Barrett's esophagus (BE) is a precancerous disease that can lead to esophageal adenocarcinoma (EAC). Recently, the incidence of EAC arising from BE has been increasing, and EAC has now become a threat in many countries. However, there are many gaps among the various countries in terms of definitions and concepts and these gaps prevent discussing BE on the same footing. In order to eradicate BE, it is a global necessity to fill in these remaining gaps. We focused on the gaps and reviewed recent evidence and trends as well as the background of gaps between the US and Japan as two of the leading countries in the field of medical research. We also review the rapid advances in endoscopic techniques in relation to both diagnosis and therapy that are considered to be useful to eliminate the gaps between countries.

Objective Persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major causative factors of hepatic cirrhosis and hepatocellular carcinoma. However, the development of antiviral treatment has enabled their suppression. Therefore, the early detection and treatment of these infections are important. The objective of this study was to assess the level of awareness among healthcare professionals about hepatitis virus infection and electronic medical records alert system.

Methods We surveyed healthcare professionals from 10 institutions with electronic medical records alert systems. All participants attended a lecture about the reactivation risk due to HBV infections, the most recent antiviral treatment for HCV infections, and the electronic medical records alert system. They participated in a questionnaire-based survey about their awareness of these infections, current status of intra-hospital referral, need for intra-hospital referrals before and after the lecture, and reasons for non-referral of patients to specialists.

Results Responses were received from 1,281 healthcare professionals. Physicians and pharmacists had a high level of awareness about HBV and HCV. Among physicians, the level of awareness of those in the surgical field and other fields was significantly lower than that of the professionals in the internal medicine field. The awareness of the need to refer patients to hepatologists increased from 84.7-85.4% before to 93.0% after the lecture. The most frequent reasons for not referring patients previously were "I had no knowledge and/or interest" (28.1% of responses) and "All I did was explain the results orally" (24.2%).

Conclusion More widespread education of healthcare personnel is important to increase the number of individuals receiving appropriate treatment from specialist physicians.

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment.

Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure.

Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline.

Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.

Objective In patients on peritoneal dialysis (PD), it was reported that colonoscopy, but not upper gastrointestinal endoscopy, could cause peritonitis as a complication. A guideline of the International Society for Peritoneal Dialysis recommends preemptive intravenous antibiotics administration of ampicillin and aminoglycoside with or without metronidazole, to prevent colonoscopy-associated peritonitis. In this study, we retrospectively evaluated the effects of preemptive antibiotics therapy by oral administration instead of intravenous administration.

Methods We investigated the incidence of colonoscopy-associated peritonitis in a single center. In 170 patients undergoing PD between January 2010 and December 2019, 50 colonoscopies were performed, including 49 with oral administration of amoxicillin and ciprofloxacin and/or metronidazole as preemptive therapy 1 hour before the colonoscopy procedure, and 1 without.

Results We observed no incidence of colonoscopy-associated peritonitis.

Conclusion Generally, oral administration of preemptive antibiotics is less painful and more convenient than intravenous administration, especially in outpatient procedures, such as a colonoscopy. Our results suggest that oral antibiotic administration might be effective for preventing colonoscopy-associated peritonitis in PD patients.

Objective The burden of diabetic peripheral neuropathic pain (DPNP) is poorly understood. The present study reported on the current status of DPNP in Japan, to improve our understanding of this condition among healthcare providers and inform future clinical research on its prevalence, diagnosis, and management.

Methods A cross-sectional, observational study (UMIN000037023) was conducted via a web-based survey. The primary endpoints were the frequency of patients with bilateral foot symptoms, consulting a doctor, understanding DPNP, and reporting problems in daily life, as well as the treatment awareness of patients.

Patients Adults ≥20 years old who were registered in the Rakuten Insight Disease Panel and receiving anti-diabetic therapy in Japan were included.

Results Bilateral foot pain symptoms were reported by 1,768/7,754 (22.8%) respondents, most commonly intense numbness (13.0%). Of those with symptoms, 55.3% consulted a doctor; the most common reason for not seeking consultation was feeling that symptoms were insufficiently severe to bother their doctor (89.4%). Nearly 60% reported understanding the causes of their symptoms, with diabetes-associated neurologic deficits (58.8%) most commonly identified. About one-quarter reported daily life problems, including an inability to walk for long periods (58.3%) and feeling anxious (58.1%). Treatment awareness was reported by 18.2%; oral medications were commonly recognized (64.6%).

