Objective Endoscopic papillary large-balloon dilation (EPLBD) with limited endoscopic sphincterotomy (EST) is widely used for removing multiple large common bile duct (CBD) stones. However, the safety and effectiveness of immediate EPLBD after limited EST and EPLBD at an interval after limited EST is unclear. Thus, this multicenter retrospective study was conducted to examine this matter.

Methods Propensity score-matching was performed to adjust the baseline characteristics between the immediate and interval EPLBD groups. We compared the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) complications and the early outcomes of ERCP between the 2 matched groups, which comprised 66 patients each.

Results The complete stone clearance rate in each study group was 100%. The overall incidence of post-ERCP complications in the propensity score-matched interval and immediate EPLBD groups was 3/33 (9.1%) and 1/33 (3.0%), respectively (p=0.61). The immediate EPLBD group had significantly fewer mean ERCP sessions for complete stone removal and a significantly lower rate of endoscopic mechanical lithotripsy (EML) usage than the interval EPLBD group [1.6 vs. 2.4 sessions, p<0.001; and 4/33 (12.1%) vs. 12/33 (36.4%), p=0.042, respectively].

Conclusion The incidence of post-ERCP complications in the immediate EPLBD group was not significantly different from that in the interval EPLBD group. Compared with interval EPLBD, immediate EPLBD may result in a reduced number of ERCP sessions for complete stone clearance and reduce the rate of EML usage.

Objective Little is known about the time from developing a first cancer to confirming the presence of a mismatch repair (MMR) gene mutation for Lynch syndrome (LS) probands.

Methods This was a retrospective single center study. LS probands, who have an MMR gene mutation that was confirmed first in a pedigree and thereafter developed at least one cancer, were included in this study.

Results There were 21 LS probands who had developed at least one cancer; 6 with MLH1 mutations, 9 with MSH2 mutations, 4 with MSH6 mutations, and 2 with EPCAM deletions. The median ages at the first cancer and the genetic diagnosis were 47 (34-71) and 62 (38-84) years old, respectively. The mean interval between the first cancer and the genetic diagnosis was 11.0 (0-25) years, and 20 years or longer interval was required for the 5 probands. Six (28.6%) probands were older than 70 years, and 3 (14.3%) were in their 80s when they were diagnosed to have LS. The genetic diagnosis was confirmed at the first, second, third, and fourth cancer or later in 5, 5, 6, and 5 probands, respectively. Of the 16 cancers examined, 2 (12.5%) were microsatellite stable (MSS), both of whom had germline MSH6 mutations. All 17 LS probands who developed colorectal cancer met the revised Bethesda guidelines at the genetic diagnosis, but only 7 of 11 (63.6%) met them at the first cancer. Twelve out of 21 (57.1%) met the revised Amsterdam criteria.

Conclusion It took 11 years for the LS probands from the first cancer to the diagnostic confirmation by genetic tests. A quarter of the probands were in their 70s or 80s at genetic diagnosis.

Objective We previously reported that, among asymptomatic patients with type 2 diabetes mellitus (T2DM) without a history of cardiovascular disease (CVD), up to 19% of the patients with myocardial ischemia were detected by annual cardiovascular screening tests (ACVSTs). Thus, the present study assessed the long-term clinical outcomes of ACVSTs in those patients.

Methods Six hundred and fifty-seven outpatients with T2DM who received ACVSTs at least once or not at all from April 2014 to March 2018 were defined as the S and NS groups, respectively. The data were compared between these two groups.

Results This study revealed that, among outpatients with T2DM in our hospital over those four years, with the increasing frequency of receiving ACVSTs, 1) the frequency of the internal use of statins, anti-platelets, and renin-angiotensin system inhibitors, which are well-known as medications for preventing CVD, significantly increased; 2) low-density lipoprotein-cholesterol and triglyceride levels significantly improved; 3) levels of highly sensitive C-protein, a strong predictors of CVD, were significantly suppressed; 4) the progression of renal dysfunction was significantly suppressed; 5) the cumulative of four-point major adverse cardiovascular events and admissions due to heart failure significantly decreased; and 6) the cumulative of all-cause mortality was significantly suppressed.

