Duodenal diverticular bleeding (DDB) is extremely rare. We herein report 2 life-threatening cases of DDB successfully treated with endoscopy or transcatheter arterial embolization (TAE) and review 13 cases of DDB reported from Japan. When upper gastrointestinal bleeding of unknown origin is encountered in middle-aged or older adults, DDB should be included in the differential diagnosis. DDB often causes massive bleeding. It is therefore important to judge which is safer and more effective, endoscopy or TAE, based on the general condition of the patient. In addition, it is critical to attempt hemostasis via various strategies, including different gastroscopes and hemostatic devices.

Objective Gastroesophageal reflux disease (GERD), including reflux esophagitis (RE), is recognized as a common gastrointestinal disease, and its prevalence is reported to be increasing. While current cigarette smoking has been established as a risk factor for RE in several cross-sectional studies, most of these studies did not include details concerning the smoking status in their analyses. Smoking-related conditions, such as chronic lung disease and cough, are reportedly also related to GERD.

Methods To investigate the association between RE and detailed smoking habits, we performed a cross-sectional analysis of healthy men enrolled in a comprehensive health checkup program conducted in 2015 that included esophago-gastro-duodenoscopy. Smoking status was assessed using a self-reported questionnaire. Other smoking-related parameters, including the lung function, cough symptoms and presence of chronic lung disease, were also assessed. Unconditional logistic regression was applied to calculate the odds ratio (OR) with 95% confidence intervals (CIs) after adjusting for confounding factors.

Results The study included 151 subjects with RE (RE group) and 814 without RE (control group). Compared with never-smokers, former smokers (OR, 1.5; 95% CI, 0.9-2.9) and current smokers (OR, 2.4; 95% CI, 1.5-3.9) showed an increased risk of RE. An increased risk of RE was also observed among subjects with current smoking for 10-20 PYs and more than 20 PYs (OR, 2.8; 95% CI, 1.4-5.8, OR, 3.1; 95% CI, 1.6-5.7 respectively). An elevated risk was observed in former smokers who reported more than 20 PYs (OR, 2.5; 95% CI, 1.3-4.8). When former smokers were stratified according to time since smoking cessation, a significant RE risk was observed in participants who had stopped smoking less than 10 years earlier compared with never smokers (OR, 1.9; 95% CI, 1.1-3.3). No significant associations were observed between chronic cough, FEV1.0%, and RE.

Conclusion Cumulative lifetime exposure to smoking plays an important role in the risk of RE.

Objective Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination.

Methods Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares.

Results During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not.

Conclusion IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC.

Objective Clinical practice guidelines in Japan recommend surgery for all nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs), regardless of their size or associated symptoms. Because pancreatic resection is highly invasive, follow-up for small NF-PNETs is often chosen in clinical practice. However, the natural history of NF-PNET remains poorly understood. We aimed to examine the natural history of pathologically confirmed NF-PNET.

Methods This single-center retrospective case series investigated NF-PNETs that were pathologically diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) at our hospital between 2014 and 2018. Patients who were followed up without treatment due to their general condition or their wish were included in the study. Patients' background characteristics, imaging findings, pathological findings, and long-term prognoses were investigated using medical records.

Results Overall, 26 patients were diagnosed with NF-PNET by EUS-FNA during the observation period. Of these, 9 patients (3 men and 6 women; median age: 64 years old) were followed up without treatment. All of these patients were asymptomatic, and localization was noticed in 3 cases in the head, body, and tail (1 each), with a median size of 12 (range: 4-18) mm. Neuroendocrine tumor (Grade 1 [G1]) was pathologically diagnosed in all patients with EUS-FNA. The median observation period was 63 (range: 26-90) months. Tumor growth and distant metastasis were not observed in any of the nine patients who remained asymptomatic.

Conclusion Follow-up is a feasible option for asymptomatic NF-PNET ≤20 mm in size with a pathological grade of G1.

Objective The index of microvascular resistance (IMR) is an invasive method for quantifying the coronary microvasculature independent of the presence and degree of epicardial stenosis during cardiac catheterization, whereas the Selvester QRS score, which is related to myocardial damage, is a relatively simple and non-invasive measurement procedure. We investigated the relationship between the QRS score and coronary microvascular dysfunction (CMD) assessed via IMR.

Methods Data from 74 patients who underwent invasive coronary physiological measurements were retrospectively reviewed. Using a coronary wire, we measured IMR by the hyperemic mean transit time and distal coronary pressure. We also determined a simplified QRS score following the Selvester QRS score criteria by 12-lead electrocardiography. After determining the best cutoff value for the QRS score to predict IMR ≥25, which was defined as CMD by the Coronary Vasomotion Disorders International Study Group, patients were categorized into the QRS score ≥3 (n=16) and the QRS score 0-2 (n=58) groups.

