Objective Recently, a new digital peroral cholangioscopy (POCS) system, the SpyGlass DS (SpyDS), has been used for POCS-guided lithotripsy for difficult bile duct stones (DBDSs). The aim of this retrospective study was to compare the efficacy of SpyDS-guided electrohydraulic lithotripsy (EHL) for DBDS with that of a conventional digital cholangioscope.

Methods Seventeen consecutive patients who had undergone POCS-guided EHL for DBDS with the SpyDS between October 2015 and January 2019 were enrolled in this study group (SpyDS group) using a prospectively maintained database. Fifteen other consecutive patients who had undergone POCS-guided EHL with a conventional digital cholangioscope (CHF-B260) just prior to the introduction of the SpyDS between December 2006 and September 2015 were analyzed as a control group (CHF group). The main outcome measurement was the total procedure time to complete stone removal.

Results The rate of complete stone removal was 100% for both groups. The mean total procedure time for the SpyDS group was significantly shorter than that for the CHF group (67±30 minutes vs. 107±64 minutes, p=0.038). The mean number of endoscopic sessions for the SpyDS group was significantly lower than that for the CHF group (1.35±0.49 vs. 2.00±0.85, p=0.037). There were no significant differences in the rate of adverse events between the two groups.

Conclusion The SpyDS appears useful for decreasing the procedure time and number of endoscopic sessions for complete stone removal in POCS-guided EHL for DBDS compared with a conventional digital cholangioscope.

Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology.

Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated.

Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ≥1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment).

Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients.

Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.

Objective Pembrolizumab has benefited patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death-ligand (PD-L) 1 high expression, but little information is available regarding its safety for patients with interstitial lung disease (ILD). The aim of this study was to assess the efficacy and tolerability of pembrolizumab for patients with advanced NSCLC and preexisting ILD.

Methods We retrospectively reviewed the medical records of five patients with advanced NSCLC and preexisting ILD who received pembrolizumab monotherapy in a first-line setting.

Patients All patients had mild ILD and pulmonary emphysema with a forced vital capacity within the normal range. Pembrolizumab was administered at a dose of 200 mg/body on day 1 every 3 weeks.

Results The overall response rate was 60%. Four patients developed pembrolizumab-induced lung injury, which was improved in all cases by corticosteroid therapy. One patient received pembrolizumab for two years, did not experience lung injury and achieved a complete response.

Conclusion Pembrolizumab has a high risk of inducing lung injury in patients with preexisting ILD, although it may be very effective in NSCLC patients with a high PD-L1 expression, even concurrent with preexisting ILD. Further large-scale studies are needed to determine risk factors of pembrolizumab-induced lung injury in such patients.

Objective Little information is available about the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with secondary myelofibrosis from essential thrombocythemia (ET) and polycythemia vera (PV). A nationwide retrospective study of the outcome of HSCT for post-ET and post-PV myelofibrosis was conducted in Japan.

Patients and Methods Clinical data for patients with post-ET (n=29) and post-PV (n=9) myelofibrosis who had received first allogeneic HSCT were extracted from the Transplant Registry Unified Management Program, which is a registry of the outcomes of HSCT in Japan.

Results Five patients died without neutrophil recovery within 60 days after transplantation. The incidence of neutrophil recovery was significantly lower in umbilical cord blood (UCB) transplantation than in related donor transplantation (40% vs. 92%, p=0.010). The 1-year non-relapse mortality for post-ET and post-PV myelofibrosis was 35% and 27%, respectively (p=0.972). No patient or transplantation characteristics were associated with non-relapse mortality. The 4-year overall survival for post-ET and post-PV myelofibrosis was 46% and 65%, respectively (p=0.362). A univariate analysis identified UCB transplantation (vs. related donor, p=0.017) and ≥10 times red blood cell transfusions before transplantation (vs. <10 times, p=0.037) as predictive of a lower overall survival.

Conclusion Allogeneic HSCT provides a long-term survival for at least some patients with post-ET and post-PV myelofibrosis. Further studies with more patients are required to determine the best alternative donor.

