Background/Aims: The Lyon Consensus defined parameters based on upper endoscopy and 24-hour combined multichannel intraluminal impedancepH (MII-pH), that conclusively establish the presence of gastroesophageal reflux disease (GERD). However, the true role of upper endoscopy and MII-pH to evaluate patients with extraesophageal symptoms (EES) has not been well established. Hypopharyngeal MII (HMII), which directly measures laryngopharyngeal reflux (LPR) events, has been utilized to evaluate patients with EES suggestive of LPR. Methods: This was a retrospective study involving patients with EES for > 12 weeks despite proton pump inhibitor therapy, and had no endoscopic confirmatory evidence for GERD and negative MII-pH. All patients were subsequently referred for further evaluation of EES with “unknown” etiology and underwent laryngoscopy and HMII. Based on HMII, abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (reflux 2 cm distal to the upper esophageal sphincter) > 4/day. Patients with APE were offered antireflux surgery (ARS) and the outcome of ARS was objectively assessed using Reflux Symptom Index. Results: Of 21 patients with EES which was thought to be GERD-unrelated based on endoscopy and MII-pH, 17 patients (81%) had APE. Eight patients with APE who had undergone ARS had significant symptomatic improvement in the Reflux Symptom Index score (19.6 ± 4.9 pre-ARS to 5.8 ± 1.4 post-ARS, P = 0.008). Conclusions A conventional diagnostic approach using endoscopy and MII-pH may not be sufficient to evaluate patients with EES suggestive of LPR. HMII is essential to evaluate patients with EES, and APE could be a reliable indicator for successful treatment outcomes.

Objective: BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. Methods: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (gBRCA1m), germline BRCA2 mutation (gBRCA2 m) and germline BRCA wild-type (gBRCAwt) were found in 185, 42 and 241 OC patients, respectively. Results: The average age at diagnosis of OC in gBRCA1m and gBRCA2 m was 51.3 and 58.3 years, respectively, and the difference from gBRCAwt (53.8 years) was significant. The gBRCA2 m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1, and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2 . The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. Conclusion There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed.

Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

Spinal cord injury (SCI) is a main concern in patients who undergo thoracic endovascular therapy (TEVAR), because the blood flow of the vertebro-basilar artery may be reduced due to the left subclavian artery (LSA) occlusion. If the left vertebral artery originates directly from the aorta, which is called the isolated left vertebral artery (ILVA), a technical consideration for strategies regarding blood perfusion of the ILVA during TEVARs is required. We hereby aim to report three patients (No.1, No.2, and No.3) who underwent an ILVA translocation and TEVAR with Zone 2 landing for aortic dissection. The diameter of the ILVA was 4.2, 2.3, and 2.2 mm, respectively, and the right vertebral artery (RVA) was dominant in all cases. In Patient No.1 and No.2 (ILVA diameter: 4.2 and 2.3 mm, respectively), the ILVA was anastomosed directly to the left common carotid artery. In Patient No.2, the translocated ILVA was occluded resulting in SCI, but the SCI improved when blood pressure was augmented. In Patient No.3 (ILVA diameter: 2.2 mm), the saphenous vein graft was interposed between the ILVA and the bypass artery because the ILVA diameter was small, but postoperatively, the ILVA remained patent, and no paraplegia was observed. The occlusion of ILVA could cause SCI, even if the RVA is larger than the LVA. Reconstruction of the ILVA is a critical procedure to prevent postoperative SCIs in patients undergoing TEVARs.

Background/Aims: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children. Methods: This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data. Results: A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn’s disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturingon-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01). Conclusions Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.

BACKGROUND/AIMS: Tacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis.METHODS: We retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged < 17 years treated with tacrolimus between 2000 and 2012. Patients’ characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score < 10; treatment response was defined as a PUCAI score reduction of ≥ 20 points compared with baseline.RESULTS: Patients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11–15] years). Thirty-nine patients were steroid-dependent and 26 were steroidrefractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05–0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P< 0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy.CONCLUSIONS: Tacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children.
Adult ; Asian Continental Ancestry Group ; Biological Factors ; Child ; Colectomy ; Colitis ; Colitis, Ulcerative ; Female ; Humans ; Immunologic Factors ; Japan ; Prednisolone ; Remission Induction ; Retrospective Studies ; Tacrolimus ; Ulcer

