Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations.

Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER).

Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017.

Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 μm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005).

Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated.

Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated.

Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p<0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (<65 years old) (p<0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity.

Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging.

Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017.

Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p<0.001).

Conclusion Hemodialysis patients with intracerebral hemorrhaging who were bedridden showed poor outcomes. The major causes of death were infections. Therefore, these patients should be carefully monitored for infections in order to improve their prognosis.

Objective We evaluated the change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers from three to six months after the administration of the BNT162b2 vaccine among healthcare workers.

Methods A total of 337 healthcare workers who received 2 doses of the BNT162b2 vaccine were included in this study. Factors associated with SARS-CoV-2 antibody titers at three and six months and the change in SARS-CoV-2 antibody titers between three and six months after vaccine administration were analyzed using a logistic regression analysis.

Results The SARS-CoV-2 antibody titer at 3 months was 4,812.1±3,762.9 AU/mL in all subjects and was lower in older workers than in younger ones. The SARS-CoV-2 antibody titer at 6 months was 1,368.9±1,412.3 AU/mL in all subjects. The SARS-CoV-2 antibody titers that were found to be high at three months were also high at six months. The change in SARS-CoV-2 antibody titers from 3 to 6 months was -68.9%±16.1%. The higher SARS-CoV-2 antibody titers at three months showed a more marked decrease from three to six months than lower titers.

Conclusion This study demonstrates that SARS-CoV-2 antibody titers at three months decreased with age and were associated with the antibody titers at six months and the change in titer from three to six months. Older individuals in particular need to be aware of the declining SARS-CoV-2 antibody titers at six months after the BNT162b2 vaccine. The results of this study may provide insight into COVID-19 vaccine booster strategies.

Fontan-associated liver disease (FALD) caused by long-term systemic venous congestion following the Fontan procedure may eventually lead to hepatocellular carcinoma (HCC). Treatment strategies for HCC due to FALD (FALD-HCC) remain unclear. We herein report a 35-year-old man with FALD-HCC that was well controlled by 3 cycles of continuous infusion of 5-fluorouracil and low-dose cisplatin (low-dose FP therapy) combined with 60 Gy of radiation therapy. However, the patient ultimately died of extrahepatic metastases. A pathological autopsy revealed more than 90% necrosis in the primary HCC lesion. This case suggests that low-dose FP therapy might be effective in FALD-HCC.

Pancreatic colloid carcinoma, also known as mucinous non-cystic carcinoma, is a rare subtype of pancreatic cancer accounting for 1-3% of the pancreatic malignant neoplasms. We herein report a woman who initially presented for acute pancreatitis. Computed tomography showed pancreatic swelling due to acute pancreatitis and a 16-mm mass with an enhanced margin in the pancreatic tail. We performed endoscopic ultrasound fine-needle aspiration. The patient was diagnosed with pancreatic colloid carcinoma, and distal pancreatectomy was performed. This case indicates that pancreatic colloid carcinoma should be considered as a differential diagnosis of pancreatic tumor presenting with acute pancreatitis.

A 68-year-old man was transferred to our hospital because of sudden right costal pain with unmeasurable hypotension. Ultrasonography revealed possible hemorrhagic shock due to ruptured hepatocellular carcinoma (HCC). As the patient was not hemodynamically stable after primary treatment, resuscitative endovascular balloon occlusion of the aorta (REBOA) was performed, and hemodynamic stability was then achieved. Contrast-enhanced computed tomography confirmed the diagnosis. Transcatheter artery embolization with gelatin sponge particles and coils eliminated the extravasation. The patient was discharged on day 36 post-procedure. Our observations suggest that REBOA may help achieve hemodynamic stability in cases of ruptured HCC.

A 54-year-old man was admitted to our hospital due to intermittent chest pain. He had a history of acute myocardial infarction, and peri-stent contrast staining had been observed at the stent implantation site. The patient previously underwent anticoagulation therapy for left ventricular thrombus and antiplatelet therapy to prevent stent thrombosis. More than one year after implantation of a drug-eluting stent, antiplatelet drugs were discontinued, and anticoagulant alone was prescribed according to the guidelines, which resulted in very late stent thrombosis. The risks of both bleeding and thrombosis must be fully considered when deciding whether or not to discontinue antiplatelet therapy during anticoagulation therapy.

