Objective The diagnostic accuracy of an endoscopic ultrasound-guided fine-needle aspiration cytology/biopsy combined with a cell-block method (FNA-CB) for gastrointestinal subepithelial lesions (GI-SELs) has not been fully studied.

Methods A total of 109 patients (with 110 GI-SELs) were evaluated to clarify the rate of obtaining evaluable histology specimens using FNA-CB. In addition, we investigated the following: 1) the accuracy for determining the histology, 2) effects of the number of cell clusters obtained via FNA-CB, 3) correlation of the Ki67 labelling index (Ki67LI) of the gastrointestinal stromal tumor (GIST) lesions between FNA-CB and resected specimens, and 4) clinical courses for patients followed up after FNA-CB.

Results Of the 110 GI-SELs for which FNA-CB was performed, 95 (86%) were able to be histologically evaluated using the first FNA-CB. For the 70 resected GI-SELs, the accuracy of FNA-CB to determine histology was 96%, remaining at 90% even when only a few cell clusters were obtained. The concordance rate of the risk-grouping of GIST (high-risk, Ki67LI ≥8; low-risk, <8) between FNA-CB and resected specimens was 84%. Of the 29 patients followed up after the first FNA-CB, 12 with benign GI-SELs determined using the first FNA-CB showed no obvious increases in their GI-SEL sizes.

Conclusion Since FNA-CB can be used to determine the histology and reproductive activity of GI-SELs accurately, not only preoperative histological confirmation but also reliable information to determine clinical plans, such as follow-up without surgery or neoadjuvant chemotherapy, can be obtained.

Objective Esophageal diverticulum is rare, and the concomitance of esophageal motility disorders (EMDs) and the efficacy of novel endoscopic treatment have not been investigated in Japan.

Methods An examination including high-resolution manometry (HRM) was performed for patients with both EMDs and epiphrenic diverticulum. EMD-related epiphrenic diverticulum and Zenker's diverticulum were treated using salvage peroral endoscopic myotomy (s-POEM) and endoscopic diverticulotomy, respectively.

Results Six cases of epiphrenic diverticulum were diagnosed in this study. Among 125 patients with achalasia and spastic disorders, concomitant epiphrenic diverticulum was observed in 4 (3.2%). Of these, three showed a normal lower esophageal sphincter pressure on HRM, although gastroscopy and esophagography revealed typical findings of an impaired lower esophageal sphincter relaxation. These four patients were successfully treated with s-POEM, and the Eckardt score improved from 6.3 to 0.25 at 32.5 (range: 13-56) months of follow-up, with equivalent treatment efficacy to that observed for achalasia and spastic disorders without epiphrenic diverticulum. In contrast, the two remaining cases of epiphrenic diverticulum had normal esophageal motility. Six cases of Zenker's diverticulum were diagnosed, and endoscopic diverticulotomy was successfully performed in all. The dysphagia score decreased from 2.8 to 0.17 at 14.8 (range: 2-36) months of follow-up. Overall, 12 endoscopic treatments were performed for esophageal diverticulum; no adverse events were observed.

Conclusion In epiphrenic diverticulum patients, concomitant EMDs are not rare and should be carefully diagnosed. A normal lower esophageal sphincter pressure on HRM does not always mean a normal lower esophageal sphincter relaxation. S-POEM and endoscopic diverticulotomy are effective minimally invasive treatment options for EMD-related epiphrenic diverticulum and Zenker's diverticulum.

Objective The relationship between the prognosis and magnitude of a decrease in tumor blood flow according to estimated tumor differentiation remains unclear. This study investigated the relationship between reductions in the rate of mean computed tomography (CT) attenuation values and the clinical prognosis.

Methods We evaluated 63 consecutive patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). The oncological aggressiveness of the tumors was estimated using classification by dynamic CT enhancement patterns. The utility of changes in mean CT attenuation values of intra-hepatic targets during treatment to estimate the prognosis was investigated by calculating the progression-free survival (PFS) and post-progression survival (PPS). A multivariate analysis was used to identify potential confounders for the survival after progression during lenvatinib therapy.

Results The rate of decrease in the mean CT attenuation value gradually increased according to the degree of deterioration in estimated tumor differentiation, and the rate of a decrease in attenuation ≥40% showed a tendency to increase (p=0.064). This trend was reflected by a better objective response in oncological aggressiveness heterogeneous enhancement patterns (Type-3 and Type-4) than a homogeneous enhancement pattern (Type-2) (83% vs. 56% of modified Response Evaluation Criteria in Solid Tumors). This resulted in a similar PFS between the groups (p=0.773), whereas the PPS was significantly worse when the rate of decrease in the attenuation value was ≥40% (p=0.012). A multivariate analysis confirmed that a rate of decease in attenuation value ≥40% was a poor prognostic factor for the PPS (hazard ratio, 2.993; 95% confidence interval, 1.196-7.490; p=0.019).

