Tzeon Jye Chiou

N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data

Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3–4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85xa0mg/m2) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200xa0mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2–4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Rituximab therapy increased post-transplant cytomegalovirus complications in Non-Hodgkin’s lymphoma patients receiving autologous hematopoietic stem cell transplantation

The use of monoclonal antibody, rituximab, had been reported to be associated with some severe viral infections. The inference of rituximab therapy and post-transplant cytomegalovirus (CMV) infectious complications in non-Hodgkin’s lymphoma (NHL) patients is still unclear now. From 2002 to 2005, 46 patients with relapsed indolent or high-risk aggressive B cell NHL who received rituximab (17 patients) or not (29 patients) before autologous hematological stem cell transplantation (HSCT) in one institute were retrospectively analyzed for the risk factors of CMV complications after transplantation. Pre-transplant and post-transplant CMV infectious conditions, conditioning regimens, transplant types, and post-transplant complications were recorded. Post-transplant infectious complications were followed up until 6xa0months after transplantation.Seventeen of 46 patients received rituximab before HSCT. Three of them suffered from CMV infection and two of them developed CMV disease. All of the patients with CMV disease recovered after ganciclovir and CMV-specific immunoglobulin therapy. Twenty-nine of 46 patients without rituximab treatment before HSCT did not have CMV complications after HSCT. The risks to develop CMV infections after autologous HSCT were higher in rituximab-treated patients (17.6% vs 0%, pu2009=u20090.045, Fisher exact test, two-sided). The risks to develop CMV diseases had higher trend with rituximab therapy than without rituximab therapy (11.7% vs 0%, pu2009=u20090.131, Fisher exact test, two-sided). The NHL patients receiving rituximab therapy had higher risk to develop CMV infectious complications after autologous HSCT.

Retinoblastoma in Taiwan: Survival Rate and Prognostic Factors

PurposeThe mortality rate of patients with retinoblastoma still varies in developing countries, and data for Asia and Taiwan are relatively scarce. In this retrospective study, we aimed to describe the survival characteristics and prognostic factors of 54 retinoblastoma cases diagnosed at the Taipei Veterans General Hospital between 1982 and 2004.MethodsFrom medical records, we retrospectively analyzed the data of 54 consecutive children diagnosed in our hospital between 1982 and 2004 as having retinoblastoma. Data on sex, laterality, age at diagnosis, presenting signs, family history, duration of symptoms, lag time for treatment, spread of tumor, treatment mode, and survival time were collected.ResultsSeventy-five percent of the cases were unilateral and 25% of the cases were bilateral. The mean patient age at the time of diagnosis was 26.3 months. The mean duration of symptoms was 2.96 months. After diagnosis, the mean lag time before treatment was 2.59 months. The most common presenting signs were leukocoria (71.4%), red, painful, or tearing eye (18.4%), strabismus (14.3%), and blurred vision (14.3%). Only 3 of 52 cases (5.8%) were familial. The most common sites of extraocular invasion included the central nervous system (seven cases) and the orbit (seven cases). In 13.7% of the cases, parents had refused the treatment suggested by the doctors. None of the patients developed a secondary neoplasm. The 5-year overall survival rate was 80.9% (unilateral, 88.1%; bilateral, 64.3%). The survival rate of patients with an interval between onset and treatment of <5 months was 90.9%, and that for an interval of >5 months was 60.9%. The survival rate of those with a lag time of <2.5 months was 90.0%, and that of those with one of >2.5 months was 31.3%. The survival rate of patients with intraocular and extraocular disease was 96.9% and 39.2%, respectively. Extraocular disease was an independent factor indicating a poor prognosis, determined by multivariate analysis.ConclusionsThe mortality rate of patients with retinoblastoma is higher in Taiwan than in developed countries. The proportion of patients parents refusing or delaying treatment in Taiwan is high. The factors for a poor prognosis were an interval between onset and treatment of >5 months, a lag time before treatment of >2.5 months, and extraocular disease. The duration of symptoms was not a prognostic factor. The only independent factor indicating a poor prognosis was extraocular disease.u2003Jpn J Ophthalmol 2006;50:242–249

Candidemia in cancer patients: Impact of early removal of non-tunneled central venous catheters on outcome

