Yamaguchi University Graduate School Research Articles

First person – Yuka Kobayashi

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Yuka Kobayashi is first author on ‘ Early manifestations and differential gene expression associated with photoreceptor degeneration in Prom1-deficient retina’, published in DMM. Yuka is assistant professor in the lab of Prof. Kazuhiro Kimura at Yamaguchi University Graduate School of Medicine, Ube, Japan, investigating ophthalmology.

Laparoscopic total biopsy for suspected gallbladder cancer: A case series.

Background and aimsImaging diagnosis of gallbladder cancer remains difficult to achieve preoperatively. We developed a novel approach based on laparoscopic whole‐layer cholecystectomy (LWLC) and laparoscopic gallbladder bed dissection (LGBD) for total biopsy, for ultimately determining the optimal treatment strategy for suspected gallbladder cancer detected on preoperative imaging. Here, we describe a case series of patients who underwent this procedure at our institution.MethodsWe retrospectively examined clinicopathological data of consecutive patients with suspected gallbladder carcinoma at Yamaguchi University Graduate School of Medicine from September 2016 to July 2018 on which a laparoscopic approach was used. Preoperative imaging findings suggestive of gallbladder cancer were defined as follows: elevated lesion >10 mm in diameter, increasing tumor size over time compared with the previous imaging, sessile lesion, irregular wall thickness lesion mimicking cancer, elevated lesion with dense enhancement, or positive results on fluorodeoxyglucose positron emission tomography. LWLC was performed for early‐stage or suspected malignant lesions without liver invasion, and LGBD was performed for lesions with an unclear border between the gallbladder and the liver. When postoperative pathological examination revealed the presence of gallbladder cancer invading into the subserosal layer, additional gallbladder bed resection and regional lymphadenectomy were considered. Patient characteristics, perioperative findings, pathological findings, and postoperative outcomes of patients who underwent LWLC or LGBD were reviewed retrospectively, and the short‐term outcomes of the laparoscopic approach were analyzed.ResultsFifteen consecutive patients were included in the study. The median age of the patients was 63 years (IQR 42‐76 years); 7 patients were males. We performed LWLC in 12 cases and LBGD in 3 cases. Median (IQR) operation time was 159 (140‐193) min and median blood loss was 10 (5–30) mL. No bile leakage caused by intraoperative perforation of the gallbladder was seen. Median hospital stay was 7 (5–9) days. Only one patient developed postoperative complications (abdominal abscess). Histologically, gallbladder cancer was diagnosed in five cases (pT1a, n = 2; pT2, n = 3), and two of the pT2 patients underwent additional open surgery.ConclusionsOur laparoscopic‐based approach for suspected gallbladder cancer might represent a safe strategy and could play an important role in defining the optimal treatment strategy.

A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy.

We previously reported the effectiveness of the product of tumor number and size (NxS factor) for the prognosis of hepatocellular carcinoma (HCC) in patients following hepatectomy. The present study aimed to propose a new score based on the NxS factor to predict HCC recurrence following hepatectomy. A total of 406 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine were retrospectively analyzed to develop the new score. Among clinicopathological factors, including the NxS factor, the marker subset that achieved the best performance for prediction of early recurrence was assessed, and a prognostic model for HCC recurrence after curative hepatectomy (REACH) was developed. As the validation set, 425 patients who underwent hepatectomy for HCC at Yamaguchi University Graduate School of Medicine and Shimonoseki Medical Center were analyzed, and the prognostic ability of the REACH score was compared with that of well-known staging systems. Following analysis, the REACH score was constructed using six covariates (NxS factor, microscopic hepatic vein invasion, differentiation, serum albumin, platelet count and indocyanine green retention rate at 15 min). In the validation set, the REACH score predicted early recurrence in 73 of 81 samples, with a sensitivity of 89% and a specificity of 58%. The area under the curve (AUC) of the receiver operating characteristic curve of the REACH score was 0.78 and 0.74, respectively, for 1- and 2-year recurrence after hepatectomy; each AUC was higher than that of any of the other staging systems. Survival analysis indicated the REACH score had the best predictive value in disease-free and overall survival. The present findings demonstrated that the REACH score may be used to classify patients with HCC into high- and low-risk of recurrence, and to predict subsequent survival following hepatic resection.

Correction to: Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

In the original publication of the article, the first sentence was published incorrectly under the section "Patients and preoperative assessment". The correct sentence should read as, "The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)".

Characteristics of C6-7 myelopathy: assessment of clinical symptoms and electrophysiological findings.

