 0.008) were significant predictive factors of prolonged overall survival., Conclusions: Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens., (Copyright 2010 Elsevier Inc. All rights reserved.)

Over its long survival duration, marginal zone B-cell lymphoma (MZL) routinely involves frequent relapses. In this study, we conducted a retrospective analysis to identify the clinical features and outcomes of relapsed or refractory MZL. From 1995 to 2008, a total of 92 patients with relapsed MZL were retrospectively analyzed. The median age of our subjects was 53.5 years (range: 23-82 years). The most common primary sites of involvement were the orbit and ocular adnexa (28.3%) followed by the lymph node and lymphatic organs (23.9%), and multiple mucosa-associated lymphoid tissue (MALT) sites (13.0%). The median time to relapse from initial diagnosis was 25.5 months. Of the 53 patients with Stage I or II at diagnosis, 42 patients (79.2%) evidenced locoregional recurrence. Among these locoregional relapsed patients, 27 patients achieved CR (54.1%) or PR (18.9%). In addition to the 39 patients initially in advanced Stage III or IV, a total of 50 patients were in advanced stage at relapse. Among those patients with advanced stage at relapse, 44 patients were treated. The overall response rate was 54.5% (24 patients), with 18 CRs and 6 PRs. The median time to progression (TTP) was 34.1 months (95% CI: 11.3-56.9 months) and the estimated 5-year overall survival (OS) was 84.3%. The majority of them was controlled well with salvage treatment, and could achieve prolonged survival. However, patients' refractory to initial therapy and advanced relapse evidenced shorter TTP and OS. Thus, we need to consider more aggressive treatment in cases of refractory MZL or advanced relapsed MZL., ((c) 2009 Wiley-Liss, Inc.)

Aim: To gain a better understanding of the survival and persistence of Enterobacter sakazakii in severe environments., Methods and Results: We evaluated the resistance of Ent. sakazakii to various environmental stresses, including heating, drying, water activity (a(w)), and pH. The resistance of Ent. sakazakii to heat varies widely among strains. Most tested strains of Ent. sakazakii exhibited unusual resistance to dry stress, which depends on drying media. Growth of most strains occurred within 24 h at 37 degrees C when the initial a(w) of the medium was adjusted to 0.94 with sucrose or sodium chloride. The minimum pH for growth within 24 h at 37 degrees C was 3.9 or 4.1 for most strains tested. Additionally, there did not appear to be any relationship between resistance to stresses and biofilm-forming ability in Ent. sakazakii planktonic cells., Conclusions: These results indicate that Ent. sakazakii is much more resistant than other Enterobacteriaceae to environmental stresses. Moreover, it is likely that Ent. sakazakii has cross-resistance to dry and thermal stresses., Significance and Impact of the Study: The findings of this study will contribute to an improved understanding of the survival and behaviour of Ent. sakazakii, which will lead to improved strategies for preventing outbreaks of Ent. sakazakii infection.

Aims: The efficiency of eight enrichment broths for the selective isolation of Campylobacter jejuni was compared to identify an optimal enrichment broth., Methods and Results: Brucella-FBP, Preston, Doyle and Roman, modified CCD (mCCD), Park and Sanders, Bolton, Hunt and Radle and Hunt broths were compared for their recovery of (i) Camp. jejuni in suspension, (ii) Camp. jejuni from inoculated ground pork, (iii) heat-injured Camp. jejuni (55 degrees C for 20 min) in suspension and (iv) heat-injured Camp. jejuni from inoculated ground pork. Hunt broth and Bolton broth showed the highest and most rapid enrichment efficacy for the cell suspensions and ground pork, respectively. Preston, Park and Sanders and mCCD broths had relatively high enrichment efficiencies, while Brucella-FBP broth was significantly inferior to the other broths (P < 0.05)., Conclusions: Cell recovery from the eight enrichment broths was dependent on the sample type and the state of the cells. The use of the appropriate broth is important for the rapid and efficacious enrichment of Camp. jejuni. In particular, heat-injured Camp. jejuni require a longer cultivation time and a suitable enrichment broth., Significance and Impact of the Study: The results from the present study provide information for selecting the most appropriate enrichment broth for Camp. jejuni and may contribute to improved detection methods for the organism.

