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Pembrolizumab-induced adrenal insufficiency (AI) is recognized as a rare immune-related adverse event (irAE) that can be fatal if diagnosis is delayed. Clinical features of AI in patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab as the first-line treatment were observed. Five out of 49 patients with untreated advanced NSCLC developed AI between April 2017 and February 2021. Of the 5 patients, 4 developed AI with a grade >3 and were hospitalized. The median time of the onset of AI from the start of first-line treatment was 4.63 months. All the patients improved after corticosteroid replacement therapy. The efficacy of treatment was complete response in 1 patient and partial response in 4 patients. Median progression-free survival was 37.7 months, and overall survival had not been reached. This case series revealed the efficacy of immunotherapy in AI as an irAE.

Background Degenerative aortic arch aneurysms are known to develop through a pathological process of arterial atherosclerosis, which could be accompanied by peripheral artery diseases and resultant development of intrapelvic collateral arteries to the ischemic lower limbs. The aim of this study was to investigate the relationship between peripheral collateral circulation and postoperative paraplegia after total arch repair with a frozen elephant trunk in patients with degenerative aortic arch aneurysms and peripheral artery diseases. Methods Between October 2014 and March 2020, 27 patients (20 men; 69.8 ± 7.7 years old) underwent total arch repair with a frozen elephant trunk. Two of the 27 patients developed paraplegia postoperatively. The patients were divided into two groups, spinal cord ischemia (SCI) group (2 patients) and no-SCI group (25 patients). The aortic shagginess score, arterial calcification (subclavian artery; hypogastric artery) score, and the number of hypogastric artery branches, assessed using preoperative contrast-enhanced computed tomography images, were compared between the two groups. Results The ankle brachial artery pressure index (i.e., lower side value each patient) was lower in the SCI group than that in the no-SCI group (0.64, 0.71, and 1.09±0.07, respectively). There was no difference between the two groups in the arterial calcification scores or the aortic shagginess score. The number of hypogastric artery branches was greater in the SCI group than in the no-SCI group (66, 66, and 30.7±7.5, respectively). Conclusions Enhanced collateral circulation to the ischemic lower limbs in patients with combination of degenerative aortic arch aneurysms and peripheral artery diseases may be involved in paraplegia the upper thoracic spinal cord injury after total arch repair with a frozen elephant trunk.

We describe a case of frozen elephant trunk deployment unintentionally malpositioned into the false lumen. An 83-year-old man underwent total arch repair with a frozen elephant trunk for type A acute aortic dissection complicated by mesenteric malperfusion. However, intraoperative transesophageal echocardiography showed expansion of the false lumen in the descending aorta, suggesting a malpositioned frozen elephant trunk into the false lumen. Endovascular fenestration of the dissecting flap and subsequent endograft deployment from the inside of the malpositioned frozen elephant trunk graft to the true lumen of the descending aorta was successfully performed under intravascular ultrasound guidance.

Background Data on long-term cosmetic outcome, overall survival, and disease-free survival of endoscope-assisted partial mastectomy (EAPM) for breast cancer are scarce. Thus, we examined these outcomes after a 10-year follow-up period, and compared with conventional conservative method (CCM). Patients and methods Data on 257 patients with stage ≤ IIA breast cancer who underwent CCM (n = 125) or EAPM (n = 132) were analyzed. Cosmetic outcome at 2, 5, and 10 years was evaluated by 5 criteria (breast retraction assessment, nipple deviation, atrophy, skin change, scar). For overall mortality, breast cancer-specific mortality, and recurrence, the risk by operation method was tested by Cox proportional hazard models. Results EAPM performed significantly better than CCM in terms of cosmetic outcomes for location B at 2, 5, and 10 year-follow ups. As for cosmetic outcomes by individual criteria, EAPM had significantly higher proportions of satisfactory results for scar across all follow-up periods, and atrophy at 2-year and 10-year follow-up. There were no significant differences in terms of overall mortality, breast cancer-specific mortality, and recurrence between EAPM and CCM. The rates of patients who experienced local recurrence were similar between CCM and EAPM. Conclusion EAPM is better than CCM in terms of long-term cosmetic outcome, especially for location B. As a surgical treatment for breast cancer, EAPM is comparable to CCM in terms of mortality and recurrence.

This report describes 7 cases in which multichannel balloon angioplasty was performed for severely calcified common femoral artery stenosis. After the successful passage of a guidewire through the stenosis, another guidewire with a tip load of 12g or 14 g was passed through a different channel inside the calcified plaques, followed by balloon angioplasty via each route. After the procedure, ankle brachial index improved from 0.49 ± 0.23 to 0.89 ± 0.05 on an average, and 6 of the 7 patients had patent arteries at a median follow-up period of 13 months. Multichannel balloon angioplasty offers the promise of being an effective endovascular intervention to expand calcified lesions.

Background This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long‐term follow‐up. Methods In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019. Results Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin‐based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin‐based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon after surgery. Growing teratoma syndrome developed during chemotherapy in four cases. Urgent thoracic surgery was performed in three patients, but one case was inoperable. The calculated 10‐year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. During follow‐up, second non‐GCT malignancies developed in three patients (colon cancer, 190 months; thyroid cancer, 260 months; non‐small cell lung cancer, 250 months after the initial chemotherapy) and one patient with primary mediastinal seminoma was associated with multiple type I endocrine tumors. Conclusions Our experiences demonstrated that long‐term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long‐term follow‐up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs., The clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal germ cell tumors (GCT) treated at our hospital between 1983 and 2019 were examined in this retrospective study. The calculated 10‐year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. The clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied.

