Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study.

Objective Chronic fatigue syndrome (CFS) is a complex disorder, with no consensus on therapeutic options. However, Waon therapy has been reported to be an effective treatment. The purpose of this study was to evaluate changes in the cerebral blood flow (CBF) before and after Waon therapy in CFS patients and to investigate the correlation between such changes and the therapeutic efficacy of Waon therapy. Methods Eleven patients (2 men and 9 women, mean age 27 years old) diagnosed with CFS participated in the study. The disease duration was 8-129 months, and the performance status was 5-8 (on a scale of 0-9). All patients underwent CBF scintigraphy using brain single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD) before and after Waon therapy. CBF changes after Waon therapy were evaluated using a statistical analysis of imaging data, which was performed with a statistical parametric mapping software program (SPM5). Results Waon therapy reduced symptoms in all 11 patients. We also observed an increase in the CBF within the prefrontal region, orbitofrontal region, and right temporal lobe. These results indicated that an improvement in clinical symptoms was linked to an increase in the CBF. Conclusion The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients and that Waon therapy improved the cerebral function and symptoms in CFS patients by increasing the regional CBF. To our knowledge, this is the first report to clarify the CBF changes in CFS patients before and after Waon therapy.

Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy.

BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy. METHODS: We monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy. RESULTS: A preoperative increase of the serum level of sIL-2R was correlated with a higher preoperative serum level of programmed cell death 1 (PD-1)-ligand 1 (PD-L1), increased expression of phosphorylated Akt by the primary tumor, and a worse response to IFN-alpha/sequential VEGF-targeting therapy, as well as being an independent prognostic factor for a shorter overall survival time by multivariate analysis. Over time, the serum sIL-2R level largely reflected the tumor response to therapy. CONCLUSIONS: Monitoring the serum level of sIL-2R may help to predict the biological behavior of ccRCC, its response to IFN-alpha/sequential VEGF-targeting therapy, and the prognosis.

Higher preoperative serum levels of PD-L1 and B7-H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF-targeted therapy and unfavorable prognosis of renal cell carcinoma.

Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer. Although antivascular endothelial growth factor (VEGF) therapies achieve impressive responses in some patients, many tumors eventually develop resistance to such therapy. The B7 family molecules such as CTLA-4, PD-1, and PD-L1 are pivotal players in immune checkpoints that positively or negatively regulate various immune responses. Recently, immunotherapy based on blocking immune checkpoints with anti-CTLA4, anti-PD-1, or anti-PD-L1 antibodies has been proposed as a potential new approach to the treatment of metastatic RCC. Higher expression of PD-L1 and B7-H4 in the tumors is associated with a poor prognosis in RCCs, however, the clinical impact of serum levels of B7 family molecules has not been elucidated in patients with metastatic RCCs receiving VEGF-targeted agents. We assessed the preoperative serum levels of B7 family molecules, including CD80, CD86, PD-1, PD-L1, B7-H3, B7-H4, and CTLA-4, and CD28 in RCC patients, and determined their relations with various clinicopathological characteristics. Elevated preoperative serum levels of PD-L1 and B7-H4 were correlated with less differentiated tumors, higher invasive and metastatic potential, a worse response to anti-VEGF therapy, and shorter overall survival. These findings suggested that investigating preoperative serum levels of PD-L1 and B7-H4 might not only be useful to assess the biological aggressiveness of RCCs, but also to predict the efficacy of anti-VEGF therapy and the eventual prognosis, indicating the future design of clinical trials of therapies targeting immune checkpoint in advanced RCCs.

Abnormal 18F-FDG uptakes in the prostate due to two different conditions of urine reflux: a mimicker of prostate cancer.

