Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag.

Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed.

Results The median platelet count increased significantly from 4.5×10⁴/μL before lusutrombopag treatment to 7.2×10⁴/μL before the invasive procedure (p<0.01), and patients undergoing 49 of the 53 (92%) treatment regimens succeeded in undergoing invasive procedures without needing platelet transfusions. In patients who received lusutrombopag treatment repeatedly, the median platelet count significantly increased following the second administration of lusutrombopag, and the effects of lusutrombopag were similar between the first and second administration. A multivariate analysis identified the absence of diabetes mellitus (odds ratio, 5.56 for presence; p=0.04) as a significant and independent predictor of a response to lusutrombopag.

Conclusion Lusutrombopag treatment significantly increased platelet counts in patients with chronic liver disease, making it possible to receive invasive procedures. The treatment produced identical effects when it was repeated. The efficacy of lusutrombopag might be decreased in patients with diabetes mellitus.

Cholesterol crystal embolization (CCE) shows a poor prognosis and it can cause ischemic organ damage due to a cholesterol embolism from atherosclerotic lesions in large blood vessels. Such an embolism mainly affects the kidneys and skin, although cases involving digestive organs have also been reported. We encountered an autopsy case of CCE with damage mainly to the digestive organs, including the pancreas. The patient had non-specific abdominal symptoms or image findings. Symptomatic therapy failed to save him. CCE can involve the digestive organs, and so must be differentiated from abdominal pathologies. Moreover, conventional treatments may be ineffective, and new treatments might thus be necessary.

A 72-year-old women was referred to our hospital because of lower left abdominal pain. Computed tomography showed prominent sigmoid colon dilation and double tumors on both the oral and anal sides. Surgical resection revealed an expanded sigmoid colon involved in double cancer that showed strong adhesion to the surrounding tissues. The pathological findings revealed obstructive colitis and minor perforation in the dilated colon. The minor perforation was considered to have been caused by fecal impaction in the closed cavity between the two tumors, resulting in an increase in colon pressure.

Cecal volvulus is an uncommon cause of colonic obstruction. First-line treatment for cecal volvulus is surgery, as nonoperative management is rarely achievable. We herein report an extremely rare case of a patient with spontaneously resolved cecal volvulus; no recurrence occurred without elective surgery. A 47-year-old woman presented with acute lower abdominal pain. She was misdiagnosed with small bowel obstruction and treated conservatively. A few hours later, she was correctly diagnosed with cecal volvulus. Subsequently, her symptoms and computed tomography findings of cecal volvulus completely disappeared. She refused elective surgery, but no recurrence occurred during five months of follow-up.

A 58-year-old woman presented to our hospital with complaints of dysphagia. Esophagogastroduodenoscopy showed an esophagogastric junction tumor with multiple duodenal intramural metastases, and computed tomography showed peritoneal metastasis. In the middle of her fourth cycle of chemotherapy, she displayed symptoms of a left-sided multi-cranial nerve palsy. She was diagnosed with Garcin syndrome caused by meningeal carcinomatosis from gastric cancer based on the results of gadolinium-enhanced brain magnetic resonance imaging and cytology of the cerebrospinal fluid. It is important not to overlook meningeal irritation symptoms or paralysis of cranial nerves and to consider the possibility of Garcin syndrome caused by meningeal carcinomatosis.

An 80-year-old man was admitted due to biliary stricture with autoimmune pancreatitis. Although radiographical examinations suggested Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), punched biopsies from the bile duct revealed adenocarcinoma. In the resected specimen, abundant N-terminus of Forkhead box P3 (Foxp3)-positive cells were localized in cholangiocarcinoma (CCA) tissue, while IgG4-positive cells were spread around the entire bile duct. Therefore, the case was diagnosed with IgG4-SC accompanied by CCA, not sporadic CCA. We herein report an informative case wherein IgG4-positive cells were abundant in CCA tissue and Foxp3 immunohistochemical staining allowed us to determine that this case had two entities.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition affecting multiple organs; however, the involvement of skin lesions is rare. We herein report a 65-year-old man who presented with pruritic punctate purpura on both legs and elevated liver enzyme levels. Computed tomography showed enlargement of the pancreas and thickening of the bile duct wall. Magnetic resonance cholangiopancreatography showed diffuse irregular constriction of the main pancreatic duct, stricture of the lower common bile duct, and dilation after confluent stricture. A histopathologic examination of the pancreas and his enlarged salivary gland showed infiltration of IgG4-positive plasma cells. Ultimately, the patient was diagnosed with IgG4-RD.

