Nagoya Journal of Medical Science

This randomized, observer-blinded prospective study aimed to compare the postoperative analgesic effects of ultrasound-guided rectus sheath block with those of local anesthetic infiltration of the surgical field in children undergoing inguinal hernia repair. Children aged 2 to 14 years, scheduled for elective single-incision laparoscopic percutaneous extraperitoneal closure, were randomly allocated to receive ultrasound-guided rectus sheath block (group R) or local anesthetic infiltration of the surgical field (group L). In group R, 0.5 ml/kg of 0.25% ropivacaine (per side) was administered after intubation. In group L, 0.4 ml/kg of 0.5% ropivacaine was administered after peritoneal closure. Postoperative pain was assessed using the Face Scale and Face, Legs, Activity, Cry, Consolability scale at various time points, including the primary endpoint of 2 h after leaving the operation room. Additional analgesic drugs were used according to the Face Scale scores. Patient characteristics, the amount of additional drugs, and complication rate were evaluated in both groups. The patient and surgical characteristics were comparable between groups. The Face Scale and Face, Legs, Activity, Cry, Consolability scale scores were not significantly different between group R (n = 38) and group L (n = 38) at 2 h after leaving the operation room. The amount of additional drugs administered at 2 h after leaving the operation room were also comparable between groups. Our findings suggest that the postoperative analgesic efficacy of ultrasound-guided rectus sheath block is not superior to that of local anesthetic infiltration of the surgical field for pediatric single-incision laparoscopic percutaneous extraperitoneal closure.

This study aimed to evaluate the treatment outcomes of patients who received high-dose-rate intracavitary brachytherapy (HDR-BT) using Iridium-192 with or without external beam radiotherapy as definitive treatment for recurrent cervical cancer after hysterectomy. Thirty-six patients with local recurrence after hysterectomy received radiotherapy including HDR-BT from 2005 to 2013. Overall survival, local control rate, and progression-free survival were estimated retrospectively via the Kaplan-Meier method. Late adverse events were also scored using the Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time was 38 (range, 7.4–101.3) months. The 3-year estimates of overall survival, local control rate, and progression-free survival were 100.0%, 82.8%, and 76.8%, respectively. Two patients (5.6%) had grade 2 lymphedema, but no other adverse events greater than grade 2 were reported. In conclusion, HDR-BT was an effective treatment modality for patients with cervical cancer recurrence in the vaginal stump.

Cilostazol is a phosphodiesterase III-inhibiting antiplatelet agent that is often used to prevent stroke and peripheral artery disease, and its administration has shown significant improvements for cognitive impairment. We investigate the potential of cilostazol for reducing or restoring cognitive decline during con-valescent rehabilitation in patients with non-cardioembolic ischemic stroke. The study sample included 371 consecutive patients with lacunar (n = 44) and atherothrombosis (n = 327) subtypes of non-cardioembolic ischemic stroke (224 men and 147 women; mean age, 72.9 ± 8.1 years) who were required for inpatient convalescent rehabilitation. Their medical records were retrospectively surveyed to identify those who had received cilostazol (n = 101). Patients were grouped based on cilostazol condition, and Functional Independence Measure (FIM) scores (total and motor or cognitive subtest scores) were assessed both at admission and discharge. The gain and efficiency in FIM cognitive scores from admission to discharge were significantly higher in patients who received cilostazol than those who did not (p = 0.047 and p = 0.035, respectively); we found no significant differences in other clinical factors or scores. Multiple linear regression analysis confirmed that cilostazol was a significant factor in FIM cognitive scores at discharge (β = 0.041, B = 0.682, p = 0.045); the two tested dosages were not significantly different (100 mg/day, n = 43; 200 mg/day, n = 58). Cilostazol can potentially improve cognitive function during convalescent rehabilitation of patients with non-cardioembolic ischemic stroke, although another research must be needed to confirm this potential.