AIM: The J-SMART study was the first national survey of Japanese patients undergoing laparoscopic sleeve gastrectomy (LSG). We performed a subgroup analysis of J-SMART focusing on the differences in patient background and diabetes remission between patients with BMI 32–34.9 kg/m(2) and those with higher BMI. METHODS: In this multi-institutional retrospective study at 10 certified bariatric institutions, 203 Japanese with type 2 diabetes (T2D) and BMI of 32 kg/m(2) or higher were analyzed (mean age: 49.2 years, BMI: 43.8 kg/m(2), HbA1c: 7.6%). Patients were stratified into five groups according to preoperative BMI. RESULTS: Background characteristics in BMI 32.0–34.9 group were higher adjusted HbA1c, higher visceral/subcutaneous fat area ratio, higher prevalence of diabetic retinopathy, higher frequency of insulin use and lower serum C-peptide. Although 2-year percent total weight loss (21.7%) and diabetes complete remission (CR) rate (52.4%) were lower in BMI 32.0–34.9 group, diabetes improvement rate was 81.0%, and the decrease in HbA1c and number of antidiabetic drugs were comparable or greater than those with higher BMI. Higher BMI and no insulin use were significant independent predictors of diabetes CR. No significant independent predictor was identified for diabetes improvement. CONCLUSION: The patients with 32–34.9 kg/m(2) were characterized by more severe visceral obesity, T2D and the complications, and lower intrinsic insulin secretion capacity. LSG should be considered as a treatment option for patients with BMI 32–34.9 kg/m(2), to improve diabetes control.

The incidence of pleomorphic adenoma (PA) of the minor salivary glands is reported to be 10%, and while the histological findings in PA can be diverse, keratin-filled cysts lined by squamous epithelium are rarely reported. The condition can, however, present with cyst formation in some cases. We review a rare case of pleomorphic adenoma in the buccal mucosa that involved the formation of multiple squamous epithelium-lined cysts in a 69-year-old woman. Magnetic resonance imaging (MRI), fine needle aspiration cytology, and histopathological examination were performed. Physical examination revealed a painless, mobile, elastic hard mass in the right buccal mucosa, measuring 2.5 × 1.0 cm. The MRI revealed a well-defined lesion with different signal intensities in the medial and distal regions of the right cheek. The medial side of the lesion showed a low signal intensity on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI), while the distal side showed a low signal intensity on T1WI, and a high signal intensity on T2WI and short tau inversion recovery (STIR) imaging. Fine needle aspiration of the lesion was performed under local anesthesia and a cytological diagnosis of an epidermoid or dermoid cyst was made. The tumor was completely resected under local anesthesia combined with intravenous sedation. The histopathological examination demonstrated the proliferation of atypical tumor cells with poor atypia and the formation of glandular, alveolar, large, and small cysts. The cysts were lined by keratinized squamous epithelial cells, their cavities were filled with keratinous material, and foreign body reaction was observed after rupture. Histopathological evaluation led to the diagnosis of pleomorphic adenoma. The patient had no evidence of recurrence, 2 years and 3 months after the surgery. In conclusion, the presence of multiple cysts lined by squamous epithelium can pose a significant diagnostic challenge in patients with PA. It is important to make the correct diagnosis in order to avoid unnecessarily aggressive therapy.

Background: Oral potentially malignant disorders, which include oral lichen planus (OLP), are clinical presentations that carry a risk of development to cancer in the oral cavity. Oral lichenoid lesions (OLLs) are also termed interface/lichenoid mucositis. Malignant transformation of them remains controversial, but distinct clinical and histological criteria for how to differentiate OLP from OLLs have not been developed. Objectives: The purpose of this study was to elucidate findings that can allow histopathological differentiation of OLP and OLLs using histomorphological and immunohistochemical analyses. Materials and Methods: Analyses were performed in 10 cases diagnosed with OLP and 9 cases diagnosed with OLLs. Cytokeratin 19 (CK19), Ki-67 and CD3 were used as primary antibodies to detect basal cells, proliferative activity and T-cell distribution, respectively, and Perlecan and COX-2 to evaluate epithelial intracellular arrangements and interstitial distributions of proteoglycans and enzymes. Results: For CK19, positive cells were significantly found in OLLs at both the prominent area and site adjacent to the lesion comparison with those of OLP’s. The number of COX-2 positive cells was significantly higher in spinous and basal layers in OLLs of the prominent area. Additionally, OLLs showed mild to moderate expression for perlecan in the basal to spinous layers and in subepithelial tissue. Conclusion: Almost no basal cells were noted in the prominent area in OLP. COX-2 and perlecan were found in the basal to spinous layers in OLLs. Although there are restrictions, these suggested the possibility of helping to distinguish between OLP and OLLs.

Alport syndrome (AS) is a hereditary glomerular nephritis caused by mutation in one of the type IV collagen genes α3/α4/α5 that encode the heterotrimer COL4A3/4/5. Failure to form a heterotrimer due to mutation leads to the dysfunction of the glomerular basement membrane, and end-stage renal disease. Previous reports have suggested the involvement of the receptor tyrosine kinase discoidin domain receptor (DDR) 1 in the progression of AS pathology. However, due to the similarity between DDR1 and DDR2, the role of DDR2 in AS pathology is unclear. Here, we investigated the involvement of DDR2 in AS using the X-linked AS mouse model. Mice were treated subcutaneously with saline or antisense oligonucleotide (ASO; 5 mg/kg or 15 mg/kg per week) for 8 weeks. Renal function parameters and renal histology were analyzed, and the gene expressions of inflammatory cytokines were determined in renal tissues. The expression level of DDR2 was highly elevated in kidney tissues of AS mice. Knockdown of Ddr2 using Ddr2-specific ASO decreased the Ddr2 expression. However, the DDR2 ASO treatment did not improve the proteinuria or decrease the BUN level. DDR2 ASO also did not significantly ameliorate the renal injury, inflammation and fibrosis in AS mice. These results showed that Ddr2 knockdown by ASO had no notable effect on the progression of AS indicating that DDR2 may not be critically involved in AS pathology. This finding may provide useful information and further understanding of the role of DDRs in AS.