Conclusions Given the above, it may be important to continue ACVSTs in outpatients with T2DM without a history of CVD for several years.

Objective Since patients with thoracic aortic aneurysm (TAA)/abdominal aortic aneurysm (AAA) are often complicated with coronary artery disease, it is common for those patients to undergo percutaneous coronary intervention (PCI). The ankle brachial index (ABI) is usually measured in patients with TAA/AAA to screen the presence of peripheral arterial disease. The present study investigated the association between the ABI and clinical outcomes following PCI in patients with TAA/AAA.

Methods We divided 200 TAA/AAA patients who underwent PCI into a normal ABI group (n=137) and an abnormal ABI group (n=63) according to the ABI cut-off level of 1.00. The primary endpoint was one-year major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, non-fetal myocardial infarction, stroke, target vessel revascularization, and hospitalization for heart failure.

Results Mean ABIs in the normal and abnormal ABI groups were 1.12±0.09 and 0.86±0.11, respectively (p<0.01). Kaplan-Meier curves showed MACE were more frequent in the abnormal ABI group than in the normal ABI group (p=0.01). A multivariate Cox hazard analysis revealed that an abnormal ABI was significantly associated with 1-year MACE (vs. ABI ≥1.0: HR 3.02, 95% confidence interval 1.00-9.08, p=0.049).

Conclusion Among patients with TAA/AAA who underwent PCI, abnormal ABI was significantly associated with 1-year MACE, suggesting the utility of the ABI measurement in this high-risk population.

Objective Although lowering the low-density lipoprotein cholesterol (LDL-C) levels using statins can reduce cardiovascular risk, 70% of the cardiovascular risk remains despite treatment with statins. Several studies have shown that elevated triglyceride (TG)-rich lipoprotein is the primary therapeutic target for reducing the residual risk. However, conventional treatment with fibrates is frequently associated with adverse drug reactions, especially in patients with chronic kidney disease (CKD), and even with a reduction in TG. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) with fewer side effects and greater effectiveness that can overcome these challenges. We aimed to investigate the safety and efficacy of pemafibrate in patients with CKD and herein present a real-world profile of pemafibrate.

Methods Between January 2019 and January 2020, 126 consecutive patients with hyperglyceridemia from two institutions (54 patients with CKD; 43%) who received pemafibrate were enrolled in this retrospective observational study. Blood samples were collected before (baseline) and at 24 weeks after commencing pemafibrate therapy. The primary endpoint was a decrease in the serum lipid levels. The secondary endpoints were the incidence of rhabdomyolysis, hepatargy, and an exacerbation of CKD.

Results All patients, including 51% of patients who were concurrently taking statins, reported significantly reduced total cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), LDL-C, and TG, and increased HDL-C (p<0.05). The subgroup of patients with CKD showed similar results without increased HDL-C. No adverse events were observed in any patients.

Conclusion Pemafibrate has a good safety profile and efficacy for treating patients with serum lipid abnormalities, including those with CKD.

Objective The aim of this study was to clarify the circadian and seasonal variations in addition to identify sex-based differences in Japanese patients with Takotsubo syndrome (TTS).

Methods The authors conducted a retrospective observational study to analyse the differences between the groups based on sex.

Patients The patients were registered out of each institute registry of the acute coronary syndrome (ACS) which contains a total of 10,622 cases in eight academic hospitals in east Japan.

Results Data for 344 consecutive TTS (73 male and 271 female) were extracted from each hospital registry. In-hospital mortality was higher in the male group than in the female group (18% vs. 7%; p=0.005). With regard to the circadian variations in all study patients, TTS events occurred most often in the afternoon and least often during the night. Moreover, the patterns of circadian variations in the female and male groups were the same as that of all study patients. TTS events occurred most frequently in the autumn and least often in the spring in the whole study cohort. Moreover, the seasonal variation in the female group showed the same pattern as that of the whole cohort. However, there were no significant seasonal differences in the incidence of TTS in the male group.

