Palonosetron and dexamethasone for the prevention of nausea and vomiting in patients receiving allogeneic hematopoietic stem cell transplantation.

PURPOSE: The primary aim of this study was to evaluate the efficacy of palonosetron combined with dexamethasone in the prevention of vomiting, and especially nausea, in patients receiving allogeneic stem cell transplantation. METHODS: Palonosetron 0.25 mg was given to 27 patients receiving allogeneic transplantation on the first day of conditioning, and then every other day during the entire conditioning period. Dexamethasone was given daily also during conditioning. Vomiting and nausea were recorded daily according to CTCAE version 4.0 from the start of conditioning to Day 7 after transplantation. In addition, MASCC antiemetic tool (MAT) was also used in parallel to evaluate the intensity of nausea. RESULTS: The treatment was well tolerated; 25.9 and 40.7 % of the patients had grade 2/3 vomiting and nausea respectively during conditioning. The incidences of grade 2/3 vomiting and nausea were even higher in the first week after transplantation (40.7 and 51.8 %, respectively). The score of MAT correlated well with the grade of CTCAE. However, the difference in the mean intensity of nausea between period of conditioning and the first week after HSCT was significant only by using MAT (0.96 ± 1.829 vs. 3.81 ± 3.386, p=0.001) but not CTCAE (1.26 ± 0.903 vs. 1.63 ±0.967, p=0.152). CONCLUSION: Palonosetron combined with dexamethasone is effective in preventing vomiting during conditioning. However, more effort should be made to alleviate nausea during conditioning and both nausea and vomiting in the first week after transplantation. Furthermore, MAT has a higher discriminant power than CTCAE in assessing the intensity of nausea in patients receiving allogeneic transplantation.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy.

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC (J Clin Oncol 2019; 37: 3223-3233), NCT04165772 (N Engl J Med 2022; 386: 2363-2376), and PROSPECT (N Engl J Med 2023; 389: 322-334). In this review, we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Neoadjuvant Chemotherapy With/Without Radiotherapy for Locally Advanced Rectal Cancer: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The role of neoadjuvant radiotherapy in the management of patients with locally advanced rectal cancer (LARC) who have undergone neoadjuvant systemic therapy has been the subject of recent debate. PATIENTS AND METHODS: We identified eligible rectal cancer patients diagnosed between 2011 and 2020 using data from the Taiwan Cancer Registry. In our primary analysis, we applied propensity score weighting (PSW) to balance observable potential confounders. We then compared the hazard ratio (HR) of death the neoadjuvant concurrent chemoradiotherapy (nCCRT) group and the neoadjuvant chemotherapy without radiotherapy (nCT) group. Additionally, we conducted a comprehensive assessment of other outcomes and performed various supplementary analyses. RESULTS: The primary analysis included 2,298 patients. The overall survival did not exhibit statistically significant differences, with a PSW-adjusted HR of 0.72 (95% confidence interval=0.33-1.56, p=0.40) when comparing the nCCRT group to the nCT group. These findings were consistent with those of other long-term outcomes and supplementary analyses. CONCLUSION: In patients with LARC who have undergone neoadjuvant systemic therapy, the addition of radiotherapy did not yield statistically significant differences in long-term clinical outcomes.

Clinical Features and Outcomes of Primary Breast Diffuse Large B-Cell Lymphoma: A Matched-Pair Study.

Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. PATIENTS AND METHODS: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. RESULTS: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. CONCLUSION: nRT was associated with improved OS in our study population.

Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

Modified Albumin-Bilirubin Model for Stratifying Survival in Patients with Hepatocellular Carcinoma Receiving Anticancer Therapy.