Objective To achieve an accurate quantification in diabetic polyneuropathy (DPN), we developed a new electrophysiological index that we called the DPN index. The relationship between the DPN index and the neurological findings in diabetic patients was assessed.

Methods The DPN index was calculated by the mean value of percentages of four parameters (tibial compound muscle action potential amplitude / F wave minimum latency, sural sensory nerve action potential amplitude / sensory nerve conduction velocity) against the mean normal values. Twenty healthy subjects were recruited as a control group.

Patients A total of 348 diabetic patients who were hospitalized in our hospital during the period from December 2016 to August 2019 were retrospectively studied. The correlations between the DPN index and five neurological findings (subjective sensory symptoms, diminished or absent Achilles tendon reflex, impaired tactile and vibration sense, low coefficient of variation of R-R interval) were evaluated.

Results The DPN index in healthy subjects was 129.3±32.7%. The DPN index in diabetic patients with one or more neurological findings was significantly lower than that in diabetic patients without any neurological findings (p<0.01: 89.3±27.8% vs. 118.4±21.2%). For each of the five neurological findings, the DPN index in the group with an abnormality was significantly lower than that in the group without any abnormality (each p<0.01). Spearman's correlation coefficients indicated that a greater number of neurological findings resulted in a lower DPN index (r=-0.711, p<0.01).

Conclusion Our study suggested that the DPN index is useful for evaluating the severity of DPN.

Objective To investigate the clinical outcomes of rheumatoid arthritis (RA) patients who discontinued infliximab (IFX) treatment at our hospital.

Methods Among 249 patients receiving IFX from 2007 to 2015, we retrospectively investigated the clinical courses of 18 who discontinued IFX after achieving the 28-joint disease activity score based on the erythrocyte sedimentation (DAS28-ESR) clinical remission (CR) and whose clinical courses were available continuously for 96 weeks after discontinuation.

Results At IFX introduction, the median age was 56.9 (range 36.1-72.4) years, and the disease duration was 5.2 (0.4-25.6) years. The median duration of maintaining either CR or a low disease activity (LDA) with IFX was 37.2 (4.0-91.4) months, and the total duration of IFX therapy was 45.8 (17.1-96.9) months. After discontinuation, 8 patients (44.4%) maintained CR/LDA for 96 weeks (no-flare group), and 10 (55.6%) experienced flares (DAS28-ESR≥3.2) within 96 weeks (flare group). In the no-flare group, six patients receiving intensified conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy to prevent flare ups simultaneously either with or immediately after discontinuing IFX. In the flare group, four patients received intensified csDMARD therapy. Six patients restarted biological DMARDs (bDMARDs), and all achieved CR again. Ultimately, 12 patients (66.7%) maintained a Bio-free disease control for 96 weeks. A comparison of the clinical backgrounds between the flare and no-flare groups showed no marked difference in their disease duration, IFX dosage, duration of maintaining CR with IFX, or concomitant csDMARDs use.

Conclusion Irrespective of the RA disease duration, more than half of all patients maintained a Bio-free condition for 96 weeks. Continuing LDA with IFX for a sufficiently long period of time before discontinuation and preventive intensification of csDMARD therapy may help maintain a Bio-free condition.

A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis.

A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed. Based on these findings, we diagnosed him with eosinophilic gastroenteritis and started prednisolone. Consequently, his eosinophil counts and abdominal symptoms dramatically improved.

Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esophageal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18 previously reported cases are summarized. This case series and literature review will encourage the accurate diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.

A 78-year-old man was referred to our hospital for a detailed examination of a pancreatic tumor that filled the main pancreatic duct (MPD). The histological diagnosis of the endoscopic biopsy specimen was neuroendocrine tumor (NET) G3. The patient subsequently underwent total pancreatectomy. The histological diagnosis of the surgical specimen was also NET G3. This is the first report of a NET that occupied the MPD and was diagnosed by a preoperative endoscopic biopsy through the papilla of Vater. This case is a good example of a histopathological diagnostic method for pancreatic tumors invading the entire MPD.