Aim: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer., Methods: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007., Results: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median, 48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clinical or pathologic tumor, node and metastasis stage of the primary gastric cancer was IV in 38 patients (70%). The median interval from diagnosis of the primary malignancy to the diagnosis of LMC was 6.3 mo, ranging between 0 and 73.1 mo. Of the initial endoscopic findings for the 45 available patients, 23 (51%) of the patients were Bormann type III and 15 (33%) patients were Bormann type IV. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combination with hydrocortisone/+/- Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Seventeen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918)., Conclusion: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.

Background: We conducted a prospective phase II trial of IrOx in patients with advanced non-small cell lung cancer to evaluate the efficacy and toxicity., Patients and Methods: Patients with histologically or cytologically proven non-small cell lung cancer (NSCLC), aged > or =18 years, Eastern Cooperative Oncology Group performance status 0-1, at stage IIIB (pleural effusion)/IV or with recurrent disease not suitable for primary surgical treatment, with no palliative chemotherapy or radiotherapy to the chest or immunotherapy or biologic therapy, the presence of measurable disease by RECIST, and who had given signed written informed consent, were eligible. Treatment consisted of irinotecan 65 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 1, repeated every 3 weeks., Results: A total of 18 patients were enrolled in June and August 2007, the median age was 59 years (47-73). In total, 71 cycles were administered with a median of 4 cycles per patient (range, 1-6 cycles) and 18 patients were evaluable for treatment response. An independent review of tumor responses gave an overall response rate of 27.7% (CR: 0, PR: 5/18; 95% CI, 7-48.4%) by intent-to-treat analysis. The median overall survival of all patients was 14 months and the median time-to-progression was 4.2 months (95% CI, 1.959-6.441). The most common grade 3/4 toxicities were diarrhea (7% of all cycles) and neutropenia (5.6% of all cycles). Grade 3 peripheral neuropathy occurred in one patient and one patient died due to sepsis., Conclusion: This study suggests that IrOx combination therapy has moderate activity with a tolerable toxicity profile. However, it was not warranted to evaluate further this regimen as first-line treatment for patients with advanced or metastatic NSCLC using the current dosages and schedule.

Foodborne diseases occur worldwide, including through the consumption of contaminated meat. This study was conducted to investigate the prevalence of Escherichia coli contamination in fresh beef, poultry, and pork, and to determine whether any isolated E. coli possessed genes associated with pathogenicity. Three thousand meat samples were collected from 2004 to 2006 and were tested for the presence of E. coli. Two hundred and seventy-three E. coli isolates were obtained from beef, poultry, and pork, resulting in an overall isolation rate of 9.1%. Of these isolates, 201 were obtained from 1350 pork samples (14.9%), followed by 41 of 900 poultry samples (4.6%) and 31 of 750 beef samples (4.1%). A total of 39 pathogenic E. coli isolates from the three meat types were categorized into three virulence groups, namely enterotoxigenic E. coli (43.6%), enterohemorrhagic E. coli (EHEC) (35.9%; 22.6% of beef, 7.3% of poultry, and 2.0% of pork), and enteropathogenic E. coli (20.5%). Fourteen strains were identified as belonging to the EHEC, which included O18, O136, O119, O86, O8, O111, O15, O128, and O6. This study demonstrated that pathogenic E. coli are found in meat in Korea, and could act as a transmission vehicle for human infection as suggested by the occurrence and classification of pathogenic E. coli in retail meats. Furthermore, the data from this study could be used in the risk assessment of foodborne illnesses linked to meat consumption.

Pulmonary neuroendocrine tumors are a distinct subset of neoplasms with indolent to aggressive behavior. This study was conducted to evaluate the prognostic role of L1 cell adhesion molecule (L1CAM) in pulmonary neuroendocrine tumors. We retrospectively analyzed L1 expression in 55 cases of completely resected carcinoids and large-cell neuroendocrine carcinomas, by the immunohistochemistry with monoclonal antibody A10-A3 against human L1. L1 immunoreactivity was detected in 34 (61.8%) of 55 specimens. There was a significant correlation between L1 expression and the World Health Organization classification of this tumor (Spearman rank correlation, rho=0.60, p<0.001). With median follow-up of 52.0 months, the 5-year survival rate for patients with low expression of L1 (<20% of tumor cells stained) was significantly better compared with those with high expression of L1 (82.6% vs. 43.7%, p=0.005). L1 was also a significant independent predictor of disease-free survival, and patients with high L1 expression have a higher risk for recurrence compared with those with low L1 expression (hazard ratio, 3.0; 95% confidence interval, 1.2-8.3; p=0.034). L1 expression is significantly associated with aggressiveness and further studies with larger samples are needed to validate potential prognostic value for pulmonary neuroendocrine tumors.

