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Purpose: To test the efficacy and safety of a triweekly reduced-dose docetaxel (60 mg/m) regimen combined with a standard dose of cisplatin in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Patients and methods: Patients with R/M HNSCC were enrolled. All eligible patients received intravenous docetaxel 60 mg/m combined with cisplatin 75 mg/m on day 1 and then every 3 weeks thereafter. Treatment was continued until disease progression, patient intolerance, or death. Results: In total, 58 patients were enrolled and 41 patients were evaluated. Among the evaluated population, one patient achieved a complete response (2.4%) and nine patients achieved a partial response (22%), resulting in an overall response rate of 24.4%. Furthermore, 17 patients had stable disease (41.5%), which corresponds to a disease control rate of 65.9%. With a median follow-up of 24 months (1-43 months), progression-free survival was 170 days (95% confidence interval 97.9-242.1) and the median overall survival was 265 days (95% confidence interval 89.0-441.0) in evaluable population. The most common toxicities (≥grade III) were leucopenia (66.7%) and anemia (33.3%). Conclusions: Triweekly reduced-dose docetaxel 60 mg/m combined with cisplatin is effective and feasible for Taiwanese patients with R/M HNSCC. However, the hematologic toxicity of this regimen should be carefully monitored and managed. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed the impact of donor characteristics and HLA matching on outcomes in Chinese patients undergoing unrelated hematopoietic stem cell transplantation (HSCT). A total of 693 patients with hematologic malignancies who underwent HSCT between 2005 and 2010 had available survival data at 100 days or 1 year posttransplantation in the Buddhist Tzu-Chi Stem Cell Center database. The overall survival rates at 100 days and 1 year were 83.3% and 65.2%, respectively. Mismatches of HLA-A, -B, and -DRB1 at the antigen or allele level, along with inadequate cell dose, were associated with a significant risk of mortality (hazard ratio [HR] = 2.36, P < .001; HR = 1.44, P = .005; and HR = 2.20, P = .009, respectively). In 107 donors with matched HLA-A, -B and -DRB1 and known HLA-C match status, 22.4% had an HLA-C antigen mismatch, resulting in an HR of 2.87 for mortality relative to complete 8/8 matches (P = .005). Recipients with unknown HLA-C match status also had a significantly worse outcome (HR = 1.73; P = .039). Multivariate analysis revealed that cell dose and HLA-A, -B, -C, and -DRB1 antigen match status significantly affected the final outcome of survival (P = .012 and <.001, respectively). Our data indicate that HLA-C match status should be confirmed before HSCT from an unrelated donor. Inadequate cell dose remains an important determinant of poor transplantation survival. Further studies to elucidate the importance of matching of specific HLA loci are needed to better understand the risk of HSCT and improve patient outcomes. [Copyright &y& Elsevier]

Purpose: Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations. Patients and Methods: Patients >70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were analyzed with univariate and multivariate Cox regression. Results: We included 63 patients aged 70-79 years and 51 patients ≥80 years old. The results of multivariate Cox regression in the 70-79 years age group revealed white blood cell count ≤104/ml [p = 0.033; hazard ratio (HR) 2.51, range 1.079-5.840] and albumin ≥3.5 g/dl (p = 0.007; HR 3.38, range 1.398-8.177) as independent factors. In the group of patients ≥80 years old, Eastern Cooperative Oncology Group performance status <1 (p = 0.020), white blood cell count ≤104/ml (p = 0.001), albumin ≥3.5 g/dl (p = 0.006), lactate dehydrogenase (LDH) ≤250 U/l (p = 0.002) and non-chest metastasis (p = 0.043) were significantly better with univariate analysis. Multivariate Cox regression revealed albumin ≥3.5 g/dl (p = 0.007; HR 3.28, range 1.389-7.745) and LDH ≤250 U/l (p = 0.045; HR 3.18, range 1.026-9.848) as independent factors. Conclusions: For elderly patients with CUP, the serum albumin level seems to be a consistently independent prognostic factor. In patients >80 years old, serum LDH plays an important role in prognosis. This study is helpful in predicting the outcome and management for this group of patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection. [ABSTRACT FROM AUTHOR]

We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other groups. In the univariate analysis, risks of death in MN-EP patients included the morphologic features of PEL, very poor cytogenetic risk by IPSS-R, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high LDH, and poor PS. In the multivariate analysis, independent predictors of death were morphologic features of PEL (adjusted hazards ratio [HR] 3.48, 95% confidence interval [CI] 1.24–9.74, p = 0.018), very poor cytogenetic risk by IPSS-R (adjusted HR 2.73, 95% CI 1.22–6.10, p = 0.015), hypoalbuminemia (< 3.7 g/dl) (adjusted HR 2.33, 95% CI 1.10–4.91, p = 0.026) and high serum LDH (≥ 250 U/L) (adjusted HR 2.36, 95% CI 1.28–4.36, p = 0.006). Poor or unfavorable risk in different cytogenetic risk systems independently predicted death and UKMRC-R was the best model. [ABSTRACT FROM AUTHOR]

Background: Enumerating hematopoietic progenitor cells (HPCs) by using an automated hematology analyzer is a rapid, inexpensive, and simple method for predicting a successful harvest compared with enumerating circulating CD34+ cells. However, the optimal HPC cutoff count and the indicating factors to be considered for improved predicting have not yet been determined.Study Design and Methods: Between 2007 and 2012, a total of 189 consecutive patients who proceeded to peripheral blood stem cell (PBSC) harvesting were retrospectively recruited. Baseline characteristics were analyzed to identify the risk factors for a failed harvest, which were defined as less than 2 × 10(6) CD34+ cells/kg. Variables identified by multivariate logistic regression and correlation analysis for predicting a successful harvest were subjected to classification and regression tree (CART) analysis.Results: PBSCs were successfully harvested in 154 (81.5%) patients. An age of at least 60 years, a diagnosis of a solid tumor, at least five prior chemotherapy cycles, prior radiotherapy, and mobilization with granulocyte-colony-stimulating factor alone or high-dose cyclophosphamide were independent baseline predictors of poor mobilization. In CART analysis, patients with zero to two host risk factors and either higher HPC (≥28 × 10(6) /L) or mononuclear cell (MNC; ≥3.5 × 10(9) /L) counts were categorized as good mobilizers and their harvest success rate was 92.3%. By contrast, 30.3% of harvests were adequate in the patients with three to five host risk factors and lower HPC and MNC counts.Conclusion: A CART algorithm incorporating host predictors and HPC and MNC counts improves predictions in a successful harvest and might reduce the necessity of monitoring peripheral CD34+ cells. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients. Methods: Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables. Results: During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin's lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not. Conclusions: Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered. [ABSTRACT FROM AUTHOR]