Conclusion In Japan, 22.8% of patients with diabetes have bilateral foot pain symptoms; some experience problems in their daily life without understanding the causes of their symptoms. This supports the importance of actions to increase awareness and minimize DPNP-associated impairment of daily life in patients with diabetes.

Objective To determine the clinicopathological features of levodopa or dopamine agonist (DA) responders with multiple system atrophy (MSA), an autopsy-confirmed diagnosis is vital due to concomitant cases of MSA and Parkinson's disease (PD). We therefore aimed to investigate the effectiveness of levodopa and DA in autopsy cases of MSA without PD and thereby clarify the clinical course, magnetic resonance imaging (MRI) findings, and pathological features of levodopa-responsive MSA cases.

Methods The medical records (clinical data, MRI findings, and pathological findings) of 12 patients with MSA were obtained, and the patients were pathologically confirmed to not have PD. The clinical diagnoses of the patients were MSA with predominant parkinsonism (MSA-P) (n=7), MSA with predominant cerebellar ataxia (MSA-C) (n=4), and progressive supranuclear palsy (PSP) with a concomitant pathology of MSA (n=1).

Results Nine patients received a maximum dose of 300-900 mg of levodopa as treatment, which was effective in two MSA-P patients and mildly effective in another two MSA-P patients. DA was mildly effective in one MSA-C patient. The levodopa responders showed marked autonomic dysfunction relatively late and became bedridden after 10 years. Additionally, they exhibited bilateral hyperintense putaminal rims in MRIs after six and nine years, respectively, after disease onset. One levodopa responder and one DA mild responder showed relatively mild neurodegeneration of the putamen.

Conclusion Levodopa responders, despite having MSA-P, may show a relatively slow progression in putaminal neurodegeneration, and might maintain prolonged daily life activities in cases without an early occurrence of autonomic dysfunction.

A 60-year-old man had received octreotide for a metastatic neuroendocrine tumor (NET) in the rectum. Computed tomography and ultrasonography revealed a cardiac tumor, diffuse thickness of the ventricular wall and pericardial effusion, which was diagnosed as cardiac metastasis. The metastatic lesions continued to grow despite the alteration of chemotherapy, and the patient complained of repeated syncope and was admitted to our hospital at 11 months after the diagnosis of cardiac metastasis. An electrocardiogram during syncope showed sustained ventricular tachycardia, which was considered to be caused by the cardiac metastasis. We herein report a case of NET with cardiac metastasis which caused lethal arrhythmia along with a review of the pertinent literature.

Appropriate management of constipation in hemodialysis patients has not been established, although constipation is the most frequent gastrointestinal complication in dialysis patients. We herein report the efficacy and safety of polyethylene glycol in constipated hemodialysis patients assessed prospectively. Seven patients using stimulant laxatives participated in this study. Polyethylene glycol was administered to reduce stimulant laxatives during the six-week intervention period. The amount of stimulant laxatives decreased and spontaneous bowel movements with ideal stool consistency increased significantly after the intervention. No serious adverse effects were observed throughout this study. In conclusion, polyethylene glycol can be a useful tool for managing constipated hemodialysis patients.

Anti-tumor necrosis factor (TNF) α agents, widely used for the treatment of Crohn's disease (CD), can sometimes induce skin-associated adverse events, which mainly include psoriasis-like eruptions, eczema, and cutaneous infections. In contrast, purpura caused by vasculitis is rarely seen. We herein report a unique case of leukocytoclastic vasculitis induced by infliximab administered for CD in which intermittent purpura development was noted. Fluorescent immunostaining showed no immunoglobulin A deposition on the vessel walls. No purpura was initially seen after starting infliximab, but it appeared approximately 10 months later; however, administration did not have to be discontinued, and the condition was later resolved. The present findings provide important details regarding vasculitis induced by anti-tumor necrosis factor-α agent administration.

We herein report the first case of foveolar-type gastric adenocarcinoma that developed after the initiation of vonoprazan (VPZ). A 51-year-old man had heartburn at the first visit and reflux esophagitis endoscopically, so he started taking VPZ. An approximately 5-mm-sized reddish polyp with a raspberry-like morphology was detected at the anterior wall of the upper body of the stomach 156 weeks after starting maintenance therapy with VPZ 10 mg/day. It was diagnosed as foveolar-type gastric adenocarcinoma based on a biopsy. Another approximately 4-mm-sized foveolar-type gastric adenocarcinoma was also detected at the posterior wall of the middle body of the stomach.