Background Management of diminutive pharyngeal neoplasms is controversial. Thus, we conducted a single-center, prospective pilot study to investigate the efficacy and safety of endoscopic excision with cold forceps biopsy (CFB) of these lesions. Patients and methods Thirty-nine lesions endoscopically diagnosed with narrow-band imaging as pharyngeal neoplasms of 3 mm or smaller were excised with CFB using jumbo biopsy forceps (cap diameter 2.8 mm, jaw volume 12.4 mm3 ). The primary outcome was endoscopically determined local remnant/recurrence rate 3 months after CFB. The secondary outcomes were histopathologically determined local remnant/recurrence rate; risk factors associated with the endoscopic remnant/recurrence; and incidence of intraoperative or delayed bleeding and other adverse events. Results Histological diagnosis of the 39 CFB-excised lesions were: 11 high-grade dysplasia (28.2%), 22 low-grade dysplasia (56.4%), two basal cell hyperplasia (5.1%) and four atypical squamous epithelium (10.3%).Twenty-seven patients (30 lesions) underwent follow-up endoscopy 3 months after CFB; the endoscopic and pathological local remnant/recurrence rate was 20% (6/30; 95% confidence interval (CI), 7.7-36.6%) and 16.7% (5/30; 95% CI, 5.6-34.7%), respectively. Location of the lesion in the hypopharynx was a significant risk factor associated with the endoscopic local remnant/recurrence (P = 0.049). No significant adverse events occurred. Conclusions Cold forceps biopsy with jumbo biopsy forceps appears to be a safe and effective technique for excising diminutive pharyngeal neoplasms. Although small, the excised lesions may have a remarkably high frequency of high-grade dysplasia. (Clinical trial registration number: UMIN000037980).

Here, we present a case of acute myocardial infarction caused by an aortic valve tumor. Electrocardiography (ECG)-gated four-dimensional computed tomography revealed obstruction of the right coronary ostium by a mobile mass during systole. To ensure an accurate diagnosis of angina in patients without significant coronary artery disease, ECG-gated four-dimensional computed tomography is useful because it can simultaneously visualize the coronary ostium and arteries, aortic valve leaflets, and mass.

Background Sinus of Valsalva aneurysm (SVA) is a rare cardiac abnormality occurring in 0.09% of the general population, but few reports have examined its recurrence. Unruptured SVAs are usually asymptomatic. Case summary A 50-year-old woman presented with chest pain and a history of surgery for a ruptured right coronary SVA 32 years prior. Echocardiography showed the recurrence of an unruptured SVA of the non-coronary sinus with moderate aortic regurgitation, severe mitral regurgitation, and severe tricuspid regurgitation. Cardiac computed tomography (CT) revealed compression of the right coronary artery (RCA) between the SVA and sternum. Adenosine triphosphate stress myocardial perfusion imaging (MPI) identified reversible ischaemia of the inferior wall. The patient underwent patch closure of the SVA, aortic valve replacement, mitral valvuloplasty, and tricuspid annuloplasty. Post-operative MPI showed no residual ischaemia, and CT confirmed both successful repair of the SVA and intact RCA. Discussion This case provides two noteworthy findings. First, the SVA recurred after 32 years. Second, a non-coronary SVA causing myocardial ischaemia is extremely rare given the long anatomical distance between the non-coronary sinus and coronary arteries. In our patient, the non-coronary SVA grew large enough within the anterior mediastinum to cause RCA compression.

Background Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively. Patients and methods We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naive patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs. Results All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions. Conclusion This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.

Background Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE. Methods We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan–Meier method. Results Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/μL; white blood cell count: 8810 /μL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/μL, p p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan–Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p Conclusions Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE.

Purpose Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC). Methods and Materials Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors. Results The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments. The median follow-up duration was 54 months (range, 7-103 months). All surviving patients were followed for more than 51 months. Two patients experienced grade 3 acute skin reactions, but no other grade 3 or higher toxicities were observed in any organ. No patient exhibited an increase in the Child-Pugh score of 2 or more points after CIRT. The local tumor control rates at 1, 3, and 5 years were 98%, 91%, and 91% after CIRT, respectively. All lesions that failed to respond to previous treatments were successfully controlled by CIRT. The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 45%, respectively. Conclusions Two-fraction CIRT was a well-tolerated and effective treatment for patients with HCC.

Objective The aim of this study was to investigate the effect of frozen elephant trunk deployment from the zone 0 aorta to the descending aorta on early and midterm postoperative results in patients with acute type A aortic dissection. Methods Between October 2014 and April 2018, 108 patients underwent a combined strategy of frozen elephant trunk deployment, ascending aortic replacement, and arch vessel reconstruction ("zone 0 arch repair" strategy) for acute type A aortic dissection (excluding DeBakey type II). Of the 108 patients, 32 (29.6%) had primary tears of the aortic arch or descending aorta. Results The 30-day mortality rate was 2.8% (3 patients), and in-hospital mortality rate was 6.5% (7 patients). New-onset permanent neurologic dysfunction and spinal cord injury occurred in 3.7% and 0% of patients, respectively. Five of the 101 survivors underwent thoracic endovascular aortic repair during hospitalization (2 for rapid false lumen enlargement; 3 for true lumen stenosis). The overall survival was 89.8%, 88.1%, and 88.1% at 1, 2, and 3 years, respectively. The cumulative incidence of distal aortic reintervention was 5.8%, 9.1%, and 9.1% at 1, 2, and 3 years, respectively. Two patients underwent thoracic endovascular aortic repair for distal aortic enlargement after discharge. Conclusions The use of the "zone 0 arch repair" strategy can eliminate the need for invasive aortic arch resection. It also eliminates the false lumen and produces satisfactory early and midterm postoperative results. Therefore, it can be an alternative to hemiarch and total arch replacements, which are based on a conventional "tear-oriented resection" strategy.

