Objective The utility of capsule endoscopy (CE) findings in the route selection for double balloon endoscopy (DBE) has not been adequately discussed. The PillCam Progress Indicator in the RAPID 6.5 software program graphically demonstrates the progress of the capsule endoscope through the small-bowel. This study aimed to clarify the usefulness of the PillCam Progress Indicator in choosing the initial DBE route.

Methods We retrospectively examined 50 consecutive patients with 50 target lesions detected on both CE and DBE at Hiroshima University Hospital from January 2011 to February 2018. In this study, we selected antegrade DBE on the basis of % Capsule Progress <50% as a clinical trial. The association between the PillCam Progress Indicator data and the DBE route to the target lesion was analyzed.

Results The target lesion was reached via the initial DBE route in 96% (48/50) of cases. The cutoff values for selecting an antegrade route for DBE were 50% for % Capsule Progress and 42% for % SB Time. At the cutoff value, the sensitivity, specificity, and positive and negative predictive values for route selection were 100%, 91%, 93%, and 100% for % Capsule Progress and 96%, 91%, 93%, and 95% for % SB Time.

Conclusion The PillCam Progress Indicator was useful for determining the appropriate initial DBE route.

Objective Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are both complicated by arteriosclerosis, resulting in increased rates of cardiovascular events. No previous studies have compared the index between RA and T2DM. We assessed the vascular endothelial function in early-stage arteriosclerosis for each disease to determine the influential factors and compared the extent to which these two diseases cause vascular endothelial dysfunction.

Methods This study is a retrospective study based on medical records. Differences in the reactive hyperemia index (RHI) among the groups and factors affecting the RHI in each group was analyzed. The vascular endothelial function was assessed by measuring the RHI using peripheral arterial tonometry.

Patients The study subjects were 114 patients with non-functional thyroid tumors (healthy n=14), T2DM (T2DM n=64), and RA (RA n=36).

Results The RHI was 2.29 in the control, 1.85 in the T2DM, and 1.83 in the RA group, with values lower in the T2DM and RA groups than in the control group (p=0.033) but not markedly different between the two disease groups. The RHI distribution (<1.68/1.68 to <2.10/≥2.1) was as follows: control group: 14.3%/28.6%/57.1%; T2DM group: 42.2%/39.1%/18.8%; and RA group: 36.1%/44.4%/19.4% (p=0.031), respectively. A multivariate analysis identified the triglyceride level and dyslipidemia in the control group and the Disease Activity Score in 28 joints with the erythrocyte sedimentation rate and fasting plasma glucose level in the RA group to influence the RHI.

Conclusion The vascular endothelial function was impaired in approximately 80% of patients with T2DM and RA, with comparable degrees of impairment between the two diseases. No factors affecting the function were identified in the T2DM group, while the function was more impaired in patients with a higher disease activity in the RA group.

Objective Extracorporeal life support (ECLS) is effective for improving the survival rate of patients with refractory cardiac arrest (rCA). As little data are available regarding the impact of ECLS on a favorable neurological outcome, the predictors of a favorable neurological outcome were evaluated in this study.

Methods Between January 2007 and August 2016, we retrospectively recruited patients with rCA caused by cardiac events treated with ECLS in our institute. A favorable neurological outcome was defined as a Glasgow-Pittsburgh cerebral performance category score 1 at discharge. The study endpoint was the clinical outcomes and predictors of favorable neurologic patients at discharge.

Results During the study period, 67 patients with CA caused by cardiac events (acute coronary syndrome, 57 patients; idiopathic ventricular fibrillation, 10 patients) were included. Of these, 20 patients (29.9%) were classified into the favorable neurological group. No marked difference was observed in the patient characteristics between those with and without a favorable outcome except for in the time from CA to starting ECLS (ECLS initiation time). A short ECLS initiation time resulted in a favorable outcome (37.8±28.1 minutes vs. 53.6±30.7 minutes, p=0.05). The cut-off time of ECLS initiation was 46 minutes, which was prolonged by the temporary return of spontaneous circulation before ECLS [odds ratio (OR), 3.69; 95% confidence interval (CI), 1.34-10.19; p=0.01] and transfer to the angiographic room (OR, 4.07; 95% CI, 1.44-11.53, p=0.008).

Conclusion The early initiation of ECLS (within 46 minutes) might be associated with a favorable neurological outcome for patients with rCA caused by cardiac events.

Objective The early integration of palliative care into standard cancer treatment has become a global standard. The Palliative care Emphasis program on symptom management and Assessment for Continuous medical Education (PEACE) has been conducted in Japan, and previous studies have reported that the PEACE workshop was able to improve various palliative care skills of participants. However, whether or not the effects of the program are long-lasting and if the program consequently changed physicians' practice with regard to lung cancer patients have been unclear.