A 74-year-old man presented with abdominal swelling. Computed tomography revealed massive ascites and localized thickening of the small intestinal wall. Enteroscopy showed ulcerative lesions along the circumference of the jejunum. Histological examination showed dense proliferation of large lymphoid atypical cells, and immunohistochemistry showed CD20 and CD10 positivity, CD3 negativity, and Ki67 labeling index >80%. Cytology of the ascitic fluid revealed large lymphoid cells. These findings suggest that small intestine primary diffuse large B-cell lymphoma (DLBCL) caused the ascites. Massive ascites as an initial symptom of primary DLBCL of the jejunum is rare. Herein, we describe this unusual presentation.

A 70-year-old man was diagnosed with multiple lung metastases from hepatocellular carcinoma, and lenvatinib was initiated. Three months later, the response was progressive disease. Sorafenib therapy as a second-line drug was started. Three months later, the lung metastases had shrunk. After the sorafenib failure, the patient received regorafenib treatment for six months until failure. After the regorafenib failure, sorafenib rechallenge therapy as a fourth-line treatment was initiated. The sorafenib rechallenge, which continued for two months, induced a partial response. Sorafenib after lenvatinib failure and sorafenib rechallenge may be a good option, but further prospective studies are needed.

We herein report a 67-year-old woman with malignant lymphomas of the bile duct that developed after regression of a pancreatic head mass. Computed tomography suggested the mass was pancreatic head cancer. Endoscopic ultrasonography showed a low-echoic mass with hyperechoic strands resembling autoimmune pancreatitis. Her serum IgG4 concentration was elevated to 674 mg/dL. After the pancreatic head mass spontaneously diminished, three masses were detected in the common bile duct. A biopsy of the major papilla revealed high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangement. Systemic chemotherapy with rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin resulted in complete remission.

A 54-year-old woman underwent chemotherapy including rituximab and autologous peripheral blood stem cell transplantation (auto-PBSCT) for diffuse large B-cell lymphoma. Before the treatment, she exhibited a resolved hepatitis B virus (HBV) infection. She was diagnosed with HBV reactivation based on positive serum HBV-DNA test results, 55 months after her last treatment. Subsequently, he was treated with tenofovir alafenamide fumarate (TAF) therapy and her liver function improved. Patients undergoing chemotherapy including rituximab and auto-PBSCT are at a high risk of HBV reactivation. In such cases, careful and long-term observations may be required to detect HBV reactivation.

We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.

Cardiac involvement of malignant lymphoma is relatively common, although such a phenomenon has subclinical manifestations that are difficult to detect. We herein describe a patient with atrial fibrillation and sick sinus syndrome as the main symptoms. Computed tomography showed a mass in the right atrium extending into the superior vena cava (SVC). We implanted the patient with a leadless pacemaker. Transvenous biopsy revealed a diffuse large B-cell lymphoma. The patient was treated successfully with chemotherapy including rituximab. This case suggested that cardiac lymphoma may cause sick sinus syndrome, and leadless pacemaker implantation is a safe treatment option in patients with partial SVC obstruction.

Two patients, a 60-year-old man and 43-year-old woman, presented to our hospital with symptoms of respiratory tract infection. These patients showed imaging findings of multiple small nodules, ground-glass opacities, and consolidations. In case 1, although antibiotics were started, bilateral shadows spread widely, which made us suspect interstitial pneumonia. The condition improved after steroid administration, and there has been no recurrence since completing this treatment. In case 2, the patient recovered rapidly with antibiotics only. In both cases, we performed bronchoalveolar lavage, in which only human rhinovirus infection was detected by multiplex polymerase chain reaction testing, and primary rhinovirus pneumonia was diagnosed.

An 83-years-old woman diagnosed with advanced Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma was administered afatinib as a first-line treatment. On Day 17, the patient presented with grade 3 diarrhea and a blood test analysis showed an increased inflammatory response. Afatinib treatment was discontinued on the same day. On Day 26, the patient displayed blepharedema and multiple irregular erythema covering her entire body. Drug-induced hypersensitivity syndrome (DIHS) was suspected, and the systemic administration of 30 mg/day prednisolone was administered. The symptoms subsided thereafter. A blood test analysis 3 weeks after onset revealed a reactivation of Human herpesvirus 6 (HHV-6) and a diagnosis of DIHS due to afatinib therapy was confirmed.