Conclusion In a multicenter study in Japan, seasonal variation was observed in the female group but not in the male group. Circadian variation was observed in both groups. These results suggested that the pathogenesis and clinical features of TTS might therefore differ according to sex.

Objective We studied three types of estimated glomerular filtration rate (eGFR) equations and evaluated which type was strongly associated with comorbidities in living kidney transplantation (LKT) donors.

Methods We compared the Japanese modified eGFR, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations (Jm-eGFR, Jm-MDRD, and Jm-CKD-EPI, respectively) for Japanese LKT donors with respect to their relationships with obesity, hypertension, diabetes, cardiovascular disease, and stroke.

Results Of the 8,176 enrolled Japanese LKT donors, the eGFR calculated using Jm-CKD-EPI (eGFR/Jm-CKD-EPI) detected significant differences in 4 of 5 comorbidities between the comorbidity-positive and comorbidity-negative groups, whereas the eGFR calculated using Jm-MDRD (eGFR/Jm-MDRD) and Jm-eGFR (eGFR/Jm-eGFR) detected only 3 and 1 comorbidities, respectively. The area under the receiver operating characteristic curve of Jm-CKD-EPI was larger than those of Jm-eGFR and Jm-MDRD for all five comorbidities.

Conclusion We found that the eGFR/Jm-CKD-EPI correlated better with comorbidities than the eGFR/Jm-eGFR and eGFR/Jm-MDRD in Japanese LKT donors. We recommend using the eGFR/Jm-CKD-EPI for the initial assessment of the renal function in LKT donor candidates when evaluating the presence of associated comorbidities.

Objective A central venous catheter (CVC) is often needed to treat hematologic diseases, but it is accompanied by many complications. Ultrasound guidance (USG) or a peripherally inserted central venous catheter (PICC) can reduce such complications.

Meterials We collected data of patients with attempted CVC placement in our hematology unit in 2012 (before introduction of USG and PICC) and 2018 (after introduction) and compared both periods.

Results In total, 187 CVC insertions were attempted in 2018 and 198 in 2012. USG was used 154 times (82%) in 2018 and 4 times (2%) in 2012 (p<0.001). The success rates of insertion were 95% in 2018 and 89% in 2012 (p=0.063). The incidence of acute complications was 4.3% in 2018 and 9.1% in 2012 (p=0.069). The incidence of CVC removal owing to delayed complications was 26% in 2018 and 21% in 2012 (p=0.327). The sites of approach in 2018 and 2012 were the internal jugular in 42 (22%) and 54 (27%), subclavian in 52 (28%) and 128 (65%), brachial (PICC) in 89 (48%) and 14 (7%), and femoral in 4 (2%) and 2 (1%), respectively (p<0.001).

Conclusion USG has become commonplace since its introduction. The landmark-based subclavian approach was largely replaced by PICC with USG in 2018. USG and PICC can help improve success rates and safety profiles.

Objective The present study analyzed the psychological status of healthcare workers in Japan and the influencing factors during the 2019 coronavirus disease pandemic.

Methods An online survey was conducted from July 22 to August 21, 2020. A total of 328 of the 1,029 medical staff members in our university hospital participated in the study. Their mental health was assessed using the 12-item General Health Questionnaire. A multivariate regression analysis was performed to identify the factors associated with the mental health outcomes.

Results Of the respondents, 78.0% reported psychological distress. Overall, we found that women, non-physicians, those who lived alone, and younger respondents had significantly greater psychological distress than their counterparts. The multivariate regression analysis showed that four factors were extracted as independent 12-item General Health Questionnaire-related factors: the lack of a sense of mission as a medical professional, the burden of the change in the quality of work, the lack of understanding about virus infectivity, and a strong sense of duty.