Methods Web-based surveys, including the palliative care knowledge test (PEACE-Q), the Palliative Care self-reported Practice Scale (PCPS), and the Palliative Care Difficulties Scale (PCDS), were conducted among lung cancer physicians in Japan. The differences in the survey results between participants and non-participants of the PEACE workshop were examined.

Results Among 923 respondents (455 respiratory physicians, 345 pulmonary surgeons, and 123 others), 519 had participated in the PEACE workshop. The total PEACE-Q score was significantly higher in the PEACE workshop participants than in non-participants (28.0 versus 24.5, p<0.0001). The score was significantly higher in respiratory physicians than in pulmonary surgeons (27.4 versus 25.5). The total PCPS and PCDS scores were also significantly better in workshop participants than in non-participants (71.8 versus 67.1 and 34.3 versus 36.9, respectively), although some domains of PCDS were similar between the groups.

Conclusion The PEACE program improved the knowledge and practices with regard to palliative care and resolved difficulties associated therewith among lung cancer physicians. In regions where palliative care specialists are insufficient, such educational programs may be effective.

Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC.

Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety.

Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable.

Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Objective Dementia is a major cause of disruption for a healthy life expectancy in Japan. It has been suggested that the number of teeth is a modifiable risk factor for cognitive impairment and dementia. We therefore examined the possible association between the cognitive function and the number of natural and artificial teeth in community-dwelling Japanese elderly individuals.

Methods Among the participants in our prospective, community-based study, 210 elderly individuals (103 men and 107 women; 78.1±4.9 years; mean age±standard deviation) underwent both dental examinations and a Mini-Mental State Examination (MMSE), as well as various medical checkups, in 2016 and 2017.

Results The number of natural teeth was significantly associated with an individual's MMSE score. The percentage of cognitively normal subjects (MMSE scores: 27-30) decreased significantly with a decrease in the number of natural teeth. Among the MMSE items, the calculation ability was significantly and independently associated with the number of natural teeth. Regression was calculated as the predicted score of MMSE =21+0.3× (years of schooling) +0.1× (number of natural teeth). Among individuals with 19 or fewer natural teeth, those who had a total of 20 teeth or more, including both natural and artificial teeth, had significantly higher MMSE scores than those who had 19 or fewer natural and artificial teeth combined.

Conclusion The number of natural teeth was significantly associated with the cognitive function, especially the calculation ability, and the use of artificial teeth was associated with the preservation of the cognitive function in community-dwelling elderly individuals.

Objective Assessing daily motor fluctuations is an important part of the disease management for patients with Parkinson's disease (PD). However, the frequent recording of subjective and/or objective assessments is not always feasible, and easier monitoring methods have been sought. Previous studies have reported that the spontaneous eye-blink rate (EBR) is correlated with the dopamine levels in the brain. Thus, the continuous monitoring of the EBR may be useful for predicting the motor status in patients with PD.

Methods Electrooculograms (EOGs) were recorded for up to 7.5 hours from three PD patients using a wearable device that resembled ordinary glasses. An receiver operating characteristic (ROC) analysis was performed to compare the ability of the EBR estimates at each time-point (Blink Index) and the plasma levodopa levels to predict the motor status.

Results The Blink Index was correlated with the plasma levodopa levels. When an indicator for the first hour of the observation period was included in the model, the Blink Index discerned wearing-off and dyskinesia as accurately as the plasma levodopa level.

Conclusion Our study provides preliminary evidence regarding the utility of continuous EBR monitoring for the non-invasive evaluation of the motor status in patients with PD.

Objective Few reports have analyzed the diagnostic process of carcinoma of unknown primary site (CUP) or have focused on the frequency of nonmalignant lesions among patients with suspected malignant diseases. The aim of this study was to investigate the incidence and characteristics of nonmalignant diseases that tend to be mistaken for malignant diseases.

Patients We retrospectively analyzed the medical records of patients with suspected CUP who were referred to the National Cancer Center Hospital (Tokyo, Japan) between April 2007 and December 2014. All patients underwent a thorough history and physical examination as well as radiological and ultrasonography imaging tests for the CUP diagnostic work up.

Results Among 830 patients with suspected CUP, 46 were diagnosed with nonmalignant diseases, and 780 were diagnosed with a malignant neoplasm (409 neoplasms with detected primary site and 371 CUP neoplasms). Four patients discontinued the diagnostic workup because they refused further examinations or had a poor general status. The final diagnosis of the 46 patients with nonmalignant disease comprised 10 benign tumors, 10 benign diseases, and 26 with no evidence of disease. The nonmalignant tumors comprised three hemangiomas, two schwannomas, two uterine myomas, two pseudomyxoma peritonei, one lymphangioma, one meningioma, and one poroma.

