Objective Acute cholangitis is occasionally life-threatening and requires immediate treatment. For the management of acute cases, globally accepted diagnostic criteria and the use of severity grading, as defined in the Tokyo Guidelines 2018 (TG18), are recommended. This study was performed to explore the association between acute cholangitis and the level of adenosine 5'-triphosphate (ATP) in blood as determined with a simple measurement method.

Methods Twenty-three consecutive patients admitted for acute cholangitis and 14 healthy individuals were enrolled. Based on the TG18, the patients were categorized according to the degree of severity as Grade I, II, or III. We measured the amount of ATP in blood samples using a bioluminescence meter and evaluated the correlation with the degree of severity.

Results The ATP/total hemoglobin (tHgb) level showed a significant decline in association with an increase in severity, as that in the healthy controls was 236.60 ± 8.10 and in the Grade I, II, and III groups was 238.56 ± 6.98, 186.88 ± 7.62, and 154.60 ± 11.01, respectively (p<0.01). While no significant difference was observed between the healthy controls and Grade I patients (p=0.649), there was a statistically significant difference between Grade I and Grade II (p<0.01) in the ATP/tHgb level. According to a receiver operating characteristic analysis, the area under the curve for ATP/tHgb, used as an index for predicting the need for emergency biliary drainage (Grade II, III cases), was the highest among various examined factors.

Conclusion The present novel measurement method was found to be simple to perform and useful for detecting acute cholangitis patients with a low ATP level who may require emergency biliary drainage.

Objective Polyunsaturated fatty acids (PUFAs) are associated with heart failure (HF) as well as coronary artery disease. However, little is known about the relationships between PUFAs and the exercise responses of patients with HF. We evaluated the relationships between PUFAs and the parameters of cardiopulmonary exercise tests (CPETs) in patients with non-ischemic HF.

Methods Fifty patients with stable non-ischemic HF underwent CPETs at our hospital. Data were analyzed to evaluate the relationships between PUFAs and echocardiographic findings as well as CPET and other test parameters.

Results Correlations were significant and negative between dihomo-γ-linolenic acid (DGLA) + arachidonic acid (AA) and minute ventilation versus carbon dioxide production (VE/VCO₂) slope, and positive between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and VE/VCO₂ slope. A multivariate regression analysis selected DGLA+AA and AA as independent predictors of VE/VCO₂ slope. However, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) were not significantly correlated with the CPET parameters.

Conclusion Low levels of circulating DGLA+AA and AA among PUFAs were associated with decreased exercise responses in patients with stable non-ischemic HF. These findings suggest that high levels of omega-6 PUFAs may improve the clinical outcomes of patients with non-ischemic HF via their effects on exercise responses.

Objective We aimed to identify obstructive sleep apnea syndrome (OSAS) severity indices reflecting the anthropometric and metabolic characteristics of patients with OSAS.

Methods A total of 76 patients with OSAS underwent nasal continuous positive airway pressure (nCPAP). We also investigated the effects of nCPAP on OSAS-associated muscle sympathetic nerve activity (MSNA), risk for cardiovascular diseases, and insulin secretion and sensitivity.

Results Among the OSAS severity indices, HbA1c was significantly correlated with the apnea-hypopnea index, whereas HOMA-beta, HOMA-IR, and hepatic insulin resistance were significantly correlated with % SpO₂<90%, independent of age, gender, and body mass index (BMI). Burst incidence of MSNA was independently associated with only a 3% oxygen desaturation index. nCPAP therapy significantly lowered the OSAS severity indices and reduced the burst rate, burst incidence, and heart rate.

Conclusion The OSAS severity indices reflecting apnea/hypopnea are associated with glycemic control, whereas those reflecting hypoxia, particularly % SpO₂<90%, are associated with hepatic insulin resistance independent of obesity. Both types of OSAS severity indices, especially the 3% oxygen desaturation index (reflecting intermittent hypoxia), are independently associated with MSNA, which is dramatically lowered with the use of nCPAP therapy. These findings may aid in interpreting each OSAS severity index and understanding the pathophysiology of OSAS in clinical settings.

Blind pouch syndrome-associated anastomotic ulcer is rare, and its endoscopic features remain poorly described. A 79-year-old man was referred to our hospital for melena. Capsule endoscopy revealed multiple ulcers in the small intestine. Double-balloon endoscopy (DBE) and a gastrografin examination through DBE revealed a potential anastomotic ulcer, a blind pouch, and a side-to-side anastomosis in the middle of the small intestine. Laparoscopic partial resection of the small intestine with anastomosis was performed on the suspected blind pouch syndrome-associated anastomotic ulcer. To our knowledge, this is the first report describing the endoscopic features of a blind pouch syndrome-associated anastomotic ulcer.

Mid-esophageal diverticulum is a rare disease, formed by the traction caused by inflamed bronchial lymph nodes or by pulsion induced by motility disorder. We herein report a case of mid-esophageal diverticular bleeding in a patient with kyphosis who was taking an anti-platelet drug. She was successfully treated with endoscopic hemostasis. An 80-year-old woman presented to our emergency department with hematemesis. She had kyphosis and was taking dipyridamole for her chest pain. Emergent upper endoscopy revealed bleeding from a mid-esophageal diverticulum; hemostasis was achieved via clipping. Mid-esophageal diverticula can cause upper gastrointestinal bleeding. An endoscopic examination and hemostasis are effective treatments.