Conclusion A rate of decrease in attenuation ≥40% may reflect a good response of a highly malignant tumor to lenvatinib. Therefore, this value may have utility as a surrogate marker for estimating the oncological aggressiveness of tumors and their associated prognosis.

Objective Mapping the long-term prognosis of Budd-Chiari syndrome (BCS) is difficult, as the prognosis is associated with changes in the liver function. The present study evaluated the time course changes in the liver function in a treatment group with percutaneous old balloon angioplasty (POBA) and a non-treatment group using the albumin-bilirubin score (ALBI) and Child-Pugh score during long-term follow-up.

Methods In this retrospective study, 13 consecutive patients diagnosed with BCS at our hospital between 2007 and 2020 were categorized into a treatment group (n=8), which received POBA, and a non-treatment group (n=5). Differences in the liver function in the ALBI and Child-Pugh scores between the initial visit and one- and three-year follow-up were calculated and statistically evaluated. We investigated the changes in the liver function during the long-term follow-up, including events such as re-stenosis and re-treatment.

Results While the Child-Pugh scores in the treatment group did not differ significantly between the initial visit and 1- or 3-year follow-up, the ALBI scores in this group improved significantly between the initial visit and the 1- or 3-year follow-up visit (p=0.0078 and 0.0156, respectively). The liver function according to the ALBI score in the treatment group showed gradual improvement from the initial value but gradual worsening in the non-treatment group. The ALBI scores also revealed that the liver function varies according to re-stenosis and re-POBA in BCS patients.

Conclusion Unlike the Child-Pugh score, the ALBI score was able to capture changes in the liver function of BCS patients during the long-term course of BCS.

Objective For risk stratification of sudden cardiac death in patients with structural heart disease, more precise predictors in addition to left ventricular ejection fraction (LVEF) are clinically needed. The present study assessed the utility of galectin-3 as an independent indicator for the prognosis of heart failure patients with implantable cardioverter-defibrillators (ICD).

Methods The study population consisted of 91 consecutive patients who underwent a routine ICD checkup in our ICD outpatient clinic. Circulating galectin-3 was assessed using a commercially available enzyme-linked immunosorbent assay kit. The enrolled patients were prospectively followed. The primary endpoint was defined as the occurrence of appropriate ICD therapy (AIT), and the secondary endpoint was defined as the occurrence of unplanned overnight hospitalization due to decompensated heart failure (dHF).

Results During a mean follow-up of 472±107 days, AIT occurred in 18 patients (20%). Unplanned hospitalizations due to dHF were noted in 12 patients (13%). A receiver-operative characteristics analysis demonstrated a sensitivity of 83% and specificity of 68% for AIT occurrences with a galectin-3 cut-off value of 13.1 ng/mL (area under the curve =0.82). A Kaplan-Meier analysis demonstrated that patients with galectin-3 >13.1 ng/mL had significantly higher incidences of AIT as compared to those with lower galectin-3 (log-rank, p<0.001). This significance was also observed in both subgroup analyses with ischemic and non-ischemic etiology. Cox regression demonstrated that higher galectin-3 was an independent predictor of AIT and dHF, even after adjusting for previous arrhythmic events.

Conclusion The circulating galectin-3 level can be used as a clinical indicator of subsequent occurrence of ventricular arrhythmic events and decompensated heart failure, regardless of a history of ventricular arrhythmias.

Objective Phosphate is a fundamental element involved in a number of physiological pathways. A previous study showed abnormal laboratory findings and a higher mortality in hypophosphatemic patients than in normophosphatemic patients with pneumonia. Sporadic cases of pneumonia due to Legionella spp., Streptococcus pneumoniae, and viruses have been reported; however, the significance of hypophosphatemia in patients with pneumonia has not been adequately studied. We determined whether or not hypophosphatemia in patients with community-acquired pneumonia (CAP) was associated with specific pathogens, patient factors, disease severity, and mortality.

Method We retrospectively analyzed 600 patients with CAP who were admitted to our hospital between January 1, 2010, and December 31, 2019.