Methods for detecting norovirus (NoV) in food are crucial for investigation and prevention of outbreaks caused by NoV-contaminated food. However, current NoV detection methods have not been well examined or optimized. In this study, the effectiveness of various methods for eluting NoV from various fruit, concentrating the virus using polyethylene glycol (PEG), and extracting the viral RNA for subsequent assay by RT-PCR was optimized. First, six different buffers previously described for eluting NoV from fruit surfaces were evaluated. A known amount of NoV was spiked onto the surface of grapes, strawberries, and raspberries, and the virus was recovered with distilled water, 0.05 M glycine-0.14 M NaCl (pH 7.5), 2.9% tryptose phosphate broth-6% glycine, 100 mM Tris-HCl (pH 9.5), 50 mM glycine-50 mM MgCl(2) (pH 9.5), or 3% beef extract. Quantitation of the recovered virus using RT-PCR revealed that the most effective elution buffer was 3% beef extract. Secondly, to optimize a method for concentrating the recovered NoV, the key parameters of PEG precipitation, a typical method for concentrating enteric virus, were investigated. The influence of PEG molecular weight and the duration and temperature of the precipitation procedure were examined. NoV was concentrated most efficiently by precipitation when PEG (10,000) was used for 4h at room temperature. Finally, five different methods for nucleic acid extraction were evaluated. Among RNA extraction methods examined, QIAamp Viral RNA Mini kit showed the best recovery efficiency. Using the optimized method, approximately 6-80% of the seeded NoV was recovered from the various fruit.

Background: Excision repair cross-complementation Group 1 (ERCC1) overexpression is associated with resistance to cisplatin-based chemotherapy in patients with nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1 expression is associated with radioresistance in lung cancer cells. The aim of this study was to evaluate the clinical implications of ERCC1 expression in stage IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery., Methods: Sixty-eight patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between August 1997 and September 2003. ERCC1 expression was assessed by immunohistochemistry from pretreatment mediastinoscopic biopsy specimens., Results: ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14 patients who obtained pathologic complete response, 6 were positive for ERCC1 expression and 8 were negative (P = .818). On univariate analysis, with median follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P = .062), and there was a statistically significant difference in overall survival between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P = .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving mediastinal nodal clearance (downstage to pathological N0 or N1) after neoadjuvant CCRT followed by surgery (P = .005) were significant independent prognostic factors for the prolongation of survival., Conclusions: These results suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a survival benefit from neoadjuvant CCRT with a platinum-containing regimen., ((c) 2008 American Cancer Society.)

Introduction: Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC)., Methods: In this study, 46 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60 mg/m(2) on days 1, 8 and 15 and cisplatin 60 mg/m(2) on day 1. The treatment was repeated every 4 weeks until patients completed the maximum six cycles., Results: Patients consisted of 37 men and 9 women, whose median age was 70 years (range 65-81 years). A complete response and a partial response were observed in 19.6% (9/46) and 56.5% (26/46), respectively. The overall response rate was 76.1% (95% C.I; 63.8-88.4%). The overall median survival was 10.4 months (range 7.6-13.2 months). The median progression-free survival was 8.32 months (range 6.8-9.8 months). Major toxicities included neutropenia (grade 3-4, 58.7%), leukopenia (grade 3-4, 49.9%), infection (grade 3-4, 39.1%) and diarrhea (grade 3-4, 30.4%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2-3 compared with ECOG performance status 0-1 (70.4% vs. 5.2%; p<0.001). There were two treatment related deaths in patients ECOG performance status 3., Conclusions: Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC who have good ECOG performance status and physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with poor ECOG performance status.