OBJECTIVEnTo explore the impact of retention of non-tunneled central venous catheters (CVCs) on survival in candidemic cancer patients, where CVCs are commonly used and essential. A second object was to determine whether early CVC removal would benefit a subset of cancer patients.nnnMETHODSnWe retrospectively evaluated 92 cancer patients who had a single, non-tunneled CVC in place. Patients were grouped according to CVC retention or removal; the later group was subdivided into early (CVC removed <or=72h after candidemia onset) and late removal. A Cox regression model was used for determining risk factors of adverse outcome and Kaplan-Meier analyses for comparing in-hospital 3-30 day survival among subgroups.nnnRESULTSnBaseline characteristics were comparable between CVC retention (n=20) or removal (n=72) groups. CVC retention was a significant risk factor of poor outcome, independent of other significant prognostic host factors (hazard ratio 7.15, 95% confidence interval 3.51-14.53, p<0.001). Patients of early CVC removal (n=40) had significant better survival than those of late removal (n=32) (p<0.001).nnnCONCLUSIONnThe results suggest that retention of CVCs has a negative impact on survival in candidemic cancer patients, and that early CVC removal should be considered in a subset of cancer patients with candidemia.

Carbon dots prepared from ginger exhibiting efficient inhibition of human hepatocellular carcinoma cells

Fluorescent carbon nanodots (C-dots; 4.3 ± 0.8 nm) from fresh tender ginger juice provide high suppression of the growth of human hepatocellular carcinoma cells (HepG2), with low toxicity to normal mammary epithelial cells (MCF-10A) and normal liver cells (FL83B). The inhibition is selective to HepG2 over other tested cancer cells, including human lung cancer cell line (A549), human breast cancer cell line (MDA-MB-231), and human cervical cancer cell line (HeLa). Western blot results reveal that the C-dots up-regulate the expression of p53 protein only in the HepG2 cell line. The 50% inhibiting concentration (IC50) value of the C-dots on HepG2 cells is 0.35 mg mL-1. Image cytometry results show significant uptake of C-dots by HepG2 cells that induce intracellular production of reactive oxygen species (ROS, 18.2-fold increased), while other cells remain almost the same in ROS levels after treatment with C-dots (1.11 mg mL-1). The C-dots trigger the pro-apoptotic factor to promote HepG2 cell apoptosis. The C-dots effectively inhibit the growth of tumors in nude mice (104 ± 14 vs. 3.7 ± 0.2 mg with and without treatment within 14 days).

Severe anaphylactic reactions in patients receiving oxaliplatin therapy: a rare but potentially fatal complication

GoalsThe most well-known adverse events of oxaliplatin are hematologic toxicity, gastrointestinal tract toxicity, and sensory neuropathy. However, hypersensitivity reaction of oxaliplatin, especially severe anaphylactic reactions (SAR), was less often reported.Materials and methodsThree hundred and three patients with colon cancer treated by oxaliplatin-containing chemotherapy in one institution were analyzed. Patients were considered to have oxaliplatin-induced SAR if they suffered from at least one of the following symptoms after oxaliplatin infusion: symptomatic bronchospasm, allergy-related edema/angioedema, unstable blood pressure, or anaphylaxis. The reported cases in published literatures that met our definition were also reviewed.ResultThere were 4 out of 303 patients suffering from SAR after receiving oxaliplatin infusion, with an estimated incidence of 1.32%. Two of them became unconscious and had hypertensive crisis, and one patient had consciousness loss with hypotension. All four patients needed various level of oxygen support. Twenty-seven cases of oxaliplatin-induced SAR were found from Medline. Among the 31 reported cases, the most frequent SAR symptom was hypotension. However, we reported two unique SAR cases with hypertension crisis. In only four out of ten cases, patients could tolerate rechallenge of oxaliplatin. There is no association between the occurrence of oxaliplatin-induced SAR and metastatic sites.ConclusionOxaliplatin-induced SAR is a rare but potentially fatal complication. Hypertension crisis can be one of the oxaliplatin anaphylactic reactions. Only few patients suffering this complication could tolerate subsequent treatment of oxaliplatin by prolonged infusion time or using a desensitization schedule, thus changing regimen might be a better alternative for them.

