Harue Tada

Risk factors for lower limb lymphedema after lymph node dissection in patients with ovarian and uterine carcinoma.

BackgroundLymph node dissection has proven prognostic benefits for patients with ovarian or uterine carcinoma; however, one of the complications associated with this procedure is lymphedema. We aimed to identify the factors that are associated with the occurrence of lymphedema after lymph node dissection for the treatment of ovarian or uterine carcinoma.MethodsA total of 694 patients with histologically confirmed ovarian (135 patients) or uterine cancer (258 with cervical cancer, 301 with endometrial cancer) who underwent lymph node dissection were studied retrospectively. Logistic regression analyses were used to identify the risk factors associated with occurrence of lymphedema.ResultsAmong ovarian and uterine cancer patients who underwent pelvic lymph node dissection, post-operative radiotherapy (odds ratio: 1.79; 95% confidence interval: 1.20–2.67; p = 0.006) was statistically significantly associated with occurrence of lymphedema.ConclusionThere was no relationship between any surgical procedure and occurrence of lymphedema among patients undergoing pelvic lymphadenectomy. Our findings are supported by a sound biological rationale because they suggest that limb lymphedema is caused by pelvic lymph node dissection.

Laparoscopic Radical Nephroureterectomy: A Multicenter Analysis in Japan

BACKGROUND Laparoscopic nephroureterectomy (LNUx) is prevalent in Japan and throughout the world, but long-term outcome data remain limited. OBJECTIVE To understand the present state of LNUx in Japan, we conducted a multicenter analysis of clinical outcome and long-term cancer control for patients who underwent the procedure. DESIGN, SETTING, AND PARTICIPANTS Between January 1995 and December 2005, 1003 patients with urothelial cancer in the upper urinary tract were treated with LNUx at 51 institutions in Japan, and patient data were collected retrospectively. MEASUREMENTS Patient profiles were gathered and analyzed for survival, intravesical recurrence, and risk factors influencing them. RESULTS AND LIMITATIONS Median operative time was 320 min. Median bleeding volume was 232 ml. Complications occurred in 93 cases (9.3%) intraoperatively and in 107 cases (10.7%) postoperatively. Overall survival rate was 70% at 5 yr. Grade 3, pT3 or pT4, multifocal tumor, lymph-node metastasis, and previous or coexistent bladder tumor were independent risk factors for overall survival. Intravesical recurrence rate was 43% at 5 yr. Intravesical recurrence occurred more frequently in males, in patients with multifocal tumors, in patients with previous or coexistent bladder tumors, and in patients who underwent the hand-assisted approach. CONCLUSIONS Our report represents the largest multicenter analysis of LNUx reported to date. Male sex and the use of the hand-assisted approach were shown for the first time to be risk factors for recurrence-free survival and intravesical recurrence. To further analyze the effectiveness of LNUx, a long-term outcome comparison with risk stratification must be made between LNUx and open nephroureterectomy.

Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid- resistant sudden sensorineural hearing loss: a prospective clinical trial

BackgroundSudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL.MethodsPatients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy.ResultsIn total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015) at 24 weeks. No serious adverse events were observed.ConclusionsTopical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment

BackgroundTo date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.MethodsWe randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events.ResultsIn the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001).ConclusionsThe positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness.Trial registrationUMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

PIEPOC: A New Prognostic Index for Advanced Epithelial Ovarian Cancer—Japan Multinational Trial Organization OC01-01

PURPOSE The purpose of this study was to construct a simple and powerful prognostic index (PI) of epithelial ovarian cancer, the PIEPOC. PATIENTS AND METHODS In a retrospective review, data from 768 women with stage III or IV epithelial ovarian cancer from 24 institutions in Japan were evaluated for clinical features predictive of overall survival. A PI and risk groups to predict overall survival after initial surgery were developed using the proportional hazards regression model. RESULTS Of six factors, the four prognostic factors that remained independently significant in the analysis of a training sample (538 randomly selected patients) were age, performance status (PS), histologic cell type, and residual tumor size. From the regression function, we derived a PI = 1 (if age 70 and above) + 1 (if PS 1 or 2) + 2 (if PS 3 or 4) + 1 (if mucinous or clear-cell) + 2 (if residual size 0.1 cm and above). Patients were classified into three risk groups (PIEPOC): low risk (PI 0-2), intermediate risk (PI 3), and high risk (PI 4-6). The PIEPOC was equally predictive in a validation sample (n = 230), identifying three groups (5-year survival: 0.67 in low, 0.43 in intermediate, 0.17 in high risk). CONCLUSION Our proposed PI, the PIEPOC, was predictive in our patient population and may have utility in clinical practice. Prospective studies would be needed to confirm the prognostic predictive ability of the PIEPOC for patients with advanced epithelial ovarian cancer.