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rank p<0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p<0.001) and hematologic malignancy (p=0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p<0.001), being male (p=0.028), and hematologic malignancy (p=0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity. [ABSTRACT FROM AUTHOR]

Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46–1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70–2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80–4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37–2.98), thyroid (SIR: 2.30, 95% CI: 2.02–2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56–2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60–47.69), skin (SIR: 8.24, 95% CI: 3.02–17.94) and head and neck (SIR: 4.41, 95% CI: 2.35–7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients. [ABSTRACT FROM AUTHOR]

Background: The association between amyloidosis and cancer remains unclear. Participants and methods: Using the Taiwan National Health Insurance Research Database we conducted a population-based cohort study. Patients newly diagnosed with amyloidosis between 1997 and 2009 were enrolled. Patients with antecedent cancer were excluded. Standardized incidence ratios (SIR) of cancers were calculated for the study cohort and compared with cancer incidence among the general population. We used a multivariate Cox regression model to evaluate the predictors of cancer development for patients with amyloidosis. Results: The study included 1,693 subjects with median follow-up of 5.63 years. A total of 68 patients developed cancer. The incidence of kidney cancer (SIR 3.42; 95 % CI 1.11-7.97; p = 0.034) and hematologic malignancies (SIR 3.88; 95 % CI 1.86-7.14; p < 0.001) were significantly higher for patients with amyloidosis. Conclusion: This is currently the largest study to evaluate cancer risk among patients with amyloidosis. The results indicate that amyloidosis may be associated with an increased risk of kidney cancer and hematologic malignancies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to evaluate the overall cancer risk among patients with the irritable bowel syndrome (IBS) by using a nationwide population-based data set.Methods: We obtained data on newly diagnosed IBS patients (age ≥ 20 years) without antecedent cancer from the Taiwan National Health Insurance Research Database for the period between 2000 and 2010. Standardized incidence ratios (SIRs) were calculated for various types of cancer in the IBS patients.Results: A total of 1,043 people among the 29,838 IBS patients had developed cancer, and the follow-up was 139,185 person-years (median, 4.56 years), leading to a significantly increased SIR (1.18; 95% confidence interval [CI]) = 1.11-1.26) among all cancer types. However, after excluding cancer that developed within the first year after IBS diagnosis, the increased SIR of overall cancer was nonsignificant. In particular, the IBS patients exhibited an increased risk of cancers of the colon and rectum (SIR = 1.51; 95% CI = 1.31-1.73), liver and biliary tract (SIR = 1.40; 95% CI = 1.21-1.62), pancreas (SIR = 1.56; 95% CI = 1.02-2.28), and kidney (SIR = 1.56; 95% CI = 1.10-2.15).Conclusions: An increased SIR in IBS patients was observed only within the first year of IBS diagnosis. The findings of this study might have resulted from detection bias, localized symptoms, or paraneoplastic syndromes associated with IBS-like symptoms. Additional prospective studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: With the improved survival of non-Hodgkin lymphoma (NHL) patients, development of second primary malignancy (SPM) has become an increasingly important issue in these long-term survivors. Methods: We conducted a retrospective study to analyze NHL patients diagnosed between January 1997 and December 2010 in Taiwan. Standardized incidence ratios (SIRs) were applied to compare the risk of SPMs in NHL patients and the general population. Multivariate analysis was performed to determine the independent predictors of SPM. Result: NHL patients have a significantly greater risk of developing SPM [SIR 1.43; 95 % confidence interval (CI) 1.32-1.55; p < 0.001). A significantly high SIR was noted for leukemia, myeloma, and neoplasms of the bone and soft tissue, thyroid, central nervous system, skin, stomach, head and neck, liver and biliary tract, and the lungs and mediastinum. Multivariate analysis revealed that age ≥60 years [hazard ratios (HR) 2.04], being male (HR 1.22), comorbidities of chronic obstructive pulmonary disease (HR 1.34), liver cirrhosis (HR 1.50), hepatitis C infection (HR 1.94) and therapy containing radiotherapy (HR 1.38) were the significant predictors for SPM occurrence. The median follow-up time and survival time were 3.37 and 9.45 years, respectively. Conclusion: This Taiwanese population-based study provides updated data about the risk of SPM in NHL patients, demonstrating an approximately 1.5 time greater risk of SPM compared to the general population. A high risk of SPM for myeloma and hepatocellular carcinoma is unique to Asian patients. [ABSTRACT FROM AUTHOR]

Reactivation of hepatitis B virus (HBV) following rituximab (R)-containing chemotherapy for lymphoma is a major concern, and risk factors remain to be defined. We enrolled 190 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) and resolved hepatitis B, receiving first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based regimens. Twenty-seven patients (14.2%) developed HBV reactivation during a median follow-up of 23.6 months. Two independent risk factors were identified: cycles of rituximab > 8 (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.184–6.612) and lymphocyte/monocyte ratio (LMR) < 2.50 (HR, 2.733; 95% CI, 1.122–6.657). Two-year overall survival in patients with or without HBV reactivation was 53.8% vs. 77.6% (p= 0.025). Regarding the negative impact on clinical outcome, patients at “super high risk” of HBV reactivation, including those receiving more than eight cycles of R and having low LMR at diagnosis, may warrant first priority for antiviral prophylaxis. [ABSTRACT FROM PUBLISHER]

Pericardial effusion ( PE) is a rare but potentially life-threatening complication for allogeneic haematopoietic stem cell transplantation ( HSCT) recipients. The risk factors, aetiology, incidence and therapy are largely unclear. To investigate this issue, we reviewed 391 adult patients undergoing allogeneic HSCT between January 2003 and December 2013. Twelve out of 391 patients (3·1%) developed PE of moderate to large amounts, including 9 out of 12 patients (75%) identified as late-onset PE. Two out of the nine patients with late-onset PE experienced recurrent effusion. The median age at HSCT was 44·5 years (range: 22-63 years) among the 12 patients with PE and 47 years in the late-onset patients. Multivariate analysis revealed that multiple transplant procedures was a significant risk factor for PE ( P = 0·036) and a trend as risk factor in patients aged>50 years ( P = 0·066). For late-onset PE, pre-transplant age>50 years ( P = 0·032) and extensive chronic graft-versus-host disease ( cGVHD) ( P = 0·006) remained statistically significant on multivariate analysis. Currently, there are no published data exploring the risk factors for post-transplant PE in adult patients of allogeneic HSCT. Our study determined the risk factors and incidence for the post-transplant PE, especially in the late-onset group. [ABSTRACT FROM AUTHOR]