A 69-year-old man with lung cancer underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for staging. FDG PET/CT showed high uptakes in the prostate gland with calcification, and magnetic resonance imaging was recommended to check the prostatic malignancy. T2-weighted images revealed midline cystic lesion at the base to midgland level and cystic lesion in right apical peripheral zone. We suspected urine reflux conditions. Voiding cystourethrography demonstrated those cystic lesions were communicating with the urethra. Therefore these lesions were diagnosed as the prostatic utricle cyst and the dilated prostatic duct in peripheral zone. We conclude that the urine reflux condition should be recognized as a prostate benign lesion with FDG accumulation.

Effects of Waon therapy on chronic fatigue syndrome: a pilot study.

OBJECTIVE: Chronic fatigue syndrome (CFS) is a disabling condition of unknown etiology, and no definitive therapy has been identified to date. We developed Waon therapy, a form of thermal therapy using a far-infrared dry sauna, and in this study herein examined its feasibility and safety in patients with CFS. METHODS: Ten consecutive inpatients with CFS stayed in a 60°C sauna for 15 minutes and then rested on a bed under a blanket for an additional 30 minutes outside the sauna room. The treatments were performed once a day, five days a week for four weeks. Perceived fatigue, the primary outcome measure, was evaluated using a numerical rating scale before, during (two weeks after the commencement of therapy) and after therapy. The pain level, evaluated using a numerical rating scale, mood, assessed using the Profile of Mood States questionnaire, and performance status, assessed using a scale developed for CFS patients were also examined before and after therapy. RESULTS: Perceived fatigue significantly decreased after therapy, although no significant reductions were observed during therapy. In addition, a negative mood, including anxiety, depression and fatigue, and the performance status significantly improved after therapy. However, the levels of pain and vigor did not change significantly. No patients reported any adverse effects during the therapy. CONCLUSION: These findings suggest that Waon therapy may be a useful and safe treatment for CFS.

Clinical significance of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma.

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P < 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P < 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P < 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P < 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R = 0.550, P < 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.

The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells.

BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.

Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.

BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. METHODS: Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). RESULTS: Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report.

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. METHODS: We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. RESULTS: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. CONCLUSION: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration-resistant prostate cancer: a prospective analysis of consecutive cases.

INTRODUCTION/BACKGROUND: Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes. PATIENTS AND METHODS: Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively. RESULTS: A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities. CONCLUSION: Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.

Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma.

BACKGROUND: The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. METHODS: To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. RESULTS: Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. CONCLUSIONS: These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.

Prolonged post-hyperventilation apnea in two young adults with hyperventilation syndrome.

BACKGROUND: The prognosis of hyperventilation syndrome (HVS) is generally good. However, it is important to proceed with care when treating HVS because cases of death following hyperventilation have been reported. This paper was done to demonstrate the clinical risk of post-hyperventilation apnea (PHA) in patients with HVS. CASE PRESENTATION: We treated two patients with HVS who suffered from PHA. The first, a 21-year-old woman, had a maximum duration of PHA of about 3.5 minutes and an oxygen saturation (SpO2) level of 60%. The second patient, a 22-year-old woman, had a maximum duration of PHA of about 3 minutes and an SpO2 level of 66%. Both patients had loss of consciousness and cyanosis. Because there is no widely accepted regimen for treating patients with prolonged PHA related to HVS, we administered artificial ventilation to both patients using a bag mask and both recovered without any after effects. CONCLUSION: These cases show that some patients with HVS develop prolonged PHA or severe hypoxia, which has been shown to lead to death in some cases. Proper treatment must be given to patients with HVS who develop PHA to protect against this possibility. If prolonged PHA or severe hypoxemia arises, respiratory assistance using a bag mask must be done immediately.

Renal metanephric adenoma mimicking papillary renal cell carcinoma on computed tomography: a case report.

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.

Effects of Silodosin on Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia: Evaluation by Frequency/Volume Chart.