Albumin−bilirubin (ALBI) grade is an objective and reproducible model for evaluating overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the original ALBI grade was established for patients with Child−Pugh classes A−C. HCC patients with Child−Pugh class C or poor performance status (Barcelona Clinic Liver Cancer (BCLC) stage D) usually receive hospice care. Thus, optimized cutoffs for the ALBI grade for stratifying OS in HCC patients receiving anticancer therapy are pertinent for accurate prognostication. This study retrospectively enrolled 2116 patients with BCLC stages A−C HCC after the exclusion of those ineligible for receiving anticancer therapy. The modified ALBI (mALBI) grades were: an ALBI score ≤−3.02 for mALBI grade 1, an ALBI score >−3.02 to ≤−2.08 for mALBI grade 2, and an ALBI score >−2.08 for mALBI grade 3. The original ALBI and mALBI grades were independent predictors of OS in all the enrolled patients and those receiving transarterial chemoembolization. In patients receiving curative therapy (radiofrequency ablation and surgical resection), the mALBI grade (grade 2 vs. 1 and grade 3 vs. 2) was an independent predictor of OS. Original ALBI grade 2 vs. 1 was an independent predictor of OS but not ALBI grade 3 vs. 2. The mALBI model can differentiate between patients with early, intermediate, or advanced HCC who received anticancer therapy into three prognostic groups. External validation of the proposed mALBI grade is warranted.

In anemia zinc is recruited from bone and plasma to produce new red blood cells.

Anemia is highly prevalent in people with chronic kidney disease (CKD), and CKD patients always have lower plasma but higher erythrocyte Zn levels than healthy people. To date, no satisfactory mechanism has explained these Zn metabolism abnormalities. We collected blood samples from patients on hemodialysis, 5/6 nephrectomized rats and phenylhydrazine (PHZ)-induced anemic mice and rats and compared them with their normal counterparts. We found that all the anemic animals had significantly decreased plasma Zn levels but elevated erythrocyte Zn levels. We also found that in anemic mice, new red blood cells (reticulocytes) had a ~7-fold higher Zn concentration than mature erythrocytes. When excess Zn was supplied to the rats, there was a ~1.2-fold increase in the Zn level in the rat bones. When Zn was depleted in the rats, the bones lost the greatest amount of Zn in the body (a 45% decrease). We prepared Zn-depleted rats and rendered these rats anemic by treating them with PHZ, and we compared them with normal rats. We found that in PHZ-induced anemia, rats released ~16% of Zn from their bones. Rat bones not only act as a 'reservoir' to adjust the excess or deficient Zn levels but also release Zn in anemia, and the released Zn stimulates erythropoiesis in the bone marrow. In anemia, Zn is redistributed from the plasma (causing the plasma Zn level to decreases) and bones to the bone marrow to produce reticulocytes (causing erythrocyte Zn level elevation).

Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies.

Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions. Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment. Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results. Conclusions: The changes in specific taxa and ß-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.

Prognostic Significance of Oligometastatic Disease Classification by the ESTRO/EORTC of Cancer for Patients With Lung Cancer Treated With Definitive Radical Radiotherapy.

BACKGROUND: Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. PATIENTS AND METHODS: We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. RESULTS: We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. CONCLUSION: We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.

A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial.

UNLABELLED: Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P < 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation-related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-naïve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation. CONCLUSION: Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.

Significant association of Ku80 single nucleotide polymorphisms with colorectal cancer susceptibility in Central Taiwan.

AIM: To evaluate the association between the polymorphisms of the Ku80 gene and the risk of colorectal cancer in Central Taiwan. MATERIALS AND METHODS: In this hospital-based case-control study, the association of Ku80 G-1401T rs828907, Ku80 C-319T rs11685387 and Ku80 intron 19 rs9288518 polymorphisms with colorectal cancer risk in a central Taiwanese population was investigated. In total, 362 patients with colorectal cancer and 362 age- and gender-matched healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped. RESULTS: A significantly different distribution was found in the frequency of the Ku80 G-1401T genotype, but not the Ku80 C-319T or intron 19 genotypes, between the colorectal cancer and control groups. The T allele Ku80 G-1401T conferred a significantly (p=0.0069) increased risk of colorectal cancer. As for Ku80 C-319T and intron 19 polymorphisms, there was no difference in distribution between the colorectal cancer and control groups. Gene interactions with smoking, but not with alcohol consumption, were significant for Ku80 G-1401T polymorphism. The Ku80 G-1401T GT and TT genotype in association with smoking conferred an increased risk of 2.537 (95% confidence interval=1.398-4.601) for colorectal cancer. CONCLUSION: These results provide the first evidence that the T allele of the Ku80 G-1401T may be associated with the development of colorectal cancer and may be a novel useful marker for primary prevention and anticancer intervention.

Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.

Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. ß-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.

Nano-Diamino-Tetrac (NDAT) Enhances Resveratrol-Induced Antiproliferation by Action on the RRM2 Pathway in Colorectal Cancers.

Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvß3 to trigger cancer cell death via nuclear translocation of COX-2. Here we report that resveratrol paradoxically activates RRM2 gene expression and protein translation in colon cancer cells. This unanticipated effect inhibits resveratrol-induced COX-2 nuclear accumulation. RRM2 downregulation, whether achieved by RNA interference or treatment with NDAT, enhanced resveratrol-induced COX-2 gene expression and nuclear uptake which is essential to integrin αvß3-mediated-resveratrol-induced antiproliferation in cancer cells. Elsewhere, NDAT downregulated resveratrol-induced RRM2 expression in vivo but potentiated the anticancer effect of the stilbene. These findings suggest that RRM2 appears as a cancer cell defense mechanism which can hinder the anticancer effect of the stilbene via the integrin αvß3 axis. Furthermore, the antagonistic effect of RRM2 against resveratrol is counteracted by the administration of NDAT.

Impact of Undertreatment of Cancer Pain With Analgesic Drugs on Patient Outcomes: A Nationwide Survey of Outpatient Cancer Patient Care in Taiwan.

CONTEXT: Undertreatment of cancer pain among outpatient cancer patients needs to be addressed to enhance care and improve patients' quality of life (QoL). OBJECTIVES: This prospective, cross-sectional, patient-focused study aimed to explore the prevalence of pain and undertreatment of cancer pain in outpatients in Taiwan. METHODS: A total of 2652 non-selected outpatients with cancer and aged 20 years or older from 16 medical centers across Taiwan were included in this survey. All patients completed a questionnaire based on the Brief Pain Inventory. Pain management index (PMI) was used to evaluate the adequacy of pain management. Possible clinical variables of patients with positive PMI were examined by univariate and multivariate logistic regressions. RESULTS: A total of 1659 (62.6%) outpatients had experienced some degree of pain; among these, 32.4% had negative PMI. Patients with a negative PMI score had significantly poor outcomes of QoL and a significantly higher tendency toward dissatisfaction with pain control by the physician and with the prescribed analgesic drugs. Female gender, primary tumor from breast, non-cancer-related cause of pain, and hospital locations from north Taiwan were independent variables that predicated patients with undertreatment of cancer pain. Most importantly, a forward trend of undertreatment of pain among patients who presented with lower prevalent rate of pain was observed. CONCLUSION: One-third of Taiwanese outpatients experienced pain because of undertreatment. Awareness of the prevalence of undertreatment of cancer pain and identification of the vulnerable subjects may assist in enhancing patient care and improving patient's QoL.

A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1mutation /FLT3- internal tandem duplication (ITD)negative were independent prognostic factors for the entire cohort. Among patients with intermediate-risk cytogenetics, patients with mutations in CEBPAdouble mutation , IDH2, and NPM1 in the absence of FLT3-ITD were associated with improved Overall survival (OS), similar to those with favorable-risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable-risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next-generation sequencing (NGS)-based multi-gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions.

Effectiveness of neoadjuvant concurrent chemoradiotherapy versus up-front proctectomy in clinical stage II-III rectal cancer: A population-based study.