The true frequency of the JAK2 46/1 haplotype in patients of myeloproliferative neoplasms (MPN) with CALR mutations was unknown. Totally 187 MPN cases with diagnosis of polycythemia vera (PV) and essential thrombocythemia (ET) were recruited. The frequency of 46/1 haplotype was significantly higher in JAK2V617F-positive PV (51%, p < 0.001) and ET (41%, p = 0.005) compared to normal controls. The exact location of JAK2V617F mutation was located at the cis-46/1 haplotype in 86.4% (32/37) PV patients and 87.5% (28/32) ET patients, respectively. Among the 51 patients of ET without JAK2V617F mutation, 38 (75%) patients harbored CALR mutations and 3 patients had MPL mutation. The frequency of 46/1 haplotype in the 38 ET patients with CALR mutations was 27%, which is not significantly different from that of normal control (p value = 0.879). Compared to non-46/1 haplotype, the presence of 46/1 haplotype had a trend to have higher white blood cell count in JAK2V617F-mutated PV and ET patients but not in CALR-mutated ET. We conclude that the 46/1 haplotype could have functioning effect but only in the context of JAK2V617F mutation. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate the risk of cancer in patients diagnosed with cholecystitis and possible interactions between cholecystitis and cholecystectomy. Methods A retrospective population-based cohort study was conducted among patients diagnosed with cholecystitis that were registered in the National Health Insurance Research Database in Taiwan between January 1, 2000 and December 31, 2010. Standardized incidence ratios (SIRs) were calculated to compare the incidence of cancer in these patients to that of the general population. Adjusted hazard ratios (HRs) were also calculated to investigate whether cholecystitis increased the risk for specific cancers. Results During a median observation period of 5.4 years, 1541 cancers occurred in 20,431 patients with cholecystitis, yielding a SIR of 1.97 (95% confidence interval [CI], 1.88-2.07). A significantly greater risk of biliary tract cancer (adjusted HR 1.72; 95% CI, 1.08-2.75) was observed after adjusting for potential risk factors. In contrast, cholecystectomy was found to attenuate the cancer risk, with the reduction of adjusted HR from 2.34 (95% CI, 1.62-3.37) to 1.28 (95% CI, 0.76-2.14). Conclusion Cholecystitis is an independent risk factor to extrahepatic biliary tract cancers, whereas cholecystectomy can attenuate the cancer risk of cholecystitis. [ABSTRACT FROM AUTHOR]

Background: To evaluate the risk and sites of metachronous secondary primary malignancies (SPMs) among patients with esophageal cancer. Methods: Newly diagnosed esophageal cancer patients between 1997 and 2011 were recruited. To avoid surveillance bias, SPMs that developed within one year were excluded. Standardized incidence ratios (SIRs) of metachronous SPMs in these patients were calculated by comparing to the cancer incidence in the general population. Risk factors for SPM development, included age, sex, comorbidities and cancer-related treatments, were estimated by Cox proportional hazards models. Results: During the 15-year study period, 870 SPMs developed among 18,026 esophageal cancer patients, with a follow-up of 27,056 person-years. The SIR for all cancers was 3.53. The SIR of follow-up period ≥ 10 years was 3.56; 5–10 years, 3.14; and 1–5 years, 3.06. The cancer SIRs of head and neck (15.83), stomach (3.30), lung and mediastinum (2.10), kidney (2.24) and leukemia (2.72), were significantly increased. Multivariate analysis showed that age ≥ 60 years (hazard ratio [HR] 0.74), being male (HR 1.46) and liver cirrhosis (HR 1.46) were independent factors. According to the treatments, major surgery (HR 1.24) increased the risk, but chemotherapy was nearly significant. Conclusions: Patients with esophageal cancer were at increased risk of developing metachronous SPMs. The SIR remained high in follow-up > 10 years, so that close monitoring may be needed for early detection of SPM among these esophageal cancer patients. [ABSTRACT FROM AUTHOR]

Thymosin β4 (Tβ4) is a multifunctional protein already used clinically to treat various diseases; however, the promoting effect of this protein on tumor malignancy should not be neglected. Here, we assessed whether Tβ4 alteration influences normal intestinal epithelial cells because Tβ4 is deemed a novel target for treating colorectal cancer (CRC). For this purpose, we examined the consequences of shRNA-mediated knockdown of Tβ4 in IEC-6 normal rat small intestinal cells and found that inhibiting Tβ4 expression significantly suppressed their growth and induced apoptosis in some cells. Flow cytometric analysis further revealed a marked decrease of G0/G1 population but a drastic increase of polyploid ones in these cells. The increase of polyploidy likely resulted from DNA re-replication because not only the de novo DNA synthesis was greatly increased but also the expression levels of Cdc6 (a replication-licensing factor), cyclin A, and phosphorylated-checkpoint kinase 1 were all dramatically elevated. Moreover, marked reductions in both RNA and protein levels of Emi1 (early mitotic inhibitor 1) were also detected in Tβ4-downregulated IEC-6 cells which might be accounted by the downregulation of E2F1, a transcription factor capable of inducing Emi1 expression, mediated by glycogen synthase-3β (GSK-3β). To our best knowledge, this is the first report showing that inhibiting Tβ4 expression triggers DNA re-replication in normal intestinal epithelial cells, suggesting that this G-actin sequester may play a crucial role in maintaining genome stability in these cells. More importantly, clinical oncologists should take this novel activity into consideration when design CRC therapy based on targeting Tβ4. J. Cell. Physiol. 229: 1639-1646, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer. Methods: Between April 2005 and March 2012, patients ( n = 158) diagnosed with metastatic colorectal cancer after at least four courses of first-line bevacizumab-based ( n = 95) or cetuximab-based triplet ( n = 63) were retrospectively analyzed. The KRAS genotypes were sequenced for all patients. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards models were used for univariate and multivariate analyses. Results: Cetuximab-based triplet was associated with a higher objective response rate (66.0 vs. 47.2 %, p = 0.037) and a higher conversion rate to resectability (39.7 vs. 20.0 %, p = 0.007) compared to bevacizumab-based triplet. Compared with bevacizumab-based triplet, cetuximab-based triplet significantly increased progression-free survival in patients with measurable metastatic colorectal cancer who achieved objective tumor response (responders) (median 13.1 vs. 10.5 months, p = 0.023), but no significant increase was observed for overall survival. After adjustment for group differences in baseline characteristics and combined chemotherapy agents, cetuximab-based triplet remained an independent determinant of progression-free survival in responders as compared with bevacizumab-based triplet. KRAS mutation was not a prognostic factor in patients with metastatic colorectal cancer. Conclusions: As compared with bevacizumab-based triplet, cetuximab-based triplet as the first-line treatment of metastatic colorectal cancer was associated with better progression-free survival in patients with measurable tumors who achieved objective tumor response to bio-chemotherapy. [ABSTRACT FROM AUTHOR]

Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (<1 × 10/l) was an independent risk factor for infection ( P = 0.039; 95 % confidence interval, 1.033-3.599; odds ratio, 1.928). The time to infection event is significant shorter in those of low ALC, compared with those of higher ALC ( P = 0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was significantly higher in those patients who developed an infection ( P = 0.001). ITP patients with a low absolute lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival. [ABSTRACT FROM AUTHOR]

Purpose: A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer. Methods: Five colon cancer cell lines were used for in vitro studies. Signal transduction pathways were assessed by immunoblotting. The synergism between studied drugs was analyzed with combination indexes. Gene silencing was performed using small interfering RNAs. The efficacies of temsirolimus and cetuximab were tested in nude mice with colon cancer xenografts. Transcriptional activity was assessed using a reporter assay. The inhibitors leupeptin, chloroquine, and MG132 were used to assess protein degradation. The association between CIP2A, clinicopathological parameters, and survival was examined by immunohistochemical staining using a tumor tissue microarray. Results: Temsirolimus decreased the resistance of cells to cetuximab by both inhibiting transcription of CIP2A and increasing degradation of CIP2A through the lysosomal-autophagy pathway. The mammalian target of rapamycin (mTOR) protein immunoprecipitated along with CIP2A. Temsirolimus decreased expression of phosphorylated extracellular regulated protein kinase (pErk) and phosphorylated v-akt murine thymoma viral oncogene (pAKT) and decreased the interaction of CIP2A and mTOR in cell lines without the K-ras codon 12 mutation. CIP2A was a prognostic marker only in colon cancer patients with weak expression of pErk or pAKT. Conclusions: Temsirolimus decreases cellular resistance to cetuximab by regulating CIP2A expression in colon cancer cells. Potential biomarkers for CIP2A inhibitors include pErk and pAKT. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. Patients and Methods: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Results: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36–59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Conclusions: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of cancer among patients with nonapnea sleep disorders (SDs).Methods: We included newly diagnosed SD patients aged 20 years and older without antecedent cancer between 2000 and 2010 from the National Health Insurance Research Database. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of patients with SD with that of the general population.Results: During the 10-year study period, 2062 cancers developed among 63,381 SD patients, who were observed for 382,826 person-years (median follow-up of 6.23 years). The SIR for all cancers was 1.19 (95% confidence interval [CI], 1.14e1.24). For specific cancer types, SD patients exhibited an increased SIR for liver and lung cancers (1.44; 95% CI, 1.28e1.61 and 1.34; 95% CI, 1.18e1.51, respectively).Conclusions: We observed that overall cancer risk is increased among Asian SD patients. In terms of individual cancers, the risks of liver and lung cancers were elevated. Clinicians should be aware of the possibility of increased liver and lung cancers among SD patients in Taiwan. A prospective study is necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the risk of cancer among patients with nonapnea sleep disorders (SDs). Methods: We included newly diagnosed SD patients aged 20 years and older without antecedent cancer between 2000 and 2010 from the National Health Insurance Research Database. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of patients with SD with that of the general population. Results: During the 10-year study period, 2062 cancers developed among 63,381 SD patients, who were observed for 382,826 person-years (median follow-up of 6.23 years). The SIR for all cancers was 1.19 (95% confidence interval [CI], 1.14–1.24). For specific cancer types, SD patients exhibited an increased SIR for liver and lung cancers (1.44; 95% CI, 1.28–1.61 and 1.34; 95% CI, 1.18–1.51, respectively). Conclusions: We observed that overall cancer risk is increased among Asian SD patients. In terms of individual cancers, the risks of liver and lung cancers were elevated. Clinicians should be aware of the possibility of increased liver and lung cancers among SD patients in Taiwan. A prospective study is necessary to confirm these findings. [Copyright &y& Elsevier]

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % ( P = 0.039); OS, 38.2 vs. 62.5 % ( P = 0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % ( P = 0.179); OS, 76.2 vs. 69.8 % ( P = 0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation. [ABSTRACT FROM AUTHOR]

Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1 × 10/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies. [ABSTRACT FROM AUTHOR]

Objective The objective of this study is to assess the incidence and risk of mood disorders, including major depression, anxiety, and bipolar disorders, in Taiwanese patients after the diagnosis of breast cancer compared with a matched cohort. Methods From January 2000 to December 2005, 26,629 newly diagnosed breast cancer patients were enrolled by the Taiwan National Health Insurance program database. The control cohort was selected randomly from 1,000,000 National Health Insurance beneficiaries from a population of 21,400,826 enrolled throughout Taiwan. Each patient was matched with one subject without breast cancer by age, sex, and presence of comorbidities with the same diagnosis index date. The diagnosis of mood disorders was defined by compatible International Classification of Diseases, 9th revision, clinical modification codes plus the prescription of antidepressants for at least 30 days. Results The overall incidence rate ratio of mood disorders was 1.33 (95% CI 1.28-1.39, p < 0.001) in the breast cancer cohort compared with the matched cohort. The incidence rate ratios for specific mood disorders were 2.06 for bipolar disorder (95% CI 1.37-3.15 p = 0.0003), 1.94 for major depressive disorder (95% CI 1.76-2.13 p < 0.001), and 1.22 for anxiety (95% CI 1.16-1.27 p < 0.001). Independent risk factors for developing mood disorders included breast cancer, as well as age, hypertension, chronic obstructive pulmonary disease, autoimmune disease, ischemic heart disease, and cerebrovascular disease. Conclusions Breast cancer is a prominent risk factor for mood disorders, including major depressive disorder, anxiety, and bipolar disorder. The impact is most potent in the first year after diagnosis. Psychological support is a critical issue in these patients. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: To evaluate the risk of cancer among Taiwanese female registered nurses (RNs) using a nationwide population-based dataset. Methods: We recruited female RNs without antecedent cancer from the Taiwan National Health Insurance Research database during 2000–2010. Standardized incidence ratios (SIRs) of cancer were calculated. We also compared rates of Papanicolaou (Pap) smear use between the RNs and the general population matched by age and sex. Results: A total of 2,077 cancers developed among 184,809 female RNs, with a follow-up of 1,371,910 person-years (median follow-up of 7.86 years), leading to an increased SIR of 1.10 [95% confidence interval (CI) 1.05–1.15]. RNs aged between 40–59 years also had a significantly increased SIR (1.14, 95% CI 1.08–1.21). For specific cancer types, RNs had an increased SIR for breast (1.28, 95% CI 1.19–1.37), thyroid (1.26, 95% CI 1.10–1.43), lung and mediastinum (1.36, 95% CI 1.13–1.62), and uterine cancers (1.23, 95% CI 1.01–1.49). A decreased SIR was found for cervix (0.48, 95% CI 0.37–0.61) and liver and biliary tract cancers (0.68, 95% CI 0.50–0.90). Pap smear use averaged 5.80 times per person among female RNs aged 35 years or older and 5.50 times per person in the age-matched control group (p = 0.009). Conclusion: This study found that overall cancer risk was higher among female RNs than general population. For individual cancers, the risks of breast, lung, thyroid and uterine cancer were higher and the risks of cervix and liver cancer were lower than general population. The lower risk of cervical cancer might be partially explained by the increased use of Pap smears in the RNs group. Further large, unbiased population-based prospective studies are needed to investigate the association between nurses and cancer risk and identify the risk factors of cancer in nurses. [ABSTRACT FROM AUTHOR]

