Objective The progression of liver fibrosis and a male sex are risk factors for hepatocarcinogenesis under nucleos(t)ide analog (NA) therapy. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for hepatocarcinogenesis. This study aimed to investigate the factors involved in hepatocarcinogenesis during NAs therapy, including MAFLD.

Methods This study is a retrospective study [observation period: median 9.4 years (2.1-19.6 years)]. The subjects were 164 patients taking NAs for more than 2 years and were hepatitis B envelope antigen (HBeAg)-negative with undetectable hepatitis B virus (HBV)-DNA. The patient had no history of hepatocellular carcinoma (HCC). We investigated the profile of HCC onset after NAs therapy using a decision tree analysis

Results HCC developed in 20.7% (34/164) of the patients during the observation period. The prevalence of MAFLD was significantly higher in the HCC group than in the non-HCC group (64.7% vs. 43.9%, p=0.03). In particular, in the low-medium risk group classified by PAGE-B, MAFLD increased the risk of HCC development. According to a multivariate analysis, fibrosis-4 (FIB-4) index≥2.67, a male sex, and MAFLD (OR 2.4, 95%CI 1.0-6.0, p=0.04) were independent factors associated with the onset of HCC. In a decision tree analysis, MAFLD was the second classifier for the onset of HCC, next to the FIB-4 index (MAFLD 62.5%, non-MAFLD 28.5%).

Conclusions We found that MAFLD was an independent risk factor for HCC in HBeAg-negative patients with undetectable HBV-DNA after NAs therapy. We further revealed that MAFLD was the second-best classifier for hepatocarcinogenesis, next to the FIB-4 index. MAFLD therefore appears to have a synergistic effect on hepatocarcinogenesis with hepatic fibrosis.

Objective Recent developments in ultrasound elastography (UE) and ultrasound attenuation imaging (UA) have enabled the detection of advanced liver fibrosis and steatosis in patients with steatotic liver disease (SLD), which is prevalent worldwide. In patients with SLD, the presence of advanced liver fibrosis determines the risk of hepatocarcinogenesis, and UE and UA are expected to play important roles in liver cancer surveillance. We conducted a questionnaire survey among medical facilities in Saga Prefecture regarding the actual status of awareness and implementation of UE and UA.

Methods A 16-item questionnaire was sent to 275 facilities that employed members of the Liver Cancer Control Medical Association in Saga Prefecture. The response rate was 56% (153 facilities), and data from 142 facilities were analyzed after excluding 11 facilities.

Results The most common facilities were outpatient clinics (60%) followed by hospitals with ≥100 beds (14%). In 48% of the facilities, an average of 10-49 abdominal ultrasound examinations were performed monthly. The rates of recognition that UE and UA are useful for fibrosis and steatosis were 65% (92/142) and 41% (58/142), respectively. The actual availability of UE and UA in facilities with ultrasound machines was 21% (30/142) and 12% (17/142), respectively; UE and UA were used in 90% (27/30) and 88% (15/17) of these facilities, respectively.

Conclusion Even among medical facilities in Saga Prefecture that are active in liver cancer surveillance, awareness of UE and UA is not high. The availability of UE and UA may be inadequate, considering the high prevalence of SLD.

Objective Gangliocytic paraganglioma (GP) significantly affects patients' quality of life. However, studies on endoscopic papillectomy (EP) for ampullary GP are limited. We therefore evaluated the safety and efficacy of EP for treating ampullary GP.

Methods We retrospectively reviewed the clinicopathological characteristics of patients with GP who underwent EP at Nagoya University Hospital and conducted a literature survey.

Results We enrolled six patients with a median tumor diameter of 17 mm. Complications related to EP were observed in three patients: two experienced bleeding, one had mild acute pancreatitis, and one had perforation (duplicate patients included), all of whom improved conservatively. Five resected specimens were confined to the submucosal layer, and one was beyond the submucosal layer. All patients were monitored without surgery, and no disease recurrence was observed after a median follow-up of 73 months. A literature review identified 14 patients, and additional surgery due to a positive vertical margin after EP revealed lymph node metastasis in 2 patients. There was no disease recurrence or death.

Conclusion EP led to good long-term outcomes and effectively treated ampullary GP. Considering the potential for lymph node metastasis, additional surgery is recommended if the tumor exceeds the submucosal layer.

Objective The impact of Helicobacter pylori infection on gastric endoscopic findings in non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) remains unclear. This study investigated the influence of H. pylori infection on the prevalence and distribution of gastric lesions.

Methods The details of 75 patients diagnosed with non-EoE EGIDs were retrospectively reviewed. Of the 56 patients with a definitive diagnosis according to the Japanese criteria (any GI tract; ≥20 eosinophils/high-power field), 25 patients with pathologic gastric eosinophilic infiltration (EI) (gastric EI; ≥30 eosinophils/high power field) were investigated in detail. The prevalence and distribution of gastric endoscopy findings were assessed according to the gastric mucosal atrophy status, an indicator of H. pylori infection.

