Nagoya Journal of Medical Science

In a world of increasing academic mobility, most universities seek to give their students opportunities to experience education in different countries, which is especially true for senior research students. The Nagoya University Graduate School of Medicine started a joint degree program (JDP) for PhD students with the University of Adelaide, Faculty of Health Science (Australia) in 2015 and with Lund University Faculty of Medicine (Sweden) in 2017. Furthermore, we have started a new JDP with the University of Freiburg, Faculty of Medicine (Germany) in 2018. This article reports the issues specific to counterpart medical schools, including student’s recruitment, the curriculum, and the general differences between each schools. JDPs are not only important for educational collaboration, but also as a strategy to encourage international research collaboration, which is a core criterion to a university’s world-ranking reputation. Acquiring knowledge about educational strategies that are implemented in different foreign medical schools represents a unique opportunity to improve our own curriculum.

Malignant ovarian neoplasm is one of the most lethal malignancies among cancers of the female reproductive system. Occasionally, these tumors originate from non-ovarian organs as metastatic lesions since the ovary is a frequent metastatic target of many cancers. However, there limited clinical information on metastatic ovarian carcinoma (MOC) and its hallmarks are unknown. During the period of 1986–2015, 4,284 patients with malignant ovarian neoplasm were identified using the Tokai Ovarian Tumor Study Group (TOTSG) database. Of these, excluding borderline malignant tumor, 3,478 patients with malignant ovarian cancer were extracted. The pathological slides were evaluated under central pathological review. Among them, a total of 143 (4.1%) patients with MOC were identified. The median age of patients with MOC was 54 (29–82) years. The most and second most frequent original tumors were colorectal (43%, N=62) and gastric (29%, N=42) carcinoma, respectively. The rates of carcinoma of the appendix, breast, and pancreas were 8, 6, and 4%, respectively. This is the one of the largest studies clarifying the rates of MOC among malignant ovarian neoplasms. Although the rate is low, we should keep in mind that MOC, particularly from colorectal and gastric cancer should be considered when encountering clinical practice of ovarian cancer.

In 2008, Japan introduced a metabolic syndrome screening and intervention program specifically targeting individuals aged 40 to 74 years of age. However, the consultation and follow-up rates for the intervention are still low. The present study aims to identify characteristics of health-related behavior of the people who neglect it. We conducted a group interview targeting public health nurses and qualified dieticians of “A” prefectural branch office of the Japan Health Insurance Association who were regularly involved in performing the intervention. Qualitative content analysis was used to analyze the data, and four themes were extracted: Self-taught practices, Defiance, Hesitation, and Resignation. Our results suggest that the public health advisors recognize the importance of modification of clients’ health-related misperception, improve their skills to develop a positive rapport with clients, and be involved in creating a supportive environment conducive to a healthy lifestyle.

Differences of the effect of annuloplasty rings on the mitral annulus and leaflets, and differences between types of annuloplasty rings are not well known. We analyzed annular motion and leaflet movement with a rigid or flexible ring and without a ring using an isolated swine working heart model. Hearts of 10 swine (weight: 40–50 kg) were used for a rigid ring (n=5) and a flexible ring (n=5). Four ultrasound crystal tips were fixed around the annulus and an annuloplasty ring was implanted in the isolated heart. In the working heart mode, measurement of mitral annular dimension was acquired by sonomicrometry. Images of mitral valve motion were acquired by a high-speed video camera. The same analyses were performed after removing the artificial ring. The antero-posterior diameter of the diastole distance was significantly reduced in the flexible ring (21.59±0.71 mm) and rigid ring (15.93±1.88 mm) compared with no ring (23.51±2.01 mm). The flexible ring made the transverse diameter shrink significantly more than did the rigid ring. The contraction range of the transverse diameter was significantly smaller in the flexible ring compared with no ring. The duration of opening to closing of the mitral leaflet with the rigid (124.7±4.4 ms) and flexible rings (107.9±3.5 ms) was significantly shorter than that with no ring (168±36.5 ms). Annuloplasty rings allow simplicity of leaflet motion, regardless of the type of artificial ring. In a flexible ring, the mitral annulus shows a vertically long shape, suggesting preservation of posterior annular movement.