A 17-year-old boy with acute coronary syndrome was admitted to our hospital. He had xanthomas over his elbow and Achilles tendon and a high level of low-density lipoprotein cholesterol; therefore, his initial diagnosis was familial hypercholesterolemia. However, a genetic analysis revealed a compound heterozygous mutation in the ABCG5 gene with a high serum level of sitosterol, leading to the diagnosis of sitosterolemia. After lipid-lowering treatment, percutaneous coronary intervention was performed. Furthermore, a persistently high C-reactive protein level and images of large arteries led to a diagnosis of Takayasu arteritis. To our knowledge, this is the first case of sitosterolemia complicated by Takayasu arteritis.

We herein report a 14-year-old boy with repetitive nocturnal syncope related to medication-refractory long QT syndrome (LQTS). Although the use of an implantable cardioverter-defibrillator (ICD) was inevitable to prevent sudden cardiac death, he refused immediate implantation in order to play in a baseball competition six weeks away. Given his genetic diagnosis of type 2 LQTS, which is associated with cardiac events unrelated to exercise, we prescribed a wearable cardioverter defibrillator (WCD) to be donned at night, without limiting his exercise participation. An ICD was implanted after the competition. We successfully performed the preplanned treatment while maximizing the patient's quality-of-life with a WCD and genotype-specific risk stratification.

A 51-year-old woman was admitted because of hypercalcemia. Neck ultrasonography and computed tomography revealed the presence of parathyroid cysts on both sides. After primary hyperparathyroidism was diagnosed by technetium-99m-methoxyisobutylisonitrile scintigraphy, the patient was successfully treated with total parathyroidectomy and autotransplantation. She also had a non-functioning pancreatic neuroendocrine tumor, prolactinoma, and adrenal tumors with subclinical Cushing's syndrome. Given these clinical features and her family history, multiple endocrine neoplasia type 1 (MEN1) was suspected, and germline DNA sequencing revealed a missense mutation (c.1013T>G, p.Leu338Pro) in exon 7 of MEN1. This case demonstrates the phenotypic and genetic diversity of MEN1.

A 61-year-old man with a history of total gastrectomy for cancer with Roux-en-Y reconstruction showed severe postprandial hypoglycemia accompanied by endogenous hyperinsulinemia. Abdominal ultrasonography and contrast-enhanced computed tomography showed no abnormal findings in the pancreas. A selective arterial secretagogue injection test showed the marked induction of serum immunoreactive insulin when calcium was injected into the splenic artery. A pathological analysis following distal pancreatectomy with splenectomy revealed a pancreatic neuroendocrine microadenoma containing insulin-producing cells in the resected pancreas. This case highlights the importance of carefully evaluating refractory and severe hypoglycemia in patients with a history of gastric surgery to exclude insulinoma.

During the ongoing coronavirus disease 2019 (COVID-19) pandemic, it is critical to ensure the safety of COVID-19 vaccines. We herein report a 51-year-old Japanese woman who developed acute-onset type 1 diabetes with diabetic ketoacidosis six weeks after receiving the first dose of a COVID-19 messenger ribonucleic acid (mRNA) vaccine. Laboratory tests indicated exhaustion of endogenous insulin secretion, a positive result for insulin autoantibody, and latent thyroid autoimmunity. Human leukocyte antigen typing was homozygous for DRB1*09:01-DQB1*03:03 haplotypes. This case suggests that COVID-19 vaccination can induce type 1 diabetes in some individuals with a genetic predisposition.

A 64-year-old Japanese man who worked at a butcher shop was hospitalized for a fever, headache, and deafness. We diagnosed him with sepsis and meningitis caused by Streptococcus suis infection. The patient's renal function declined rapidly, and hemodialysis was performed temporarily. A renal biopsy was performed, and the renal function tended to improve with antimicrobial therapy. This case seemed rather similar to one of staphylococcal-associated nephritis in that it showed mesangial proliferative nephritis with immunoglobulin A deposition, even though the nephritis was caused by streptococci. Similarly, intramembranous electron-dense deposits were characteristic findings. We present new findings of an in vivo renal biopsy in a case of S. suis-associated glomerulonephritis.