Primary cardiac lymphoma is a rare condition with a poor prognosis, and patients are at risk for sudden cardiac death. A prompt diagnosis and early treatment are therefore essential. A 68-year-old woman was admitted for shortness of breath and peripheral edema. Echocardiograms showed massive pericardial effusion and a mass on the free wall of the right atrium and ventricle. Subsequent pericardial effusion cytology revealed diffuse large B-cell lymphoma. We started chemotherapy with rituximab and achieved a good clinical course. This case is made unique by the use of pericardial effusion cytology, which allowed us to diagnose primary cardiac lymphoma promptly and safely.

Cardiac side effects associated with immune checkpoint inhibitors (ICIs) are an uncommon but serious complication with a relatively high mortality. We experienced a case of cardiomyopathy induced by nivolumab. Echocardiography showed diffuse hypo-kinesis of the left ventricular cardiac wall and a significant decrease in the ejection fraction, like dilated cardiomyopathy. The myocardial biopsy showed non-inflammatory change; cardiac function gradually improved after treatment of acute heart failure without a corticosteroid. Although non-inflammatory left ventricular dysfunction induced by ICIs is rare, it is a reported cardiovascular toxicity. Physicians should consider this complication when treating patients with ICIs for malignant diseases.

We herein report 3 cases of acute aortic dissection (AAD) in which the initial 12-lead electrocardiogram showed typical ST elevation consistent with acute pericarditis. All patients exhibited small pericardial effusion but did not suffer from rupture into the pericardium or clinical tamponade. Slow leakage or exudate stemming from the dissecting hematoma appeared to have caused inflammation, resulting in pericarditis. Therefore, we highlight the fact that AAD may masquerade as acute pericarditis. Physicians should be aware of the possibility of type A AAD as an important underlying condition, since the early diagnosis and subsequent surgical treatment may save patients' lives.

A 69-year-old woman presented with appetite loss, fatigue, and a low-grade fever. She had been receiving certolizumab pegol for rheumatoid arthritis for six years. Computed tomography of the chest showed multiple micronodules in both lungs and bilateral hilar and mediastinal lymphadenopathy. An ophthalmic examination showed the findings of uveitis. Lymphocytosis with an increased CD4/CD8 ratio was seen in the bronchoalveolar lavage fluid. Video-assisted thoracoscopic biopsy specimens obtained from the right lung and a right hilar lymph node showed noncaseous epithelioid cell granulomas. Anti-tumor necrosis factor-α-induced sarcoidosis was diagnosed, and she was successfully treated with cessation of certolizumab pegol and systemic corticosteroid therapy.

Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence.

In the 2013 updated classification of the American Thoracic Society/European Respiratory Society, airway-centered interstitial fibrosis (ACIF) is included as a bronchiolocentric pattern of interstitial pneumonia (IP) among idiopathic IPs. We encountered a case of severe pulmonary hypertension (PH) with chronic IP. The patient initially presented with shortness of breath and often lost consciousness due to PH, and seven years after his first visit, he ultimately died. An autopsy revealed ACIF and usual IP. In particular, the ACIF comprised non-atypical smooth muscle hyperplasia, and pulmonary hypertensive vascular degeneration was detected. This case may represent a new pathological feature of ACIF.

A 70-year-old woman was hospitalized for exacerbation of chronic idiopathic thrombocytopenic purpura (ITP) and disseminated intravascular coagulation (DIC) from old aortic dissection. Initially, we increased the dose of prednisolone for ITP. However, her bleeding tendency caused by DIC worsened despite the rapid recovery of her platelet count, and the required amount of fresh-frozen plasma for transfusion increased. The administration of edoxaban for atrial fibrillation led to the marked improvement of her DIC status without serious adverse events. This case suggests that a direct oral anticoagulant may be an effective treatment for DIC caused by aortic dissection.

We herein report a 64-year-old man who was treated with pembrolizumab for relapsed Hodgkin lymphoma. After the third administration of pembrolizumab, he showed acute anemia with a positive direct anti-globulin test. Because of the markedly erythroid hypoplasia, he was diagnosed with pure red cell aplasia (PRCA) caused by pembrolizumab. He was initially treated with prednisolone, but the reticulocytes decreased after tapering prednisolone. He then received high-dose intravenous immunoglobulin (IVIG) with prednisolone, and PRCA was successfully treated. Although the pathogenesis of PRCA caused by immune checkpoint inhibitors (CPIs) remains unclear, IVIG treatment may be effective for some steroid-refractory CPI-induced PRCA cases.