This is a single-center retrospective study. The objective of this study was to study the clinical symptoms and electrophysiological features of C6-7 myelopathy. This study was conducted at the Department of Orthopedic surgery, Yamaguchi University Graduate school of medicine, Japan. A total of 20 patients with cervical compressive myelopathy were determined by spinal cord-evoked potentials or a single level of obvious magnetic resonance imaging (MRI)-documented cervical spinal cord compression. Neurological examinations included manual muscle testing and investigation of deep tendon reflex, including Hoffmann sign, and of sensory disturbance areas. Motor-evoked potentials (MEPs), compound muscle action potentials (CMAPs) and F-wave were recorded from bilateral abductor digit minim and abductor halluces muscles. Central motor conduction time was calculated as follows: MEPs latency-(CMAPs latency+F latency-1)/2 (ms). Eighteen patients (90%) had negative Hoffmann sign. Eight patients (40%) had no sensory disturbance in the upper limbs and 8 patients (40%) had no muscle weakness in the upper limbs. We determined that patients had cervical myelopathy when their central motor conduction time measured in abductor digit minim was longer than 6.76 ms (+2 s.d.). Using this definition, the sensitivity for myelopathy was 42.8%. Patients with C6-7 myelopathy may lack clinical symptoms in their hands and central motor conduction time measured in abductor digit minim tended to be less prolonged, and it only showed symptoms in their lower limbs as gait disturbance. Surgeons should bear in mind the possibility of disorders of caudal C6-7 when they encounter patients with no or few symptoms in their hands and with leg weakness or numbness.

Application of diffusion tensor imaging for the diagnosis of segmental level of dysfunction in cervical spondylotic myelopathy

A retrospective study. Diffusion tensor imaging (DTI) reflects pathological change in the spinal cord more sensitively than conventional magnetic resonance imaging (MRI). Electrophysiological examination enables quantitative assessment of spinal cord function. Few studies have addressed the correlation between intraoperative spinal cord-evoked potentials (SCEPs) and DTI. The purpose of this study was to examine whether DTI is an objective index for the diagnosis of the segmental level of dysfunction in cervical spondylotic myelopathy (CSM). Yamaguchi University Graduate School of Medicine, Japan. Using 3.0-Tesla MRI, DTI values for the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured at the disc level C2/C3 through C6/C7 in 11 normal subjects and 10 subjects with CSM. Subjects with CSM were divided into two groups based on the extent of compression according to conventional MRI: single level (n=3) and multilevel (n=7). Intraoperative SCEPs were measured in subjects with CSM. For each group, the ADC and FA values were compared with SCEPs with respect to the segmental levels of dysfunction. For all three subjects with single-level compression and six of seven with multilevel compression, the maximal ADC value was observed at the segmental level of dysfunction as per the SCEP. Minimum FA values were observed at those sites in two of three patients with single-level compression and in only two of seven with multi-level compression. Our results suggest that ADC might serve as a supplementary diagnostic indicator of the segmental levels of dysfunction in CSM.

The examination of recurrent pregnancy loss in our hospital

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 7 endometrium 3.6±2.3% vs. 1.8±1.4%, P<0.05, respectively). Conclusions: It was suggested that both NKp46+NK cells and NKp44+NK cells are capable to produce IL-22, but the former may role more important than the latter. http://dx.doi.org/10.1016/j.jri.2014.09.015 A woman case of familial Mediterranean fever accompanied with periodic fever during menstruation R. Maekawa1,∗, M. Sinagawa1, M. Okada1, H. Asada1, T. Taketani1, Y. Yamagata1, H. Tamura1, N. Sugino1, M. Kubo2 1 Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Japan 2 Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine,

A woman case of familial Mediterranean fever accompanied with periodic fever during menstruation

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 7 endometrium 3.6±2.3% vs. 1.8±1.4%, P<0.05, respectively). Conclusions: It was suggested that both NKp46+NK cells and NKp44+NK cells are capable to produce IL-22, but the former may role more important than the latter. http://dx.doi.org/10.1016/j.jri.2014.09.015 A woman case of familial Mediterranean fever accompanied with periodic fever during menstruation R. Maekawa1,∗, M. Sinagawa1, M. Okada1, H. Asada1, T. Taketani1, Y. Yamagata1, H. Tamura1, N. Sugino1, M. Kubo2 1 Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Japan 2 Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine,

Preoperative diagnosis of the responsible level in CCM using CMAPs: comparison with SCEPs

A retrospective study. To elucidate the correlation between compound muscle action potentials (CMAPs) amplitudes and responsible level of compressive cervical myelopathy (CCM), and the accuracy of level diagnosis by using CMAPs. This study was conducted at the Department of Orthopedic surgery, Yamaguchi University Graduate School of Medicine, Japan. A total of 28 patients with CCM were investigated in this study. Erb's point-stimulated CMAPs were measured from deltoid, biceps, triceps in all patients as compared with 88 healthy subjects. We performed a level diagnosis on the basis of CMAPs amplitudes. We performed a level diagnosis on the basis of CMAPs amplitudes and using an index that measures the deviation of CMAPs amplitudes between triceps and deltoid or biceps. Significant correlations between the mean CMAPs amplitudes and responsible level were showed for deltoid (6.82±2.33 mV) at C3/4 (P<0.01) and biceps (8.75±4.42 mV) at C4/5 (P=0.015). Despite considerable individual variability in CMAP amplitudes, there were correlations among CMAPs amplitudes for deltoid, biceps and triceps in the same individual. The sensitivity was 75.0%, specificity 75.0% in the index for diagnosis of C3/4. The sensitivity was 75.0%, specificity 66.7% in the index for diagnosis of C4/5. This study showed small CMAPs amplitudes in the deltoid indicated a C3/4 level of myelopathy and in biceps at the C4/5 level and could help exclude clinically silent cord compression and determine the surgical procedure to the suitable level of concern.