A slowly progressive middle-aged man initially diagnosed with thin basement membrane nephropathy based on extensive thinning of the glomerular basement membrane (GBM) was subsequently diagnosed with Alport syndrome (AS) by a serial renal biopsy eight years later. The ultrastructural analysis of the second biopsy indicated thickening and wrinkling with mild reticulation in the GBM, consistent with AS. However, a retrospective analysis of the first biopsy revealed mild attenuation of type IV collagen α5 chain staining, suggesting a potential diagnosis of AS, despite the lack of ultrastructural features of AS. We herein report the clinical usefulness of type IV collagen staining in the early diagnosis of AS.

Lenvatinib is a multi-targeted tyrosine kinase inhibitor available for the treatment of unresectable hepatocellular carcinoma (HCC). We herein report an 84-year-old-man with interstitial pneumonia caused by lenvatinib. Four months after the start of lenvatinib administration for HCC, chest computed tomography revealed bilateral ground-glass opacity. However, he continued to take lenvatinib for four more months until he complained of dyspnea on exertion. This is a case of lenvatinib-induced interstitial pneumonia that progressed relatively slowly with a long asymptomatic period despite the appearance of pneumonia on image findings.

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.

Two adult patients with acute leukemia developed transplantation-associated microangiopathy (TAM) related to graft-versus-host disease (GVHD). Both patients were resistant to standard therapy for TAM and GVHD, which led to markedly elevated serum total bilirubin levels of 47.5 and 10.6 mg/dL, respectively. Transdermal isosorbide tape as a nitric oxide donor was applied to Patients 1 and 2 on post-transplantation days 60 and 66, respectively, which rapidly improved their jaundice after 1 day. This is the first report to describe the efficacy of transdermal isosorbide tape for adult patients with jaundice associated with TAM related to GVHD.

Myeloid sarcoma (MS) is a relatively rare manifestation of myeloid neoplasms at sites other than the bone marrow. The rarity of gastrointestinal (GI) MS is attributed to certain factors, such as misdetection due to insufficient endoscopic assessments at the initial presentation with acute myeloid leukemia (AML) as well as the difficulty of making a histologic assessment of leukemic involvement of the GI tract. We herein report a case of AML with gastric involvement and discuss the importance of screening examinations and therapies considering the location of MS and the data of cytogenetic and molecular mutation.

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.

Muscle phosphorylase b kinase (PHK) deficiency is a rare mild metabolic disorder caused by mutations of the PHKA1 gene encoding the αM subunit of PHK. A 16-year-old boy experienced myalgia during the maximal multistage 20-m shuttle run test targeting the maximal oxygen consumption. Although an ischemic forearm exercise test was normal, a muscle biopsy revealed subsarcolemmal glycogen accumulation. He harbored a novel insertion mutation in the PHKA1 gene that resulted in premature termination of the αM subunit close to the C-terminus. Compared with previously reported cases, his reduction in PHK activity was relatively mild.

We herein report a case of recurrent multifocal, distal-dominant-sensorimotor neuropathy with ophthalmoplegia, IgM anti-GM1 antibody, and pyrexia-associated relapse. The patient developed sensory disturbance in her limbs after febrile disease at 50 years old. She had experienced several similar episodes and was admitted to the hospital at 56 years old. Based on a pathological study and electrophysiological findings consistent with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), maintenance IVIg therapy was administered and produced partial improvement with no relapse at one-year follow-up. Immunohistochemical studies suggested the presence of IgG (not IgM) anti-myelin antibodies. Chronic neuropathy with ophthalmoplegia and pyrexia-associated relapse may be a unique variant of CIDP.

We herein report a case of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 24-year-old woman developed unilateral optic neuritis 3 weeks after contracting coronavirus disease 2019 (COVID-19), followed by intracranial demyelinating lesions and myelitis. Since serum anti-MOG antibody was positive, we diagnosed MOG antibody-associated disease. Immunotherapy with steroids resulted in the rapid improvement of neurological symptoms. This is a suggestive case, as there are no reports of MOG antibody-associated disease with multiple neurological lesions occurring after COVID-19. The response to immunotherapy was favorable. This case suggests that it is important to measure anti-MOG antibodies in patients who develop inflammatory neurological disease after COVID-19.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by infiltration of extensive IgG4-positive plasma cells and lymphocytes. Although IgG4-RD has been observed in almost all organs, it rarely affects the myocardium. Cardiovascular lesions of IgG4-RD appear as aortic (aortic aneurysm and aortitis) and pericardial (constrictive pericarditis) lesions as well as pseudotumors around the coronary arteries. We herein report a case of IgG4-RD with a cardiac mass in the right atrium involving a sinus node. This condition caused arrhythmia and repeated strokes. We successfully treated the patient through resection of the cardiac mass, catheter ablation and immunosuppressive therapy.

