Hirofumi Koga

Habitual Intake of Lactic Acid Bacteria and Risk Reduction of Bladder Cancer

Introduction: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. Methods: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). Results: The OR of smoking was 1.61 (95% confidence interval: 1.10–2.36). Those of previous (10–15 years ago) intake of fermented milk products were 0.46 (0.27–0.79) for 1–2 times/week and 0.61 (0.38–0.99) for 3–4 or more times/week, respectively. Conclusion: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.

Clinical impact of whole body FDG-PET on the staging and therapeutic decision making for malignant lymphoma

Objectives: The aim of this study is to evaluate the clinical impact of whole-body FDG-PET for the pre-therapeutic evaluation of malignant lymphoma and compared to that of 67Ga-scintigraphy when added to non-RI examinations. Methods: We examined 46 patients with malignant lymphoma including 42 newly diagnosed cases and 4 relapsed cases. Whole-body FDG-PET was started 63 minutes after the administration of FDG with ECATEXACT HR+. The clinical stage of each patient was determined based on the results of a non-RI examination (consisting of physical examination, CT, gastrointestinal studies and bone marrow aspiration), 67Ga planar images and FDG-PET. Discrepant findings were verified based on the response to treatment and the findings of a follow-up examination more than 6 months after treatment. Finally, 152 nodal regions and 19 extranodal tissues were found to be involved by disease. Results: In the 152 nodal lesions, FDG-PET detected 54 nodal lesions in addition to 98 lesions detected by non-RI examinations, whereas 67Ga-scintigraphy detected 14 additional lesions. The sensitivity of non-RI, non-RI+67Ga and non-RI+FDG was 64.5%, 73.7% and 100.0%, respectively. In 19 extranodal lesions, FDG-PET detected 5 extranodal lesions in addition to 13 lesions detected by non-RI examinations, whereas 67Ga-scintigraphy detected 1 additional lesion. The sensitivity of non-RI, non-RI+67Ga and non-RI+FDG was 68.4%, 73.7% and 94.7%, respectively. When combining the FDG-PET findings with the non-RI findings, the improvement of the detectability was much higher than that when 67Ga findings were combined to the non-RI findings. For the staging of lymphoma, the non-RI and non-RI+67Ga findings accurately diagnosed 76.1% and 80.4%, respectively, whereas the non-RI+FDG findings accurately diagnosed 82.6%. Finally, FDG-PET resulted in changes in the clinical management of 8 patients (17.4%). Conclusions: FDG-PET offers more information in addition to the findings of conventional diagnostic methods than 67Ga-scintigraphy in order to accurately detect malignant lymphoma. FDG-PET can therefore play an important role in therapeutic decision making on lymphoma.

Comparison of18FDG-PET with99mTc-HMDP scntigraphy for the detection of bone metastases in patients with breast cancer

ObjectiveBone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients.MethodsForty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards.ResultsOn a region basis, the sensitivity, specificity, and accuracy of18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of18FDG-PET were mostly osteoblastic metastases.18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%).ConclusionsThis study shows that18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions.18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy.

Docetaxel Plus Prednisolone for the Treatment of Metastatic Hormone-refractory Prostate Cancer: A Multicenter Phase II Trial in Japan

BACKGROUND Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Western patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with prednisolone in Japanese patients with HRPC. METHODS Patients aged 50-74 years with measurable metastatic HRPC were included in this non-comparative Phase II study. Treatment consisted of docetaxel 70 mg/m(2) once every 3 weeks plus prednisolone 5 mg twice daily, for a maximum of 10 cycles. The primary endpoint was overall tumor response rate, assessed by Response Evaluation Criteria in Solid Tumors; secondary endpoints included prostate-specific antigen (PSA) response and toxicity. RESULTS A total of 43 patients were evaluable for efficacy and toxicity. The response rate was 44.2% (90% CI, 31.2-57.8%), with partial responses in 19/43 patients. The median duration of response was 19.3 weeks. PSA responses were recorded in 44.4% of patients (95% CI, 27.9-61.9%). The most common non-hematological adverse events (of any grade) possibly related to treatment were alopecia (88.4%), anorexia (65.1%) and fatigue (53.5%). Grade 3/4 leukopenia and neutropenia occurred in 81.4 and 93.0% of patients, respectively; however, the grade 3/4 rates of febrile neutropenia (16.3%) and infection without fever (14.0%) were lower. CONCLUSION The combination of docetaxel and prednisolone was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in Western patients.