Evaluation of host quality of life and immune function in breast cancer patients treated with combination of adjuvant chemotherapy and oral administration of Lentinula edodes mycelia extract

PurposeAnthracycline-based chemotherapies for breast cancer are well known to have adverse effects and can also negatively affect host immune function. There is therefore a necessity for an adjuvant that maintains the quality of life (QOL) and immune function of cancer patients receiving anthracycline-based chemotherapies.Patients and methodsThe present study investigated the effectiveness of the concomitant use of Lentinula edodes mycelia extract (LEM), an oral immunomodulator, with FEC75 (5-fluorouracil + epirubicin + cyclophosphamide) therapy on host QOL and immune function in breast cancer patients with nodal metastases. Ten breast cancer patients with nodal metastases receiving surgery were enrolled in this study. Treatment with 5-fluorouracil (500 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (500 mg/m2) was performed every 21 days for two courses, and LEM (1800 mg/day by mouth) was administered during the second course.ResultsIn the first course, hematological toxicity was observed and host QOL and immune function were exacerbated. In the second course, however, the number of white blood cells and lymphocytes did not decrease and host QOL was maintained. Furthermore, the cytotoxic activities of natural killer (NK) and lymphokine-activated killer cells and the proportion of activated NK and NK T-cells in lymphocytes were maintained in the second course.ConclusionIt has been suggested that the concomitant use of LEM with FEC75 therapy can maintain host QOL and immune function, and offer important implications for an application of LEM as a useful oral adjuvant to anthracycline-based chemotherapies.

Relative vulnerability of various spinal tracts in C3-4 cervical spondylotic myelopathy: multi-modal spinal cord evoked potentials

Retrospective study. To investigate the progression of spinal tract lesions in cervical spondylotic myelopathy (CSM) at C3-4 intervertebral level using spinal cord-evoked potensials (SCEPs). This study was conducted at the Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Japan. A total of 30 patients with CSM were investigated in this study. In all patients, only the C3-4 intervertebral level was symptomatic, as shown by examination of SCEPs. SCEPs were recorded following median nerve stimulation (MN-SCEPs), transcranial electric stimulation (TES-SCEPs) and spinal cord stimulation (spinal-SCEPs). The incidence of abnormalities varied in the order of MN-SCEPs (100%), TES-SCEPs (90%) and spinal-SCEPs (67%). Patients were grouped into three types according to SCEPs: transverse (all SCEPs abnormal), post-erolateral (abnormalities in the MN-SCEPs and TES-SCEPs) and upper limbs sensory (abnormal only for MN-SCEPs). In all, 20 of the 30 patients (67%) were the transverse type, 7 (23%) the post-erolateral type and 3 (10%) the upper limbs sensory type. The present study showed the lateral part of the posterior funiculus mediating upper limb sensory function was more vulnerable than the lateral corticospinal tract, which is consistent with numbness tending to appear at an early stage of mild CSM.

A longitudinal study of fronto-limbic brain structures in bipolar I patients during lithium treatment

Salih Selek1, 2, Mark Nicoletti 1, Giovana B. Zunta-Soares 1, John P. Hatch3, Fabiano G. Nery1, Koji Matsuo4, Jair C. Soares1 1UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, 2Psychiatry Department, Harran University Faculty of Medicine, Sanliurfa, Turkey, 3 Departments of Developmental Dentistry and Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 4Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

Routine Diagnostic Venous Ultrasound and LAS for Leg Edema of Unknown Cause

To verify the diagnostic efficiency of venous duplex ultrasound and lymphangioscintigraphy (LAS) in establishing the cause of leg edema and to clarify the pathology of these leg edemas. Between April 2009, and March 2010, 62 patients with leg edema of unknown origin were referred to the Edema Clinic of the Yamaguchi University Graduate School of Medicine. All patients underwent a venous duplex ultrasound scan and LAS. Of 62 patients, lymphatic insufficiency, venous insufficiency or both was diagnosed in 42 (68%), and lymphedema, in 29 (47%). Venous duplex ultrasound detected obvious venous disorders in only 13 (21%), and for 20 patients, the ultrasound and LAS did not reveal any abnormalities; however, for 15 of the 20 (24% of all patients), venous edema was attributed to functional causes. Venous duplex ultrasound and LAS assisted in the diagnosis of leg edema of unknown origin and also proved useful in establishing treatment strategies.

OPEN CLINICAL STUDY OF EYE-DROPS CONTAINING TETRAPEPTIDES DERIVED FROM SUBSTANCE P AND INSULIN-LIKE GROWTH FACTOR-1 FOR TREATMENT OF PERSISTENT EPITHELIAL DEFECTS ASSOCIATED WITH NEUROTROPHIC KERATOPATHY

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Original study reprint requests: Dr Yamada N, Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube City, Yamaguchi 755-8505, Japan. E-mail address: [email protected].