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.

The authors report a case of transudative pleural effusion associated with extramedullary hematopoiesis due to the presence of a myeloproliferative neoplasm, which was unclassified. A 71-year-old man presented with right pleural effusion during an exacerbation of thrombocytosis. The pleural effusion was transudative, although there was no history of cardiac failure or hypoalbuminemia, and treatment with diuretics failed. Extramedullary hematopoiesis was diagnosed in bilateral paravertebral soft tissue and the liver on ¹¹¹In bone marrow scintigraphy. The administration of hydroxyurea simultaneously reduced peripheral blood platelet count and pleural effusion within 2 weeks. The possible cause of transudative pleural effusion in association with extramedullary hematopoiesis is discussed.

An 86-year-old woman was admitted for the investigation of atelectasis of the upper lobe of her right lung with a mass shadow in the hilum (Golden S sign). Chest computed tomography revealed swollen connective tissue around the right bronchus, and needle aspirate grew Bifidobacterium longum and Veillonella species. She was diagnosed with peribronchial connective tissue infection, and her condition improved with antibiotics. Although this sign is strongly suggestive of malignant disease, benign disease should be considered in the differential diagnosis. Pulmonary infection caused by Bifidobacterium longum is extremely rare; however, clinicians should consider it as a possible cause of pulmonary infections.

We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.

Few reports have so far described central nervous system (CNS) involvement in multiple myeloma (MM), which shows a poor prognosis owing to its resistance to several treatments. We herein describe a 45-year-old woman who had MM (diagnosed with IgA-κ type) with CNS relapse early after undergoing autologous hematopoietic stem cell transplantation. Because no standard treatment for CNS lesions of MM has been established, we conducted a literature review on the cerebrospinal fluid (CSF) transferability of drugs for MM, since it was considered to be a useful tool for CNS involvement. Immunomodulatory-drugs including pomalidomide exhibit a good CSF transfer ability, and, therefore, may be beneficial against the CNS involvement of MM.

Mild palmar digital neuropathy may be underestimated because selective nerve conduction studies (NCS) of the palmar digital nerve are challenging. We herein report two cases of palmar digital neuropathy. We performed sensory NCS in each finger using the standard approach. Both cases showed a decrease in the amplitude of sensory nerve action potential (SNAP) in the localized finger. Furthermore, the sensory nerve inching test identified the lesion site. When performing NCS in patients with finger sensory impairment, we recommend recording the SNAP in each finger using standard NCS at the wrist, as well as sensory nerve inching testing.

We experienced two cases of post-intubation laryngotracheal stenosis (PILS) occurring in patients after acute coronavirus disease (COVID)-19 in a relatively narrow time period. The patients required mechanical ventilation for 9 days in one and 28 days in the other. In both cases, the patients were discharged but later developed symptoms of cough and dyspnea, which were later diagnosed as PILS. Persistent cough and dyspnea are common symptoms in both PILS and the recovery phase of severe COVID-19. For this reason, PILS should be considered in the differential diagnosis post-COVID-19 patients. In addition, the prevalence of PILS may be greater than that of other critical diseases in severe COVID-19 patients.

An outbreak of coronavirus disease 2019 (COVID-19) that began in Wuhan, China, has spread rapidly to many countries. We herein report four cases of COVID-19 confirmed in Japan among passengers of the cruise ship Diamond Princess and describe the clinical features, clinical course, and progression of chest computed tomographic images, chest radiographs, and treatment. Although these four patients had symptoms that included a fever, malaise, runny nose, and cough, one patient had no symptoms on admission. Two of the four patients needed mechanical ventilation due to respiratory deterioration. One of the patients who required mechanical ventilation was transferred to a higher-level medical institution. Except for that patient, the other three patients were able to return home under their own power. Every patient took lopinavir/ritonavir, which was considered the most effective treatment at the time. We used it after receiving approval from the ethics committee in our hospital. In this case report, we emphasize that some patients need to be carefully monitored, even if their respiratory condition is stable at the initial presentation, as their respiratory status may deteriorate rapidly within a few days after oxygen administration begins.