Relapsed acute lymphoblastic leukemia (ALL) has a poor prognosis. Inotuzumab Ozogamicin (InO) is a novel therapeutic drug for the treatment of relapsed ALL. InO has received attention as a bridging therapy before transplantation due to its high complete remission (CR) rate. However, the significance of InO in non-transplant patients remains unclear. We retrospectively evaluated four non-transplant patients treated with InO. All cases achieved CR after receiving at least two cycles of InO. Three of the four cases survived for more than 11 months without relapse. Moreover, all patients received InO as outpatients, because the adverse events were well-controlled. InO therefore appears to be a beneficial treatment even for non-transplant patients.

A 61-year-old woman was diagnosed with rheumatoid arthritis 12 years ago and received multiple treatment regimens before achieving symptomatic stability with methotrexate plus tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, about 2 years prior to the current presentation. Sixteen months after tocilizumab initiation, she exhibited dysarthria and disorientation; five months later, she was hospitalized with movement difficulties. Her neurological symptoms deteriorated thereafter, accompanied by enlarged cerebral white matter lesions on magnetic resonance imaging. A biopsy of the right frontal lesion confirmed progressive multifocal leukoencephalopathy (PML). While several therapeutic monoclonal antibodies have been linked to PML, this is the first case associated with tocilizumab.

Bacterial endophthalmitis is a rare complication of infective endocarditis (IE). We herein report a case of IE with no underlying disease for which endophthalmitis could have been the first symptom. A 58-year-old man was admitted to our hospital with a fever, vision disturbances, and pain in the left hand joint. His left eye was removed because fusion on the cornea progressed. Streptococcus agalactiae was detected in blood cultures, fluid cultures from his left hand joint, and the removed eye. Bacterial endophthalmitis may present as the first symptom of IE and develop without underlying disease due to S. agalactiae infection.

Odontogenic infections, generally caused by dental caries and periodontal disease, can result in fatal illness. We herein report a 71-year-old Japanese woman with type 2 diabetes and hemodialysis who suffered from multiple dentofacial abscesses mainly caused by multidrug-resistant Streptococcus oralis. She complained of pain and swelling of her face, with an extraoral fistula from the left cheek. Following 3 surgical debridement procedures and partial mandibulectomy, in addition to 12 weeks of antimicrobial therapy, the multiple dentofacial abscesses were ameliorated. A combination of surgical and antimicrobial treatments following an early diagnosis is essential for reducing further complications.

A 74-year-old man with interstitial lung disease (ILD) underwent surgical excision of a growing retroperitoneal tumor and was diagnosed with spindle cell sarcoma. Just after the surgery, skin eruption and muscle weakness emerged. Based on his symptoms and examination findings, we diagnosed him with anti-synthetase syndrome (ASS) with positive anti-glycyl-transfer ribonucleic acid synthetase antibody (anti-EJ) as paraneoplastic syndrome. Immunosuppressive treatments kept his progressing ILD stable for 21 months, although an expanding lung metastatic lesion from primary sarcoma was detected. Measurements of myositis-specific antibodies may enable the prediction of the efficacy of immunosuppressive treatments for paraneoplastic syndrome, even if the primary disease becomes progressive.

Splenic sarcoidosis is often diagnosed by splenectomy or an ultrasound-guided splenic biopsy. However, splenectomy is invasive and costly, and a percutaneous biopsy is sometimes difficult. We herein report a case of splenic sarcoidosis diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 71-year-old man was referred to our hospital for abnormal shadows on a chest roentgenogram. Computed tomography showed multiple lesions in the spleen and pulmonary consolidations. Bronchoscopy revealed no definitive diagnosis. We therefore performed EUS-FNA for a splenic lesion that led to the diagnosis. This case suggests that EUS-FNA is useful in confirming the diagnosis of sarcoidosis with suspected splenic lesions.