A 49-year-old Japanese man with a 2-month history of a fever, headache, and bilateral conjunctival hyperemia was admitted. His condition fulfilled the giant cell arteritis classification criteria (new headache, temporal artery tenderness, elevated ESR) and atypical Cogan's syndrome (CS) with scleritis and sensorineural hearing loss (SNHL). The interleukin (IL)-6 serum level was extremely high. Two weeks after his insufficient response of SNHL and scleritis to oral prednisolone, we administered tocilizumab (TCZ); rapid improvements in scleritis and SNHL occurred. Early IL-6 target therapy can help prevent irreversible CS-induced sensory organ damage.

Ruxolitinib, a Janus kinase inhibitor, improves symptoms in patients with myelofibrosis. However, its association with the development of opportunistic infections has been a concern. We herein report a 71-year-old man with primary myelofibrosis who developed disseminated tuberculosis and concurrent disseminated cryptococcosis during ruxolitinib treatment. We also reviewed the literature on disseminated tuberculosis and/or cryptococcosis associated with ruxolitinib treatment. This is the first case of disseminated tuberculosis and concurrent disseminated cryptococcosis during treatment with ruxolitinib. We therefore suggest considering not only disseminated tuberculosis but also cryptococcosis in the differential diagnosis of patients with abnormal pulmonary shadows during ruxolitinib treatment.

Sarocladium kiliense is ubiquitous in the human environment and is an emerging opportunistic pathogen, especially among immunocompromised hosts. A 77-year-old man diagnosed with aplastic anemia suffered from non-valvular endocarditis. After he passed away, fungal hyphae were observed in several lesions on a postmortem examination. Polymerase chain reaction (PCR) and a DNA sequence analysis revealed S. kiliense as the causative organism. This is the first case report of non-valvular fungal endocarditis caused by S. kiliense identified by PCR and a DNA sequence analysis in an immunocompromised patient. Although rare, invasive fungal infection caused by S. kiliense should be considered in immunocompromised hosts.

A 61-year-old woman was transferred with a complaint of a fever and productive cough. She had tested positive for Mycobacterium avium and Nocardia cyriacigeorgica at least twice, and Streptococcus pneumonia (PISP) was isolated (3+) from her purulent sputum. As radiological findings, a lower lung field-dominant infiltration shadow and nodular shadow with cavity were recognized in the bilateral lung fields. We diagnosed her with pneumococcal pneumonia co-infection with M. avium and N. cyriacigeorgica. She was treated with MEPM for pneumococcal pneumonia, a standard regimen containing clarithromycin for pulmonary M. avium complex (MAC) disease, and sulfamethoxazole/trimethoprim for pulmonary nocardiosis. She improved with appropriate treatment.

A 92-year-old woman diagnosed with dementia and end-stage gastric cancer received end-of-life care on the island where she lived. Informed consent concerning remote death certification based on the Japanese government's guidelines was obtained from a family member in case a physician was unavailable. A physical examination after cardiopulmonary arrest was conducted, supported by telemedicine and a well-trained registered nurse under remote supervision of the physician who last saw the deceased directly. Death certification was provided accordingly. To our knowledge, this was the first case of remote death certification using telemedicine in Japan.

We herein report a 93-year-old woman diagnosed with acute myocardial infarction (AMI) based on typical laboratory findings of severe chest pain accompanied by throat pain. This condition was initially interpreted as referred pain of cardiac origin. However, the patient had persistent throat pain after successful percutaneous coronary intervention. Upper esophageal perforation with life-threatening acute mediastinitis was unexpectedly identified by a further examination. Clinicians should have a high index of suspicion in cases with persistent symptoms thought to be referred pain among AMI patients, as these symptoms may not be of cardiac origin but rather a sign of another concomitant critical disease.

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.