BACKGROUND: In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database, the authors conducted a population-based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study included 6418 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [ P = .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02-1.36 [ P = .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00-1.61; P = .046) and 1.46 (95% CI, 1.11-1.89; P = .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P = .006) for the high tertile of cDDDs compared with the low tertile. CONCLUSIONS: The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose-dependent effect. Cancer 2013;119:1699-1705. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Long-term outcomes are favorable for patients with polycythemia vera ( PV) and for patients with essential thrombocythemia ( ET). However, hemorrhage is a significant cause of morbidity and mortality in those patients. Methods We retrospectively recruited 247 patients who had received a diagnosis of PV ( n = 101) or ET ( n = 146) during the period 2001-2010. Results After a median follow-up period of 36.2 months, the cumulative incidence of hemorrhage was 39.6% in patients with PV (6.2% per person-year) and 29.7% in patients with ET (5.9% person-years). Episodes of major bleeding occurred in 9.9% of patients with PV and in 14.4% of patients with ET. Overall survival was significantly shorter among patients with hemorrhage than among those without said complication ( P < 0.001 for overall patients; P = 0.002 for patients with PV; P = 0.026 for patients with ET). In the univariate analysis, age ≥60 yr ( OR: 4.77, P = 0.046) and WBC ≥ 16 × 109/L ( OR: 4.15, P = 0.010) were predictors of hemorrhage in patients with PV, and age ≥60 yr ( OR: 3.25, P = 0.040), WBC ≥ 16 × 109/L ( OR: 2.89, P = 0.024), albumin <4.0 g/dL ( OR: 4.10, P = 0.002), and splenomegaly ( OR: 5.19, P = 0.002) were predictors of hemorrhage in patients with ET. Multivariate analysis showed that WBC ≥ 16 × 109/L was the only significant risk factor for hemorrhage in patients with PV ( OR: 3.51, P = 0.026) and that splenomegaly was the only risk factor for hemorrhage in patients with ET ( OR: 3.00, P = 0.048). Conclusion Leukocytosis in PV and splenomegaly in ET are independent risk factors for hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of cancer among patients with generalized anxiety disorder (GAD) in a nationwide population-based dataset. Methods: We recruited newly-diagnosed GAD patients aged 20 years or older without antecedent cancer from the Taiwan National Health Insurance Research database between 2000–2010. Standardized incidence ratios (SIRs) of cancers were calculated in GAD patients, and the subgroup of GAD patients diagnosed by psychiatric specialists. Results: A total of 559 cancers developed among 19,793 GAD patients with a follow-up of 89,485 person-years (median follow-up of 4.34 years), leading to a significantly increased SIR of 1.14 [95% confidence interval (CI) 1.05–1.24]. Male GAD patients had a significantly increased SIR overall (1.30, 95% CI 1.15–1.46) and for lung and prostate cancer (1.77, 95% CI 1.33–2.30 and 2.17, 95% CI 1.56–2.93, respectively). Patients over 80 years of age also had a significantly increased SIR (1.56, 95% CI 1.25–1.92), especially in males. However, psychiatrist-diagnosed GAD patients did not show increased cancer risk relative to the general population, perhaps due to having fewer physical comorbidities than non-psychiatrist-diagnosed GAD patients. Conclusion: This study found that overall cancer risk is elevated among patients with GAD. The risk of lung and prostate cancer also increased in male patients with GAD. This increased cancer risk may be due to physical comorbidities and surveillance bias. Further prospective study is necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

BACKGROUND. Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis. There is no standard therapy for CCA, and novel drugs for treating refractory CCA need to be identified. METHODS. The authors hypothesized that, if a drug could reverse the gene expression signature of CCA, then it may inhibit the carcinogenesis of CCA and, hence, would be a potential therapeutic agent. Thus, the gene expression signatures from patients with CCA were queried using the bioinformatic method Connectivity Map, resulting in the enrichment of heat-shock protein 90 (HSP90) inhibitors with therapeutic potentials. RESULTS. Two HSP90 inhibitors, 17-AAG (tanespimycin) and the synthetic diarylisoxazole amide resorcinol NVP-AUY922, demonstrated potent antiproliferative activity in in vitro studies. In a thioacetamide-induced animal model, NVP-AUY922 also had antitumor activity and resulted in objective tumor regression. In addition, NVP-AUY922 reduced the expression of client oncoproteins involved in CCA oncogenesis and inhibited downstream proteins of both the phosphatidylinositol 3-kinase catalytic subunit α/v-akt murine thymoma viral oncogene homolog 1 protein kinase (PIK3/AKT) pathway and the v-Ki-ras2 Kirsten rat sarcoma viral oncogene/mitogen-activated protein kinase (KRAS/MAPK) pathway. CONCLUSIONS. Preclinical data from the current study suggest that NVP-AUY922 may be an effective treatment option for patients with CCA. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs). Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification. Results: The presence of expression of GREM1 ( p = 0.016) and high MVD ( p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD ( p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas ( p < 0.001). Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs. [ABSTRACT FROM AUTHOR]