We herein report the first case in which an escalated dose of sunitinib was effective, even after dose reduction. A 64-year-old man with gastrointestinal stromal tumor of the small intestine discontinued adjuvant imatinib because of interstitial pneumonia. After two years, peritoneal recurrence was detected. Sunitinib was started at 50 mg/day for 4 weeks every 6 weeks, after which the dosage was reduced to 37.5 mg/day because of grade 1 gastritis, stomatitis, and a fever. Four months later, computed tomography showed progressive disease. As the adverse events were well-controlled by medication, we escalated the dose to 50 mg/day and achieved a partial response.

A 73-year-old man visited our hospital for the treatment of an early gastric cancer (GC) lesion. We performed en bloc resection using endoscopic submucosal dissection (ESD) for his GC lesion. The present GC lesion was Epstein-Barr virus (EBV)-associated poorly differentiated-type adenocarcinoma invading into the submucosal layer. Recently, accumulating data has shown that the risk of lymph node metastasis from early EBV GC without local lymphovascular infiltration is low. The present patient has been in good health for over three years since ESD. Some cases of early EBV GC with invasion into the submucosal layer may be candidates for further extension of the ESD criteria.

Flutamide, a chemotherapeutic agent for prostate cancer, is known to enhance warfarin anticoagulation. However, not much is known about its pharmaceutical interaction. We herein report the case of a patient with an implanted pacemaker for atrial fibrillation with bradycardia who was on warfarin. This patient presented with deterioration of hematuria, gingival, ear, and subcutaneous bleeding. The prothrombin time-international normalized ratio was extremely elevated after starting flutamide to treat progression of prostate cancer. Fatal bleeding complications were able to be prevented by the immediate administration of prothrombin complex concentrate, but the effect of flutamide on warfarin was prolonged for about two more weeks after the withdrawal of flutamide.

Disturbance of the normal gut microbiota has been implicated in the pathogenesis of various diseases, including chronic kidney disease (CKD). A common CKD symptom is chronic constipation. Lubiprostone is a safe and efficacious drug for treating chronic constipation. We herein report 2 patients with IgA nephropathy treated with lubiprostone (24 μg 1×/day). The lubiprostone treatment ameliorated their chronic constipation and, unexpectedly, reduced the urinary protein excretion, urinary liver-type fatty acid binding protein and urine occult blood. These results may indicate that lubiprostone is a useful therapeutic intervention against the progression of IgA nephropathy with chronic constipation.

Small cell lung cancer (SCLC) transformation of epidermal growth factor receptor (EGFR) mutant adenocarcinoma (ADC) during EGFR tyrosine kinase inhibitor (TKI) treatment is an example of a rare subset of acquired drug resistance. We herein report the case of a 75-year-old man treated with afatinib who was then diagnosed with SCLC transformation. After two years of successful treatment with afatinib, the tumor relapsed, and a re-biopsy revealed SCLC harboring EGFR exon 19 deletion. We encountered a case of transcriptional alteration, potentially important for SCLC transformation of EGFR mutant lung ADC, that was recognized via the expression of NOTCH, ASCL1 and RB1 on immunohistochemical staining.

A 69-year-old man developed bilateral polyarthritis, edematous extremities, and skin desquamation on the fingers and ears. He did not meet the criteria for any connective tissue disease, including rheumatoid arthritis. An examination revealed advanced lung cancer. His systemic manifestations were attributed to paraneoplastic Bazex syndrome and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Treatment with pembrolizumab (an anti-programmed death-1 antibody) for lung cancer relieved his symptoms and shrank the lung tumor. Bazex and RS3PE syndromes are rare paraneoplastic diseases. We herein report this unique case of synchronous development of these two paraneoplastic syndromes in the presence of advanced lung cancer.

Primary pleural melanoma is an extremely rare neoplasm, and to the best of our knowledge, there have been only 8 case reports of this condition in the English literature. We herein report a rare case in which the cytological and immunocytochemical analyses of pleural fluid and ultrasonography (US)-guided biopsy of a pleural lesion were useful for the diagnosis primary pleural melanoma. This case highlights the importance of careful physical examinations, cytomorphologic and immunocytochemical analyses of pleural fluid, as well as the utility of US-guided biopsy of the pleural lesions in the diagnosis of primary pleural melanoma.

A 69-year-old man who had undergone chemoradiotherapy for advanced pulmonary adenocarcinoma had bilateral testicular and adrenal gland masses on a routine follow-up examination. We performed left orchiectomy, and the histopathological examination confirmed metastatic pulmonary adenocarcinoma involving the extracted testis. He was treated for disease progression with nivolumab after unsuccessful cytotoxic chemotherapy, which resulted in regression of recurrent adrenal and right testicular tumors. We reviewed the existing literature on metastatic testicular tumors and found that testicular metastasis from lung cancer is rare and poses a chemotherapeutic challenge. Based on our experience, immune checkpoint inhibitors seem to have good efficacy for treating testicular metastasis.