Completion rate for specific health guidance (SHG) based on specific health checkup (SHC) status in Japan is very low. This study aimed to clarify factors affecting the rate using questionnaire survey, which was conducted by mail between December 2016 and January 2017 for insurers in the Tokai Region of Japan. The subjects were 69 insurers and the collection rate was 25.1%. The SHG participation rate was 26.3%, and the SHG completion rate was even lower (23.6%) than the participation rate. The rate was significantly lower in dependents than in insured persons. Multiple regression analysis with SHG completion rate as the dependent variable indicated that only “participation rate in SHG” was positively related to completion rate. With SHG participation rate as the dependent variable, however, having an insurer who “implemented SHG,” “provided a thorough explanation to the subscribers of the objectives and significance of SHC and SHG when the programs were begun,” and “provided health guidance to non-obese individuals” and SHC implementation rate were positively correlated with participation rate. Multiple regression analysis using completion rates for the two types of SHG, i.e., motivational and active support, as the dependent variables indicated that SHG participation rate was a positive factor for each type. Participation rate in each type was positively correlated to “ex-post assessment of the SHG,” and/or insured persons. The primary factor affecting SHG completion rates was the SHG participation rate. It is also important, however, that insurers encourage participation of subscribers, especially dependents, in SHG.

Stereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is associated with limited local control and neurotoxicity, while hypofractionated stereotactic radiotherapy (HFSRT) has emerged as a promising option. We retrospectively evaluated 61 patients with BM larger than 2 cm in the maximum diameter, who were treated with HFSRT (mainly 35 Gy/5 fractions) in our center between 2006–2016, focusing on the effect of BM size on outcomes. Eligible patients were divided according to the maximum BM diameter (group A [23 patients]: ≥3 cm, group B [22 patients]: <3 cm) to assess the relationship between tumor size and prognosis or safety. The primary outcome was the local control rate (LCR), and secondary outcomes were the response rate (RR), brain progression-free survival (BPFS), median survival time (MST), and radionecrosis (RN). Univariate and multivariate analyses for LCR were conducted using Cox’s proportional hazards model. In the 45 eligible patients (58 lesions) enrolled in this study, the RR was 86.4% with an overall LCR of 64.7% at 12 months (67.1% for group A and 61.5% for group B [p = 0.45]). The median BPFS and MST were 11.6 and 14.2 months, respectively. Univariate analyses revealed that female patients and gynecological cancer patients had poorer LCR, but they were not significantly independent prognostic factors (p = 0.06, 0.09, respectively). Two patients (4.4%) experienced RN that was detected more than 4 years after HFSRT. We conclude that HFSRT is safe for large BM but further studies are needed to determine optimal doses and fractions.

Concurrent chemoradiotherapy (CCRT) is a common treatment for advanced oral cancer, and its efficacy has been reported in many reviews. We have performed concurrent CCRT with intravenous cisplatin and docetaxel in patients with advanced oral cancer. The purpose of this report was to evaluate this treatment and to compare the outcome of this treatment with that of standard CCRT treatments for advanced head and neck cancer using intravenous administration.
The patients were treated for primary advanced oral squamous cell carcinoma in our department between February 2003 and November 2015. In all, 17 patients (14 men, 3 women) with stage III (2 patients) stage IVA (10 patients), and stage IVB (5 patients) oral cancer were treated. The patient ages ranged from 44 to 87 years (average age: 65.4 years). The follow-up duration ranged from 5 to 117 months (average follow-up duration: 41 months, median follow-up duration: 39 months). The primary cancer sites were the maxillary gingiva (7 cases), mandible gingiva (3 cases), buccal mucosa (3 cases), tongue (3 cases), and floor of the mouth (1 case). The 3-year and 5-year survival rates were 52.9% and 33.0%, respectively, and both the 3-year and 5-year locoregional control rates were 50.9% as determined by the Kaplan-Meier method. The response rate was 94% (CR: 8 cases: 47% and PR: 8 cases: 47%). The incidences of toxicity greater than grade 3 included dermatitis and stomatitis in 9 cases each (52.9%), anemia in 3 cases (18.7%) and liver dysfunction in 1 case (6.2%).
We found that the results of this therapy were equivalent to those of standard CCRT treatments for advanced head and neck cancer using intravenous administration, and the incidences of toxicity were lower than those of standard treatments. These findings suggested that this treatment is safe and useful for advanced oral cancer.