The patients with metastatic or recurrent esophageal cancer are incurable. A number of patients who progress after first-line chemotherapy may still be fit for second-line treatment. However, there is no currently established effective and tolerable salvage chemotherapy. We investigated the activity and tolerability of MIC in patients who had failed to prior chemotherapy for metastatic or recurrent esophageal squamous cell carcinoma. MIC (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) was given in day 1 as an outpatient regimen and repeated every 3 weeks. All 32 enrolled patients were male with median age of 57 years. Prior esophagectomy had been performed in 21 patients (65.6%) and 11 patients (34.4%) were metastatic disease at initial diagnosis. Nineteen patients (59.4%) were treated with MIC as second-line chemotherapy. Prior first-line chemotherapy regimens consisted of 5-FU/cisplatin and capecitabine/cisplatin combinations. Overall response rate was 12.5% with no CR, and disease control rate was 37.5%. Grade 3/4 neutropenia was observed in 21 % of patients and grade 3/4 febrile neutropenia was seen in only one patient. There was no treatment-related mortality. Median PFS was 2.0 months (95%CI = 1.4-2.5) and the median OS was 5.2 months (95%CI = 3.3-7.0) with no significant difference between numbers of prior chemotherapy regimen. MIC chemotherapy has modest activity as a salvage regimen with tolerable toxicity, and could be one of the chemotherapy treatment options for patients with advanced or recurrent esophageal squamous cell carcinoma for whom previous chemotherapy has failed.

Many natural compounds have been shown to prevent cancer cell growth through the redox regulation of transcription factors. NF-kappaB, a redox transcription factor, has been implicated in the apoptotic cell death of several cancer cells. This study examined whether or nor 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone (DDMP) isolated from onions can modulate the activity of NF-kappaB, thereby induce the apoptotic cell death of colon cancer cells. Treatment with different DDMP concentrations (0.5-1.5 mg/mL) for various periods (0-48 h) inhibited the growth of colon cancer cells (SW620 and HCT116) followed by the induction of apoptosis in a dose dependent manner. It was also found that DDMP modulated tumor necrosis factor-alpha (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced NF-kappaB transcriptional and DNA binding activity. Moreover, DDMP suppressed the NF-kappaB target anti-apoptotic genes (Bcl-2), whereas it induced the expression of the apoptotic genes (Bax, cleaved caspase-3 and cleaved PARP). These results suggest that DDMP from onions inhibit colon cancer cell growth by inducing apoptotic cell death through the inhibition of NF-kappaB.

Intestinal marginal zone B-cell lymphoma of the MALT type (I-MZL) is a relatively uncommon form of lymphoma. Twenty-seven patients with histologically-confirmed I-MZL were analyzed. The patients initially presented with abdominal pain (62.9%), and diarrhea (22.2%). The most common involved site was the ileo-caecal area (40.7%). Musshoff's stage I(E), II(E)1, II(E)2, III(E) and IV were present in 44%, 15%, 11%, 7.4% and 22% respectively. Sixty-three percent were in the low-risk group according to the Follicular Lymphoma International Prognostic Index. Complete response and partial response were achieved in 82% and 4% patients. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were 86% and 54%. Stage > or = II(E)2 was determined to be a poor prognostic factor for PFS and OS. I-MZL commonly manifests in an early-stage, low-risk state and tends to respond well to local and systemic treatment with favorable prognosis. I-MZL tends to be an indolent disease - characterized by prolonged survival with frequent relapses, similarly to other site MZLs.

The efficacy of salvage regimens for small cell lung cancer remains to be established. We evaluated the efficacy and safety of the paclitaxel and ifosfamide (PI) combination chemotherapy salvage regimen in heavily pretreated small cell lung cancer (SCLC) patients. Thirty-five patients who had received more than two prior chemotherapy regimens were treated with PI chemotherapy. Paclitaxel (175 mg/m(2)) was administered on day 1 and ifosfamide (2500 mg/m(2)) on day 1-2 every 3 weeks. Thirty-three patients were available for treatment response evaluation. Median age was 63 years (range, 40-78) and Eastern Cooperative Oncology Group (ECOG) performance scores of 0/1/2 were 29.4%, 61.8%, and 11.8%, respectively. A median of 2 cycles (range, 1-6) of chemotherapy were administered. The overall response rate (RR) in the intent-to-treat population was 20.0% (95% Confidence Interval (CI), 6.7-33.3%) with 7 partial responses (PR) and no complete response (CR). Patients who responded to previous chemotherapy just before PI showed significantly higher RR than non-responders (RR, 57.1% versus 10.7%, P=.023). After a median follow-up of 8.8 months (range, 1.6-14.7), the median time to progression was 3.3 months (95% CI, 2.3-4.4) and the median overall survival was 7.6 months (95% CI, 6.7-8.5). The most common toxicity observed was mild nausea/vomiting and grade 3/4 adverse events were observed in 4 (11.4%) patients. There were no treatment-related deaths in the study. Our findings suggest that salvage PI chemotherapy is a feasible and well tolerated regimen for previously treated SCLC patients. Further studies are warranted to define the effects of PI chemotherapy on quality of life and survival benefits.

