A prospective survey of delayed adverse reactions to iohexol in urography and computed tomography

We investigated 7505 inpatients who underwent intravenous urography or contrast-enhanced computed tomography to assess risk factors for delayed adverse drug reactions to iohexol, a non-ionic iodinated contrast medium. Focusing on delayed adverse reactions, all adverse events were prospectively investigated for 7 days after injection of iohexol. To explore the relevant risk factors, the relationship between occurrence of adverse reactions to iohexol and 17 different variables was evaluated by logistic regression analysis. To assess the influence of seasonal factors, adverse reactions were separately evaluated during two periods: February to April (the pollinosis period in Japan) and July to September (the non-pollinosis period). The prevalence of delayed adverse events and delayed adverse reactions was 3.5 and 2.8%, respectively, whereas the prevalence of adverse events and adverse reactions was 5.7 and 5.0%, respectively. Multivariate analysis showed that six parameters had a significant influence on delayed adverse reactions to iohexol, including (a) a history of allergy, (b) season, (c) radiographic procedure, (d) age, (e) concomitant surgery or other invasive procedures, and (f) concomitant medication. The prevalence of delayed reactions was lower than in previous large-scale studies. Significant risk factors included a history of allergy and performance of radiography during the pollinosis period, suggesting that allergy was involved in delayed adverse reactions. The type of radiographic procedure also had an influence. Electronic Publication     

Complete appendiceal intussusception induced by primary appendiceal adenocarcinoma in tubular adenoma: a case report

A case of complete intussusception induced by appendiceal carcinomais reported. The patient was a 49-year-old man complaining ofrectal bleeding. Barium enema and colonoscopy revealed a cecalpolyp; it was interpreted as an inverted appendix with a tumor.Computed tomography showed an invaginated appendix into thececal cavity. During surgery, the appendix was found to be invertedcompletely into the cecum; ileocecal resection with regionallymph node dissection was performed. Microscopic examinationrevealed well-differentiated adenocarcinoma in tubular adenoma.Diagnosis of intussusception with carcinoma of the appendixis often difficult because appendiceal carcinoma with intussusceptionof the appendix is a rare condition. Although this conditioncan be diagnosed by radiographic imaging or colonoscopy, computedtomography has also been useful. The clinical manifestationof appendiceal intussusception with primary appendiceal tumorresembles a large cecal polyp, but its treatment differs greatly.Failure to recognize this condition may result in unexpectedcomplications such as consequent peritonitis in case of endoscopicremoval. ⁺ For reprints and all correspondence: Minoru Takahashi, Departmentof Surgery, Gunma Cancer Center Hospital, 617–1, Takabayashi-nishi,Ota, Gunma 373-8550, Japan. E-mail: minoru{at}gunma-cc.jp     

Efficacy and safety of novel oral fluoropyrimidine anticancer drug, TS-1 for advanced and recurrent gastric cancer patients

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.     

Evidence-based management of chemotherapy related thrombocytopenia

The availability of G-CSF increases the safety margin of chemotherapy use, especially in the management of infection. This in turn makes administration of a more intense regimen of chemotherapy possible. However, this improvement in neutropenic management could lead to an undesirable concurrent rise in thrombocytopenia risk due to the higher dose of chemotherapy administered. Although mortality from thrombocytopenia is generally quite rare, transfusions of platelets are often expensive and can be associated with side effects such as fever, hypersensitivity reaction, and occasionally infection. Therefore, transfusion of platelets should be performed when it is truly indicated. In general, the threshold for platelet transfusion is accepted as being when the platelet count drops below 10,000/microliter, unless there is an obvious bleeding lesion or other coagulation abnormality, such as DIC being identified in the patients. On the other hand, thrombotic microangiopathy (TMA) can also occur as a rare complication of the malignancy itself or from the associated cancer chemotherapy. The major features of TMA are thrombocytopenia and marked increases of destroyed erythrocytes and LDH in peripheral blood. Despite a low incidence, its high mortality rate makes it important for all physicians caring for cancer patients to be aware of it, especially in view of the ready availability of successful treatments (e.g., plasma exchanges). Early diagnosis of TMA in patients receiving chemotherapy requires special attention because some characteristics of TMA are often masked by common side-effects of chemotherapy such as bone marrow suppression. Since delay in initiation of plasma exchange could result in higher mortality, urgent hematology consultation should be obtained if TMA is ever suspected.     

Comparison of antimalarial activity of the alkaloidal fraction of Hydrangea macrophylla var. Otaksa leaves with the hot-water extract in ICR mice infected with Plasmodium yoelii 17 XL

The antimalarial activity of the fractions isolated from the leaves of Hydrangea macrophylla Seringe var. Otaksa Makino was evaluated against Plasmodium yoelii 17 XL in mice. Four different fractions were prepared in the usual manner to obtain an alkaloid fraction. All mice treated with the fraction containing febrifugine and isofebrifugine mixture at 1 mg/kg twice a day for 5 consecutive days survived during the experiment, and the change of mean parasitemia level showed almost the same pattern as that from mice treated with the hot-water extract of the same plant leaves. Activity of this fraction, however, was markedly reduced compared with the hot-water extract. Furthermore, no antimalarial activity was shown in the hotwater extract from H. macrophylla var. Otaksa roots or Dichroa febrifuga Lour. leaves.     