In endovascular coil embolization for intracranial aneurysms, as coils are filled in the aneurysm and the stage of procedure is advanced, the force to push forward the coil delivery wire (insertion force) increases. However, the coil insertion force that interventionist’s felt at his fingertips does not directly reflect the stress of the aneurysm and is affected by the resistance generated inside the microcatheter through that the wire passes. The authors evaluated this force discrepancy by subtracting the loading force at the tip of delivery wire from the insertion force of delivery wire and examined the relationship among them. Experiments were performed with the device that applies a constant loading force to the delivery wire tip with the coil removed. A force gauge was connected to the end-tip of the delivery wire to measure the insertion force. The force was measured by changing delivery wire in different coil brands and the conditions of microcatheter (straight or bent position). The results demonstrated that force discrepancy generated inside the microcatheter increased as the loading force increased in a linear relationship. Different coil delivery wires produced differences in the way that force discrepancy changed, thus reflecting the properties of each wire. Microcatheters with more curvature were associated with a higher force discrepancy. In conclusions, as the loading force increases, the force discrepancy increases, and it means that the coil insertion force that the interventionist feels at his fingertips also increases. This force discrepancy is impacted by the delivery wire properties and microcatheter curvature.

Neonates who swallow a considerable amount of maternal blood may exhibit vomiting and suckling disorder during the first few days of the postnatal period. Some clinicians treat these neonates with gastric lavage (GL) to prevent vomiting and the establishment of enteral feeding empirically, but there was no study assessing the effect of GL for neonates with coffee-ground emesis. We designed a multicenter randomized controlled trial to evaluate the efficacy and safety of GL in neonates with coffee-ground emesis. Vigorous neonates with birth weight ranging from 2500 g to 3999 g and gestational age between 37w0d and 41w6d who presented with coffee-ground emesis on more than twice and diagnosed as false melena, were divided into two groups using computerized randomization. We defined feeding intolerance (FI) as (1) ≥2 vomiting episodes in 4h or ≥3 episodes in 24h and/or (2) feeding failure on at least two occasions because of retching or poor sucking. Primary outcome is percentage of infants who present FI within 24 hours from admission. We also assessed the residual volumes, number of vomiting episodes, percentage of weight reduction at postnatal day 4, rates of body weight gain at 1 month of age, and peak serum total bilirubin value before discharge. To our knowledge, this is the first study to evaluate the safety and efficacy of GL for neonates with coffee-ground emesis. This trial is registered at UMIN Clinical Trials Registry as UMIN000026483.

The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m² nab-paclitaxel and 800 mg/m² gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET–CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.

Many researchers suggested that ultrathin endoscopy improves patient acceptance of endoscopic examinations. However, ultrathin endoscopy provides less image resolution and luminous intensity. Therefore, we focused on the visibility of early gastric cancer on ultrathin endoscopy with Flexible spectral imaging color enhancement (FICE) in this study. Thirty-six patients with early gastric cancer were prospectively enrolled. One endoscopist performed the endoscopic examinations by white light conventional endoscopy (W-CE), white light ultrathin endoscopy (W-UE), FICE ultrathin endoscopy (F-UE) and white light plus FICE ultrathin endoscopy (WF-UE) in the patients. Four other endoscopists were asked to evaluate the visibility of gastric cancer on the W-CE, W-UE, F-UE and WF-UE images with a 5-point Likert scale. The lesions were classified as uncolored, normocolored or reddish. We examined the color difference between early gastric cancer and the surrounding mucosa. To examine the relationship between the color difference and the vessel density, we also measured the difference in vessel density using pathologic specimens stained with hematoxylin and eosin. The Likert score of WF-UE was significantly higher than those of the other three methods (p<0.001). The color difference of F-UE was higher than that of W-CE in the reddish group (p=0.049). The difference in vessel density was higher in the reddish group than in the normocolored group (p=0.048). In conclusion, the visibility of early gastric cancer from the surrounding mucosa using ultrathin endoscopy with FICE was better than that using white light conventional endoscopy, especially for reddish lesions.

Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

The activity of fibrinogen has been reported to decrease soon after the onset of major bleeding and to be an important determinant of the final extent of bleeding and postoperative outcome. A device that measures the perioperative fibrinogen level using the dry hematology (DH) method has recently become available. The aim of this study was to compare perioperative fibrinogen levels measured by the DH method with those measured by the conventional Clauss method and to assess the effects of heparin on these measurements. The study included 206 samples from 36 patients undergoing major surgery who received high-dose heparin (HH group, 23 samples), low-dose heparin (LH group, 57 samples), or no heparin (C group, 126 control samples). Each sample was measured using the DH and Clauss methods. After excluding samples outside the effective measurement range, the three study groups (HH group, n=23; LH group, n=49; C group, n=115) were compared. The mean fibrinogen level measured by the DH method in the HH group (87.9 ± 3.1%) was significantly lower than that measured by the Clauss method. There were no significant differences between the fibrinogen measurements obtained by the two methods between the LH and C groups. In patients on high-dose heparin, the mean fibrinogen level measured by the DH method was significantly lower than that measured by the Clauss method. When hemorrhage requires emergency treatment, a method that can measure the fibrinogen level rapidly is important. The DH method may be useful for decision-making with regard to perioperative coagulation factor replacement.