Background: Liquid-based cytology (LBC) is a method of manufacturing cyto-diagnostic specimens. Improved accuracy is expected from standardizing specimen production and use of this method is rapidly spreading in oral cytology. On the other hand, LBC reportedly requires training to show peculiar cell findings compared to those of conventional smear cytology (CVC). Few studies have compared detailed cell findings for oral CVC and LBC. Objectives: The aim of this study was to compare cytological findings between CVC and LBC using cytomorphological image analysis. Materials and Methods: Cytological specimens were collected from 20 patients (negative for squamous neoplasia in 10, dysplasia in 5, squamous cell carcinoma in 5) and 5 controls of the tongue between January 2017 and December 2018. Two different preparation techniques were investigated cytomorphologically for CVC and LBC (BD CytorichTM). Results: LBC showed significantly higher cell numbers than CVC for all lesions. LBC-to-CVC ratio ranged from 9.52 (hyperkeratosis) to 1.87 (deep cells in oral squamous cell carcinoma (OSCC)). Nuclear area of normal, hyperkeratosis, and inflammation were significantly higher in LBC than those of CVC. Hyperchromasia was significantly more frequent with CVC than with LBC for hyperkeratosis, inflammation, dysplasia and OSCC. There was no significant difference in circularity between CVC and LBC among all lesions. Conclusion: Only one cytomorphological disadvantage was seen with LBC, in the form of decreased hyperchromasia. Further clarification of the advantages and disadvantages of LBC is needed, including management of precision and screening practices.

Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

Background and aims We have started a new population‐based endoscopic gastric cancer screening program in Kurashiki city with consideration of Helicobacter pylori infection status based on endoscopic features. We aimed to verify the feasibility of this attempt in a prospective case‐registration study (UMIN000028629). Methods Data were collected from 1784 subjects without past eradication of H. pylori and who underwent endoscopic gastric cancer screening in Kurashiki Central Hospital Preventive Healthcare Plaza from September 2017 to June 2018. Endoscopic judgment of H. pylori infection status was made according to the Kyoto classification of gastritis. For comparison, a combination serum test of anti‐H. pylori antibody and pepsinogen I and II, the ABC method, was used. Results The endoscopic diagnoses were nongastritis, 1215 (68.1%); active or inactive gastritis, 469 (26.3%); and undefined, 23 (1.3%). With the ABC method as a reference standard, the false‐negative rate of the endoscopic judgment for H. pylori infection was 16.3% (95% confidence interval: 13.1%‐20.0%). Most false‐negative cases were of Group B in the ABC method, which is considered gastritis with mild mucosal atrophy. Antibody titers in this population were mostly in the weak‐positive range but clinically significant elevation of the antibody suggesting current infection was observed in some cases. Conclusions Endoscopic diagnosis of H. pylori infection status in a population‐based gastric cancer screening program is mostly reliable, but false‐negative results may occur, especially in patients with mild gastric atrophy. To avoid this limitation, we recommend adding H. pylori antibody test to the program.

Introduction Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. Methods This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. Results Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. Conclusions This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

Background An aortic sinus of Valsalva aneurysm (SVA) often remains undiagnosed until it ruptures. An SVA filled with thrombus can be challenging to diagnose accurately. Case summary A 70-year-old man was admitted with a clinical diagnosis of well-tolerated complete atrioventricular block (AVB). Transthoracic echocardiography revealed a spherical mass (43 × 49 mm) at the interatrial septum. Enhanced computed tomography (CT) showed a well-defined, hollow, and non-enhanced mass suggesting a cardiac tumour. However, 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) showed no uptake in the mass. After implantation of a permanent pacemaker, anticoagulant therapy was started for paroxysmal atrial fibrillation. Two months later, follow-up evaluation by echocardiography and enhanced CT revealed an increase in size of the hollow interior cavity, suggesting thrombolysis by the anticoagulant. We diagnosed a non-coronary SVA filled with thrombus, which masqueraded as a cardiac tumour and may have caused complete AVB. Conclusions We describe a rare case of a giant thrombosed SVA masquerading as a cardiac tumour. Initial 18F-FDG PET/CT and serial imaging studies were helpful in distinguishing it from a cardiac tumour.

Objective This study investigated whether the Dementia Assessment Sheet for the Community-based Integrated Care System is useful for decision-making or problem detection in the treatment and care of older patients with inoperable advanced non-small cell lung cancer compared with the current standard model using performance status. Methods This study retrospectively examined 1595 cases admitted to the Department of Respiratory Medicine at the Tokyo Metropolitan Geriatric Hospital between 26 July 2016 and 28 January 2020. Among these, 29 and 31 patients who received pharmacotherapies and best supportive care were extracted, respectively. The performance in identifying best supportive care using the Dementia Assessment Sheet for the Community-based Integrated Care System was evaluated in comparison with performance status. The ability to detect impairments in each Dementia Assessment Sheet for the Community-based Integrated Care System domain was also assessed. Results The Dementia Assessment Sheet for the Community-based Integrated Care System total score had an area under the curve of 0.831 (95% confidence interval, 0.694–0.914), which was statistically equivalent to performance status. The discriminatory cut-off value for identification of best supportive care was set at 29 with a sensitivity and specificity of 0.742 and 0.897, respectively. Dementia Assessment Sheet for the Community-based Integrated Care System total score showed good concordance with performance status especially when reported by family members or caregivers. Deficits other than activities of daily living were recognized (2.8–19.4%) in patients with good performance status. Impairments were more frequently detected when reported by family members or caregivers. Conclusions The Dementia Assessment Sheet for the Community-based Integrated Care System discriminates the best supportive care for older patients with inoperable advanced non-small cell lung cancer. Moreover, it can identify vulnerabilities especially when reported by family members or caregivers that cannot be detected by performance status.