Results Hypophosphatemia was found in 72 (12.0%) of the 600 patients. The most frequent causative microbial agents of CAP in patients with hypophosphatemia were S. pneumoniae, Legionella spp., and influenza virus, whereas in severely ill patients with hypophosphatemia, influenza virus was the most common. Legionella spp., diabetes mellitus, and severe pneumonia were the independent factors for hypophosphatemia in the multivariable analysis. An impaired performance status, severe status on admission, interstitial pneumonia, bacteremia, and guideline-discordant therapy were the independent factors associated with mortality in the multivariable analysis. Hypophosphatemia was not significantly associated with mortality but showed a trend towards higher mortality in the multivariable analysis.

Conclusion Hypophosphatemia was not associated with the prognosis in patients with CAP. However, the significance of hypophosphatemia for clinicians lies in the laboratory findings that predict abnormal glucose metabolism, Legionella infection, and severe disease.

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood.

Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019.

Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men.

Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy.

Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis.

Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors.

Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.

An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.

Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis.

A de novo cardiac malignant tumor is rare and sometimes challenging to diagnose. We encountered a 67-year-old man without any medical history complaining of dyspnea on effort. On admission, his hemodynamics were deteriorated due to cardiac tamponade, which was improved by percutaneous drainage of 1,200 mL pericardial effusion, showing 11.0 g/dL of hemoglobin. We suspected primary cardiac malignancy following multidisciplinary tests, and a cardiac biopsy via sternotomy demonstrated the definitive diagnosis of primary malignant tumor (angiosarcoma) infiltrating the right atrial myocardium. We initiated weekly paclitaxel therapy. Further studies are warranted to establish the optimal diagnostic and therapeutic strategy for de novo cardiac malignancy.

Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.

Rosai-Dorfman-Destombes disease (RDD) is a non-Langerhans cell histiocytosis characterized by the accumulation of histiocytes inside the lymph nodes or extranodally. The association between RDD and IgG4-related disease (IgG4-RD) is discussed. We herein report a case of RDD manifesting as acute tubulointerstitial nephritis mimicking IgG4-RD. The first renal biopsy showed severe tubulointerstitial nephritis with infiltration of S100-positive histiocytes and IgG4-positive plasma cells; storiform fibrosis and obliterative phlebitis were not confirmed. After prednisolone therapy, IgG4-positive cells and S100-positive histiocytes were decreased, but the IgG4/IgG ratio increased despite clinical improvement. These findings indicated extranodal RDD in the kidney presenting as tubulointerstitial nephritis.

A 28-year-old woman experienced gross hematuria after the administration of the second dose of an messenger ribonucleic acid (mRNA) vaccine (BNT162b2). She was diagnosed with Immunogloblin A nephropathy (IgAN) by a renal biopsy two weeks after vaccination, which revealed a mild increase in mesangial cells and a matrix with co-depositions of galactose-deficient IgA1 and C3 in the mesangial region. The gross hematuria and proteinuria gradually improved without any medication, suggesting that immune activation by the mRNA vaccine may not elicit continuous disease progression of IgAN. Thus, further studies investigating the relationship between mRNA vaccines against COVID-19 and the progression of IgAN should be conducted.

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.

This is the first report describing primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with the high expression of IgG4. The histological findings were compatible with the diagnostic criteria for MALT lymphoma and IgG4-related respiratory disease (IgG4-RRD). An unfixed sample for Southern blotting was not obtained since computed tomography findings showed multiple lung cysts, which is rare in patients with MALT lymphoma. However, polymerase chain reaction using paraffin sections showed the clonality of the immunoglobulin heavy chain variable region gene rearrangement, confirming a diagnosis of MALT lymphoma. This is an instructive case in which primary pulmonary MALT lymphoma was histologically compatible with IgG4-RRD.

Right neck swelling and pain occurred in a 49-year-old man. A Blood count showed a slight increase in platelet count without leukemoid reaction. After a biopsy of the cervical mass and bone marrow aspiration, a diagnosis of extramedullary blast crisis (EBC) of chronic myeloid leukemia (CML) was made. Fluorescence in situ hybridization (FISH) analysis showed a BCR-ABL1 fusion signal, but results of real-time polymerase chain reaction (RT-PCR) for major and minor BCR-ABL1 transcripts were negative. We identified a rare e1a3 BCR-ABL1 fusion transcript. Administration of dasatinib resulted in disappearance of the extramedullary tumor. This is the first reported case of CML-EBC with e1a3 transcript. An aleukemic extramedullary tumor can be the initial presentation of CML.