Eye problems are an adverse reaction sometimes found in chemotherapy. Although not life-threatening, they can reduce patients’ quality of life. The highest incidence of eye problems is reported for the combination anticancer drug S-1 (tegafur–gimeracil–oteracil), and methods to prevent or treat the eye problems caused by this drug are presently lacking. To determine early detection methods and treatment for adverse ocular reactions, we measured changes in tear volume and levels of tegafur (FT) and 5-fluorouracil (5-FU), an active metabolite of FT, in the tears of patients with long-term use of S-1. A total of 11 patients receiving S-1 monotherapy as adjuvant chemotherapy after gastric cancer surgery were included. Tear volume and FT and 5-FU levels in tears were measured by liquid chromatography with tandem mass spectrometry during a maximum of 8 treatment cycles (48 weeks). For analysis, patients were divided into two groups: “watering eyes” (n=6, complaints of watering eyes at least once during the treatment period) and “no watering eyes” (n=5, no complaints of watering eyes). Both groups exhibited increased FT and 5-FU levels in tears upon initiation of S-1 treatment, and levels rapidly decreased upon discontinuation. Our findings suggest a relationship between FT level in tears and tear volume in patients with long-term S-1 use. The symptom of watering eyes may thus be linked to FT level in tears.

Although the lower limit of normal (LLN) of FEV1/FVC detects at-risk patients for postoperative outcomes among Japanese chronic obstructive pulmonary disease (COPD) patients with resected lung cancer, there was a lack of a Japanese reference equation to calculate the LLN of FEV1/FVC. Renewed Japanese spirometric reference variables might enable us to verify clinical impact of the LLN of FEV1/FVC among the Japanese population. To evaluate the clinical impact of the LLN of FEV1/FVC by using this renewed reference, data were retrospectively analyzed from 609 newly diagnosed lung cancer patients who had undergone thoracic surgery between 2006 and 2011. The combined assessment of the 0.70 fixed ratio and the LLN of the FEV1/FVC ratio classified the 609 subjects into the COPD (214 subjects), non-COPD (337 subjects), and in-between (58 subjects) groups, respectively. All of the relative odds ratios (ORs) of postoperative outcomes for the comparison between the in-between and non-COPD groups did not show significant confidence intervals (CIs). On the other hand, the adjusted ORs of postoperative outcomes for the COPD group versus the non-COPD group were 2.840 (95% CI: 1.824–4.421) for prolonged oxygen therapy (POT), 1.836 (95% CI: 1.166–2.890) for prolonged postoperative stays, and 1.637 (95% CI: 1.007–2.663) for combined complications. Adjusted comparisons of POT between the in-between and COPD groups also showed a significant relative OR of 2.984 (95% CI: 1.447–6.153). A standardized assessment of the LLN of FEV1/FVC by a renewed Japanese spirometric reference provides risk stratification for postoperative outcomes in the population.

Pseudomonas aeruginosa is capable of biofilm formation. In this study, we investigated the effects of aqueous Tradescantia pallida extract on Pseudomonas aeruginosa growth and biofilm formation. Aqueous Tradescantia pallida extracts significantly inhibited both bacterial growth and biofilm formation. However, methanolic Tradescantia pallida extracts inhibited neither. Aqueous Tradescantia pallida extracts were deactivated by heating but were not deactivated by light exposure. The ingredients retained the inhibitory effect on the bacterial growth and biofilm formation after ultrafiltration of aqueous Tradescantia pallida extract. Furthermore, polyphenol-rich Tradescantia pallida extracts inhibited bacterial growth, thus, polyphenols are possible to be an active ingredient.
We observed the biofilm by scanning electron microscopy, and quantitative and qualitative differ-ences in the biofilm and cells morphology. Interestingly, the biofilm treated aqueous Tradescantia pallida extracts remained premature. We postulated that premature biofilm formation was due to the inhibition of swarming motility. Indeed, aqueous Tradescantia pallida extracts inhibited swarming motility. These results demonstrate that Peudomonas aeruginosa growth and biofilm formation are inhibited by aqueous Tradescantia pallida extracts.

This study aimed to understand the clinical state of locomotive syndrome (LS) in patients with rheumatoid arthritis (RA) and to validate the use of the 25-question Geriatric Locomotive Function Scale (GLFS-25) in patients with RA and compare it side-by-side with the Health Assessment Questionnaire-Disability Index (HAQ-DI). Subjects were 159 patients with RA (female, 112 (70.4%); mean age, 66.2 ± 12.0 years) who consecutively visited Yokkaichi Municipal Hospital between June and August 2017. Mean disease duration was 11.4 ± 9.3 years, mean HAQ-DI score was 0.5 ± 0.7 points, and mean GLFS-25 score was 17.8 ± 19.1 points. The correlation between GLFS-25 and HAQ-DI was analyzed using Spearman’s rank correlation coefficient. The cut-off point of GLFS-25 corresponding to HAQ-DI≤0.5, which represents functional remission in patients with RA, was calculated by ROC analysis. GLFS-25 and HAQ-DI were positively and strongly correlated (correlation coefficient=0.798). The cut-off point of GLFS-25 correspond-ing to HAQ-DI≤0.5 was 20 points (sensitivity, 81%; specificity, 90%). Thus, the cut-off point of GLFS-25 corresponding to functional remission is higher than that for developing LS (i.e., 16 points). Moreover, the proportion of patients with LS among those with HAQ-DI ≤0.5 was 17.9%. In conclusion, our findings suggest that some patients with RA in remission may have LS, as well as the need to consider appropriate interventions for such patients.