Background Stereotactic body radiation therapy (SBRT) has high efficacy for early-stage hepatocellular carcinoma (HCC) and is an accepted alternative to radiofrequency ablation (RFA). However, SBRT for HCC may cause subacute liver injury leading to negative clinical outcomes. In this study, we compared changes of liver function and prognosis after SBRT or RFA in patients with single, small HCC by using a propensity-score matching analysis. Methods We reviewed medical records of 140 patients with single ≤3 cm HCC treated with SBRT or RFA at Kurashiki Central Hospital between January 2014 and February 2019. Changes of albumin-bilirubin (ALBI) score, local recurrence, and overall survival were compared between the propensity-score matched groups (31 patients treated with SBRT and 62 treated with RFA). Results The ALBI score increased modestly but significantly after SBRT, while it was unchanged in the RFA group; the intergroup difference was statistically significant (P=0.004). No local recurrence was identified in the SBRT group, whereas the cumulative recurrence incidence was 9.7% in the RFA group (P=0.023). Overall survival was not significantly different between the two groups (hazard ratio: 1.32, 95% confidence interval: 0.60-2.89, P=0.401). Conclusions SBRT had modestly negative impact on liver function but with appraisable local control of HCC. Our findings should contribute to the selection of this modality for treatment of single, small HCC.

Background Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare complication of infective endocarditis and aortic valve replacement. Ruptured P-MAIVF and angina due to compression of the coronary arteries are severe complications of this condition. Case presentation We report a case of P-MAIVF that was diagnosed accidentally during a routine checkup. The patient was asymptomatic; however, she had a systolic murmur. She had a history of infective endocarditis, which was treated conservatively without open-heart surgery. In addition, she was diagnosed with aortic valve stenosis, aortic valve regurgitation, bicuspid aortic valve, right coronary artery stenosis, and an ascending aortic aneurysm. She was treated with surgery, which involved patch closure of P-MAIVF with aortic valve replacement, coronary artery bypass grafting, and ascending aorta replacement. After the operation, echocardiography showed no leakage from the P-MAIVF. Conclusions It is necessary to have knowledge of P-MAIVF. Following up cases of infective endocarditis and post-aortic valve replacement using echocardiography is important for both, diagnosing P-MAIVF and preventing serious complications such rupture and angina.

Background It is difficult to distinguish between multicentric Castleman’s disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung. Methods We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected. Results In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level. Conclusion Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.

Background The efficacy of amrubicin for relapsed small-cell lung cancer (SCLC) has been reported in previous studies. Few reports, however, describe the efficacy and survival benefit of third-line amrubicin chemotherapy in patients with extensive disease (ED)-SCLC. Methods We retrospectively analyzed the clinical records of ED-SCLC patients treated with amrubicin salvage chemotherapy as a third-line chemotherapy between January 2005 and July 2016 (salvage amrubicin group). The efficacy and toxicities of amrubicin were evaluated. Overall survival (OS) in the amrubicin salvage group was compared with OS among ED-SCLC patients treated with at least second-line chemotherapy between May 2000 and July 2016 and without subsequent amrubicin salvage chemotherapy. Results A total of 18 patients with a median age of 70 years were analyzed in the amrubicin salvage group. The median number of treatment cycles of amrubicin was four. The response rate was 27.8% (95% confidence interval (CI), 7.1%-48.5%), and the disease control rate (DCR) was 66.7% (95% CI, 44.9%-88.4%). Median progression-free survival was 2.9 months (95% CI, 1.0-4.9 months), and median OS after an initial chemotherapy was 18.1 months (95% CI, 10.2-26.0 months). OS in the amrubicin salvage group was significantly longer than in the no-amrubicin group (n = 19; 12.6 months, 95% CI, 11.5-13.8 months, P = 0.005). The frequency of neutropenia greater than grade 3 was 72.2%, with febrile neutropenia developing in 38.9% of patients in the amrubicin salvage group. Conclusions Despite a high frequency of febrile neutropenia, amrubicin salvage chemotherapy may improve OS in patients with relapsed ED-SCLC.

Background Peripheral pulmonary lesions are rarely observed directly before transbronchial biopsy. This study aimed to characterize the differences between malignant and benign peripheral pulmonary lesions according to the findings of direct observation using probe-based optical fiberscopy. Methods Thirty patients who underwent probe-based optical fiberscopy in combination with bronchoscopy using endobronchial ultrasonography with a guide sheath for the evaluation of peripheral pulmonary lesions were prospectively included in this study. The patients were divided into the malignant and benign groups according to their final diagnosis. The findings of probe-based optical fiberscopy in the two groups were compared. Results The numbers of patients who were diagnosed using histological or bacteriological analyses via bronchoscopic sampling in the malignant and benign groups were 20/23 (87.0%) and 2/7 (28.6%), respectively. On probe-based optical fiberscopy, angiogenesis and vascular engorgement were observed only in the malignant group. The disappearance of subepithelial microvessel transparency and presence of bronchiolar stenosis were observed more frequently in the malignant group (78.3% and 60.9%) than in the benign group (28.6% and 28.6%), whereas increased mucus secretion was observed more frequently in the benign group (71.4%) than in the malignant group (8.7%). Conclusions These results suggest that the findings of direct observation using probe-based optical fiberscopy are useful for differentiating malignant from benign peripheral pulmonary lesions. Trial registry UMIN-CTR; UMIN000018796; URL: https://www.umin.ac.jp/ctr/index.htm .