Results IMR in the QRS score ≥3 group was significantly higher in comparison to the QRS score 0-2 group (31; IQR: 19-57 vs. 20; IQR: 14-29, p<0.01). The percentage of patients with IMR ≥25 in the QRS score ≥3 group was significantly higher than that in the QRS score 0-2 group (69% vs. 34%, p=0.01).

Conclusion A higher QRS score was associated with CMD, as estimated by IMR. The Selvester QRS score is noninvasive parameter that is potentially useful for predicting CMD.

Objective High pleural amylase levels have been reported in patients with malignant pleural effusion; however, the characteristics of this association are uncertain. Therefore, this study investigated the factors, such as cancer type and oncogenic drivers, related to pleural amylase levels in patients with malignant pleural effusion.

Methods We retrospectively collected the data of 362 cancer patients [lung adenocarcinoma (n=256), lung squamous carcinoma (n=12), small-cell lung carcinoma (n=32), other lung cancers (n=5), mesothelioma (n=31), and metastatic cancer (n=26)] with malignant pleural effusion at Fukujuji Hospital from January 2012 to October 2022. Pleural amylase levels were compared.

Results Pleural amylase levels were significantly higher in patients with lung adenocarcinoma [median 58.6 IU/L (interquartile range (IQR) 33.8-139.3)] than in those with small-cell lung carcinoma [median 37.2 IU/L (IQR 26.3-63.7), p=0.012]. The median pleural amylase level was higher in patients with lung adenocarcinoma than in those with other cancer or histologic types, although the difference was not significant. Pleural amylase levels were higher in epidermal growth factor receptor (EGFR) mutation-positive patients than in EGFR mutation-negative patients [median 95.8 IU/L (IQR 52.7-246.5) vs. median 51.2 IU/L (IQR 27.8-96.9), p<0.001]. The Kaplan-Meier survival curves of pleural amylase ≥75 IU/L were higher than those of pleural amylase <75 IU/L [log-rank test p<0.001, hazard ratio 0.54 (95% confidence interval: 0.41-0.71)].

Conclusion This study demonstrates that pleural amylase levels were elevated in patients with lung adenocarcinoma and EGFR mutations. Furthermore, a high pleural amylase level was associated with a good prognosis.

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency.

Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied.

Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study.

Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O₂ treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI.

Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O₂ treatment was higher in SLI group than in those without SLI.

We herein report a rare case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC) in a 60-year-old man. The patient, who had been treated with infliximab for Crohn's disease of the colon for 13 years, was referred to our hospital for lower back pain. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging revealed multiple cystic lesions in the right retroperitoneum, the calcification of the cyst, and bone lesions. Bone and CT-assisted biopsies of the retroperitoneal lesions revealed poorly differentiated adenocarcinoma. The patient was diagnosed with PRMC with bone metastases using immunohistochemical staining and positron emission tomography/CT.

A 79-year-old woman was diagnosed with transverse colon cancer, moderately differentiated adenocarcinoma. She underwent surgery and postoperative adjuvant chemotherapy. At 80 years old, the patient exhibited changes in skin tone at the chest and abdomen with CK7+/CK20-/CDX2- immunostaining that was later identified as poorly differentiated adenocarcinoma. The diagnosis was cancer of unknown primary origin. The patient passed away three months after the detection of the skin lesion. Autopsy revealed recurrence at the transverse colon, multiple organ metastases, a similar postmortem immunostaining pattern, and high-frequency microsatellite instability (MSI-high). We herein report this case of CK7+/CK20-/CDX2- and MSI-high transverse colon cancer showing cutaneous metastasis.

We herein report a case of hepatitis C virus (HCV)-associated cryoglobulinemic livedo reticularis in a woman in her 60s that improved with direct-acting antivirals (DAAs). Hyperpigmentation was observed in both lower legs, and a skin biopsy confirmed livedo reticularis, suggesting a relationship with cryoglobulinemia and HCV infection. DAAs with an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir) were administered for eight weeks, and a sustained virological response (SVR) was obtained. The disappearance of serum cryoglobulin was confirmed approximately two years after an SVR was obtained and livedo reticularis was improved. DAA therapy can be an effective therapeutic option for extrahepatic complications associated with HCV infection.

We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment for Parkinson's disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treated with pericardiectomy. The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP.

A 46-year-old man presented to our hospital with chest pain followed by coughing and dyspnea. His myocardial enzyme levels were almost normal, and electrocardiography and echocardiography showed no obvious abnormalities. Chest radiography revealed congestion. He was diagnosed with heart failure with a preserved ejection fraction (HFpEF). Although subjective symptoms improved with intravenous diuretics, the patient was admitted to the hospital for a close examination. Coronary angiography showed no obvious stenosis, and a subsequent spasm provocation test demonstrated the presence of multi-vessel and diffuse spasms. Coronary spasm should be considered as a differential cause of heart failure, even in patients with HFpEF.