There has been growing interest in magnetic resonance imaging (MRI)-guided interventional procedures such as percutaneous needle biopsy. Although open MRI is preferable for MRI-guided procedures in terms of patient accessibility, its inferior imaging capability due to lower field strength is a substantial limitation. In this situation, the high-field (1.2T) open MRI has recently become available. This novel MRI system is expected to provide excellent image quality as well as good patient accessibility, potentially contributing to safe and accurate device manipulation. This trial is designed to investigate the feasibility of MRI-guided percutaneous needle biopsy with this system. Patients with lesions needing percutaneous needle biopsy for pathological diagnosis are included. The enrollment of ten patients is intended. The primary endpoint of this study is the feasibility of biopsy needle insertion under real-time MR-fluoroscopy guidance based on the presence of the notch of the biopsy needle within the target lesion. The secondary endpoints are adverse events, device failures, and success of specimen acquisition. Once the feasibility of MRI-guided biopsy with 1.2T open MRI is validated by this study, it may potentially encourage widespread use of MRI-guidance for biopsy procedures. Furthermore, it may lead to development of the other MRI-guided interventional procedures using this MRI system.

We investigated the otological aspects of Fabry disease (FD) in patients with normal hearing. Forty-one patients (21 men, 20 women) with bilaterally normal hearing were recruited, and their otological symptoms and hearing evaluations, which included pure tone audiometry (PTA) and distortion product otoacoustic emission (DPOAE), were investigated. Ten of the 21 male (47.6%) and eight of the 20 female (40.0%) patients had otological symptoms, of which tinnitus was the most frequent. Cardiac dysfunction was more frequently observed in female patients. The average thresholds on PTA were below 25 dB at all frequencies, but DPOAE amplitudes were significantly lower in female patients at some frequencies. Otological symptoms were frequently observed in patients with FD, despite their normal hearing levels on PTA. DPOAE might provide useful information regarding cochlear disturbances related to the disease.

Treatment of cancer patients undergoing chemotherapy with L-carnitine (LC) supplementation is becoming increasingly popular in the clinic. The present study aimed to examine the possible effects of polymorphisms in CPT1B and CPT2 (CPT1B G320D, S427C, c.282-18 C>T, and p.E531K, and CPT2V368I) on the plasma concentration of carnitine in humans. The subjects were the 218 participants of the Iga Cohort Study. Differences in plasma-free carnitine levels by genotype were examined. Genotyping was conducted by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). The plasma carnitine levels were significantly higher in males (P<0.001; Student’s t-test), and there was no significant difference in plasma carnitine levels between the age groups (P=0.202; ANOVA). One-way ANOVA revealed the plasma levels of carnitine were neither significantly different by CPT1B G320D, S427C, c.282-18 C>T, or p.E531K, nor by CPT2 V368I genotypes (P=0.133, P=0.538, P=0.636, P=0.509, and P=0.398, respectively). When analysis of covariance (ANCOVA) adjusted for age and sex was applied, the plasma levels of carnitine were not statistically significantly different according to these genotypes (P=0.299, P=0.715, P=0.980, P=0.851, and P=0.674, respectively). The present study did not identify any statistically significant differences in plasma carnitine levels between subjects with different CPT1 and CPT2 genotypes, suggesting that there may be no need to tailor treatments to patients’ genotypes when determining the dose/amount of LC to be administered to cancer patients undergoing palliative care.