Conclusion In summary, we found a high prevalence of psychological distress among healthcare workers during the 2019 coronavirus disease outbreak in Japan. Independent risk factors for psychological distress were the burden of the change in the quality of work, the lack of understanding about virus infectivity, a sense of responsibility, and the lack of a strong motivation and drive to help.

We herein report a case of intraperitoneal abscess as a postoperative complication of gastric endoscopic submucosal dissection (ESD). A 70-year-old man who underwent ESD for early gastric cancer sought consultation for abdominal pain on postoperative day 28. Abdominal computed tomography revealed intraperitoneal abscess rupture. He underwent image-guided laparoscopic irrigation. His postoperative course was favorable, and he was discharged after 27 days. Intraoperatively, a white plaque adhering to the gastric wall was surrounded by a large pus volume and suspected to be ESD-associated. We present this case with a literature review of the association between intraperitoneal abscess and ESD.

Although cases of gastrointestinal toxicity of pembrolizumab have been reported, cases of acute immune-mediated colitis accompanied with metachronous esophageal disorders (esophagitis and ulcer) are rare. We herein report a case of acute colitis and metachronous esophageal ulcers due to an immune-related adverse event following concomitant pembrolizumab chemotherapy for lung adenocarcinoma. To our knowledge, there have so far been no reports of cases in which both acute immune-mediated colitis and metachronous esophageal ulcers developed. We therefore report the details of this case along with a review of the pertinent literature.

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated. Although the biliary stricture and pancreatic swelling improved after prednisolone treatment, the pancreatic enzyme levels increased rapidly. The entire main pancreatic duct exhibited remarkable dilatation, which led to the diagnosis of mixed-type IPMN. The clinical characteristics of IPMN in the main pancreatic duct appear to have been initially masked by AIP.

A 64-year-old man was admitted to our hospital to undergo examination of a pancreatic tumor accompanied by sudden epigastric pain. The tumor had a well-defined oval shape that was mostly less enhanced, with the exception of part of the tumor on the pancreatic head side, on contrast enhanced (CE)-CT. However, CE-CT performed one-month later revealed that the viable part of the tumor grew toward the pancreatic tail with the reduction of necrotic tissue. We performed distal pancreatectomy and the tumor was diagnosed as acinar cell carcinoma (ACC). One important characteristic of ACC is that it may develop morphological changes within a short period of time.

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.

A 66-year-old Japanese woman developed pulseless electrical activity following an acute pulmonary embolism and was treated with thrombolytic therapy. She remained hemodynamically unstable and therefore underwent extracorporeal membrane oxygenation (ECMO). While receiving treatment with ECMO, blood clots induced by endobronchial hemorrhage caused tracheobronchial airway obstruction, leading to ventilatory defect. Furthermore, her cardiac function improved, resulting in cerebral hypoxemia progression. Therefore, the blood clots were removed with a Fogarty balloon catheter and endobronchial urokinase administration, resulting in improvement in her respiratory condition. Finally, ECMO was decannulated, and the patient was discharged from our hospital without difficulties in her activities of daily living.

Anthracyclines have cardiotoxic side effects. Cardioprotective drugs such as angiotensin-converting enzyme inhibitors and beta-blockers are therefore recommended for patients with anthracycline-induced cardiomyopathy. We herein present a 54-year-old woman with recurrent metastatic breast cancer who developed heart failure (HF) with a left ventricular ejection fraction (LVEF) of 22% after undergoing epirubicin chemotherapy. However, her HF symptoms and low LVEF persisted despite 5 months of cardioprotective therapy and additional oral pimobendan. Pimobendan was discontinued because of ventricular arrhythmia and hypotension. After the start of low-dose (0.125 mg daily) digoxin, her LVEF increased to 42%, and her HF symptoms improved with no adverse events.

