Electroneurography Values Based on Degree of Facial Muscle Contraction Response to Electroacupuncture in Patients with Peripheral Facial Nerve Palsy: A Retrospective Study.

Objective: Japanese acupuncture practice cannot easily predict the prognosis of patients with peripheral facial palsy. Electroneurography (ENoG) predicts prognosis in patients with peripheral facial palsy; however, the difference between ENoG values and degree of facial muscle contraction response (FMCR) to electroacupuncture stimulation (ES) targeting the affected facial nerve is unexplored. Therefore, an exploratory evaluation of the differences in ENoG values was conducted across the degrees of FMCR induced by ES targeting the affected facial nerve in patients with peripheral facial nerve palsy. Methods: In total, 90 patients with peripheral facial nerve palsy were selected who underwent acupuncture treatment at the Department of Oriental Medicine, Saitama Medical University Hospital, between January 2005 and December 2014. The FMCR degree and ENoG values were assessed through patients' medical records. The patients were divided into excellent, moderate, and noresponse groups (65, 16, and 9 patients, respectively) according to the FMCR degree. The differences in ENoG values were analyzed among the groups. Results: The ENoG values were 26.6% (10.4%-55.9%), 2.45% (0.35%-8.80%), and 2.00% (0.00%-5.10%) for the excellent, moderate, and no-response groups, respectively. These values significantly differed between the excellent group and the no-response (P < 0.01) and moderate (P < 0.01) groups. Conclusion: The ENoG values varied according to degree of FMCR induced by ES targeting the facial nerve in patients with peripheral facial nerve palsy. This might allow to predict the prognosis based on the ES-induced FMCR.

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

PURPOSE: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. METHODS: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. RESULTS: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). CONCLUSIONS: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

Histopathological evaluation of the effectiveness of oral Eppikajutsuto treatment for lymphatic malformation.

BACKGROUND: Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs. METHODS: LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels. RESULTS: Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations. CONCLUSION: TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.

Relationship of daily hot water bathing at home and hot water spa bathing with underlying diseases in middle-aged and elderly ambulatory patients: A Japanese multicenter cross-sectional study.

The purpose of this study was to clarify the relationship of daily hot water bathing at home (DHW) and hot water spa bathing (HSPA) with the number of underlying diseases in middle-aged and elderly ambulatory patients. We defined the number of underlying diseases as the main outcome and dependent (criterion) variable. The frequency and time of DHW and the frequency of HSPA were set as explanatory variables. Multiple logistic regression analysis was performed for each frequency and time, adjusted age and sex. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Among the 1261 patients who participated, there was no significant difference in age between males (n = 508, 72.8 ± 6.8 years) and females (n = 753, 73.5 ± 6.9 years). There was also no significant age difference between males (number of diseases: 2.7 ± 2.0 pts.) and females (number of diseases: 2.7 ± 2.1 pts.) in the occurrence of underlying diseases. Frequency and time of DHW were not associated with the occurrence of underlying diseases. However, compared with participants who utilized hot water spa at least once a week, the occurrence of underlying diseases was significantly associated with bathing frequency: one to three times per month (OR 2.72, 95% CI 1.63-4.52); twice or five times a year (OR 1.92, 95% CI 1.25-2.94). In conclusion, lower frequency of HSPA was significantly associated with increased risk of the occurrence of underlying diseases in middle-aged and elderly ambulatory patients. However, the relationship between proactive use of hot water spa and patients' mental and physical support should be clarified by well-designed cohort studies. The present study was registered as UMIN000033018 by the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) in Japan (refer: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037643).

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

[The practical use of acupuncture and moxibustion treatment cooperated with neurological practice].

The greatest number of patients in our department are those referred from the Department of Neurology. These patients usually present symptoms or conditions such as peripheral facial paralysis, primary headache, or cerebrovascular disorders; acupuncture and moxibustion treatment have resulted in an overall favorable effect. Regarding the effect of acupuncture and moxibustion treatment on the prevention of migraine attacks, a two-month course of acupuncture has been shown to decrease the number of days with a slight or moderate headache. Furthermore, we have seen a relation between the alleviation of headache and that of muscular tenderness in the neck-shoulder region and masticatory muscles. The results of Arterial Spin-Labeling MRI, by which we determine changes in cerebral blood flow before and after acupuncture stimulation in patients with migraine, have revealed that acupuncture stimulation induces an increase of blood flow in the thalamus and hypothalamus, opercular part, cingulate gyrus, and islet. This differs from the response obtained in healthy individuals. It has been shown that acupuncture and moxibustion for tension headache is highly effective and the action mechanism of acupuncture and moxibustion is associated with relaxation of masticatory muscles hypertonicity in the neck-shoulder region and normalization of circulation dynamics, contributing thereby to the alleviation of headache. Moreover, the automatic nervous system has been found to be related to such analgesic mechanism. Based on our experience, we consider that traditional medicine based on acupuncture and moxibustion is highly effective in patients with neurological symptoms.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

BACKGROUND: The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. PATIENTS AND METHODS: Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. RESULTS: Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. CONCLUSION: Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Effectiveness of intraperitoneal hyperthermo-chemotherapy for malignant peritoneal mesothelioma and estimation of its effect by repeated FDG-PET: a case report.