Adult T-cell leukemia/lymphoma (ATL) is a refractory T-cell lymphoma with variable clinical profiles, commonly exhibiting extra-nodal involvement. The myocardial involvement of ATL is often detected at an autopsy; however, the development of a symptomatic cardiac mass due to ATL is extremely rare. We herein report a 65-year-old man with ATL who developed cardiac symptoms due to a rapidly enlarging left ventricular mass soon after the initiation of systemic chemotherapy. We also summarize previously reported cases of symptomatic ATL with cardiac involvement.

We herein report a case of sudden-onset parkinsonism, with no other symptoms, caused by intracranial dural arteriovenous fistulas (DAVFs). Diffusion-weighted magnetic resonance imaging (MRI) revealed an increased signal intensity in the bilateral lenticular nucleus. Endovascular embolization improved the patient's parkinsonism and MRI findings. DAVF should be suspected in cases of sudden-onset parkinsonism.

We herein report two P/Q-type voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS) patients who responded dramatically to cholinesterase inhibitors. Patient 1, a 76-year-old man, had small-cell lung cancer and developed LEMS during chemotherapy. When symptomatic treatment was started with pyridostigmine, gait disturbance was ameliorated, and his modified Rankin scale decreased from 4 points to 3 points. Patient 2, a 68-year-old man, had cancer-free LEMS. Distigmine bromide was very effective and ameliorated not only his gait disturbance but also autonomic symptoms, and his modified Rankin scale decreased from 2 points to 1 point. Cholinesterase inhibitors alone may be effective in a small portion of LEMS patients.

After BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination, a 30-year-old man developed bilateral lateral gaze palsy, diplopia, absent tendon reflexes, and ataxic gait. Serum anti-GQ1b and anti-GT1a immunoglobulin G (IgG) antibodies were strongly positive. Based on those findings, he was diagnosed with Miller Fisher syndrome (MFS). Intravenous immunoglobulin therapy was administered, and his symptoms fully recovered within approximately 3 months. To the best of our knowledge, this is the first report to describe the development of MFS after COVID-19 mRNA vaccination.

Myoclonus and ataxia, with or without opsoclonus, have recently been recognized as a central nervous system syndrome associated with coronavirus disease-2019 (COVID-19). A 52-year-old Japanese man developed myoclonus and ataxia 16 days after the onset of COVID-19. Brain single-photon emission computed tomography (SPECT) revealed hyperperfusion in the cerebellum and hypoperfusion in the cerebral cortices with frontal predominance during the acute stage, which improved over two months. This study indicates that brain perfusion SPECT can be effective in detecting functional alterations in COVID-19-related myoclonus and ataxia.

We herein report a case of Behçet's disease with renal infarction due to mucormycosis. A 76-year-old man with entero-Behçet's disease had been treated with glucocorticoid and tumor necrosis factor (TNF) inhibitors. His entero-Behçet's disease was refractory to these treatments, and ileocecal resection was performed. After the operation, renal infarction that was unresponsive to anticoagulation therapy developed. He ultimately died of renal failure due to renal infarction. At the autopsy, histopathology of abundant hyphae in the renal vessel wall revealed mucormycosis. Renal mucormycosis is an important cause of renal failure with renal infarction in immunocompromised patients.

Myositis-specific autoantibody is associated with the clinical phenotype and prognosis of dermatomyositis. Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are generally mutually exclusive. We herein present an extremely rare case of dermatomyositis which showed double positivity for anti-MDA5 and anti-ARS antibodies. There have been very few reported cases of double positive anti-MDA5, anti-ARS antibodies. In such cases, the clinical characteristics of each autoantibody can coexist. Thus, we should pay attention to the rapidly progressing features of anti-MDA5 as well as the chronic relapsing features of anti-ARS for the better management of this rare condition.

African tick bite fever (ATBF) is an acute febrile illness caused by Rickettsia africae. ATBF is an important differential diagnosis of acute febrile illness among returned travelers. However, little information is available on ATBF cases imported to Japan, as only seven have been reported to date. To characterize the epidemiological and clinical profiles of patients diagnosed with ATBF in Japan, we reported three new ATBF cases at our hospital between May 2015 and April 2018 and conducted a literature review.

Duloxetine is widely used for pain control and depressive syndromes. One of its potential side effects is syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Duloxetine-induced SIADH causes hyponatremia, which leads to a variety of symptoms and has previously been reported in the elderly. In the present case, we experienced a case of the rapid onset of SIADH in a super-elderly woman receiving low-dose duloxetine. Elderly patients tend to have lower duloxetine doses and an earlier onset than non-elderly patients. When hyponatremia occurs after duloxetine administration, duloxetine-induced SIADH should be considered, especially in high-risk elderly patients, regardless of the duloxetine dose or duration of treatment.

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient's chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.