Fatal Fulminant Hepatitis B after Withdrawal of Prophylactic Lamivudine in Hematopoietic Stem Cell Transplantation Patients

Hepatitis B virus (HBV) reactivation can give rise to acute hepatitis and even fatal fulminant hepatitis in patients receiving immunosuppressive or cytostatic treatment. Recently, the prophylactic use of lamivudine for HBV reactivation in HBV surface antigen-positive chronic-disease patients undergoing hematopoietic stem cell transplantation (HSCT) has been reported. However, the appropriate duration for this prophylactic therapy is unclear. Here, we report 2 cases of fatal fulminant hepatitis B reactivation in HSCT patients after lamivudine withdrawal. One patient with non-Hodgkin’s lymphoma completed 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and autologous peripheral blood SCT (PBSCT). Lamivudine was discontinued 3 months after transplantation. The second patient had acute myeloid leukemia. He received induction chemotherapy and postremission allogeneic PBSCT as late intensified consolidation therapy. Lamivudine treatment was discontinued 10 months after transplantation. In both patients, HBV reactivation 2 to 3 months following lamivudine cessation led to fatal fulminant hepatitis. We suggest that the duration of prophylactic use of lamivudine in chronic HBV carriers receiving HSCT be prolonged until the patient’s immune system has been reconstituted.

Higher fungal infection rate in elderly patients (more than 80 years old) suffering from diffuse large B cell lymphoma and treated with rituximab plus CHOP

Although adding rituximab to standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is an efficacious and well-tolerated regimen in elderly patients with diffuse large B cell lymphoma (DLBCL), it may increase susceptibility to opportunistic infections, and such cases have been reported. Our study was to identify the risk factors for fungal infection in a retrospective case-control matched study of 34 elderly DLBCL patients treated with rituximab plus CHOP (R-CHOP) and 35 control patients treated with the standard CHOP regimen at the Taipei Veterans General Hospital, Taiwan. The rate of overall infection was similar in both groups. However, subgroup analysis found that the fungal infection rate was significantly different, 41.7 and 17.1%, in the R-CHOP and CHOP groups, respectively, (Pu2009=u20090.03). Univariate analysis identified the rituximab plus CHOP chemotherapy regimen (Pu2009=u20090.03), age older than 80xa0years (Pu2009=u20090.04), and bone marrow involvement (Pu2009=u20090.04) as risk factors for development of fungal infection, whereas, multivariate regression analysis identified only rituximab plus CHOP and old age. Adding rituximab to the standard CHOP regimen in elderly DLBCL patients might increase the incidence of fungal infection especially in those older than 80xa0years old.

Relapse of Graves' disease after successful allogeneic bone marrow transplantation.

As shown in many reports, allogeneic BMT can help cure autoimmune diseases. Conversely, we present a 24-year-old woman with Graves disease, which was diagnosed just before BMT for CML. The Graves disease remitted immediately after BMT but relapsed 18 months later. Since the donor was free from thyroid diseases and the patient showed a rapid shift to complete donor chimerism after BMT, the autoimmune problem seemed neither to arise directly from the donor nor simply from the recipients residual lymphocytes. On the contrary, it was most likely compounded by chronic GVHD as suggested by the accompanying GVHD symptoms and the absolute donor karyotype in bone marrow cells. A Graves disease-susceptible HLA allele was also shared between recipient and donor, possibly enhancing the chances of this condition developing. Thus, allogeneic BMT may facilitate relapses in autoimmune diseases as well as alleviating them.Bone Marrow Transplantation (2001) 28, 1151–1153.

Impact of bloodstream infections on outcome and the influence of prophylactic oral antibiotic regimens in allogeneic hematopoietic SCT recipients.

This study aimed to determine the impact of blood stream infections (BSIs) on outcome of allogeneic hematopoietic SCT (HSCT), and to examine the influence of old (non-levofloxacin-containing) and new (levofloxacin-based) prophylactic antibiotic protocols on the pattern of BSIs. We retrospectively enrolled 246 allogeneic HSCT recipients between January 1999 and June 2006, dividing patients into BSI (within 6 months post-HSCT, n=61) and non-BSI groups (n=185). We found that Gram-negative bacteria (GNB) predominated BSI pathogens (54%). Multivariate analyses showed that patients with a BSI, compared with those without, had a significantly greater 6-month mortality (hazard ratio, 1.75; 95% confidence interval, 1.09–2.82; P=0.021) and a significantly increased length of hospital (LOH) stay (70.8 vs 55.2 days, P=0.014). Moreover, recipients of old and new protocols did not have a significantly different 6-month mortality and time-to-occurrence of BSIs. However, there were significantly more resistant GNB to third-generation cephalosporins and carbapenem in recipients of levofloxacin-based prophylaxis. Our data suggest that BSIs occur substantially and impact negatively on the outcome and LOH stay after allogeneic HSCT despite antibiotic prophylaxis. Levofloxacin-based prophylaxis, albeit providing similar efficacy to non-levofloxacin-containing regimens, may be associated with increased antimicrobial resistance.