A 46-year-old woman with exacerbating hemoptysis and dyspnea was diagnosed with diffuse alveolar hemorrhage (DAH). High doses of glucocorticoids were initiated, but afterward, paroxysmal hypertension (210/140 mmHg) with headache and abdominal pain appeared. A 50-mm left adrenal tumor with an intense uptake by iodine-123 metaiodobenzylguanidine scintigraphy and catecholamine hypersecretion revealed complication with pheochromocytoma. Because high doses of glucocorticoids, sometimes required for DAH, can provoke life-threatening paroxysmal hypertension in pheochromocytoma and paraganglioma (PPGL), our case suggests that PPGL needs to be recognized as the cause of DAH and should be detected with whole-body imaging before starting glucocorticoids.

A 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy.

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.

A 70-year-old woman was hospitalized with dyspnea. A transthoracic echocardiogram indicated an elevated systolic pulmonary artery pressure, and the cytology specimens obtained using a pulmonary artery catheter confirmed adenocarcinoma metastasis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected high-signal-intensity lesions in the urinary bladder. The patient died of respiratory failure and a postmortem examination was performed. Tumor cells in the bladder were immunohistochemically positive for GATA3, indicating micropapillary urothelial carcinoma, which is a rare variant of urothelial carcinoma and considered an adenocarcinoma subtype. This case is the first autopsy case of pulmonary tumor thrombotic microangiopathy (PTTM) associated with micropapillary urothelial carcinoma of the urinary bladder.

A 30-year-old non-smoking man was referred to our hospital for the further examination of abnormal shadows revealed by chest X-ray. He had mild shortness of breath. Chest computed tomography revealed a fine-grained dendritic shadow with diffuse calcification in both lungs and as well as emphysematous changes in the upper lung lobes. A surgical lung biopsy histology revealed diffuse pulmonary ossification complicated with lung laceration, vascular disruption, hemosiderosis, and emphysema, suggesting vascular Ehlers-Danlos syndrome (vEDS). However, the patient had no external physical signs or family history of vEDS and no COL3A1 gene mutations. We are closely monitoring this patient in the clinic.

Lymphoproliferative diseases have been associated with various autoimmune diseases. We experienced a case of non-chronic lymphocytic leukemia type monoclonal B-cell lymphocytosis (MBL) that was exacerbated by increasing prednisolone for dermatomyositis and then improved by decreasing the dosage. Because MBL is difficult to diagnose, cases like ours may not be rare. These findings will facilitate our understanding of the mechanism underlying lymphoproliferative diseases and autoimmune diseases.

We herein report two cases of thrombotic thrombocytopenic purpura (TTP) complicated by other autoimmune disorders, autoimmune hepatitis and immune thrombocytopenia, respectively. In both cases, corticosteroids were continuously administered for the treatment of preceding autoimmune disorders. However, a sufficient objective response for TTP was not obtained by plasma exchange and corticosteroid treatment. Once a week rituximab (375 mg/m²) treatment for 4 times was initiated within 2 weeks from the diagnosis. Both patients achieved a sufficient response, and have never had any recurrence as of the last follow-up dates. The early introduction of rituximab could be an effective treatment option in TTP patients complicated with other autoimmune disorders.

Exposure to quinolones is known to be an independent risk factor for aortic dissection; however, the association with vertebral artery dissection remains unclear. We report two cases of vertebral artery dissection that occurred 4 and 8 days after exposure to levofloxacin, respectively. Both patients had risk factors for vertebral artery dissection, and quinolone use could have been avoided. These two cases indicate that quinolone exposure can be a risk factor for vertebral artery dissection. Considering the possible mechanism, it is better to avoid the prescription of quinolones to patients who have insufficient connective tissues to avoid vertebral artery dissection.

Multifocal enlargements with the alteration of a normal fascicular pattern are considered to be sonographic peripheral nerve features in multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), a subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We herein present the case of an 18-year-old patient with MADSAM in whom intensive sonological assessments revealed multifocal nerve enlargement within clinically affected cranial nerves. Our case demonstrated that, if systematically investigated with ultrasound, morphological changes similar to those in the peripheral nerves may be detected in a large proportion of clinically affected cranial nerves in MADSAM, boosting the future applications of cranial nerve ultrasound in CIDP.