To define prognostic impact of Epstein-Barr virus (EBV) infection in diffuse large B-cell lymphoma (DLBCL), we investigated EBV status in patients with DLBCL. In all, 380 slides from paraffin-embedded tissue were available for analysis by EBV-encoded RNA-1 (EBER) in situ hybridization, and 34 cases (9.0%) were identified as EBER-positive. EBER positivity was significantly associated with age greater than 60 years (P = .005), more advanced stage (P < .001), more than one extranodal involvement (P = .009), higher International Prognostic Index (IPI) risk group (P = .015), presence of B symptom (P = .004), and poorer outcome to initial treatment (P = .006). The EBER(+) patients with DLBCL demonstrated substantially poorer overall survival (EBER(+) vs EBER(-) 35.8 months [95% confidence interval (CI), 0-114.1 months] vs not reached, P = .026) and progression-free survival (EBER(+) vs EBER(-) 12.8 months [95% CI, 0-31.8 months] vs 35.8 months [95% CI, 0-114.1 months], respectively (P = .018). In nongerminal center B-cell-like subtype, EBER in situ hybridization positivity retained its statistical significance at the multivariate level (P = .045). Nongerminal center B-cell-like patients with DLBCL with EBER positivity showed substantially poorer overall survival with 2.9-fold (95% CI, 1.1-8.1) risk for death. Taken together, DLBCL patients with EBER in situ hybridization+ pursued more rapidly deteriorating clinical course with poorer treatment response, survival, and progression-free survival.

Background: Biliary tract cancer is one of the most aggressive and chemotherapy-refractory tumors. Although only curative treatment modality is surgery, most patients are not suitable for surgery due to advanced stage of the disease at diagnosis. Thus most patients with biliary tract cancer are possible candidates for palliative chemotherapy. The standard chemotherapeutic regimen is still to be defined, however. We performed a phase II study of combination chemotherapy with capecitabine and cisplatin in these patients to evaluate efficacy and toxicity of the regimen., Methods: Patients with previously untreated metastatic, recurrent, or inoperable biliary tract cancer were enrolled. Eligible patients were screened as following: (1) histologically confirmed, (2) age between 18 and 75 years, (3) at least one measurable lesion according to RECIST criteria, (4) ECOG performance status

The clinical features and prognostic factor of lymphoma-associated hemophagocytic syndrome (LAHS), diagnosed according to World Health Organization classification, were investigated by reviewing the clinical records of 29 patients between September 1994 and September 2006. Compared with patients with T or natural killer (NK)/T cell LAHS, patients with B cell LAHS were older (p = 0.022), were less likely to exhibit disseminated intravascular coagulation (DIC; p = 0.011), and had less direct involvement of bone marrow (p = 0.03). Clinical response was achieved in 15 (65.2%) and complete remission (CR) was achieved in 4 (17%) of 23 patients who received chemotherapy. Four patients received high-dose chemotherapy and autologous stem cell transplantation (A-SCT), and three of these four patients showed CR. The median survival was 36 days (95%CI, 20.2-51.8). Univariate analysis showed that poor performance status (p = 0.028), T or NK/T cell lymphoma (p = 0.016), presence of jaundice (p = 0.063), the presence of DIC (p = 0.002), and poor clinical response to treatment (p < 0.001) predicted poor overall survival. These data suggest that the clinical features differ significantly between B cell LAHS and T or NK/T cell LAHS. Intensive treatment including high-dose chemotherapy and A-SCT should be investigated.

