Objective We examined the safety and efficacy of endoscopic stone removal for choledocholithiasis in elderly patients ≥90 years of age with native papilla and compared the outcomes with those in patients 75-89 years of age.

Methods This multicenter retrospective study included 569 patients 75-89 years of age and 126 patients ≥90 years of age who had native papilla and underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis at 3 institutions in Japan between April 2012 and March 2018. The main outcomes assessed were the incidence of post-ERCP complications during hospitalization and outcomes of ERCP in patients ≥90 years of age.

Results Biliary cannulation and subsequent endoscopic sphincterotomy, endoscopic balloon dilation, and endoscopic large balloon dilation were successful in 97.7% of patients 75-89 years of age and in 98.4% of patients ≥90 years of age. There was no significant difference in the incidence of post-ERCP complications between patients 75-89 years of age and those ≥90 years of age (7.7% vs. 9.5%, respectively; p=0.47). Although the rate of use of mechanical lithotripter was not significantly different, the rate of complete stone removal in patients ≥90 years of age was lower than that in patients 75-89 years of age (81.0% vs. 94.9%, respectively; p<0.001). In all cases with incomplete stone removal in both groups, permanent biliary stent placement was successful.

Conclusion ERCP for choledocholithiasis in elderly patients ≥90 years of age is a safe and effective procedure; however, endoscopists should select appropriate strategies after considering each patient's medical condition and background.

Objective Cardiac rehabilitation (CR) improves the mortality in patients with cardiovascular disease (CVD). Even in elderly patients with CVD, CR may improve the activities of daily living (ADL).

Methods Eighty-eight outpatients over 65 years of age at the beginning of a CR program (baseline) at Fukuoka University Hospital who had CVD and could be followed-up for up to 5 years were enrolled. CVD included ischemic heart disease, postoperative valvular heart disease, dissecting aneurysm of the aorta and peripheral artery disease. The patients were divided into 2 groups according to the average estimated glomerular filtration rate (eGFR) at baseline (55.4±14.8 mL/min/1.73 m²): high (≥55.4, n=44) and low (<55.4, n=44)-eGFR groups. The anaerobic threshold (AT) during exercise and left ventricular ejection fraction (LVEF) were measured by cardiopulmonary exercise (CPX) and ultrasound cardiography, respectively. The serum brain natriuretic protein (BNP) was also measured every year.

Results The average age at baseline in all patients was 73±6 years. In all patients, the level of eGFR did not significantly change for 5 years (55±15 mL/min/1.73 m² at baseline vs. 48±14 at the end of the study). The AT (3.7±1.0 METs at baseline vs. 3.3±0.5), LVEF (57±13% vs. 64±10%) and BNP (260±452 pg/mL vs. 308±345) were also maintained for 5 years. In both the low- and high-eGFR groups, the eGFR, AT during exercise, LVEF and BNP at the end of the study were not significantly changed compared to the baseline values, although some changes were observed during the follow-up period.

Conclusion Long-term CR in CVD outpatients over 65 years of age helped maintain the AT, LVEF, BNP and eGFR for 5 years. CR afforded cardio-renal protection in elderly patients with CVD.

Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that leads to right-sided heart failure with electrocardiographic abnormalities. There are only a few reports about the effects of balloon pulmonary angioplasty for CTEPH on the electrocardiographic criteria of right ventricular hypertrophy. To determine the effect of balloon angioplasty on electrocardiography in patients with CTEPH.

Methods We evaluated electrocardiograms in 19 patients (mean age, 64±10 years) who underwent balloon pulmonary angioplasty.

Results We compared the hemodynamic parameters after balloon pulmonary angioplasty. The mean pulmonary artery pressure was decreased (p<0.001), and the cardiac index was increased (p=0.025) after balloon pulmonary angioplasty. The level of brain natriuretic peptide was decreased (p=0.001) after balloon pulmonary angioplasty (p<0.001). We applied 15 criteria for right ventricular hypertrophy to the patients, according to the American Heart Association recommendations of the electrocardiogram, after balloon pulmonary angioplasty. Among the criteria, the numbers of patients who met the criteria of deep S in V₆ (p=0.005) and max R in V_{1, 2}+max S in I, aV_L-S in V₁ (p=0.046) were significantly decreased after balloon pulmonary angioplasty. The mean numbers regarding the right ventricular hypertrophic criteria in each patient were significantly decreased after balloon pulmonary angioplasty (4.8±2.6 to 3.1±2.5, p=0.003).