Aim Laparoscopic sleeve gastrectomy (LSG) is becoming popular in Japan, but insufficient weight loss is often observed in patients after LSG. We investigated the effect of LSG on obesity‐related comorbidities and identified the background characteristics of Japanese patients with insufficient weight loss after LSG. Methods In this multi‐institutional retrospective study at 10 certified bariatric institutions, 322 Japanese patients who underwent LSG with a follow‐up period of more than 2 years were analyzed. Anthropometry, obesity‐related comorbidities and psychosocial background data were collected. Weight loss was expressed as 2‐year percent total weight loss (%TWL). Results Mean age, body weight, body mass index (BMI) and glycated hemoglobin were 46.9 years, 119.2 kg, 43.7 kg/m2 and 7.1%, respectively. Prevalence of mental disorders was 26.3%. Mean BMI declined to 30.3 kg/m2 at 2 years and %TWL was 29.9%. Improvements in the markers and prevalence of obesity‐related comorbidities were observed. Remission rates of diabetes, dyslipidemia and hypertension were 75.6%, 59.7% and 41.8%, respectively. %TWL at the respective cut‐off level of diabetes remission was 20.8%. Lower remission rates of diabetes in patients with %TWL, We investigate the effect of LSG on obesity‐related comorbidities and identify the background characteristics of Japanese patients with insufficient weight loss after LSG. This is the first nationwide survey in Japan to clarify the relationship between insufficient weight loss after LSG, metabolic remissions and psychosocial background. %TWL 20% was a candidate cut‐off point of insufficient weight loss for diabetes remission after LSG, and mental disorders might be relevant to intractable obesity in Japanese patients.

Objectives A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. Methods We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. Results A total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). Conclusions This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

To assess liver stiffness (LS) and spleen stiffness (SS) values measured by virtual touch quantification (VTQ) technique in the monitoring of portal pressure and their usefulness for the prediction of the exacerbation of esophageal varices (EV) in patients with gastric varices undergoing balloon-occluded retrograde transvenous obliteration (B-RTO). The LS, SS, and hepatic venous pressure gradient (HVPG) were measured in 20 patients both before and after B-RTO. The change in each parameter between the two groups (EV exacerbation and non-exacerbation groups) was compared by analysis of variance. The efficacy of the parameters for the prediction of the exacerbation of EV was analyzed using a receiver operating characteristic (ROC) curve analysis. 9 patients (40.9 %) exhibited an exacerbation of EV within 24 months after B-RTO. Significant changes were observed in the HVPG and SS after B-RTO between the two groups (EV exacerbation group vs. non-exacerbation group: HVPG before 12.7 ± 4.4 mmHg vs. 11.0 ± 4.4 mmHg; HVPG after 19.6 ± 6.0 mmHg vs. 13.6 ± 3.1 mmHg P = 0.003; SS before 3.40 ± 0.50 m/s vs. 3.20 ± 0.51 m/s; SS after 3.74 ± 0.53 m/s vs. 3.34 ± 0.43 m/s P = 0.016). However, no significant changes in LS were observed between the two groups. The area under the ROC curves of elevation in HVPG and SS for the prediction of the exacerbation of EV after B-RTO were 0.833 and 0.818, respectively. Elevation of the HVPG and SS measured by VTQ after B-RTO was useful for the prediction of the exacerbation of EV.ZIEL: Beurteilung der mittels Virtual-Touch-Quantification (VTQ) gemessenen Lebersteifigkeit (LS) und Milzsteifigkeit (SS) bei der Überwachung des Pfortader-Drucks und dessen Nutzen für die Vorhersage der Exazerbation von Ösophagusvarizen (EV) bei Patienten mit Magenvarizen, die sich einer Ballon-okkludierten retrograden transvenösen Obliteration (BRTO) unterziehen. LS, SS und Lebervenendruckgradient (HVPG) wurden bei 20 Patienten sowohl vor, als auch nach B-RTO gemessen. Die Veränderung jedes Parameters zwischen den beiden Gruppen (EV-Exazerbationsgruppe und Nicht-Exazerbationsgruppe) wurde durch eine Varianzanalyse verglichen. Die Wirksamkeit der Parameter für die Vorhersage der Exazerbation von EV wurde mittels Receiver-Operating-Characteristic (ROC)-Kurve analysiert. Innerhalb von 24 Monaten nach B-RTO zeigten 9 Patienten (40,9 %) eine EV-Exazerbation. Signifikante Veränderungen wurden im HVPG und in der SS nach B-RTO zwischen beiden Gruppen beobachtet (EV-Exazerbationsgruppe vs. Nicht-Exazerbationsgruppe: HVPG vorher: 12,7 ± 4,4 mmHg vs. 11,0 ± 4,4mmHg; HVPG nachher: 19,6 ± 6,0 mmHg vs. 13,6 ± 3,1mmHg; p = 0,003; SS vorher: 3,40 ± 0,50 m/s vs. 3,20 ± 0,51 m/s; SS nachher: 3,74 ± 0,53 m/s vs. 3,34 ± 0,43 m/s; p = 0,016). Es wurden jedoch keine signifikanten Veränderungen der LS zwischen den beiden Gruppen beobachtet. Die Fläche unter den ROC-Kurven für die Vorhersage einer Exazerbation der EV nach B-RTO betrug für die Erhöhung des HVPG 0,833 und für die Erhöhung der SS 0,818. Für die Vorhersage einer Exazerbation von EV war die mittels VTQ nach B-RTO gemessene Erhöhung des HVPG und der SS von Nutzen.