On June 4, 2016, the Prey Veng Provincial Health Department reported a total of 107 patients with influenza-like illness (ILI) from Chakhlanh village to the Cambodian Ministry of Health. To confirm the outbreak and evaluate its clinical and epidemiological characteristics, the investigation team visited the village and reviewed the case-based surveillance (CBS) data on severe respiratory infection (SRI) and patients’ records in health facilities. The team interviewed all households in the village from May 1 to June 5, 2016 and obtained the following data: age, medical history, date of onset, treatment, symptoms, and history of contact with patients or dead poultry. Nasal swab samples were collected from suspected ILI cases to test for influenza virus by RT-PCR. The investigation detected 498 suspected ILI cases, including 288 females. Although the incidence of suspected ILI cases who visited health centers was 63.0 per 1,000 persons per month, the attack rate was 27.1 per 100 population. The major age group was 5–14 years followed by 0–4 years. Major symptoms were cough, fever, runny nose, and headache. Six of seven nasal swab samples were positive for influenza A/H1N1 pdm09 virus. Most children with flu symptoms had contact with previous cases. This study showed that the ILI outbreak might be caused by seasonal influenza A/H1N1 pdm09 spread from person to person. Poor living conditions and poor hygiene and sanitation practices were environmental factors that caused the outbreak. As the CBS system was unable to identify this epidemic, it needs to be improved.

In Lao PDR, measurement of cognitive function has rarely been conducted among elderly individuals. This study aimed to investigate the cognitive function among elderly individuals who lived at their homes with family in Lao PDR. Participants were elderly individuals aged 60 years or over registered with the local government in urban (Vientiane capital; VC) and rural areas (Khammouane province; KP). Those with serious mental/physical diseases, those who could not walk by themselves, or those who could not speak the Lao language were excluded. The information was collected through interviews with the participants and their family members. A newly developed Lao version of the Revised Hasegawa’s Dementia Scale (HDS-R) was applied to measure cognitive function. The participants were 414 elderly individuals (224 males and 190 females) aged 60 to 98 years. The average HDS-R score was 23.0 among 115 men in VC, 22.7 among 92 women in VC, 20.3 among 109 men in KP, and 17.5 among 98 women in KP. The main caregiver was a daughter (40.6%) followed by a spouse (31.4%). Among 414 elderly individuals, 42 (10.0%) stated the necessity of support. Those with HDS-R < 20 accounted for 38.8% in men and 48.9% in women. The adjusted odds ratio of HDS-R < 20 was significant for those in rural areas (3.83) relative to those in urban areas. Among superficially healthy elderly individuals residing with their families, those with reduced cognitive function were more common among women and in rural areas.

There is little known about predictors of the effects of induction therapy in locally advanced lung cancer, including superior sulcus tumors. We analyzed whether intra-tumoral blood feeding could predict a pathologic complete response (pCR). Patients who underwent induction therapy followed by surgery for locally advanced lung cancer were retrospectively reviewed. The intra-tumoral blood feeding was defined by the CT value (HU, Hounsfield unit), which was calculated by subtracting the non-enhanced value from the contrast-enhanced value (divided into the early and delayed phase) at the maximum diameter of the tumor on dynamic CT. The cases were classified, according to the efficacy of induction therapy, into the pCR and residual tumor (pRT) group. There were 38 cases of T3 and 12 of T4; the induction therapy consisted of chemoradiotherapy in 39 patients, chemotherapy in 6, and radiotherapy in 5. A pCR was obtained in 15 (30%) patients. The mean CT values of the early and delayed phases in the pCR group were 14.8 and 30.7 HU, while those in the pRT were 15.3 and 32.2 HU, respectively. A logistic regression analysis revealed that a smaller tumor size (< 42 mm) was a non-significant predictor of a pCR (p = 0.09); the maximum standardized uptake value on FDG-PET and the CT values on the early and delayed phases of dynamic CT were not associated with the achievement of a pCR. In conclusion, intra-tumoral blood feeding of the locally advanced lung cancer did not predict the effects of induction therapy, whereas smaller sized tumors tended to show a better response.