OBJECTIVES: To prospectively evaluate the efficacy of silodosin, a new α1A -adrenoceptor selective antagonist, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) on the basis of a frequency/volume chart. METHODS: Forty male patients (71.1 ± 6.6 years old) with LUTS/BPH were treated with silodosin (4 mg twice daily). The effects of the drug were assessed by changes in International Prostate Symptom Score, uroflowmetry, and frequency/volume chart at 1 and 3 months after therapy. RESULTS: The mean total International Prostate Symptom Score, the mean total storage and voiding scores and the mean quality of life score decreased significantly at 1 and 3 months after therapy (all P < 0.01). Average and maximum flow rates increased significantly, and postvoid residual volume decreased significantly after 1 and 3 months (all P < 0.05). The frequency/volume chart showed that daytime frequency in those who initially voided over eight times/day (n = 12) decreased significantly (P = 0.0391) after 1 month, and nighttime frequency in those who initially voided over two times (n = 16) tended to decrease (P = 0.0833) after 3 months. Mean voided volume in those who initially voided less than 250 mL (n = 31) increased significantly after 1 and 3 months (P = 0.0446 and P = 0.0138, respectively), and maximum voided volume in those who initially voided less than 300 mL (n = 18) tended to increase (P = 0.0833) after 1 month. CONCLUSION: Silodosin appears to be effective for both storage and voiding symptoms by increasing bladder capacity in patients with LUTS/BPH.

Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.

OBJECTIVES: To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. METHODS: Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3-10 microM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. RESULTS: In detrusor without urothelium, maximum contraction (E(max)) decreased after administration of fasudil at 3 or 10 micromol/L (both P < 0.01), or 30 micromol/L (72.5 + or - 7.43%, 58.4 + or - 8.04% and 68.4 + or - 9.6%, respectively, of the first curve). In detrusor with urothelium, E(max) decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 micromol/L of fasudil (84.9 + or - 6.7%, 67.9 + or - 5.2% and 35.2 + or - 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 micromol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 micromol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 micromol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1-50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 micromol/L). CONCLUSIONS: Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.

Is Stat3 and/or p53 mRNA expression a prognostic marker for renal cell carcinoma?

Signal transducer and activator of transcription (Stat) 3 and p53 integrate upstream signals, and are positive and negative regulators of tumor cell proliferation, respectively. Stat3 and p53 also negatively regulate each other. However, their roles remain elusive in patients with renal cell carcinoma (RCC). We quantified Stat3 and p53 mRNA expression in paired tumor and non-tumor surgical samples from 47 Japanese patients with RCC by the real-time reverse transcription polymerase chain reaction (RT-PCR) technique. Absolute levels of Stat3 and p53 mRNA were lower in tumor tissues compared with non-tumor tissues (P < 0.0001). The absolute levels of Stat3 and p53 mRNA in RCC tissue were not correlated with tumor histology, stage, or metastatic behavior. Kaplan-Meier analysis showed that a high level of Stat3 or p53 mRNA expression was associated with shorter overall survival compared to low expression (P = 0.254 and P = 0.066, respectively). In addition, the tumor tissue levels of Stat3 and p53 mRNA expression were correlated with each other (r(2) = 0.697, P < 0.01). These findings suggest that Stat3 and p53 are cooperatively involved in the development of RCC, but assessment of their mRNA expression may not be useful for predicting the prognosis of patients with RCC.

Efficacy of Waon therapy for fibromyalgia.

OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by widespread pain with tenderness in specific areas. We examined the applicability of Waon therapy (soothing warmth therapy) as a new method of pain treatment in patients with FMS. METHODS: Thirteen female FMS patients (mean age, 45.2+/-15.5 years old; range, 25-75) who fulfilled the criteria of the American College of Rheumatology participated in this study. Patients received Waon therapy once per day for 2 or 5 days/week. The patients were placed in the supine or sitting position in a far infrared-ray dry sauna maintained at an even temperature of 60 degrees C for 15 minutes, and then transferred to a room maintained at 26-27 degrees C where they were covered with a blanket from the neck down to keep them warm for 30 minutes. Reductions in subjective pain and symptoms were determined using the pain visual analog scale (VAS) and fibromyalgia impact questionnaire (FIQ). RESULTS: All patients experienced a significant reduction in pain by about half after the first session of Waon therapy (11-70%), and the effect of Waon therapy became stable (20-78%) after 10 treatments. Pain VAS and FIQ symptom scores were significantly (p<0.01) decreased after Waon therapy and remained low throughout the observation period. CONCLUSION: Waon therapy is effective for the treatment of fibromyalgia syndrome.