Certain portions of patients with diffuse large B cell lymphoma (DLBCL) do not achieve a complete remission after first-line rituximab combining chemotherapy. This retrospective study aimed to characterize the outcome of patients with DLBCL that achieved partial remission or had stable disease after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). The effects of subsequent treatments and factors associated with event-free survival (EFS) after second-line treatments were analyzed. A total of 103 patients were enrolled and 81 (76.8 %) patients received intensive chemotherapy, whereas the others (23.2 %) received either palliative chemotherapy or supportive care post first-line treatment. Patients receiving intensive chemotherapy had significantly higher EFS (median 7.9 months) than the others; 28 (34.6 %) patients in this group received autologous stem cell transplantation (ASCT), which may have further improved the EFS. An International Prognostic Index (IPI) >2 and absolute lymphocyte count (ALC) at diagnosis <1,000/UL were significant prognostic factors associated with worse EFS. The survival advantage of ASCT remained significant after adjustment for these factors. The results suggest intensive chemotherapy plus ASCT may provide modest disease control in patients with DLBCL who achieve PR or SD to first-line R-CHOP, particularly in those with a higher IPI score and/or low ALC at diagnosis. [ABSTRACT FROM AUTHOR]

Large pericardial effusion (LPE) with cardiac tamponade is a rare but life-threatening complication in adults undergoing hematopoietic stem cell transplantation (HSCT). The incidence and pathophysiology have not been well defined. We retrospectively reviewed 601 patients (≧18 years of age) receiving HSCT (262 autologous, 189 siblings, and 150 unrelated donors) in our center from January 2001 to September 2011. We described the incidence, clinical characteristics, treatment, and outcome. In total, six patients (0.998 %) developed seven episodes (1.16 %) of LPEs with cardiac tamponade. One patient underwent unrelated allografts and the other five patients received sibling allografts. The median day of detecting LPE were 176 in the six patients and 241 in the four late-onset patients (range, 9-369). All patients had normal cardiac function before HSCT. Two patients developed LPE early after conditioning, considered as cardiac toxicity resulting from high-dose cyclophosphamide. Four patients had chronic graft-versus-host disease (GVHD) involving lung, skin and sicca syndrome concomitant with or preceding the development of LPE. All episodes of cardiac tamponade were effectively managed by pericardiocentesis and enhanced immunosuppression. In conclusion, LPE and cardiac tamponade may develop after allogeneic HSCT, either with sibling or matched unrelated donor. The etiology is probably related to chronic GVHD in cases of late onset. Emergent pericardiocentesis and enhanced immunosuppression can effectively control this life-threatening complication. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of concurrent chemoradiotherapy (CCRT) on stage IV rectum cancer. Methods: Between 2000 and 2011, 297 consecutive patients diagnosed with stage IV rectum cancer (synchronous metastasis) were enrolled. Cox proportional hazard analyses were used for prognostic factors determination, and the Kaplan-Meier method was used for survival analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matched patients for validation studies. Results: In total, 63 patients received CCRT and 234 did not. The patients in the CCRT group were younger, had more low-lying lesions, and had more T4 lesions, lung metastases, metastasectomies, and oxaliplatin-based upfront chemotherapy. Before propensity-score matching, a younger age (HR = 0.662, P = 0.016), lower carcinoembryonic antigen (CEA) level (≤20 ng/ml) (HR = 0.531, P = 0.001), no metastasectomy (HR = 3.214, P < 0.001), and no CCRT (HR = 1.844, P = 0.019) were independent prognostic factors after controlling for other confounding factors. After matching, only CEA and metastasectomy, but not CCRT, were independent prognostic factors. The survival benefit of CCRT was restricted to patients who undergo subsequent metastasectomy. Conclusions: Upfront CCRT only provided a survival benefit in patients with stage IV rectum cancer who undergo subsequent metastasectomy. [ABSTRACT FROM AUTHOR]

Objectives Type 2 diabetes mellitus is present in approximately 10% of patients at diagnosis of multiple myeloma ( MM) and is associated with increased risks of adverse events caused by novel antimyeloma agents. However, the impact of type 2 diabetes on the survival of patients with MM has not been studied. Methods We enrolled newly diagnosed patients with MM in Taipei Veterans General Hospital between 1999 and 2007 and identified those with pre-existing diabetes. The impact of pre-existing diabetes on patients with MM was evaluated by comparing clinical features, treatments and adverse reactions related to glycaemic control and overall survival ( OS) of patients with and without pre-existing diabetes. Results Of 310 patients with MM, 73% were men and 40 (12.9%) had pre-existing diabetes. Compared with their non-diabetic counterparts, MM patients with pre-existing diabetes had a significantly higher proportion of renal impairment [( RI), serum creatinine ≥2.0 mg/ dL] and International Staging System stage III at diagnosis, and a significantly lower proportion of bisphosphonate use and a lower rate of RI reversal ( P = 0.087). During the course of the disease, hyperglycaemia and hypoglycaemia of any grade were noted in 23 (67.6%) and 6 (17.6%) of these patients, respectively. Antidiabetic therapy was changed in 10 (29.4%) of 34 evaluable patients. MM patients with pre-existing diabetes had a significantly higher all-cause mortality risk (hazard ratio, 1.509; 95% confidence interval, 1.023-2.225, P = 0.037) compared with their non-diabetic counterparts. Conclusions Our study demonstrated the impact of pre-existing diabetes on clinical features and OS in patients with MM. [ABSTRACT FROM AUTHOR]

Background: This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN). Methods: We enrolled a total of 39 patients with stage III or IV colorectal cancer with chronic OIPN. They were treated with duloxetine by increasing the dose from 30 mg/day to 60 mg/day. Patients' pain intensity was rated at baseline and 12 weeks after duloxetine administration. The severity of neuropathic pain was evaluated using the visual analog scale (VAS) score and the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3 (NCI-CTCAE v3.0). Results: Nine patients (23.1%) discontinued duloxetine before the end of treatment because of adverse events. Of the remaining 30 patients, 19 patients (63.3%) had a VAS score improvement. Among them, nine (47.4%) showed a simultaneous grade improvement, and the other 10 patients (52.6%) had a stable grade according to NCI-CTCAE v3.0. Treatment with duloxetine did not impair renal or liver function and did not interfere with chemotherapy. Conclusions: Duloxetine is feasible in treating chronic OIPN with tolerable toxicity at a daily dose of 60 mg/day. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT), which is characterized by the suppression of the adhesion protein E-cadherin, is a crucial process that promotes metastasis and stem-like properties of cancer cells. However, the dissociation of cellular aggregates is not sufficient to explain why cancer cells move, and the motile nature of cancer cells undergoing EMT remains elusive. Here, we identify a mechanism in which the EMT inducer Twist1 elicits cancer cell movement through activation of RAC1. Twist1 cooperates with BMI1 to suppress let-7i expression, which results in upregulation of NEDD9 and DOCK3, leading to RAC1 activation and enabling mesenchymal-mode movement in three-dimensional environments. Moreover, the suppression of let-7i contributes to Twist1-induced stem-like properties. Clinically, activation of the Twist1-let-7i-NEDD9 axis in head and neck cancer patients correlates with tumour invasiveness and worse outcome. Our results uncover an essential mechanism to explain how Twist1 induces the motile stem-like cancer cell phenotype beyond simply suppressing E-cadherin. [ABSTRACT FROM AUTHOR]