We describe a case of meningeal carcinomatosis of the internal auditory meatus presenting as sudden deafness accompanied by dizziness. A 54-year-old woman complained of acute right-side hearing loss in October 2014. The pure tone audiometry test revealed right-side hearing loss of 47.5 dB. She was treated with oral steroids. Her hearing as well as her symptoms of dizziness worsened and she was admitted for further examination. Her right and left-side hearing had worsened to 105.0 dB and 47.5 dB, respectively. A magnetic resonance imaging scan of the head revealed bilateral enhancement of the internal auditory canal and multiple brain metastases. The chest radiograph revealed a mass in the left lung. Adenocarcinoma of the lung was diagnosed. Lumbar puncture yielded no evidence of carcinoma cells in the cerebrospinal fluid, but an increased number of lymphocytes was confirmed. A diagnosis of multiple brain metastases and leptomeningeal metastasis from the adenocarcinoma of the lung was considered. Whole-brain radiation therapy (30 Gr/10 fractions) was administered. Progressive bilateral hearing loss is a rare first manifestation of meningeal carcinomatosis. It is quite important to consider the possibility of this condition when patients present with sudden deafness.
Adenocarcinoma ; Audiometry ; Brain ; Cerebrospinal Fluid ; Diagnosis ; Dizziness ; Ear, Inner ; Female ; Head ; Hearing ; Hearing Loss ; Hearing Loss, Bilateral ; Hearing Loss, Sudden ; Humans ; Lung ; Lymphocytes ; Magnetic Resonance Imaging ; Meningeal Carcinomatosis ; Middle Aged ; Neoplasm Metastasis ; Radiography, Thoracic ; Spinal Puncture ; Steroids ; Temporal Bone

PURPOSE: To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS. MATERIALS AND METHODS: The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment. RESULTS: The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122). CONCLUSION: The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.
Adult ; Aged ; Aged, 80 and over ; Decompression, Surgical ; Female ; Humans ; Leg/*pathology ; Low Back Pain/epidemiology/etiology ; Male ; Middle Aged ; Pain/*epidemiology/*etiology ; Prospective Studies ; Questionnaires ; Spinal Stenosis/*complications/*physiopathology/surgery

PURPOSE: The pathological mechanism of lumbar spinal stenosis is reduced blood flow in nerve roots and degeneration of nerve roots. Exercise and prostaglandin E1 is used for patients with peripheral arterial disease to increase capillary flow around the main artery and improve symptoms; however, the ankle-brachial index (ABI), an estimation of blood flow in the main artery in the leg, does not change after treatment. Lumbar spinal nerve roots contain somatosensory, somatomotor, and unmyelinated autonomic nerves. Improved blood flow by medication with prostaglandin E1 and decompression surgery in these spinal nerve roots may improve the function of nerve fibers innervating muscle, capillary, and main vessels in the lower leg, resulting in an increased ABI. The purpose of the study was to examine whether these treatments can improve ABI. MATERIALS AND METHODS: One hundred and seven patients who received conservative treatment such as exercise and medication (n=56) or surgical treatment (n=51) were included. Low back pain and leg pain scores, walking distance, and ABI were measured before treatment and after 3 months of conservative treatment alone or surgical treatment followed by conservative treatment. RESULTS: Low back pain, leg pain, and walking distance significantly improved after both treatments (p<0.05). ABI significantly increased in each group (p<0.05). CONCLUSION: This is the first investigation of changes in ABI after treatment in patients with lumbar spinal stenosis. Improvement of the spinal nerve roots by medication and decompression surgery may improve the supply of blood flow to the lower leg in patients with lumbar spinal stenosis.
Adult ; Aged ; Aged, 80 and over ; Alprostadil/therapeutic use ; *Ankle Brachial Index ; Decompression, Surgical/methods ; Female ; Humans ; Low Back Pain/drug therapy/physiopathology/surgery/*therapy ; Lumbar Vertebrae/physiopathology/*surgery ; Male ; Middle Aged ; Pain/surgery ; Spinal Nerve Roots/physiopathology ; Spinal Stenosis/physiopathology/*surgery/*therapy ; Treatment Outcome

Background: Complementary medicine and alternative medicine have been included in the curricula of many medical schools and colleges; however, teaching methods have not been standardized. We gave lectures and practical instruction on acupuncture and moxibustion medicine to medical students during their clinical clerkship in anesthesiology. We used a questionnaire to evaluate the usefulness of small-group teaching.
Methods: The subjects were 93 fifth-year medical students doing clinical clerkships in anesthesiology. The clinical clerkship consists of small-group learning with 2 or 3 students per group. After a lecture and practical instruction on acupuncture and moxibustion were given, students were asked to fill out a questionnaire about their interest in and basic knowledge of acupuncture and moxibustion and whether they would like to master the technique.
Results: All 93 students answered the questionnaire （response rate, 100%）. After the small-group teaching, students became more interested in acupuncture and moxibustion and learned that the costs of treatment were covered by health insurance. Most students were interested mastering acupuncture and moxibustion in the future.
Discussion: Our results suggest that lectures and practical instruction during clinical clerkship are useful for getting medical students interested in acupuncture and moxibustion medicine.