Association of clinical characteristics with disease subtypes, initial visual acuity, and visual prognosis in neovascular age-related macular degeneration

PurposeTo comprehend the clinical characteristics and factors related to visual prognosis in two major subtypes of neovascular age-related macular degeneration (AMD)—traditional, typical AMD and polypoidal choroidal vasculopathy (PCV).MethodsMedical records of 272 eyes of 216 patients diagnosed with neovascular AMD at Kyoto University Hospital between January 2000 and March 2003 were retrospectively reviewed for up to 3 years. Ophthalmoscopic, angiographic, and optical coherence tomography (OCT) findings were collected, and univariate and multivariate analyses were performed to determine the characteristic factors, the factors associated with initial visual acuity (VA), and visual prognosis in typical AMD and PCV.ResultsWe studied 154 eyes with typical AMD and 117 eyes with PCV. The presence of classic choroidal neovascularization (CNV) and posterior confluent drusen were characteristic of typical AMD, whereas PCV was characterized by a larger number of retinal pigment epithelial detachments and a small number of drusen. Poor initial VA (<0.1) was significantly associated with subfoveal classic CNV, hard exudates, late fibrosis staining of >−1 disc area in AMD, and with blood and cystoid macular edema in PCV. Maintenance of good VA was associated with better initial VA in typical AMD and with smaller lesions in PCV.ConclusionTypical AMD and PCV revealed statistical differences both in their clinical characteristics and in the factors associated with visual prognosis.

Lizards respond to an extremely low-frequency electromagnetic field.

SUMMARY Animals from a wide range of taxa have been shown to possess magnetic sense and use magnetic compasses to orient; however, there is no information in the literature on whether lizards have either of these abilities. In this study, we investigated the behavioral responses of a diurnal agamid lizard (Pogona vitticeps) to a sinusoidal extremely low-frequency electromagnetic field (ELF-EMF; 6 and 8 Hz, peak magnetic field 2.6 μT, peak electric field 10 V m−1). Fourteen adult lizards were divided randomly into two groups (the EMF and control groups; each group had three males and four females). The EMF group received whole-body exposure to ELF-EMF and the control group did not. Lizards in the EMF group were exposed to ELF-EMF for 12 h per day (during the light period). The number of tail lifts was monitored beginning 3 days before exposure and ending after 5 days of exposure. For each individual, the average number of tail lifts per day was calculated. The average number of tail lifts per individual per day was greater in the EMF group than in the control group (20.7±6.3 and 9.1±4.5 tail lifts, respectively, N=7 each, P=0.02). We confirmed the reproducibility of this response by a cross-over trial. These results suggest that at least some lizards are able to perceive ELF-EMFs. Furthermore, when the parietal eye of the lizards was covered with a small round aluminum ‘cap’ which could block light, the tail-lifting response to ELF-EMF disappeared. Our experiments suggest that (1) lizards perceive EMFs and (2) the parietal eye may be involved in light-dependent magnetoreceptive responses.

A Data Capture System for Outcomes Studies that Integrates with Electronic Health Records: Development and Potential Uses

In conventional clinical studies, the costs of data management for quality control tend to be high and collecting paper-based case report forms (CRFs) tends to be burdensome, because paper-based CRFs must be developed and filled out for each clinical study protocol. Use of electronic health records for this purpose could result in reductions in cost and improvements in data quality in clinical studies. The purpose of this study was to develop a data capture system for observational cancer clinical studies (i.e. outcomes studies) that would integrate with an electronic health records system, to enable evaluation of patient prognosis, prognostic factors, outcomes and drug safety. At the Outpatient Oncology Unit of Kyoto University Hospital, we developed a data capture system that includes a cancer clinical database system and a data warehouse for outcomes studies. We expect that our new system will reduce the costs of data management and analysis and improve the quality of data in clinical studies.

Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

BackgroundIn Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients.FindingsWe obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0). ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%), of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD.ConclusionThe results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

Prevalence and incidence of anemia in Japanese cancer patients receiving outpatient chemotherapy.

Anemia in cancer patients has been under-recognized and little studied in Japan. To gain some insight into cancer-related anemia in Japanese patients undergoing outpatient chemotherapy, we performed a single-center retrospective study of the prevalence and incidence of anemia in 148 patients with solid tumors treated at the Kyoto University Hospital Outpatient Oncology Unit. We classified the cases of anemia in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Of 148 patients, 65 (44%) were anemic at the start of chemotherapy, 19 (13%) of whom had anemia of grade 2 or higher. Chemotherapy further increased the number of anemic patients, with 125 (84%) being anemic at some point during chemotherapy, and 61 (41 % ) of these having anemia of grade 2 or higher. Among the 83 patients without anemia at the start of chemotherapy, 60 (72%) developed anemia during chemotherapy, 15 (18%) of whom had anemia of grade 2 or higher. This is the first report showing a high prevalence and incidence of anemia in Japanese patients undergoing outpatient chemotherapy. Better recognition and management of cancer-related anemia are required in Japan. To this end, randomized controlled trials evaluating the effects of erythropoietic agents on patients’ survival and quality of life are necessary.