We report 67 patients with acute erythroid leukemia (erythroleukemia) based on the World Health Organization (WHO) 2008 classification. Reviewing the clinicopathologic features, cytogenetics and outcomes, the characteristics of erythroleukemia resembled myelodysplastic syndromes (MDS). Patients with poor performance status, advanced anemia and poor-risk cytogenetics had significantly inferior outcomes. The International Prognostic Scoring System (IPSS) for MDS is useful to differentiate the prognosis of erythroleukemia. [ABSTRACT FROM AUTHOR]

Background: Reversal of renal impairment (RI) in patients with multiple myeloma (MM) has been evaluated using the estimated glomerular filtration rate (eGFRMDRD) formula developed by the Modification of Diet in Renal Disease study group. However, the prognostic impact of eGFRMDRD at diagnosis of MM is not well studied, particularly its use in conjunction with the International Staging System (ISS). Methods: Newly diagnosed patients with MM were enrolled between 1996 and 2007. Data on clinical features, laboratory tests, and overall survival were compared in terms of corresponding eGFRMDRD. Results: A total of 387 patients with MM (median age, 71 yr) were enrolled. At diagnosis, 56% had ISS stage III disease; the median values of serum creatinine (SCr) and eGFRMDRD were 1.4 mg/dL and 38.2 mL/min/1.73 m2, respectively. Thirty-four percent of patients had SCr of ≥2.0 mg/dL, and 81.2% had chronic kidney disease stages 3-5 (CKD 3-5). Higher CKD stages were significantly more common in men, older patients (≥65 yr), and those with Durie-Salmon and ISS stage III, light-chain diseases, anemia, thrombocytopenia, hypercalcemia, elevated serum β2 microglobulin, or lactate dehydrogenase. In the Cox regression model, CKD 4-5 or CKD 5 alone was independently associated with poor survival. A diagnosis of CKD 5 was shown to be useful in identifying the subgroup of ISS-III patients at high risk - those with a median overall survival of 7.2 months. Conclusions: Our study demonstrates the prognostic impact of eGFRMDRD in patients with MM and CKD 5 as the ISS-independent surrogate predictor of poorest prognosis. [ABSTRACT FROM AUTHOR]

The applicability of the International Staging System (ISS) for Chinese patients with multiple myeloma (MM) has not been demonstrated, especially with respect to treatments with novel agents. Newly diagnosed MM patients at Taipei Veterans General Hospital were enrolled between 1996 and 2007. Data regarding clinical features, laboratory tests, and outcome at last follow-up were collected. A total of 389 MM patients (71% male) were enrolled, with median age of 71 years. At diagnosis, 72.7% had Durie-Salmon (DS) stage III disease, 56.2% had ISS stage III disease, and 34% had serum creatinine ≧2.0 mg/dL. Compared with patients diagnosed in the first calendar period 1996-2001, the patients of the second calendar period 2002-2007 were older and more of these patients had received novel agents, especially thalidomide. The median overall survival period was 20.5 months, with a significant increase of patients in the second calendar period (15.3 and 28.2 months, respectively; P = 0.002), especially for those with ISS stages I and II. In the Cox proportion model, elevated serum β microglobulin at diagnosis (≧3.5 mg/L), old age (≧65 years), and impaired renal function were found to be independently associated with poor survival. Over the entire period, the ISS was found to be effective in providing an accurate prognosis with respect to different ages and calendar periods. This is the first study to show the applicability of ISS for Chinese patients with MM, especially for those who had received thalidomide. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan. Methods: We extracted 32,454 patients with pyogenic liver abscess from a nationwide health registry in Taiwan during the period 1997-2008. The frequency of and risk factors for pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma were determined. The prognosis of these patients was compared with patients with hepatocellular carcinoma but without liver abscess. Results: A total of 698 (2.15%) patients presented with liver abscess as the initial manifestation of underlying hepatocellular carcinoma during the 12-year period. Liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and age ≥65 years were independent risk factors for liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Furthermore, these patients had a lower 2-year survival rate than patients with hepatocellular carcinoma but without liver abscess (30% vs 37%; P =.004). Conclusions: The prognosis of patients who presented with pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma was poor. Physicians should not ignore the possibility of underlying hepatocellular carcinoma in patients with risk factors for the disease in regions with a high prevalence of both pyogenic liver abscess and hepatocellular carcinoma. [Copyright &y& Elsevier]

Purpose: More and more complications of extensive hepatic resection are being encountered in patients treated for liver metastases from colorectal cancer. This study aimed to determine the impact of liver abscess after hepatic resection on overall survival (OS) and the role of adjuvant chemotherapy.Methods: This is a retrospective study of 252 patients treated by liver metastasectomy between 2001 and 2010.Results: The 5-year survival rate was 55.8%. Twenty-one (8.3%) patients developed liver abscess after liver metastasectomy. Multivariate analysis identified the size of liver metastasis, surgical margin, and the presence of liver abscess as significant prognostic factors. Patients (whether or not they developed liver abscess after hepatic resection) had similar progression-free survival (median, 9.8 vs. 12.4 months, P = 0.476), but patients who developed liver abscess had significantly shorter OS (26.6 vs. 76.0 months, P = 0.004). Subsequent adjuvant therapy significantly improved OS in these patients (16.9 vs. 38.5 months, P = 0.032).Conclusions: Liver abscess after liver metastasectomy is an independent prognostic factor, and adjuvant chemotherapy is warranted in those patients who develop liver abscess. [ABSTRACT FROM AUTHOR]