The Kaifukuki-Rehabilitation Ward (KRW) is a type of inpatient rehabilitation facility in Japan. In the KRW of our institute, mortality and frequency of emergency referrals in 2013 were rather high, 2.6% and 4.3%, respectively. We aimed to investigate the usefulness of an original gatekeeping system to reduce mortality and morbidity from cardiac complications, and to improve the quality of medical care in the KRW. A total of 370 consecutive patients admitted to the KRW of Kobayashi Memorial Hospital between 1 May 2015 and 31 March 2016 were enrolled in this prospective observational study. All patients underwent a screening evaluation in which we defined patients as being screen positive (SC-positive) if they had at least one of 20 diagnostic ECG codes and/or BNP level over 140 pg/dL at admission. A cardiologist provided weekly interventions to those among SC-positive patients who needed cardiac disease treatment during hospitalization. In all, 129 patients were classified as SC-positive (mean age 80 years, 124 [32%] male), and weekly intervention was needed in 28 patients, including start of cardiac medication in 17 cases. Mortality and frequency of emergency transfer due to cardiac disease during hospital stay were 0.3% and 0.3%, respectively. Our gatekeeping system involving a screening evaluation at admission and weekly intervention in selected patients by a cardiologist may be useful in reducing mortality and rate of transfer due to cardiac disease and may improve quality of medical care in KRWs.

Neointimal calcification after stent implantation has been reported as one of the forms of neoatherosclerosis. There are a few patients with in-stent restenosis (ISR) and an undilatable calcified neointima who require rotational atherectomy to achieve sufficient acute gain in lumen diameter. However, the clinical outcomes of rotational atherectomy for undilatable calcified ISR have not been fully elucidated. Therefore, we investigated the safety and efficacy of rotational atherectomy for treating calcified ISR. This retrospective study included 17 patients (20 lesions) who had undergone percutaneous coronary intervention including rotational atherectomy to treat ISR with severely calcified neointima. Kaplan-Meier analysis was used to analyze the data. The mean age of the enrolled patients was 67±18 years, and 71% were men. The patients had highly atherogenic characteristics: 65% had diabetes mellitus and 53% were receiving hemodialysis. Procedural success was obtained in 19 (95%) patients, and the acute gain in lumen diameter was acceptable (1.7±0.6 mm). However, during a median follow-up of 571 days, the incidences of major adverse cardiac and cerebrovascular events per patient and clinical-driven target lesion revascularizations per lesion were relatively high. There were no differences in clinical outcomes according to the baseline characteristics, type of restenotic stents, and therapeutic strategy. In conclusion, clinical outcomes of rotational atherectomy for severely calcified ISR were unfavorable despite a high success rate and acceptable acute gain in lumen diameter.

Umbilical metastasis from intra-abdominal or pelvic malignancy, which is called Sister Mary Joseph’s nodule (SMJN), is rare, and it has a poor prognosis. Its most common primary sites are the stomach and ovaries. SMJN caused by colon cancer is uncommon. A 42-year-old woman visited local clinics with complaints of an umbilical mass. After a detailed examination, she was diagnosed with peritoneal and umbilical metastasis caused by colon cancer. A radical surgery was performed after 12 months of chemotherapy. 6 months later, local recurrence and ovarian metastasis were suspected. Further radical surgery was performed, and 14 months after that (50 months after starting treatment), no recurrences have been observed. We experienced a long-term survival case of SMJN caused by colon cancer and treated with a multidisciplinary approach.

Serious problems may be encountered in arterial or venous reconstruction in cases of severe trauma and contaminated tissues. We report the use of a spiral venous graft (SVG) in a case of two-stage bypass aimed at saving first life, and then the extremity.
Severe open and contaminated injury was present in the lower abdomen and pelvic region of 29-yearold woman brought to the emergency department following a traffic accident. The patient was in shock, and was taken for emergency surgery jointly with the relevant departments. Interposition bypasses with synthetic graft were performed in the first stage. The synthetic grafts were subsequently removed due to problems developing secondary to infection at subsequent follow-up, and revascularization was established with autologous grafts together with SVG.
SVGs are alternative grafts in cases with contaminated tissues and requiring major vessel reconstruction. This technique can add to the therapeutic options available.

A 55-year-old man with a solitary kidney was diagnosed with an 8.5 cm renal cell carcinoma in the right kidney without metastasis. Twenty five months of sunitinib treatment reduced the tumor from 8.5 to 5.5 cm and enabled nephron-sparing surgery. He has no evidence of recurrence 58 months after the surgery.