Conclusion In addition to improvement in hemodynamics, improvement in right ventricular hypertrophy was also observed using the electrocardiographic criteria in patients with CTEPH after balloon pulmonary angioplasty, suggesting that we should pay more attention to these changes.

Objective To examine case reports presented at the Regional Meeting of the Japanese Society of Internal Medicine in order to clarify the underlying disease and prognosis of heart failure, which is often caused by non-cardiovascular diseases.

Methods We examined 49,693 case reports from the Japanese Society of Internal Medicine database. A total of 2,893 reports were included after excluding 46,022 reports that did not include the term "heart failure" and 778 reports with no indications of symptoms of heart failure. We assessed each patient's basal disease, and according to the abstracts, we reported their prognosis as dead or alive.

Results Of the 2,893 reports included, 1,952 (67.5%) and 941 (32.5%) had cardiovascular and non-cardiovascular diseases as the causes, respectively; these cases were attributed to 725 different diseases, 196 (27.0%) and 529 (73.0%) of which were cardiovascular and non-cardiovascular diseases, respectively. In addition, 91 different side effects were identified. The percentage of cases of heart failure-related mortality was significantly higher among the patients with non-cardiovascular diseases than in those with cardiovascular diseases (17.8% vs. 10.8%; p <0.001). Of the diseases reported as causes of heart failure in more than 10 reports, pulmonary tumor thrombotic microangiopathy (87%), multiple myeloma (50%), and amyloidosis (47%) accounted for the highest percentages of heart failure-related mortality.

Conclusion Because heart failure is often caused by non-cardiovascular diseases, a broad study of case reports on internal medicine is important for cardiologists.

Objective The association between narcolepsy and rapid eye movement (REM)-related obstructive sleep apnea (OSA) has not been reported. This study aimed to examine the prevalence of REM-related OSA in narcolepsy patients.

Methods From January 2013 to April 2018, 141 adult patients were diagnosed with narcolepsy using nocturnal polysomnography and the multiple sleep latency test. The prevalence of REM-related OSA in narcolepsy patients was retrospectively reviewed. Three criteria were used to determine REM-related OSA: Definition #1, an overall apnea-hypopnea index (AHI) ≥5 and AHI during REM (AHIREM)/AHI during non-rapid eye movement (NREM) (AHINREM) ≥2; Definition #2, an overall AHI ≥5 and AHI_REM/AHI_NREM≥2 and AHI_NREM <15; and Definition #3, an overall AHI ≥5 and AHI_REM/AHI_NREM≥2 and AHI_NREM <8 plus an REM sleep duration >10.5 minutes.

Results Of the 141 narcolepsy patients, 26 were diagnosed with narcolepsy with cataplexy (NA-CA) and 115 with narcolepsy without cataplexy (NA w/o CA). Seventeen patients with NA-CA and 39 with NA w/o CA had OSA. According to Definition #1, the prevalence of REM-related OSA was 47.1% and 41.0%, respectively, in OSA patients with NA-CA and NA w/o CA; according to Definition #2, the respective prevalence was 47.1% and 38.5%, while that according to Definition #3 was 41.2% and 25.6%. No significant differences were found in the prevalence of REM-related OSA for each definition.

Conclusion A high prevalence of REM-related OSA was confirmed in adult narcolepsy patients with OSA. Compared to previous reports, we noted a high frequency of REM-related OSA satisfying the relatively strict Definition #3. These results might reflect the pathophysiological characteristics of narcolepsy.

Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL.

Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses.

Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases.

Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.

No specific endoscopic features for eosinophilic gastroenteritis (EGE) have been reported previously. This study therefore evaluated the endoscopic findings of six patients with EGE. The diagnosis was confirmed based on gastrointestinal symptoms, pathological findings on biopsy, and the absence of other diseases. The site of the lesion was identified based on eosinophilic infiltration with ≥20 cells per high-power field during a pathological specimen analysis. Flattening of the small intestinal villi was observed in four patients; we speculate that this may be a specific feature in the diagnosis of EGE.