Background: Neoplastic diseases are common in patients with nosocomial Klebsiella pneumoniae bacteraemia. This study investigated the clinical characteristics of neutropenic and non-neutropenic adult cancer patients with nosocomial K. pneumoniae bacteraemia. Methods: Adult cancer patients with K. pneumoniae bacteraemia were retrospectively analyzed at a medical centre in northern Taiwan over a 3-y period. We compared clinical characteristics of cancer patients with nosocomial K. pneumoniae bacteraemia between neutropenic and non-neutropenic groups and identified risk factors for 14-day mortality. Results: Of the 189 patients recruited, 49 (26%) had neutropenia. Haematological malignancies, advanced cancer stage, chemotherapy treatment within 1 month and unknown origin of bacteraemia were predominant among patients with neutropenia. Patients without neutropenia tended to be older, tended to have solid tumours and tended to have bacteraemia of biliary origin. The overall 14-day mortality rate was 25.4%. There was no significant difference in 14-day mortality rate between patients with neutropenia (24.5%) and those without neutropenia (25.7%) ( p == 0.808). The duration and severity of neutropenia, administration of inadequate empirical antibiotics and presence of extended-spectrum ββ-lactamase-producing strains were not risk factors for mortality due to nosocomial K. pneumoniae. Multivariate analysis showed that septic shock was the only independent risk factor for mortality. Conclusions: Nosocomial bacteraemia due to K. pneumoniae in patients with malignancies had heterogeneous characteristics between neutropenic and non-neutropenic groups. Cancer patients in both groups have a poor prognosis. More attention should be paid to cancer patients with nosocomial bacteraemia due to K. pneumoniae despite treatment with adequate antibiotics. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma that carries a poor prognosis. This study retrospectively analyzed patients with AITL from a single institution in Taiwan, aiming to define the clinical features and prognostic factors. Patients with AITL treated at our institution from February 1988 through January 2010 were enrolled. Factors associated with overall survival (OS) were determined by statistical methods. A total of 31 Taiwanese patients (21 males) were identified. The median age was 74 years (range, 27-90). Among all patients, 67.7% were Ann Arbor stage III or IV, 58.1% presented with B symptoms, 48.4% had hypoalbuminenia (<35 g/L), and 63.3% had elevated lactate dehydrogenase (LDH) at diagnosis. First-line chemotherapy was mostly CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone)-based and complete response (CR) was achieved in 25% of patients. The actuarial 2-year survival rate was 38.7%, and the median OS was 14.9 months. In multivariate analysis, initial presentation with fever ( p = 0.035), advanced stage ( p = 0.024), and failure to achieve CR ( p = 0.029) were independent adverse factors associated with poorer OS. Interestingly, OS did not differ whether chemotherapy regimens contained anthracycline or not. Taiwanese patients with AITL were usually elderly. Despite the prognosis being generally poor, patients with AITL should be treated with the goal of achieving CR, regardless of anthracycline- or non-anthracycline-based chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to identify the causes of prolonged facial edema and its associations with other clinical factors. Facial edema sometimes is observed in patients with head and neck squamous cell carcinoma (HNSCC), but its prevalence and association with other factors is unclear.Methods: Between July 2003 and July 2007, the medical records from 264 patients with HNSCC were reviewed. Prolonged facial edema is defined as persistence of edematous status (largest thickness >5 mm by CT scan) for more than 100 days. Clinical data including age, gender, tumor stage, and tumor primary sites were recorded. Statistical analyses were performed to determine the prognostic effect of prolonged facial edema, as well as its relationship to other clinical variables. The etiology of prolonged facial edema was also analyzed.Results: Prolonged facial edema occurred in 32 (12.1%) patients. The etiologies included internal jugular vein thrombosis, local infection, neck lymph nodes dissection, flap reconstruction, and direct vessel compression by tumors or metastatic lymph nodes. There was no significant difference in the incidence of prolonged facial edema in patients receiving different treatment modalities; however, patients receiving neck dissection correlated with the occurrence of late-onset facial edema. In addition to previously demonstrated prognostic factors (T status, nodal involvement and distant metastasis), prolonged facial edema was also identified as independent prognostic indicators for HNSCC patients (P = 0.001).Conclusions: Prolonged facial edema may reflect the underlying disease status, and it can be applied as a prognostic marker in patients with HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: Cytogenetics represents the most valuable predictor for a poor outcome in patients with acute myeloid leukemia (AML), but it encompasses a heterogeneous patient population who might have diverse pathogenesis and clinical courses. In particular, the significance of complex chromosome aberrations within this cohort has seldom been addressed before. We analyzed 48 AML patients with adverse-risk cytogenetics in this study. The complex karyotype (three or more numerical/structural cytogenetic changes; 29 patients) was found to occur more frequently among the elderly than a noncomplex adverse karyotype (19 patients; median age, 71 vs. 48; P = 0.005). The patients'' performance status was the sole independent factor determining the complete remission rate among patients receiving standard induction chemotherapy. On survival analysis, two factors independently predicted a longer overall survival: noncomplex karyotypes [vs. complex karyotypes, hazard ratio (HR) 0.434, 95% confidence interval (CI) 0.189–0.994, P = 0.048] and achievement of complete remission [(CR) vs. CR not reached, HR 0.170, 95% CI 0.051–0.572, P = 0.004)]. In conclusion, among AML patients with adverse cytogenetics, complex chromosomal aberrations occurred more frequently among the elderly and predicted a poor outcome. These patients should be considered as a unique entity and be separated from those with a noncomplex adverse cytogenetic change. Exploring the underlying mechanisms of leukemogenesis could improve the therapeutic outcome for this group of patients. [Copyright &y& Elsevier]

Abstract: Lamivudine has demonstrated efficacy in the treatment and prevention of hepatitis B virus (HBV) reactivation after hematopoietic stem cell transplantation (HSCT). However, most of these studies involved short durations of prophylaxis, so there is significant concern regarding lamivudine resistance in these patients. Between March 1984 and November 2002, 71 HBV surface antigen–positive HSCT recipients, including a subgroup of 16 who received pretransplantation lamivudine therapy, which was continued into the posttransplantation period to prevent reactivation hepatitis, were enrolled onto our study. The efficacy of lamivudine therapy was first evaluated for the subgroup of 16 patients in terms of treatment response, lamivudine resistance, and viral recurrence after discontinuation by using virologic assays. Efficacy was then evaluated for all patients in terms of the hazards of lamivudine therapy for reactivation hepatitis after transplantation. During a median lamivudine therapy period of 73 weeks (range, 19-153 weeks), the initial response showed a median reduction of 2.54 log10 in serum HBV DNA (−0.28 to 6.72 range). Lamivudine-resistant mutations were detected in 10 (63%) of 16 patients during therapy, and 1 (12%) of 16 patients finally developed a viral breakthrough. At a median follow-up of 30 months after discontinuation, 3 (27%) of 11 cases had recurrence of HBV infection. Despite the emergence of the mutations, no deaths were due to HBV reactivation or severe cases of hepatitis. In the Cox proportion regression model regarding reactivation hepatitis after transplantation of all enrolled patients, lamivudine therapy was found to be the only favorable factor for the event, with a hazard ratio of 0.122 (95% confidence interval, 0.016-0.908; P = .040). In conclusion, extended lamivudine therapy is safe and effective for the prevention of HBV reactivation in an HSCT setting and significantly decreases reactivation hepatitis after transplantation. [Copyright &y& Elsevier]