Cholangiolocellular carcinoma (CoCC) is a rare primary liver cancer that is difficult diagnose due to a lack of specific imaging findings. We herein report a case of CoCC accompanied by severe alcoholic cirrhosis. Dynamic computed tomography showed a low-density tumor with a faint surrounding enhancement. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging revealed iso-intensity in the hepatobiliary phase and a maximum tumor diameter of 53 mm. ¹⁸F-fluoro-2-deoxyglucose position-emission tomography was moderately positive (maximum standardized uptake value: 4.3). CoCC was diagnosed based on the pathological findings, including immunohistochemistry. We discuss the diagnostic imaging findings and review previous reports.

Bilio-duodenal bleeding, such as post-endoscopic sphincterotomy (EST) bleeding, common bile duct (CBD) bleeding after endoscopic retrograde cholangiopancreatography (ERCP), and duodenal bleeding due to malignant tumour invasion, can sometimes become severe. Six cases of refractory bilio-duodenal bleeding were stanched via covered self-expandable metallic stent (CSEMS) insertion, even though three of the patients had a history of gastrectomy. The dumbbell-shaped CSEMS was useful for managing post-EST bleeding. Additional duodenal CSEMS insertion was useful for the patient who had previously undergone uncovered SEMS insertion, and no migration of the CSEMS was observed. CSEMS insertion was useful for treating refractory bilio-duodenal haemorrhaging.

A 62-year-old woman with activity-dependent two-to-one atrioventricular block (2:1AVB) and a normal left ventricular ejection fraction was referred to our department for the evaluation of exclusively exercise-induced marked symptoms. The treadmill test helped establish a clear correlation between 2:1AVB and symptoms. The test results demonstrated that exercise-induced marked symptoms were attributed to abrupt transient hypotension combined with relative bradycardia, probably due to increased diastolic mitral and tricuspid regurgitation because of 2:1AVB during moderate-to-heavy exercise. After pacemaker implantation for 2:1AVB, the symptoms and transient hypotension disappeared, and her exercise capacity improved.

Titration of beta-blockers is a gold-standard therapy in patients with heart failure and a reduced ejection fraction but is sometimes challenging to administer, given symptomatic hypotension. Ivabradine is a recently introduced selective I_f channel inhibitor that purely reduces the heart rate. We encountered a patient with advanced heart failure in whom a beta-blocker could not be up-titrated given his symptomatic hypotension. Following the initiation of ivabradine, an increase in blood pressure due to heart rate optimization, probably via an improvement in the cardiac output, allowed for the further up-titration of carvedilol, followed by a successful clinical course. Ivabradine might be a novel therapeutic tool to facilitate the up-titration of beta-blockers in patients with heart failure and hypotension.

Estrogen is known to increase exogenous corticosteroid levels. In this case, a 27-year-old Japanese woman was referred to our hospital for examination of an adrenal tumor and was diagnosed with Cushing syndrome. Resection of the tumor resulted in secondary adrenal insufficiency. She also developed microcytic anemia due to hypermenorrhea, which was masked by Cushing syndrome. An oral contraceptive was administered for the treatment of hypermenorrhea, but this led to a marked increase in serum cortisol and the reduction of plasma adenocorticotropic hormone, disturbing the recovery of the adrenal function. Attention is required when oral contraceptives are used to treat hypermenorrhea masked by Cushing syndrome.

Hypoglycemia should be avoided when treating patients with diabetes. Repaglinide is an insulin secretagogue with a low hypoglycemic risk because of its rapid- and short-acting effects. However, its blood concentration has been reported to increase in combination with clopidogrel, an antiplatelet drug, and in patients with severe renal insufficiency. We herein report an elderly patient with type 2 diabetes mellitus and severe renal insufficiency who received repaglinide and hypoglycemia three days after starting clopidogrel. The concomitant use of repaglinide and clopidogrel can lead to hypoglycemia, especially in patients with severe renal insufficiency.

Collagenofibrotic glomerulopathy or LMX1B-associated nephropathy is a rare disease in which type III collagen accumulates in the glomeruli. We herein report a 64-year-old Japanese woman with an elevated serum creatinine level and persistent proteinuria for 7 years. An electron microscopic study using tannic acid showed curved and frayed collagen fibers within mesangial and subendothelial regions compatible with type III collagen depositions. The distribution of type IV collagen α1-6 chains was normal. Since no pathogenic mutations were identified in the LMX1B gene, she was diagnosed with collagenofibrotic glomerulopathy and treated with angiotensin II receptor blocker and calcium antagonist to control her blood pressure.