Results Erythema (76%) was the most common finding in the gastric EI-positive group, followed by erosions (36%), ulcers (28%), ulcer scars (28%), and edema (24%). None of these lesions differed significantly in frequency between the patients with and without gastric atrophy. When erosions, ulcers, and ulcer scars were unified, they were slightly more common in the gastric bodies of patients with gastric atrophy than those without gastric atrophy; however, no preferential site was found in those without gastric atrophy. We identified six patients with active gastric ulcers, and half had large, deep ulcers with marginal swelling/irregularity.

Conclusion Gastric endoscopy findings in non-EoE EGIDs with gastric EI were evenly observed in the stomach, with no specific trend in frequency or distribution depending on atrophic gastritis, an indicator of H. pylori infection. Gastric ulcers in patients with non-EoE EGIDs should be considered in the differential diagnosis of idiopathic peptic ulcers.

Objective The mean platelet volume (MPV), a marker of platelet activity, is significantly higher in patients with aortic stenosis (AS) than in those without AS. The association between the platelet function and prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) remains unknown. Therefore, we investigated this association by measuring the MPV.

Methods Of 237 patients who underwent TAVR, 148 with a median age of 84 years old were enrolled in this study. Blood tests and transthoracic echocardiography were performed at baseline and approximately six months after TAVR. PPM was defined as an aortic valve area index ≤0.85 cm²/m² after TAVR. Variable changes from baseline to six-month follow-up were compared between patients with and without PPM.

Results Forty-five patients (30%) developed PPM. The MPV was significantly higher in patients with PPM than in those without PPM. However, regarding the magnitude of change, the MPV was significantly less reduced in patients with PPM, and the percentage of patients with reduced MPV was lower in patients with PPM than in those without PPM. A logistic regression analysis revealed that a higher MPV and lack of MPV reduction at the six-month follow-up were independent predictors of PPM.

Conclusion MPV values at the six-month follow-up were associated with PPM after TAVR in patients with AS. MPV values increase when PPM is present after TAVR and may be an indicator during the postoperative follow-up.

A 65-year-old man treated with atezolizumab plus bevacizumab for hepatocellular carcinoma was admitted to our hospital with a fever, difficulty in moving, and aphasia. The patient became comatose immediately after admission. Imaging and cerebral fluid tests revealed no evidence of malignancy or infection. A diagnosis of atezolizumab-induced encephalitis was made, and steroid pulse therapy was initiated on admission, immediately after which the patient regained consciousness and was able to talk and walk. He was discharged with slight paralysis of his legs and was able to resume chemotherapy. An early diagnosis and treatment are required to improve the prognosis of encephalitis.

We herein report a patient with Lynch-like syndrome in whom a brain tumor (glioblastoma) developed after repeated resection of colorectal cancer. The patient had a significant family history of cancer. Immunohistochemical expression of mismatch repair proteins was decreased in both brain and colon tumors, but no pathogenic variant of the related genes was detected. Although brain tumors occasionally develop in Lynch syndrome, they have not been reported in cases of Lynch-like syndrome. This first report of Lynch-like syndrome with the development of glioblastoma suggests the need for further investigation on the surveillance of brain tumors in patients with this syndrome.

Red yeast rice has been highlighted as a health-food ingredient that reduces serum cholesterol levels. Recently, an increased number of cases of renal impairment induced by a supplement containing red yeast rice have been reported in Japan. A 42-year-old man with no history of chronic kidney disease developed renal dysfunction with proximal tubular damage after supplementation with red yeast rice. An 83-year-old woman with advanced diabetic kidney disease experienced further deterioration of her renal function after supplementation with red yeast rice. We herein report cases of acute kidney injury likely induced by a supplement containing red yeast rice.

AA amyloidosis is a rare renal complication of Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL). A 66-year-old man with WM/LPL presented with nephrotic syndrome. A renal biopsy showed AA amyloidosis. Chemotherapy resulted in the remission of hematologic and nephrotic syndromes. Two years into follow-up, he became infected with coronavirus disease 2019 and had massive proteinuria, despite no relapse of WM/LPL. A second renal biopsy confirmed a diagnosis of AA amyloidosis. However, increased prednisolone did not improve proteinuria. The patient ultimately died of cryptococcal meningitis. This case highlights the diverse spectrum of renal involvement in monoclonal IgM-secreting diseases and difficulty in managing fatal complications.