Malignant peritoneal mesothelioma is a rare neoplasm derived from the peritoneum of the abdominal cavity. Here, we report on a case of malignant peritoneal mesothelioma that expanded aggressively after initial surgery, followed by successful treatment with cytoreductive surgery, intra-abdominal hyperthermo-chemotherapy, to allow the patient to perform daily activities with reduced symptoms. The therapeutic effects were monitored by FDG-PET/CT. The patient, a 55-year-old female, was referred to our hospital with a diagnosis of pelvic tumor. Laparotomy and cytoreductive surgery revealed the diagnosis of malignant mesothelioma. The tumor progressed rapidly in the abdominal cavity, so cytoreduction and intra-abdominal hyperthermo-chemotherapy were performed as strong local therapies. In addition, monthly hyperthermo-chemotherapy was performed. The patient lived for 21 months after the first surgery. Severe bowel obstruction and malignant ascites did not appear. Cancerous pain was controllable throughout this portion of her life. In conclusion, we experienced a case of malignant peritoneal mesothelioma and treated it with hyperthermo-chemotherapy. This treatment helped the patient to maintain daily activities throughout the remainder of her life. Thus, hyperthermo-chemotherapy can be considered an option in the treatment of malignant peritoneal mesothelioma.

Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects.

To verify the relationship between oxidative stress and DNA methylation in the young brain, dichlorodiphenyltrichloroethane (DDT) was administered by gavage to male young rats at doses of 0, 0.006, 0.06, 0.6, 6, and 60 mg/kg/day for a period of 4 weeks. The most conspicuous decrease in the lipid peroxidation level was observed in the 0.06 mg/kg/day group compared with controls. Microarray analysis of brain samples from the control and 0.06 mg/kg/day groups revealed that the expression of 40 genes was changed in the hypothalamus, whereas mRNA expression was unaltered in the hippocampus. This result suggests that the hypothalamus is more susceptible to low-level oxidative stress at the young period. We further examined this possibility by selecting 10 genes from the hypothalamic microarray data. RT-PCR analysis revealed that expression of 7 of these 10 genes was significantly changed in the 0.06 mg/kg/day group, compared with controls. Furthermore, RT-PCR analysis showed that mRNA expressions of Dnmt1, Hsp90 and Hsp70 in the hypothalamus were significantly lower in the 0.06 mg/kg/day group than in controls. Methylated DNA-PCR analysis in the hypothalamus revealed that 6 CpG islands were significantly hypomethylated compared with controls. Thus, we speculate that the DNA methylation machinery malfunctions under low levels of oxidative stress, thereby leading to incomplete methylation of specific gene regions. Our data indicate that a low level of oxidative stress appears to correlate positively with transcriptional down-regulation and hypomethylation, but the precise mechanisms underlying these processes are unclear.

Hepatic arterial infusion combined with oral UFT/UZEL systemic chemotherapy for unresectable liver metastasis of colorectal cancer.

BACKGROUND/AIMS: Hepatic arterial infusion (HAI) chemotherapy has a number of limitations, including a low rate of complete response and frequent extrahepatic recurrence, in colorectal cancer (CRC) patients with unresectable hepatic metastases. A clinical trial was planned to assess the safety and efficacy of combination chemotherapy of HAI and oral administration of UFT and leucovorin (UZEL) in CRC patients with unresectable liver metastases. METHODOLOGY: Sixteen CRC patients with unresectable liver metastases were treated with concurrent HAI and systemic oral UFT/UZEL. Eligible patients were previously untreated (except for adjuvant therapy) CRC patients with unresectable liver metastases, with WHO performance statuses of 0 to 2. On an outpatient basis, the patients received a treatment regimen consisting of 5-fluorouracil at 1000 mg/m2 and l-Leucovorin at 50 mg/m2 for 5 hours on days 1, 8, 15, and 22 by hepatic arterial infusion plus oral UFT (300 mg/m2) and UZEL (75 mg/body) on days 2-7, 9-14, and 23-28 followed by withdrawal for one week. The cycles were repeated every 5 weeks until disease progression. RESULTS: A total of 103 cycles of HAI with the UFT/UZEL regimen were administered (median, 5 cycles; range, 6 to 9 cycles). The response rate was 87.5% (14 partial responses and 2 stable diseases). The median progression-free survival rate was 9.2 months, and the median survival time was 22 months. No treatment-related grade 3 or 4 adverse events were observed. CONCLUSIONS: This novel locoregional HAI with an oral UFT/UZEL systemic chemotherapeutic regimen is feasible in an outpatient setting and should be considered as first-line chemotherapy for CRC patients with unresectable liver metastases.

The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer.

PURPOSE: The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated. MATERIALS AND METHODS: Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day) and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation. RESULTS: Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions. CONCLUSIONS: These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.