Korea is an endemic area for hepatitis B virus (HBV) infection. Reactivation of HBV is a well-recognized complication in patients with chronic HBV infection undergoing cytotoxic or immunosuppressive therapy, and there are some reports of hepatitis B reverse seroconversion after HSCT. This study evaluated changes in HBV serology after HSCT. We reviewed the medical records of 141 patients who had available HBV serologic data after autologous HSCT. Patient information was retrospectively collected from the BMT database. Before transplantation, 12 patients were positive for hepatitis B surface antigen (HBsAg) and received lamivudine prophylaxis. There was 1 case of reactivation of HBV among these patients. One hundred twenty-nine patients were negative for HBsAg before HSCT, of whom 110 were positive and 19 were negative for hepatitis B surface antibody (anti-HBs). Sixty-two of the 110 patients who were positive for anti-HBs were also positive for hepatitis B core antibody (anti-HBc). Eight patients were negative for anti-HBs and anti-HBc. Seven patients who were initially negative for HBsAg were identified as positive after HSCT, and 5 of those 7 patients developed acute hepatitis, thus indicating reverse seroconversion. Univariate analysis showed that reverse seroconversions were observed more frequently with multiple myeloma than another disease (P = .005; relative risk, 11.854; 95% confidence interval, 1.381-101.770). Other factors, such as age, sex, and presence of HBcAb before HSCT, had no statistically significant affect on reverse seroconversion. In conclusion, reverse seroconversion of HBV is not a rare complication of autologous HSCT, and the risk of reverse seroconversion after treatment is a serious concern due to possible complications arising from patients' suppressed immune systems.

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.

Purpose: The object of this study is to evaluate the efficacy and toxicity of induction chemotherapy followed by concomitant chemoradiotherapy in locoregional esophageal cancer., Materials and Methods: Between December 1992 and December 1999, 43 patients with locoregional esophageal cancer were enrolled in this phase II trial. Patients were treated with 2-cycles of induction chemotherapy followed by concomitant chemoradiotherapy. F-P chemotherapy consists of 1,000 mg/m2/Day of 5-FU as continuous infusion on day 1~5 and 80 mg/m2 of cisplatin as an intravenous bolus on day 1 and was repeated every 3~4 weeks. All patients received 60 Gy of external beam radiation concomitantly with F-P chemotherapy; intraluminal brachytherapy was added in 12 patients. A total of 4 cycles of chemotherapy were delivered. No further treatment was planned in patients who achieved complete remission after completion of the treatment., Results: Among the 43 patients entered, 35 patients completed the protocol. Of the 35 evaluable patients, 12 patients (34%) achieved complete response and 13 patients (37%) achieved partial response. In 26 of 33 patients, dysphagia was improved. At a median follow-up of 22 months, the 2-year and 5-year survival rates were 39% and 19%, respectively. The median survival duration of the complete responder group was 69 months (4~100 months) and the 2-year survival rate of the complete responder group was 82%. Toxicities were tolerable, comprised of mucositis and cytopenia., Conclusion: Induction chemotherapy followed by concurrent chemoradiotherapy in locoregional esophageal cancer is well tolerated and effective.

Purpose: A phase II study was conducted in patients with advanced non-small cell lung cancer (NSCLC) in order to evaluate the efficacy and toxicity of the combination chemotherapy regimen of mitomycin C, vinorelbine, and cisplatin (MVrP)., Materials and Methods: Between June 1996 and December 2000, fifty-nine patients with unresectable stage IIIB to IV, pathologically documented NSCLC were enrolled in this study. One cycle consisted of mitomycin C 10 mg/m2 i.v. day 1, vinorelbine 30 mg/m2 i.v. days 1 & 15, and cisplatin 80 mg/m2 i.v day 1 and the next cycle consisted of vinorelbine 30 mg/m2 i.v. days 29 & 43, and cisplatin 80 mg/m2 i.v day 29. Each cycle was alternated and treatments were repeated every 8 weeks., Results: We were able to evaluate fifty-three of 59 patients. Objective responses were seen in 22 (41.5%) patients (CR 0%, PR 41.5%). The median duration of response was 13.7 weeks and the median time to progression was 17.7 weeks. The median overall survival was 45.6 weeks. There was a significantly longer survival seen in responders (p=0.041). The toxicities of this regimen were acceptable without treatment related toxic death., Conclusion: This study suggests that a combination regimen of mitomycin C, vinorelbine, and cisplatin is relatively effective and well tolerated for the treatment of advanced NSCLC.