Immune checkpoint inhibitors (ICIs) improve the outcomes of several types of cancer. However, they are also associated with various immune-related adverse events including myocarditis. ICI-induced myocarditis is a rare, potentially life-threatening adverse event. We herein report two cases of corticosteroid-refractory ICI-induced myocarditis. In both cases, additional immunosuppressive therapies, such as intravenous immunoglobulin and tacrolimus, successfully resolved myocarditis. Given the corticosteroid-refractory nature of these cases, we suggest that prompt addition of other immunosuppressive drugs to corticosteroid therapy should be considered in the treatment of ICI-induced myocarditis.

A 78-year-old man with a history of pancreatic carcinoma underwent chest computed tomography (CT), which revealed a slowly enlarging consolidation in the right lower lobe. Forceps and percutaneous CT-guided lung biopsies showed no evidence of malignancy; therefore, organizing pneumonia was suspected. However, the patient's serum carbohydrate antigen 19-9 levels increased monthly, raising concerns about malignant lesions. A transbronchial cryobiopsy (TBCB) was performed to confirm the diagnosis of pulmonary metastasis of the pancreatic carcinoma. Pulmonary metastasis is an important differential diagnosis when chest CT shows consolidation, mimicking organized pneumonia. In addition, a TBCB can be a useful diagnostic tool for detecting lepidic growth patterns.

Adult multisystem Langerhans cell histiocytosis (MS-LCH) is rare and has a poor prognosis. A 67-year-old man with MS-LCH presented with a hepatic tumor rupture and multiple masses in the lungs, liver, and pancreas. Despite the initial aggressive disease course and involvement of organs at risk, the patient experienced spontaneous regression and lesion disappearance following smoking cessation without chemotherapy. A literature review revealed a distinct subset of MS-LCH that can be managed by smoking cessation and careful observation through follow-up imaging. This suggests that careful observation through follow-up imaging may be a reasonable alternative to chemotherapy in select adult cases of MS-LCH.

A 66-year-old woman was diagnosed with stage IV follicular lymphoma with a large tumor extending from the celiac artery to pelvis. Initial chemotherapy improved her lymphoma, but caused severe chylous ascites, requiring frequent paracentesis. Lymphoscintigraphy revealed radioisotope leakage into the abdominal cavity at the level of the renal hilum, indicating lymphatic vessel perforation. Lymphangiography with Lipiodol quickly resolved the chylous ascites. This case indicates that refractory chylous ascites with shrinking retroperitoneal lymphoma may require direct intervention in lymphatic vessels, and lymphangiography with Lipiodol may be effective not only as a tool for diagnosing lymphatic leakage sites but also as a treatment for lymphatic vessel damage.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder characterized by thrombocytopenia, marked megakaryocytic hypoplasia, and preserved other-lineage hematopoiesis in the bone marrow. The etiology of AAMT remains poorly understood owing to its rarity.

We encountered a diagnostically challenging case involving a 66-year-old man who showed severe thrombocytopenic bleeding with isolated megakaryocytic hypoplasia, elevated serum thrombopoietin levels, glycoprotein IIb/IIIa antibody positivity, and prolonged platelet transfusion refractoriness following mantle cell lymphoma (MCL). Treatment with corticosteroids and intravenous immunoglobulin was ineffective, while a combination of multiagent chemotherapy, including rituximab, was beneficial for both thrombocytopenia and MCL. Ultimately, the patient was diagnosed with AAMT and immune thrombocytopenia (ITP)-like platelet destruction.

This case suggests that AAMT and ITP are non-exclusive and sometimes overlap as components of a broad spectrum of platelet-related autoimmune diseases.

A 21-year-old man was diagnosed with myeloid/natural killer precursor leukemia (MNKPL) with bone marrow infiltration of blasts of cyCD3⁺, CD7⁺, CD33⁺, CD34^dim, CD56^+/-, HLA-DR⁺, cyMPO⁺, and TdT^- immunophenotypes. Although hyper-hyperfractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone therapy was unsuccessful, induction treatment with idarubicin and cytarabine resulted in complete remission (CR). The patient subsequently underwent cord blood transplantation with a myeloablative conditioning regimen, which resulted in durable CR and complete donor chimerism. He had been in good health without relapse for over nine months since transplantation. Timely allogeneic hematopoietic stem cell transplantation using an available donor source may be a promising treatment strategy for MNKPL.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a treatable form of limbic encephalitis, marked by frequent focal seizures and cognitive decline (particularly memory disturbance); however, it can be difficult to diagnose in patients with subtle cognitive decline. Ictal pouting, a rare seizure feature, has not yet been reported in anti-LGI1 encephalitis. A 73-year-old man with anti-LGI1 encephalitis presented with subacute onset of frequent ictal pouting without apparent cognitive decline. Steroid treatment alone resolved seizures and improved subtle visual memory. Middle-aged and older patients experiencing subacute-onset frequent focal seizures should be thoroughly evaluated for memory disturbances to determine the need for anti-LGI1 antibody measurement.