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. Although highly invasive, surgery is often used as the first-line treatment. We herein report the case of a 65-year-old woman who presented with complaints of progressive odynophagia and dysphagia for 2 weeks following a fish meal. Enhanced cervicothoracic computed tomography demonstrated an enhanced round mass with peripheral contrasted margins. The mass was diagnosed as a mediastinal abscess resulting from esophageal perforation caused by a fish bone. Endoscopic ultrasound-guided abscess drainage (EUS-AD) was performed using a nasobiliary drainage tube (NDT). Two weeks later, the abscess had completely disappeared. EUS-AD was safe and effective in this case; furthermore, external drainage using NDT was suitable for this abscess located very close to the upper esophageal sphincter.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

Selective immunoglobulin M deficiency (SIGMD) is an uncommon primary immunodeficiency disorder. We herein report an SIGMD patient with autoimmune hepatitis. A 21-year-old Japanese man was transferred to our hospital because of acute liver dysfunction. His serum IgM level was low, whereas those of IgG and IgA were normal, indicating that he had SIGMD. We diagnosed him with acute-onset autoimmune hepatitis, and his liver function test findings gradually recovered with corticosteroid administration. Although SIGMD with autoimmune diseases has been reported, the clinical features and pathogenesis have not yet been clarified. We have summarized previous reports on SIGMD patients with autoimmune diseases.

Spontaneous renal artery dissection (SRAD) is a rare entity and the management of this disease has not been established. A 54-year-old man presented with severe flank pain, and contrast-enhanced computed tomography images suggested SRAD in his left renal artery. After two weeks of conservative treatment, stents were placed in the renal artery. The pre- and post-procedural renal function was independently assessed by renography. After stenting, his left renal function recovered from the renal failure pattern. Renal artery stenting in an acute phase of SRAD may salvage the renal function, even if it appears to be non-functioning.

We herein report two cases of patients with thyroid storm with a delayed diagnosis due to psychosis. The patients were a 63-year-old woman with bipolar II disorder and a 37-year-old man with major depressive disorder. The psychoses in both patients were well controlled with medication. Although they both showed symptoms of thyrotoxicosis, the symptoms were ignored, presumably because the psychological manifestations of worsening of psychosis and thyroid storm are similar. When the mental or physical state of patients with psychosis changes, thyroid hormone levels should be measured for early treatment.

Hypomagnesemia, a side effect of proton-pump inhibitors (PPIs), can be asymptomatic. The presence of hypocalcemia or hypokalemia is indicative of hypomagnesemia; however, the concomitant use of PPIs and thiazide may mask hypocalcemia. A 79-year-old woman with a history of chronic heart failure and chronic kidney disease developed symptomatic hypocalcemia and hypomagnesemia. Five weeks earlier, she had developed thiazide-induced hyponatremia, so thiazide had been discontinued. Reviewing the patient's charts revealed that three discontinued thiazide administrations in the clinical course had unmasked hypocalcemia. Our case demonstrates that thiazide-induced hypercalcemia can be so prominent as to mask PPI-induced hypocalcemia and hypomagnesemia.

An 81-year-old woman with rheumatoid arthritis (RA) who had been treated with bucillamine presented with dyspnea. Computed tomography of the chest showed ground-glass opacities and consolidations in both lungs and honeycombing in both basal lung areas. An elevation of the serum Krebs von den Lungen-6 level and hypoxemia were seen. Lymphocytosis with a decreased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. A transbronchial lung biopsy specimen showed organizing pneumonia. Based on a diagnosis of bucillamine-induced pneumonitis (BIP) with RA-associated pre-existing interstitial pneumonia, she was successfully treated with the cessation of bucillamine and systemic corticosteroid therapy. The risk factors and prognosis of BIP are discussed.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma. The detection of plasma cells in the peripheral blood and monoclonal protein in the serum or urine is important for the diagnosis of PCL. However, it is sometimes difficult to diagnose PCL in patients with atypical plasma cell morphology and/or those without detectable monoclonal protein. We herein report a case of oligosecretory PCL showing atypical morphology in leukemic cells with a convoluted nucleus and basophilic cytoplasm but without detectable monoclonal protein, except for serum free light chain. A flow cytometric analysis and pathological analysis were useful for the early diagnosis of PCL.

Infectious diseases, including those caused by fungi, remain important issues in patients receiving malignant lymphoma chemotherapy. We herein report a rare case of Exophiala dermatitidis fungemia during chemotherapy in a 67-year-old woman admitted to our hospital. She had a fever that could not be resolved despite antifungal therapy. Yeast-like fungi were detected in blood culture samples, but biochemical identification was difficult. E. dermatitidis, a black mold, was identified using time-of-flight mass spectrometry. The patient finally improved after her treatment was switched to voriconazole. Fungal infection is difficult to diagnose and treat, but this novel approach can improve patients' outcomes.