Conclusion The incidence of nonmalignant diseases among patients with suspected CUP was 46 out of 830 patients in our institution. It is important to perform a thorough pathological examination in the CUP diagnostic workup. To confirm a diagnosis, some patients may need to visit specialized institutions, especially those with liver and bone lesions.

A 74-year-old man developed hepatic injury after intravesical Bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. Although hepatitis-associated disseminated BCG was suspected, granulomatous formations were undetectable. The hepatic injury was considered to have resulted from an allergic reaction to BCG therapy because a histopathological assessment revealed enlarged portal areas with eosinophils and neutrophils. The hepatic injury was resolved by prednisolone. This case suggested that hepatic injury associated with BCG therapy might be due to an allergic mechanism unrelated to disseminated BCG disease. A liver biopsy is needed to confirm the histopathological findings of hepatic injury after BCG therapy in order to differentiate allergic hepatic injury from infectious hepatic injury.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is an extremely rare benign lesion. We herein report a case of asymptomatic SANT of the spleen in a middle-aged woman with early breast carcinoma and an undiagnosed splenic mass, which was successfully treated by laparoscopic splenectomy and diagnosed postoperatively. We also review the literature on SANT to help make knowledge more accessible when clinicians encounter a splenic tumor. The present case taught us the following lesson: the presence of a splenic lesion during follow-up for malignancy is not always indicative of metastasis. Therefore, SANT should be considered in the differential diagnosis.

A 73-year-old man with worsened diabetes underwent abdominal computed tomography and was diagnosed with localized enlargement of the pancreatic tail. Based on the suspicion of autoimmune pancreatitis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. A cytologic examination showed findings suggestive of adenocarcinoma. Due to discrepancies between the imaging and pathological findings, esophagogastroduodenoscopy was performed. An extensive early gastric cancer lesion was detected in the posterior wall of the gastric corpus. It was therefore likely that puncturing through the tumor resulted in the contamination with cancer tissue. The possibility of a concomitant malignancy should be considered in EUS-FNA, and thorough examinations should be conducted.

Rupture of a pseudoaneurysm (PA) has been reported as a rare but serious adverse event associated with endoscopic biliary stenting. We herein report 2 cases of severe biliary bleeding from a PA that developed 10-14 days after placement of a self-expandable metallic stent (SEMS) for biliary malignancy. The first patient was successfully embolized with endovascular coiling. However, the second patient had wide-spreading cholangiocarcinoma and, despite being treated once by full coiling, developed a second rupture of PA two months after starting systemic chemotherapy. Clinicians should be aware of the possibility of PA and carefully follow stented patients after endovascular treatment.

We herein report the clinical potential of Impella 5.0 support, which is a catheter-mounted micro-axial left ventricular support device, in a 39-year-old man with recurrent fulminant viral myocarditis complicated with profound cardiogenic shock despite inotropic infusion and an intra-aortic balloon pumping. Switching from these therapies to the Impella 5.0 device provided sufficient systemic perfusion with well-controlled left ventricular diastolic properties to facilitate a prompt recovery from profound cardiogenic shock. The patient was uneventfully discharged on the 27th hospital day. Given its effect of cardiac protection with sufficient systemic perfusion, the Impella device should be considered the first-line therapy for the treatment of fulminant myocarditis complicated with cardiogenic shock.

Chest radiography showed a right posterior mass on the mediastinum of an 84-year-old woman. The mass had been growing gradually for four years. Surgical excision was performed, and a pathological examination found the mass to be consistent with primary synovial sarcoma (SS) of the mediastinum. To our knowledge, this is a rare case in which follow-up imaging was able to be performed over a period of four years. This disease is aggressive, and its early diagnosis is key to achieving a cure. It is important to consider primary SS in the differential diagnosis of a primary intra-thoracic tumor, even if the tumor grows slowly.

Hypertrophic pulmonary osteoarthropathy (HPO) is a paraneoplastic syndrome characterized by digital clubbing, arthritis, and periostitis. Tumor removal usually leads to the resolution of these symptoms. We herein report the efficacy of crizotinib treatment for treating the symptoms of HPO associated with c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer. A 71-year-old woman presented with a pulmonary tumor and arthritis. She was diagnosed with a ROS1-rearranged lung adenocarcinoma [stage IIIB (cT4N2M0) ] with HPO. Crizotinib dramatically reduced the tumor size and resolved the symptoms. After two months of crizotinib treatment, she underwent lobectomy, and a pathological evaluation revealed ypstage IIIA (ypT3a, ypN1). Crizotinib treatment was effective for reducing the tumor size and improving the symptoms of HPO.