A 48-year-old woman with advanced ovarian cancer was diagnosed with pulmonary tumor thrombotic microangiopathy (PTTM) by antemortem pulmonary wedge aspiration cytopathology. Despite the initiation of anti-cancer treatment, she unfortunately died due to progressive respiratory failure. Histopathology of the autopsied lung revealed multiple tumor embolization with fibrin-rich clot and fibro-cellular intimal proliferation at the pulmonary arteriole. The embolized tumor showed strong immune-positivity for pro-thrombotic and fibrotic factors (tissue factor and vascular endothelial growth factor), suggesting the underlying mechanisms of PTTM development. This case suggests that a quick antemortem diagnosis and the early induction of specific treatments might ensure a better prognosis of PTTM.

An 84-year-old man developed a membranoproliferative glomerulonephritis pattern of injury, and the most likely cause detected during a workup was monoclonal IgG-λ in the urine and serum. Predominant IgG and λ light chain deposition was confirmed only by immunofluorescence using formalin-fixed, paraffin-embedded tissue and not by immunohistochemistry. A smaller and non-linear dynamic range of immunohistochemistry makes it less quantitative than immunofluorescence staining and may explain why immunohistochemistry failed to detect the light chain restriction. This case suggests that immunohistochemistry may not serve as a substitute for immunofluorescence on formalin-fixed, paraffin-embedded tissue in detecting masked monoclonal immunoglobulin deposits, although further research is warranted.

A 58-year-old woman was admitted to our hospital. At 10 years old, she had undergone bilateral uretero-sigmoid anastomosis for congenital epispadias, and at 57 years old, she had received transverse colostomy. Biochemical tests showed marked metabolic acidosis. Computed tomography showed urine stagnation in the sigmoid colon, leading to a diagnosis of metabolic acidosis associated with transverse stoma after bilateral uretero-sigmoid anastomosis. Her bone mineral density was below normal, and the bone metabolic marker levels were high, indicating high-turnover osteoporosis. Both metabolic acidosis and bone metabolism were stabilized by treatment with a transanal urinary catheter, sodium bicarbonate, and vitamin D.

A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing β₂-microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high β₂-microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms.

A 39-year-old vegan man was admitted with diabetic ketoacidosis. He had also developed pneumonia that was unresponsive to antibiotics. Based on bronchoscopy findings, the diagnosis of Candida pneumonia was made, and the pulmonary shadow disappeared rapidly after antifungal therapy. Candida pneumonia has been mostly reported in severely immunocompromised patients. This is a rare case of Candida pneumonia that was found in a young vegan man with diabetes mellitus (DM). Although malnutrition caused by DM or an unbalanced diet is often underestimated as a cause of immunodeficiency, these conditions can be risk factors for serious opportunistic infections, including Candida pneumonia.

Pulmonary hypertension (PH) is a serious condition in which there is an abnormally high pressure in the pulmonary arteries that can occur as a complication of connective tissue diseases. Although the relationship between PH and systemic lupus erythematosus or systemic sclerosis has been well-characterized, PH rarely occurs in patients with anti-synthetase syndrome (ASS), and little is known about the pathophysiology and clinical outcome of patients with ASS-PH. We herein report a patient with anti-Jo-1-positive ASS complicated by PH and discuss the treatment strategy through a review of previously reported cases.

Infection can induce hemophagocytic lymphohistiocytosis (HLH) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We herein report a 52-year-old man who had HLH and AAV simultaneously, possibly caused by Enterococcus faecalis infective endocarditis. The HLH diagnosis was based on the HLH-2004 criteria. AAV was diagnosed based on a positive result for proteinase-3 ANCA and necrotizing vasculitis of the small vessels on a skin biopsy. He eventually died and was sent for autopsy after combination treatment of valve replacement, antibiotics, and immunosuppressants, including corticosteroids. This case involved a challenging diagnosis and treatment of HLH with various complications in an adult.

We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.

A 79-year-old man experienced a fever and immobility after receiving 6 doses of Bacillus Calmette-Guérin (BCG) intravesical instillation therapy for bladder tumor. Rhabdomyolysis and acute kidney injury occurred; therefore, hemodialysis was performed. His kidney function was restored. However, he exhibited an inflammatory reaction that was resistant to broad-spectrum antibiotics and eventually developed interstitial pneumonia. Corticosteroid treatment partially relieved the symptoms of interstitial pneumonia, although disuse syndrome persisted. He was diagnosed with disseminated BCG infection through sputum culture. BCG infection shows various symptoms and is difficult to diagnose microbiologically. It should be suspected when systemic symptoms occur after BCG intravesical instillation therapy.