Possible role of the RhoC/ROCK pathway in progression of clear cell renal cell carcinoma.

To clarify the role of the Rho small GTP-binding protein (Rho) and its major downstream target, ROCK (Rho-associated serine-threonine protein kinase), in progression of renal cell carcinoma (RCC), we examined mRNA expression for Rho and ROCK genes in surgical specimen of RCC tissues from 78 Japanese patients and in the corresponding non-tumor tissues originating from the same patient using a real-time reverse transcription polymerase chain reaction (RT-PCR). Expression of mRNA for RhoA did not differ between tumor and non-tumor tissues. RhoB mRNA expression was higher in the tumor (P < 0.05), but expression was not associated with tumor grade, stage, or prognosis. However, degree of RhoC and ROCK mRNA expression was related to tumor grade (P < 0.05) and stage (P < 0.0001). A positive relationship was seen between expression of mRNA for RhoC and that for ROCK in tumor tissues (P < 0.0001). Kaplan-Meier plots showed high RhoC and ROCK mRNA expression to be negatively associated with overall survival (P < 0.0001). Multivariate analysis showed mRNA expression of RhoC and ROCK to be independent poor prognostic factors concerning overall survival. Our findings implicate the RhoC/ROCK pathway in carcinogenesis and progression of RCC, indicating that RhoC/ROCK may be a useful prognostic marker and a possible molecular target for treatment of the disease.

[A new treatment: thermal therapy for chronic fatigue syndrome].

Thermal therapy using far-infrared ray dry sauna was performed for patients with chronic fatigue syndrome (CFS). Symptoms such as fatigue, pain, and low-grade fever were dramatically improved on two patients. And prednisolone administration was discontinued and became socially rehabilitated 6 months after discharge. On other 11 patients with CFS, physical symptoms such as fatigue and pain improved, too. Furthermore, we reported that repeated thermal therapy had relaxation effect and diminishes appetite loss and subjective complaints in mildly depressed patients. These results suggest that repeated thermal therapy may be a promising method for the treatment of CFS.

Intra- and extra-familial adverse childhood experiences and a history of childhood psychosomatic disorders among Japanese university students.

BACKGROUND: Japan has been witnessing a considerable increase in the number of children with psychosomatic disorders. The purpose of this study is to examine the relationship between the risk of psychosomatic disorder in adolescents and intra- and extra-familial adverse childhood experiences (ACEs). METHODS: A retrospective cohort study of 1592 Japanese university students (52% male, mean age 19.9 years) who completed a survey about intra- and extra-familial ACEs and the incidence of childhood psychosomatic disorders. Intra-familial ACEs included domestic violence, physical violence, emotional abuse, illness in household, parental divorce, no parental affection, and dysfunctional family. Extra-familial ACEs included physical violence or negative recognition by teachers, being bullied in elementary or junior high school, or sexual violence. RESULTS: The frequency of psychosomatic disorders among the respondents was 14.8%. Among the 7 intra-familial ACEs, emotional abuse (relative risk, RR = 1.9) and illness in household (RR = 1.7) increased the risk of psychosomatic disorders. Estimates of the relative risk for the 5 extra-familial ACEs were statistically significant and ranged from 1.5 for being bullied in elementary school or physical violence from teachers to 2.4. Students who had 3 or more intra-familial ACEs and 2 or more extra-familial ACEs had a 3.0 relative risk for psychosomatic disorder. CONCLUSION: These results suggest that intra- and extra-familial ACEs are associated with the development of psychosomatic disorders. Therefore, sufficient evaluation of ACEs should be performed in adolescent patients with psychosomatic disorder.