Although numerous recent studies have reported the development of sarcoidosis in patients treated with tumor necrosis factor alpha (TNF-α) inhibitors, it is unclear whether the pathogenesis of drug-induced sarcoidosis is identical to that of spontaneous sarcoidosis. We herein present the case of a patient who developed sarcoidosis 6 months after the introduction of etanercept as treatment for rheumatoid arthritis. Typical clinical symptoms with noncaseating epithelioid granulomas detected in a mediastinal lymph node specimen were consistent with the diagnosis of sarcoidosis. Immunohistochemistry revealed Propionibacterium acnes in the noncaseating granulomas. The present findings suggest that Propionibacterium acnes is a cause of sarcoidosis, even when the disease is induced by TNF-α inhibitors.

Lynch syndrome is caused by mutations in mismatch repair genes that lead to microsatellite instability (MSI). An increased number of mutation-associated neoantigens have been observed in patients with high-frequency MSI (MSI-H) cancer; in addition, membranous programmed death ligand-1 (PD-L1) tends to be expressed at higher levels in MSI-H cancers than in microsatellite-stable cancers. MSI-H cancer patients are therefore considered to be susceptible to immune checkpoint blockade. We herein report for the first time a case of lung adenocarcinoma with Lynch syndrome and the response to nivolumab.

Primary central nervous system vasculitis (PCNSV) is an uncommon vasculitis restricted to the small- and medium-sized vessels in the brain and spinal cord. Previously, only 9 cases have been reported that initially manifested as an isolated spinal cord lesion with subsequent brain involvement, where the longest interval from the onset to brain involvement was 1 year and 11 months. We herein report the case of an isolated spinal cord lesion with subsequent brain involvement appearing seven years and five months later. This case shows that brain lesions can develop after an extended interval from spinal onset in PCNSV.

Brain granuloma occurs under certain conditions. Herpes simplex virus (HSV) causes granulomatous encephalitis in children; however, it has been rarely reported in adults. A 74-year-old man with a history of herpes simplex encephalitis suffered recurrent seizures. Brain magnetic resonance imaging revealed a mass lesion and resection was performed. A polymerase chain reaction using a brain biopsy specimen was positive for HSV DNA; thus, the patient was diagnosed with HSV-associated granulomatous encephalitis. After administering acyclovir, the patient showed improvement. HSV can cause granulomatous encephalitis in adults, and acyclovir can be used for its treatment.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of gamma-aminobutyric acid-ergic (GABAergic) interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

A 45-year-old man was admitted due to tonic seizures, aphasia, disturbance of consciousness, and abnormal behavior. Because cerebral magnetic resonance imaging findings were normal and mild cerebrospinal fluid (CSF) pleocytosis was observed, autoimmune encephalitis was suspected. The presence of anti-N-methyl-D-aspartate (NMDA) receptor antibodies in the CSF was subsequently confirmed. ¹²³I-Iomazenil and cerebral blood flow single photon emission computed tomography (SPECT) revealed an abnormal uptake in the left frontotemporal region. Multimodal immunotherapy was administered, which remarkably improved the level of consciousness. Progressive reversibility of SPECT findings with clinical improvement suggested that the disorder-related functional deficits had been caused by anti-NMDA receptor antibodies.

We herein report a teenage girl who had been taking oral contraceptive pills for three months and complained of left lower abdominal pain that had continued for two months. A physical examination indicated anterior cutaneous nerve entrapment syndrome (ACNES), although no abnormality was found in various biochemical and imaging examinations. The pain was only transiently ameliorated by trigger-point injection, and neurectomy surgery was eventually effective. Sex steroids can be involved in the progress of local tissue edema causing ACNES. ACNES should be considered in cases of abdominal pain in patients taking oral contraceptives.

Hypertensive emergency, which occurs even in young adults, induces systemic organ damage and results in a poor prognosis. We herein report the case of a 27-year-old man who developed alveolar hemorrhaging with hypertensive emergency. He presented with bloody sputum, renal failure, and extremely high blood pressure (200/128 mmHg). Chest computed tomography revealed diffuse bilateral alveolar infiltrates suggestive of diffuse alveolar hemorrhaging. After intensive therapy with anti-hypertensive drugs, the alveolar hemorrhaging disappeared. Renal impairment was partially reversed. Therefore, we conclude that hypertensive emergency should be considered as a possible cause of hemoptysis, even in young adults.