Antitumor effect by interleukin-11 receptor alpha-locus chemokine/CCL27, introduced into tumor cells through a recombinant adenovirus vector

In this study, we examined antitumor activity of a mouse CC chemokine ILC/CCL27 and a mouse CX(3)C chemokine fractalkine/CX(3)CL1 in vivo. We generated recombinant adenovirus vectors with a fiber mutation, encoding mILC (Ad-RGD-mILC) and mFKN (Ad-RGD-mFKN). We confirmed tumor cells infected with Ad-RGD-mILC and Ad-RGD-mFKN to express and release these chemokines. Tumor rejection experiments in vivo were carried out by inoculating OV-HM cells infected with Ad-RGD-mILC or Ad-RGD-mFKN into immunocompetent mice. mILC significantly suppressed the tumor growth, whereas no such significant effect was observed by mFKN. The antitumor activity induced by mILC was T cell dependent, involving both CD4(+) and CD8(+) T cells. Immunohistochemical analysis revealed accumulation of both CD3(+) lymphocytes and NK cells in the tumor tissue transduced with mILC and mFKN. However, there was a significant difference in the distribution of infiltrating cells. Furthermore, mFKN appeared to have an angiogenic activity, which might have masked its tumor suppressive activity. Collectively, ILC/CCL27 may be a good candidate molecule for cancer gene therapy.     

Phase II study of concurrent administration of doxorubicin and docetaxel as first-line chemotherapy for metastatic breast cancer

OBJECTIVE: To evaluate the efficacy and toxicity of concurrent administration of doxorubicin and docetaxel, without prophylactic use of granulocyte colony-stimulating factor, as first-line chemotherapy in patients with metastatic breast cancer (MBC). METHODS: This multi-institutional study enrolled 40 women; 37 were assessable for efficacy and all 40 patients were evaluated for toxicity. Treatment consisted of 50 mg/m(2) doxorubicin and 60 mg/m(2) docetaxel on day 1 every 3-4 weeks. RESULTS: Patients received a total of 251 cycles of chemotherapy (median, 5 cycles; range, 1-13 cycles). Of the 37 patients assessable for efficacy, 2 had a complete response and 24 had partial responses, which accounted for a 70% objective response rate (95% confidence interval, 53-84%). The median time to treatment failure was 30.1 weeks (range, 3.3-80.7 weeks). Grade 4 neutropenia was observed in 88% of patients and was the most frequent haematological toxicity. Febrile neutropenia was seen in 40% of patients, but no severe infections were observed. Non-haematological toxicity was generally tolerable. There were 2 grade 4 adverse events, which included 1 bleeding duodenal ulcer and 1 hypersensitivity reaction, but grade 3 episodes were infrequent. None of the patients developed congestive heart failure or asymptomatic decrease of left ventricular ejection fraction to less than 50%. Fluid retention syndrome 相似文献   

Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma

BACKGROUND: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU). METHODS: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method. RESULTS: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months. CONCLUSIONS: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma.     

Preventive effect of fermented brown rice and rice bran on diethylnitrosoamine and phenobarbital-induced hepatocarcinogenesis in male F344 rats

Epidemiological and preclinical studies have suggested that nutrition plays an important role in the etiology of cancer. Our group previously demonstrated that rice germ or fermented brown rice has a preventive effect on colorectal carcinogenesis. The experiment described here was examined for the potential anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of diethylnitrosoamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis as the measure of preventive efficacy when this agent was administered at 5% and 10% levels in diet during initiation phase (during and until 1 week after carcinogen treatment) or post-initiation phase (beginning 1 week after carcinogen treatment) of the carcinogenesis. Rats were sacrificed 20 weeks after the initiation of DEN treatment (200 mg/kg body weight, once weekly for 3 weeks). Expression of liver tumors was evaluated histopathologically. Administration of 10% FBRA in the diet during the initiation phase significantly decreased the incidence (43% vs. 8%) and multiplicity (0.5+/-0.6 vs. 0.1+/-0.3) of hepatocellular carcinoma (HCC) as compared to those given the control diet. In addition, 5% and 10% of FBRA in the diet during post-initiation phase significantly decreased the incidence of HCC (43% vs. 15% and 9%, respectively) and multiplicity of hepatocellular adenoma (4.7+/-3.7 vs. 2.1+/-2.2 and 2.4+/-1.4, respectively) and HCC (0.5+/-0.6 vs. 0.2+/-0.4 and 0.1+/-0.3, respectively). These data prove that FBRA has an inhibitory effect on the hepatocarcinogenesis in rats. FBRA could be a promising chemopreventive agent for human liver as well as colorectal neoplasia.     

Wf-536 prevents tumor metastasis by inhibiting both tumor motility and angiogenic actions

The signaling pathway of Rho and Rho-associated coiled-coil forming protein kinase (ROCK) is involved in tumor metastasis. In the present study, we investigated the suppressive effect of a novel inhibitor of ROCK, Wf-536 [(+)-(R)-4-(1-Aminoethyl)-N-(4-pyridyl) benzamide monohydrochloride], on spontaneous tumor metastasis in vivo and analyzed its action on tumor cell motility and angiogenesis to clarify its action mechanism. Wf-536 (0.3-3 mg/kg/day) was found to inhibit Lewis lung carcinoma (LLC) metastasis and LLC-induced angiogenesis in orally treated mice; in vitro, it inhibited both invasion and migration by LLC cells and invasion, migration, and formation of capillary-like tubes on Matrigel by endothelial cells, without cytotoxicity or anti-proliferative action in either cell type. We conclude that Wf-536 has tumor anti-metastatic activity which may depend on inhibition of tumor motility and angiogenesis. The findings support its further clinical development as an anti-metastatic agent.