We herein report a case of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) that occurred immediately after blood transfusion. A 64-year-old Japanese woman was diagnosed with liver cirrhosis due to hepatitis B 2 years ago. She was admitted to our hospital with hemorrhagic shock due to esophageal variceal rupture. She was hospitalized with rapid blood pumping transfusion, after which consciousness disorder appeared, and her blood pressure suddenly increased. Magnetic resonance imaging revealed PRES and RCVS. We speculated that hypoalbuminemia and blood transfusion might have been involved in the development of PRES and RCVS.

Spinal and bulbar muscular atrophy (SBMA) is a progressive hereditary neuromuscular disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. A 41-year-old man with SBMA received the androgen deprivation agent leuprorelin acetate for 7 years in clinical trials and underwent castration following the trial. Suppression of testosterone levels for 14 years resulted in a slower disease progression, as measured prospectively with quantitative measurements, than the historical control data reported in previous studies. This suggests that long-term androgen deprivation delays disease progression in SBMA.

We herein report a Japanese patient with familial Mediterranean fever (FMF) who developed the clinical manifestations of mixed connective tissue disease (MCTD) and Sjögren's syndrome. The patient was a 36-year-old woman presenting with a periodic short-duration (2-3 days) fever and pleural pain. An Mediterranean fever (MEFV) gene analysis detected a complex allele mutation (P369S/R408Q) in exon 3 of the MEFV gene. Serological and clinical data showed the coexistence of MCTD and Sjögren's syndrome. Treatment with colchicine (1.0 mg/day) successfully eliminated febrile attack and pleuritis, leading to the diagnosis of FMF. Four months after the initiation of colchicine treatment, she presented with MCTD-related pulmonary artery hypertension. This is the first report of FMF coexisting with MCTD.

The number of Takayasu arteritis (TAK) cases being diagnosed at an advanced age has increased, including some who develop ischemic lesions without inflammation of the involved arteries long after the onset of TAK. However, few histopathological analyses of such patients without immunosuppressive therapy have been reported. We herein report a 92-year-old woman with atypical aortic coarctation complicating TAK who underwent bypass graft surgery and survived for 23 years without immunosuppressive therapy. Microscopic findings at the autopsy revealed clear differences between the affected and unaffected arteries. This case suggests that inflammation severe enough to destroy the structure of the aorta may not inherently be sufficient to promote systemic atherosclerosis.

We herein report a case of Campylobacter fetus meningoencephalitis in a patient with chronic alcoholism. C. fetus is a rare cause of meningitis. The patient presented with hallucinations and monology, and alcohol withdrawal was initially suspected. After he was unsuccessfully treated for alcohol withdrawal delirium, we diagnosed C. fetus meningoencephalitis. Ampicillin monotherapy gradually improved his clinical status. A previous report stated that C. fetus infection is associated with chronic alcoholism. In patients with chronic alcoholism and disturbed consciousness, an atypical bacterial central nervous system infection, such as C. fetus meningoencephalitis, should be considered.

We herein report a patient with syphilitic cervicitis and cervical cancer presenting as oropharyngeal syphilis. A 31-year-old Japanese woman with a history of unprotected vaginal and oral sex visited our hospital with right submandibular adenomas and erythema in the extremities. The fornix uteri was red, with a nodule noted. The rapid plasma reagin ratio was 1:3. She was diagnosed with syphilitic cervicitis and treated with amoxicillin for four weeks. Initial cervical cytology showed cells with mild nuclear enlargement, which was thought to be metaplasia associated with syphilis. Repeated cytology a month later showed a high-grade squamous intraepithelial lesion. A punch biopsy of the lesion led to the pathological diagnosis of cervical carcinoma in situ. We performed cervical conization, and no recurrence occurred. Human papillomavirus (HPV) immunostaining was positive in the lesion. Mucosal lesions are an infrequently reported symptom of syphilis. When oropharyngeal lesions are found, the sexual history should be ascertained, and the patient should be screened for sexually transmitted diseases. HPV is especially significant because of its association with cervical cancer. Coinfection of HPV with cervical cancer must be ruled out during follow-up for women when oropharyngeal syphilis involves genital lesions.

We present a report of a 29-year-old woman with non-dipper type refractory hypertension due to the vascular compression of the medulla oblongata. The patient was diagnosed with hypertension at 17 years of age and underwent emergency Caesarean section at 26 weeks of gestation during 2 pregnancies due to severe high blood pressure. We suspected medullary compression by the curved posterior inferior cerebellar artery as the cause of her intractable hypertension, and she underwent Jannetta's decompression surgery. After the surgery, her blood pressure swiftly decreased to almost within the normal range, and her blood pressure pattern normalized to dipper type.