Patients with atypical hemolytic uremic syndrome (aHUS) associated with a C3 p.Ile1157Thr mutation show a relatively high renal survival and low mortality rates, but renal histopathological findings after recurrence have been rarely reported. A 30-year-old man with a C3 p.Ile1157Thr mutation experienced a third recurrence of thrombotic microangiopathies with neurological and gastrointestinal disorders. A renal biopsy performed during the recovery phase of acute kidney injury revealed collapsed glomeruli and arteriolar vacuolization. Approximately 10% of glomeruli were globally sclerotic, despite the absence of arterio-/arteriolo-sclerosis. These findings suggest substantial progression of irreversible injuries in multiple organs, including kidneys, which occurs in aHUS patients with repeated thrombotic microangiopathies.

We herein report a case of thymic carcinoma that initially exhibited dysphagia and an intraesophageal mass lesion. A 68-year-old man was admitted to our hospital because of dysphagia. An endoscopic examination revealed a mass on the middle esophagus. Chest computed tomography (CT) showed a huge anterior mediastinal mass and subcarinal lymph node swelling, directly invading into the esophageal lumen. An immunohistological examination of the esophageal and anterior mediastinal masses revealed squamous cell carcinoma originating from the thymus. This is the first report of a thymic carcinoma spreading into the esophageal lumen and forming a mass lesion.

Spontaneous regression is rare in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). An 85-year-old man presented with pancytopenia and skin lesions, and the bone marrow exhibited 79.6% CD4+, CD56+, CD123+, and TCL-1+ abnormal cells, with a normal karyotype; he was thus diagnosed with BPDCN. While being followed without chemotherapy, he was admitted due to sepsis induced by Serratia marcescens, which was successfully treated with antibiotics. Notably, his blood cell counts improved, and the skin lesions disappeared. To our knowledge, this is the first reported case of spontaneous regression of BPDCN with a decrease in tumor cells in the bone marrow following sepsis.

Cerebral rheumatoid vasculitis (CRV) is a rare, fatal, and diagnostically challenging disorder. We herein report an 81-year-old woman with a 4-year history of rheumatoid arthritis who presented with a fever, progressive disturbance of consciousness, high level of rheumatoid factor, and hypocomplementemia. The enhancement of the perforating branches in the left middle cerebral artery led us to suspect CRV. A brain biopsy could not be performed. After we intensified steroid therapy, the size of the cerebral lesions temporarily decreased. However, recurrence in the left frontal lobe occurred one month later, and the patient subsequently died. Early intensive treatments may be needed for CRV.

We herein report a patient with neuronal intranuclear inclusion disease (NIID) who presented with encephalitis-like episodes. A neurological examination revealed a disturbance of consciousness without any evidence of encephalitis or epilepsy on laboratory tests. Brain perfusion single-photon emission computed tomography revealed an elevated cerebral blood flow during the encephalitis-like episode and reduced cerebral blood flow in the chronic phase with clinical recovery. This report suggests that the cerebral blood flow of patients with NIID can change over the clinical course. Encephalitis-like episodes of NIID should thus be considered in the differential diagnosis of acute disturbance of consciousness.

A 59-year-old woman with small-cell lung carcinoma achieved tumor disappearance after cisplatin-based chemotherapy (CBC) and radiation treatment but subsequently experienced right hemiparesis and aphasia. Brain magnetic resonance imaging revealed a left middle cerebral artery territory acute infarction and left internal carotid artery occlusion. Ultrasonography revealed a mobile thrombus in the left common and internal carotid arteries, and contrast computed tomography revealed a mural thrombus in the ascending aorta. Based on these findings, embolic stroke due to aortic mural thrombus following CBC was diagnosed. Aortic mural thrombus is a rare complication of CBC but carries a risk of embolic stroke.

We herein report a 39-year-old woman who had aggravated body pain, waddling gait, and fatigability for the past 2 years. A neurological examination showed hyperreflexia and proximal muscle weakness. The serum calcium level was normal (10.1 mg/dL). However, serum alkaline phosphatase (3,855 IU/I) and parathyroid hormone (1,008 pg/mL) levels were remarkably high. Cervical ultrasonography revealed parathyroid goiter. The patient was diagnosed with hyperparathyroidism. Her muscle weakness and pain improved within three months after parathyroidectomy. Our findings suggest that clinicians should consider hyperparathyroidism as a differential diagnosis in patients with proximal muscle weakness, even if the serum calcium level is normal.