AIMS: Neoadjuvant concurrent chemoradiotherapy (NCCRT) is currently the preferred treatment for rectal cancer of clinical stage II-III based on its efficacy in clinical trials. The population-based effectiveness of NCCRT is rarely reported on in the literature. The purpose of our study is to investigate the nationwide population-based effectiveness of NCCRT as compared with up-front proctectomy. METHODS: In this retrospective cohort study, we identified the study population by linking datasets including the cancer registry, death registry and other related files in Taiwan. We identified all patients with rectal adenocarcinoma of American Joint Committee on Cancer clinical stage II or III who were diagnosed in 2007 or 2008 and received either NCCRT or up-front proctectomy. We included patients' age, gender, residence, socioeconomic status and clinical stage as covariables. We used overall survival as the measure of effectiveness. The Cox proportional-hazards regression model was used for statistical analyses. We further conducted sensitivity analyses, one in only those who received optimal postoperative chemotherapy and one in two subgroups matched for propensity score. RESULTS: We included 1933 patients (NCCRT: 424; up-front proctectomy: 1509) in the study population. NCCRT was associated with improved survival as compared with up-front proctectomy (adjusted hazard ratio of death 0.656; 95% confidence interval 0.495-0.871). Our results were robust in the sensitivity analyses. CONCLUSION: We demonstrated that the use of neoadjuvant concurrent systemic therapy and radiotherapy is associated with better effectiveness in rectal adenocarcinoma of clinical stage II-III as compared with up-front proctectomy. Further studies are needed to elucidate the subgroups most likely to benefit and to clarify NCCRT's cost-effectiveness.

Hepatitis C infection is associated with hepatic toxicity but does not compromise the survival of patients with diffuse large B cell lymphoma treated with rituximab-based chemotherapy.

The influence of hepatitis C virus (HCV) infection on the outcome of patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab-based chemotherapy is controversial. We retrospectively analyzed the characteristics and clinical outcomes of 168 patients with DLBCL diagnosed between January 2005 and December 2011. Twenty-nine patients who were HCV-positive before lymphoma treatment were compared with 139 patients who did not have HCV infection. The median follow-up duration was 3.0 (0.07-8.02) years. HCV infection resulted in more hepatic toxicity in both univariate (p=0.001) and multivariate (p=0.003) analyses. In addition, HCV-positive DLBCL patients were more likely to have treatment delay (20.1% vs. 0.7%, p<0.001). For patients who developed hepatic toxicity during immunochemotherapy, HCV-positive patients had significantly higher folds of aspartate aminotransferase elevation (p=0.042) and total bilirubin elevation (p=0.012) compared with those who were HCV negative. However, HCV did not influence the 5-year progression-free survival rate (p=0.412) or 5-year overall survival rate (p=0.410). In conclusion, HCV infection is associated with increased hepatic toxicity and delayed chemotherapy without compromised survival in DLBCL patients treated with rituximab-based chemotherapy.

Fusidic acid-induced leukopenia and thrombocytopenia.

Fusidic acid is an active agent against a wide variety of gram-positive bacteria, and it has been increasingly used in methicillin-resistant Staphylococcus aureus infection. The major adverse effects are mild gastrointestinal discomfort and diarrhea. The hematological side effects such as granulocytopenia and thrombocytopenia have been rarely reported in western countries, but have not been documented in Asian population. Between January and April 2001, we identified 2 cases of fusidic acid-induced leukopenia and thrombocytopenia after 2 weeks of fusidic acid treatment. In both cases, hematological abnormality resolved in 3 to 6 days after discontinuation of fusidic acid. The published literature regarding hematological adverse effects caused by fusidic acid is reviewed in this report, and an immune-mediated mechanism possibly by drug-dependent antibody is speculated. We recommend periodic complete blood count check in patients receiving long-term fusidic acid treatment to avoid serious hematological adverse effects.