Forest walking or Shinrin-yoku is a health promotion activity in Japan. Although some studies have reported the acute effects of walking a few hours in forested areas in reducing blood pressure level compared to other environments, studies investigating whether successive walking has long-term effects in lowering blood pressure levels or lowering prevalence of hypertension are rare. This study aimed to reconfirm the presence or absence of an association between the frequency of forest walking and prevalence of hypertension in a Japanese population. This J-MICC Daiko Study was conducted targeting residents in Nagoya City. A total of 5,109 participants (1,452 men and 3,657 women; age, mean ± standard deviation: 52.5 ± 10.3 years) were included in the analysis. Age-adjusted blood pressure level by frequency of forest walking was not significant. After adjusting for age and lifestyle, the adjusted odds ratios (aORs) of the most frequent group (n=88, 1.7%; once a week or more group) relative to the less than once a month group (n=4,558, 89.2%) for prevalence of hypertension were not also significant [0.80 (95% CI: 0.40–1.62) for men and 1.48 (95% CI: 0.73–3.00) for women]. This study reconfirmed that either lowering blood pressure level or lowering the prevalence of hypertension is not associated with frequency of forest walking, similar to the results of our previous J-MICC Shizuoka Study. Given that these two studies were cross-sectional studies, cohort studies investigating the causal relationship are required to evaluate the effect of frequent forest walking on the prevention of hypertension.

The survey involves examining the applications from 142 institutions that have consented to make available all certification applications from 2015 and 2016 to a research project for building a certification system for an ethics committee run by the Agency for Medical Research and Development. The number of certified institutions is 20 (14.1%). In the applications from uncertified institutions, there are cases in which requirements of ethics guidelines are unmet, and there is insufficient information provided on regulation and procedure.
An analysis of the committee members who can contribute as members of the general public (general public committee members) has indicated that the number of committee members who do not belong to an institution in which an ethics committee is instituted (external committee members) is 41 (95.7%) among the certified institutions and 224 (84.5%) among the uncertified institutions. The proportion of general public committee members drawn internally from institutions tends to be higher among uncertified institutions.
While a separate committee examined conflicts of interest in research in 19 certified institutions (95.0%), such conflicts were found in 41 uncertified institutions (33.9%) by the ethics committee.
The survey confirms that the challenge lies in increasing the number of external committee members and in further improving the system to manage conflicts of interest, and the education and training regime.

Despite the rapid progress of vascular neurosurgery with the development of microsurgical and endovascular techniques, the optimal strategy for surgical treatment of multiple cerebral aneurysms has not yet been developed. The indications for choosing one-stage or multi-stage surgery remain unsolved. This is a summary of the departmental routine reports at the Clinic of Neurosurgery, National Hospital of the Kyrgyz Republic. Subjects were 235 patients (124 males and 111 females) with ruptured multiple cerebral aneurysms admitted to the hospital. Their ages ranged from 18 to 72 years (average and standard deviation: 44.3 ± 9.7 years) and 48.1% of patients had 3 or more aneurysms. Among aneurysms that ruptured, 20.4% were a giant aneurysm (>25 mm) and 43.0% of patients had grade IV or V according to the Hunt-Hess Scale. Among 228 patients who were operated on, 147 were treated by single-stage surgery and 81 by multi-stage surgery. Microsurgical operations with clipping of the aneurysm neck were performed in 141 (61.8%) patients (97 single-stage and 44 multi-stage), while 40 (17.5%) patients (16 single-stage and 24 multi-stage) were operated using the endovascular technique. The number of palliative surgeries (trapping, ligation of the internal carotid artery, and reinforcement of the aneurysm wall) was significantly less (p=0.011) with multi-stage surgery (9 out of 81 cases, 11.1%) than with single-stage surgery (38 out of 147 cases, 25.9%). Among 600 aneurysms, 583 (97.2%) were treated by either single-stage surgery (n=296) or multi-stage surgery (n=287). There were no differences in prognosis at discharge between single-stage and multi-stage surgery.

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myelo-Fibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman’s disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients’ clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gastrointestinal stromal tumor. A 47-year-old man was diagnosed with recurrence of gastrointestinal stromal tumor adjacent to the prostate after abdominoperineal resection 10 years prior. With imatinib administration for 18 months, the local recurrence decreased in size but did not separate from the prostate. We performed urinary diversion with conventional total pelvic exenteration. Ileal conduit necrosis was suspected the following day and emergency surgery was performed. The serosa of the ileal conduit showed segmental necrosis extending about 10 cm from the orifice. The ureterointestinal anastomotic site was opposite the orifice and was not necrotic. We resected the necrotic ileum and reconstructed an ileal conduit. The patient was discharged without any symptoms 46 days after surgery for further adjustment to use of a urostomy.