We report the case of a 74-year-old woman with Parkinson's disease (PD) who developed acute dysphagia, dysarthria, and hoarseness. A neurological examination and nasopharyngeal fiberscopy revealed paralysis of the left glossopharyngeal, vagus, and hypoglossal nerves. No skin rash was observed. Cerebrospinal fluid testing showed lymphocytic pleocytosis, and an elevated varicella-zoster virus (VZV) IgG antibody index. She was diagnosed with zoster sine herpete unilaterally affecting multiple lower cranial nerves. Although dysphagia is common in patients with PD, acute exacerbations of dysphagia require careful investigation of various potential causes, including VZV infection.

A 46-year-old woman with Turner syndrome (TS) (45,X/46,X,idic(X)(p11.4) mosaic) presented with a fever, unresponsiveness, hyperhidrosis, and rigidity approximately one month after episodes of confusion and suicide attempts, prompting a diagnosis of schizophrenia. Cerebrospinal fluid (CSF) showed mild hypercellularity with oligoclonal bands. Brain and abdominal magnetic resonance imaging showed no abnormalities. Bizarre upper-extremity movements and spasms followed the trial administration of acyclovir, and autoimmune encephalitis was suspected. Intensive immunotherapy was initiated, and the symptoms improved. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis was diagnosed based on the presence of anti-NMDAR antibodies in her spinal fluid. This case represents a rare presentation of anti-NMDAR encephalitis in TS, which is susceptible to autoimmune disease complications.

A 69-year-old man was admitted to our hospital because of a sudden gait disturbance. Based on the neurological examination performed upon admission, the patient exhibited ataxic movement in his right lower limb and body lateropulsion toward the right side. Magnetic resonance imaging revealed a lower lateral medullary infarction limited to the lateral surface. A motion analysis revealed ipsilateral lower-limb ataxia. Lower lateral medullary infarction can cause ipsilateral lower limb ataxia, particularly impaired hip joint coordination, resulting in body lateropulsion in dynamic conditions.

Abnormalities in genes on the X chromosome or large defects in the X chromosome itself cause X-linked intellectual disability. The proband was a 27-year-old man. His medical history included strabismus, cryptorchidism, and severe intellectual disabilities. He also had epilepsy. His mother seemed to have slight intellectual disability. A physical examination revealed malformations. The lateral and fourth ventricles were dilated using computed tomography. CGG repeats in the 5' untranslated region of FMR1 gene were normal. G-banding and spectral karyotyping revealed a novel unbalanced X-autosomal translocation, with a karyotype of 46,Y,der(X)t(X;9)(p22.33;p12); distal trisomy of 9p and distal Xp nullisomy.

A 59-year-old man without risk factors for atherosclerosis was diagnosed with coronavirus disease 2019 (COVID-19). Four days later, he developed dysarthria and gait disturbance. Neurological examination revealed slurred speech, ataxia, and mild cognitive decline. Brain magnetic resonance imaging revealed multiple infarcts in the bilateral middle cerebellar peduncles and leukoencephalopathy, indicating the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genetic testing confirmed a pathogenic NOTCH3 variant (c.505C>T, p.Arg169Cys) (NM_000435.3). A skin biopsy supported the diagnosis. He was treated with cilostazol and after three months of rehabilitation, he regained an independent walking ability. COVID-19 increases the risk of ischemic stroke in CADASIL patients, with bilateral middle cerebellar peduncle infarctions being notable in the present case.

A 58-year-old Japanese woman with rheumatoid arthritis (RA) presented with the sudden onset of cognitive dysfunction. A random skin biopsy revealed intravascular large B-cell lymphoma (IVLBCL), which resolved spontaneously with methotrexate withdrawal. However, four months later, the disease relapsed with liver injury. After completion of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, both RA and IVLBCL remained in remission for two years. Among the pathological subtypes of RA-associated lymphoproliferative diseases, reports on IVLBCL are limited, and little is known about its clinical course. Our literature review summarizes the clinical course and mortality of 11 patients with RA-IVLBCL.

Multiple myeloma (MM) is a plasma B-cell malignancy characterized by immune dysfunction, with infection representing a major complication. Bacteria, including Streptococcus pneumoniae, are common pathogens in patients with MM, but reports on infections with nontuberculous mycobacteria (NTM) have been limited. We herein report a case of disseminated NTM infection in a patient with MM undergoing treatment with immunomodulatory drugs. At the diagnosis, the patient showed lymphocytopenia and was treated with clarithromycin, rifampicin, and ethambutol; however, culture positivity persisted, and the patient died. The possibility of NTM infection should be considered in cases of unexplained deterioration of the MM patient's general condition.