Validation of Partin Tables and Development of a Preoperative Nomogram for Japanese Patients With Clinically Localized Prostate Cancer Using 2005 International Society of Urological Pathology Consensus on Gleason Grading: Data From the Clinicopathological Research Group for Localized Prostate Cancer

PURPOSE We validated the 2001 Partin tables and developed an original nomogram for Japanese patients using the 2005 International Society of Urological Pathology consensus on Gleason grading. MATERIALS AND METHODS Prostatectomy specimens from 1,188 Japanese men who underwent radical prostatectomy for clinically localized prostate cancer (cT1-2) between 1997 and 2005 were analyzed. Polychotomous logistic regression analysis was used to construct a nomogram to predict final pathological stage (organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement) from 3 variables, including serum prostate specific antigen, clinical stage and biopsy Gleason score. The area under the ROC curve was used to compare the new nomogram with the Partin tables. RESULTS Preoperative serum prostate specific antigen and biopsy Gleason score were higher in the Japanese cohort than in the Partin cohort. The distribution of clinical and final pathological stages was similar in the 2 cohorts. The AUC for predicting organ confined disease was 0.699 and 0.717 for data applied to the Partin tables and to the new nomogram, respectively. The AUC for predicting lymph node involvement was 0.793 and 0.863, respectively. CONCLUSIONS To our knowledge this is the first preoperative nomogram developed for clinically localized prostate cancer in Japanese patients. Although the new nomogram predicted the pathological stage of prostate cancer in Japanese patients more accurately than the Partin tables, it did not satisfactorily predict organ confined disease. However, other predictive variables, such as more detailed pathological features of biopsy specimens or magnetic resonance imaging, may further improve prediction accuracy.

Quantitative MRI findings and cognitive impairment among community dwelling elderly subjects

Objectives: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. Methods: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. Results: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123–2.208), cerebral atrophy (OR 0.761, 95%CI 0.587–0.987), and lower education (OR 0.682, 95%CI 0.544–0.855) for subjects with a cognitive impairment. Conclusions: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia.

An analysis of the physiological FDG uptake pattern in the stomach

The purpose of this study was to clarify the normal gastric FDG uptake pattern to provide basic information to make an accurate diagnosis of gastric lesions by FDG PET.We examined 22 cases, including 9 of malignant lymphoma, 8 of lung cancer, 2 of esophageal cancer, and 3 of other malignancies. No gastric lesions were observed in any of the 22 cases on upper gastrointestinal examinations using either barium meal or endoscopic techniques. The intervals between FDG PET and the gastrointestinal examination were within one week in all cases. The stomach regions were classified into the following three areas: U (upper)-area, M (middle)-area, and L (lower)-area. The degree of FDG uptake in these three gastric regions was qualitatively evaluated by visual grading into 4 degrees, and then a semiquantitative evaluation was carried out using the standardized uptake value (SUV).Based on a visual grading evaluation, the mean FDG uptake score in the U-, M-, and L-areas was 1.14 ± 0.96, 0.82 ± 0.96, and 0.36 ± 0.49 (mean ± S.D.), respectively. The FDG uptake scores obtained in the three areas were significantly different (Friedman test, p < 0.05). Furthermore, the rank order of the FDG uptake score in each case (U ≥ M ≥ L) was found to be statistically significant (Cochran-Armitage trend test, p < 0.05). The mean SUVs of 11 cases in the three areas were 2.38 ± 1.03, 1.91 ± 0.71, and 1.34 ± 0.44 (mean ± S.D.), respectively. The SUV in the U-area was significantly higher than that in the L-area (Friedman test, p < 0.05). A significant difference in FDG uptake was observed among the three gastric areas, and the FDG uptake extent in all cases was U > M > L. In conclusion, the physiological gastric FDG uptake was significantly higher at the oral end. A stronger gastric FDG uptake at the anal end may therefore be suggestive of a pathological uptake.

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer.

Study Type – Therapy (RCT)

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer

We investigated whether a new marker of bone turnover, pyridinoline cross‐linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis.

Updated Japanese Urological Association Guidelines on prostate-specific antigen-based screening for prostate cancer in 2010

The exposure rate of screening for prostate cancer using prostate‐specific antigen (PSA) in Japan is still very low compared with that in the USA or western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8‐fold higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death. PSA screening, which can reduce the risk of death as a result of prostate cancer, should be offered to all men at risk of developing prostate cancer with fact sheets showing updated benefits and drawbacks of screening for prostate cancer.