The anti-programmed cell death-1 protein monoclonal antibody, pembrolizumab is an immune checkpoint inhibitor. While it improves the prognoses of patients with advanced non-small-cell lung cancer, it has been reported to induce various kinds of immune-related adverse events, including hepatotoxicity. Despite the frequency of hepatotoxicity, there is only limited information available regarding the pathophysiology and treatment. We herein report a 48-year-old man with lung adenocarcinoma who was treated with pembrolizumab and developed cholestatic liver injury. In this case, the importance of evaluating the histology of hepatotoxicity and the effectiveness of ursodeoxycholic acid for cholestatic liver injury is indicated.

We herein report the case of a 74-year-old woman with a lung tumor. She presented with complaints of blurred and rapid, progressively impaired vision. A visual field examination revealed bilateral concentric contraction of the visual field and a ring scotoma in the right eye. She was diagnosed with cancer-associated retinopathy (CAR) combined with large-cell neuroendocrine carcinoma (LCNEC) of the lung via a visual field examination and underwent thoracoscopic surgery. CAR has been mostly associated with small-cell lung cancer (SCLC). Combined LCNEC is relatively rare and accounts for 10.6% of all LCNECs. This is the first case report of CAR-combined LCNEC.

Hyperprogressive disease (HPD) is a paradoxical phenomenon involving the acceleration of tumor progression after treatment with immune checkpoint inhibitors (ICIs). A 66-year-old male smoker with advanced lung adenocarcinoma started pembrolizumab for progressive disease following first-line chemotherapy. He developed HPD after two cycles, and a re-biopsy revealed transformation to small-cell carcinoma. He subsequently underwent two lines of chemotherapy for small-cell carcinoma until progression and ultimately died. Transformation to small-cell carcinoma may be a cause of HPD during ICI therapy. The possibility of pathological transformation should be considered in cases of HPD with resistance to ICI therapy.

A 71-year-old woman with abnormal pulmonary shadows and multiple enlarged thoracic lymph nodes was diagnosed with stage IIB lung adenocarcinoma, pulmonary sarcoidosis, and sarcoidosis-associated lymphadenopathy after biopsies from multiple organ sites. She also had rapidly progressive renal dysfunction, microhematuria, and high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) concentrations. A renal biopsy revealed granulomatous tubulointerstitial nephritis and necrotizing glomerulonephritis with crescent formation. She was diagnosed with nephritis caused by both sarcoidosis and ANCA-associated vasculitis. Oral prednisolone was administered to treat her nephritis, resulting in improvement in both her renal dysfunction and her sarcoidosis-associated lymphadenopathy.

A rare case of lung cancer with the simultaneous production of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) is reported. A 79-year-old man was admitted to our hospital due to cachectic symptoms and an increased inflammatory response. Laboratory tests and imaging studies suggested metastatic lung cancer with high serum levels of G-CSF and IL-6. He died of progressive disease, and an autopsy showed that the lung tumor had positive protein expression of both cytokines and a solid growth of large-cell carcinoma with sarcomatoid changes, possibly resulting from the epithelial-mesenchymal transition mediated by IL-6 and leading to widespread metastases.

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder, and only a few cases have been reported to be complicated with autoimmune hemolytic anemia (AIHA). A 43-year-old man who presented with multiple swollen lymph nodes was diagnosed with iMCD. He was also diagnosed with AIHA based on laboratory findings, including the results of a bone marrow aspiration study. The patient was treated with tocilizumab; however, the effect was limited, probably due to anti-drug antibodies. Tocilizumab was therefore switched to rituximab, and his anemia was improved. Complication with AIHA should be carefully considered when iMCD patients present with severe anemia.

Antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) associated encephalitis is an important syndrome associated with MOG-IgG. However, there have been no reports of MOG-IgG-associated optic neuritis or demyelination following meningitis without encephalitic symptoms. A 55-year-old woman presented to our hospital with headache, nausea, fever, and nuchal rigidity that had persisted for more than a month. She was hospitalized due to aseptic meningitis and recovered with conservative therapy. However, she was re-admitted due to left optic neuritis and demyelinating lesions. We diagnosed MOG-IgG-associated neuromyelitis optica spectrum disorder (NMOSD). She responded to treatment with intravenous methylprednisolone and oral prednisolone. Aseptic meningitis may be an initial manifestation of MOG-IgG-positive NMOSD.

The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4⁺ and CD8⁺ T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.

A 71-year-old woman being treated with methotrexate (MTX) and tacrolimus (TAC) for rheumatoid arthritis (RA) was admitted to our hospital and underwent surgery for gastric perforation and peritonitis. An endoscopic examination six days post-surgery showed an extensive ulcer in the stomach, and a biopsy revealed diffused large B-cell lymphoma. We diagnosed her with immunodeficiency-associated lymphoproliferative disorder (LPD) and discontinued the MTX and TAC. She underwent gastrectomy due to stenosis approximately two months after the first operation, but the histopathological findings of lymphoma had disappeared. LPD should be considered as a potential cause of gastric perforation during RA treatment.