Exposure to pesticides can induce neurobehavioral effects in rodents, as well as in other mammals, including humans. However, the effects of the toxicity of pesticides on the central nervous system (CNS) remain largely unclear. The expression of the activity-regulated cytoskeleton-associated protein gene (Arc) is induced in a neuronal-activity-dependent manner and is implicated in synaptic and experience-dependent plasticity. We previously developed Arc-promoter-driven luciferase transgenic (Tg) mouse strains to monitor the neuronal-activity-dependent gene expression under physiological and pathological conditions in vivo. In this study, we examined the effect of acute administration of four different pesticides (deltamethrin, glufosinate, methylcarbaryl, and imidacloprid) on neuronal activity using Arc-Luc Tg mice. The change in the bioluminescence signal in mouse brain upon treatment with deltamethrin and glufosinate occurred more slowly than that of kainic acid, a potent neuroexcitatory amino acid agonist. These two pesticides also caused convulsive responses in adult Arc-Luc Tg mice. In the case of glufosinate, we detected the long-term upregulation of bioluminescence signal intensity of Arc-Luc over 24 h after the treatment. Furthermore, we observed greater changes of bioluminescence signal in adults than in juveniles, and a lower incidence of convulsions at the juvenile stage. In contrast to the acute treatment, we detected a decrease of bioluminescence signal after low-dose chronic treatment with glufosinate, without neuronal overexcitation. From these results, we suggest that Arc-Luc Tg mice are useful for assessing the acute and chronic effects of pesticides on the CNS.

An advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a central role in the pathogenesis of diabetic vascular remodeling. This study was conducted to clarify the role of RAGE in nondiabetic atherosclerosis. We used the aortic and coronary atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits prone to myocardial infarction (WHHLMI) at 1 to 14 months. Immunohistochemistry demonstrated the significant expression of RAGE as early as at 1 month with the stronger expression at 3 and 7 months, which was remarkably diminished at 14 months. RAGE expression was concordant with AGE accumulation. The major original sources of RAGE expression were macrophages and smooth muscle cells in addition to endothelial cells, and RAGE expression was distributed in the areas of phospholipid products, a component of oxidized LDL and nitrotyrosine. The concentrations of serum AGE did not alter significantly with aging. These findings suggested the expression of RAGE was induced by hyperlipidemia and oxidative stress independent of diabetes in WHHLMI rabbits. Additionally, our in vitro study showed that silencing of RAGE tended to attenuate oxidized-LDL-triggered PAI-1 expression in human cultured macrophages, as well as oxidized-LDL-induced tissue factor expression in peritoneal macrophages, suggesting a possible role of RAGE in prothrombogenic molecular regulation. In conclusion, the present study provides in vivo evidence that RAGE plays an integral role in the initiation and progression of nondiabetic atherosclerosis, suggesting that RAGE may be a novel target for treating not only diabetic but also nondiabetic vascular complications.

Introduction: Small-cell lung cancer (SCLC) is a very chemosensitive solid tumor but is characterized by rapid progression. The modified Glasgow prognostic score (mGPS) has been shown to be an independent prognostic factor in various tumors. However, there have been few reports regarding the prognostic value of mGPS in extensive disease (ED)-SCLC. Objective: This study was designed to clarify the clinical significance of mGPS focusing on its usefulness as a prognostic indicator for the survival and serial administrations of chemotherapies in patients with ED-SCLC. Methods: We retrospectively analyzed the clinical records of ED-SCLC patients diagnosed and treated at Shinshu University School of Medicine between January 2005 and December 2018. Overall survival (OS) was compared according to mGPS and we examined whether mGPS could be a prognostic factor in ED-SCLC using the Kaplan-Meier method and univariate and multivariate Cox hazard analyses. Results: Eighty-three patients were enrolled in this study. The median OS of mGPS 0, mGPS 1, and mGPS 2 groups were 13.6, 9.2, and 5.7 months, respectively. The OS of the mGPS 0 group was significantly longer than those of mGPS 1 and mGPS 2 groups (log-rank, p = 0.025 and 0.008, respectively). The rates of second-line chemotherapy administration in mGPS 0, mGPS 1, and mGPS 2 groups were 79.4, 61.9, and 33.3%, respectively. The rate in the mGPS 0 group was significantly higher than that in the mGPS 2 group (p = 0.003). Multivariate analyses indicated that mGPS 2 was an independent unfavorable prognostic factor in addition to old age (≥75 years), poor performance status (2–3), and elevated serum lactate dehydrogenase level (≥223 IU/L). Conclusion: In ED-SCLC patients, mGPS was useful as a prognostic indicator for OS.

Oral squamous cell carcinoma (OSCC) often causes lymphatic metastasis, particularly to the regional cervical lymph nodes. Although lymphatic metastasis is closely associated with lymphangiogenesis in the tumor tissues, the detailed mechanisms are not yet fully understood. The purpose of this study was to examine the morphological association of lymphangiogenesis in the tumor stromal tissue with cervical lymph node metastases in OSCC. The medical records of 13 patients treated for OSCC affecting the tongue at the Department of Oral Surgery of Nihon University School of Dentistry at Matsudo Hospital between November 2003 and March 2011 were reviewed. The 13 cases were divided into two groups, with 7 cases in the metastasis group and 6 cases in the non-metastasis group. Histopathological (hematoxylin-eosin stain) and immunohistochemical (D2-40 antibody) examinations were performed. Lymphatic vascular density and lymphatic vascular area, lymphatic vascular morphology, and the number of lymph vessels were quantified using ImageJ software. The lymphatic vessels in the metastasis group were distributed with higher density and ran irregularly, with more remarkable deformation than those in the non-metastasis group. Cervical lymph node metastasis is one of the factors affecting progression and the prognosis of OSCC patients. In the present study, lymphatic vessels were found in the OSCC stroma, which also suggests that an increased density of lymphatic vessels leads to cervical lymph node metastases.

Background Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear. Methods and Results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes. Conclusions We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.

This Review Article overviews the literature on diabetes insipidus (DI) associated with pregnancy and labor in Japan published from 1982 to 2019. The total number of patients collected was 361, however, only one-third of these cases had detailed pathophysiologic information enabling us to identify the respective etiology and subtype. Pregnancy-associated DI can be divided into 3 etiologies, central (neurogenic) DI, nephrogenic DI, and excess vasopressinase-associated DI. Neurogenic DI has various causes: for example, DI associated with tumoral lesions in the pituitary and neighboring area, DI associated with Sheehan's syndrome and/or pituitary apoplexy, and DI associated with lymphocytic infundibuloneurohypophysitis (LINH, stalkitis). Nephrogenic DI results from defective response of the kidney to normal levels of vasopressin. However, the most interesting causal factor of pregnancy-associated DI is excess vasopressinase, caused either by excess production of vasopressinase by the placenta or defective clearance of vasopressinase by the liver. Hepatic complications resulting in pregnancy-associated DI include acute fatty liver of pregnancy (AFLP) and HELLP syndrome (syndrome of hemolysis, elevated liver enzymes, low platelets), as well as pre-existing or co-incidental hepatic diseases. A possible role of glucose uptake in putative stress-induced DI and the importance of correct diagnosis and treatment of pregnancy-associated DI, including use of 1-deamino 8-D arginine vasopressin, are also discussed.

Background The geriatric nutritional risk index (GNRI) is a simple and useful marker for predicting prognosis and treatment efficacy among patients with various cancers. However, to the best of our knowledge, there are no previous reports regarding the prognostic value of GNRI among patients with non‐small cell lung cancer (NSCLC) who were treated with immune checkpoint inhibitors (ICIs). Methods We retrospectively evaluated 85 patients with previously treated advanced NSCLC who were administered ICIs at Shinshu University Hospital between February 2016 and October 2020. Progression‐free survival (PFS) and overall survival (OS) were compared between groups with high (≥89.5) and low (, This retrospective study evaluated the prognostic value of the geriatric nutritional risk index (GNRI) among patients with previously treated advanced non‐small cell lung cancer (NSCLC) who subsequently underwent immunotherapy. A high GNRI was associated with good outcome among patients with NSCLC. These results can be applied in clinical practice to evaluate patient prognosis and response to therapy.

Background and aim Duodenal ulcer bleeding has a higher risk of mortality than bleeding from other portions of the gastrointestinal tract. AIMS65 is an effective risk-scoring system to predict prognosis of upper gastrointestinal bleeding and can be easily calculated without endoscopic findings. In this study, we investigate the usefulness of AIMS65 to predict prognosis of patients with duodenal ulcer bleeding. Methods Two hundred and fifty-five patients with endoscopically diagnosed duodenal ulcer bleeding at Kurashiki Central hospital from July 2007 to June 2017 were studied. We compared AIMS65, Glasgow Blatchford score (GBS), admission Rockall, and full Rockall scoring systems for predicting in-hospital mortality by calculating area under the receiver operating characteristic curve (AUROC). Results In-hospital mortality due to duodenal ulcer bleeding occurred in 17 (6.7%). Scores of all scoring systems were significantly higher in patients with in-hospital mortality than in patients without it. AUROC values for predicting in-hospital mortality was 0.83 in AIMS65, 0.74 in GBS, 0.76 in admission Rockall score, and 0.82 in full Rockall score, a statistically insignificant difference among the systems. In AIMS65, score more than or equal to 2 was an optimal value to predict in-hospital mortality, with sensitivities of 88.2% and specificities of 59.7%, respectively. Conclusions AIMS65 predicted in-hospital mortality of patients with duodenal ulcer bleeding as accurately as did other scoring systems. Given its simplicity of calculation, AIMS65 may be a more clinically practical system in the management of bleeding duodenal ulcer patients.

Background AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). Methods Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. Results The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p = 0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p = 0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. Conclusion Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

We present a case of ruptured type A acute aortic dissection with pulmonary trunk compression by mediastinal hematoma. This condition mimicked a pulmonary embolism on the early arterial phase of computed tomography angiography, whereas the correct diagnosis was determined from the late arterial phase and unenhanced computed tomography. We highlight the importance of carefully interpreting triphasic computed tomography angiography to assess the status of aortic dissection.

Purpose: The development of immune-related adverse events (irAEs) in patients undergoing immunotherapy has been reported to be a favorable prognostic factor in several studies. We aimed to examine the correlation between irAEs and prognosis in patients with non-small cell lung cancer (NSCLC) and further reveal the patient characteristics associated with response to immunotherapy among treatment responders who developed irAEs. Methods: We retrospectively enrolled 80 patients with NSCLC who received immunotherapy at Shinshu University Hospital between February 2016 and February 2020. Progression-free survival (PFS) and overall survival (OS) were compared between patients with and those without irAEs. We examined the prognostic factors associated with PFS and OS using univariate and multivariate Cox proportional-hazards models. We further analyzed the patients who developed irAEs by classifying them into responders and non-responders. Results: Twenty-five patients developed irAEs. The median PFS and OS of the patients with irAEs were significantly longer than those of the patients without irAEs (6.8 vs. 1.9 months, p < 0.001, and 37.8 vs. 8.1 months, p < 0.001, respectively). Multivariate analysis associated with PFS and OS indicated that the development of irAEs was an independent favorable prognostic factor. Among the patients developing irAEs, the responder group had a significantly higher incidence of multiple irAEs than the non-responder group (41.7 vs. 0.0%, p = 0.009). Conclusion: Our findings revealed that the development of irAEs was associated with clinical benefits in NSCLC patients who received immunotherapy. In particular, patients with multiple irAEs might have good prognoses.

[Background] AminoIndexTM Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC).[Methods] Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed.[Results] The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p=0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p=0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. [Conclusion] Preoperative AICS (lung) abnormalities are a high-risk predictor of postoperative recurrence in NSCLC patients undergoing curative resection.