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PURPOSE In aortic stenosis (AS), the discrepancy between moderately accelerated flow and effective orifice area (EOA) continues to pose a challenge. We developed a method of measuring the vena contracta area as hemodynamic EOA using cardiac MRI focusing on AS patients with a moderately accelerated flow to solve the problem that AS severity can currently be determined only by echocardiography. METHODS We investigated 40 patients with a peak transvalvular velocity > 3.0 m/s on transthoracic echocardiography (TTE). The patients were divided into highly accelerated and moderately accelerated AS groups according to whether or not the peak transvalvular velocity was ≥ 4.0 m/s. From the multislice 2D cine phase-contrast MRI data, the cross-sectional area of the vena contracta of the reconstructed streamline in the Valsalva sinus was defined as MRI-EOAs. Patient symptoms and echocardiography data, including EOA (defined as TTE-EOA), were derived from the continuity equation using TTE. RESULTS All participants in the highly accelerated AS group (n = 19) showed a peak velocity ≥ 4.0 m/s in MRI. Eleven patients in the moderately accelerated AS group (n = 21) had a TTE-EOA < 1.00 cm2. In the moderately accelerated AS group, MRI-EOAs demonstrated a strong correlation with TTE-EOAs (r = 0.76, P < 0.01). Meanwhile, in the highly accelerated AS group, MRI-EOAs demonstrated positivity but a moderate correlation with TTE-EOAs (r = 0.63, P = 0.004). MRI-EOAs were overestimated compared to TTE-EOAs. In terms of the moderately accelerated AS group, the best cut-off value for MRI-EOAs was < 1.23 cm2, compatible with TTE-EOAs < 1.00 cm2, with an excellent prediction of the New York Heart Association classification ≥ III (sensitivity 87.5%, specificity 76.9%). CONCLUSION MRI-EOAs may be an alternative to conventional echocardiography for patients with moderately accelerated AS, especially those with discordant echocardiographic parameters.

Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.

Background Cardiac erosion after percutaneous atrial septal defect (ASD) closure is a rare complication that requires immediate life-saving emergency surgery. In this report, we present our successful life-saving strategy for cardiac arrest due to cardiac tamponade caused by erosion 6 years after the percutaneous closure of an ASD. Case presentation The patient was a 50-year-old man who received treatment using an Amplatzer septal occluder (St. Jude Medical, St. Paul, MN, USA) treatment for ostium secundum atrial septal defect (size: 29.5 × 27.0 mm) at another institution when he was 44 years old. Conclusions This case report presents a bailout surgical strategy for patients who are hemodynamically unstable with risks of coagulopathy and multiple organ failure. This case shows that cardiac surgeons need to be aware of percutaneous ASD-closure complications and should consider a bailout surgical strategy for patients at risk of multiple organ failure.

Background Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. Methods We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients’ clinical characteristics and the diagnostic accuracy and safety of each needle. Results A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p p p (p-adj) p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. Conclusions The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Aim Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. Methods We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. Results The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). Conclusions The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.

Dose-dense (DD) chemotherapy is a treatment option for patients with high-risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29-year-old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple-negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD-DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm3. The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38°C), and an ANC of 297/mm3. Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Edwardsiella tarda is a bacterium that is associated with both an asymptomatic oral carrier state and self-limiting diarrhoeal illness in humans. We herein report a case of sepsis and liver abscess caused by E. tarda and review the patients with E. tarda sepsis who presented at our hospital. An 85-year-old woman developed enterocolitis and sepsis caused by E. tarda. She was administered intensive care and thus was able to soon show a good recovery, however, she subsequently developed a liver abscess. During a complicated course, she continued to be treated with antibiotics and after a successful course was discharged on the 44th day after admission.

Controversy still exists about the influence of prosthesis-patient mismatch on outcomes after aortic valve replacement in the elderly. Our aim was to evaluate the effect of prosthesis-patient mismatch on survival and the extent of left ventricular (LV) mass regression after aortic valve replacement for aortic stenosis in Japanese patients agedor=65 years.A total of 84 patients who underwent isolated aortic valve replacement for aortic stenosis between 1986 and 2006 were retrospectively analyzed. Patients were divided into two groups based on the definition of prosthesis-patient mismatch (indexed effective orifice areaor=0.85 cm(2)/m(2)), and long-term results were compared. The mean follow-up time was 4.5 +/- 4.5 years. In 49 patients, follow-up echocardiography was performed at least 6 months after surgery, and the extent of LV mass regression was analyzed according to the presence of a prosthesis-patient mismatch.Eight years after surgery, there was no significant difference between patients with and without mismatch in terms of actuarial freedom from cardiac-related death (P = 0.159) or death from any valve-related events (P = 0.107). The postoperative transvalvular pressure gradients were not significantly different between the two groups, and significant absolute and relative LV mass regression were observed in both groups.Although a moderate prosthesis-patient mismatch appeared to be tolerable, the criteria of prosthesis-patient mismatch may have to be reassessed for elderly Japanese patients.

Objectives The surgical treatment of Kommerell diverticula is associated with high mortality and morbidity rates. In the mid-2000s, hybrid aortic arch repair was developed, and the procedure has since been used to repair Kommerell diverticula. In the present study, we focused on the postoperative outcomes of two-stage hybrid repair of Kommerell diverticula that required supra-aortic debranching (type I hybrid arch repair). Methods From August 2010 to July 2013, a total of four patients (aged 73.5 ± 9.5 years) underwent two-stage hybrid repair (type I hybrid arch repair) for Kommerell diverticula, and their cases were retrospectively studied. All four patients had right aortic arches and aberrant left subclavian arteries. The repair procedure consisted of two stages: (1) debranching of the supra-aortic vessels via a median sternotomy; (2) exclusion of the Kommerell diverticulum by performing thoracic endovascular repair via a femoral approach and coil embolization of the orifice of the aberrant subclavian artery. Results There were no in-hospital deaths. One patient developed an acute kidney injury and required hemodialysis on postoperative day 2, although his renal function recovered within 48 hours. No strokes, paraplegia, or early aortic events were observed in our series. The mean follow-up period was 19.5 months (range, 5–47 months). All patients remained free from aortic events and endoleaks during the follow-up period. Conclusion The early and mid-term outcomes of hybrid repair for Kommerell diverticula that require supra-aortic debranching, which are less invasive and do not involve hypothermic circulatory arrest, are acceptable. However, this procedure requires the insertion of an endograft into the ascending aorta, and careful and long-term follow-up is required to confirm its efficacy.

Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression.

An 82-year-old man presented with typical signs and symptoms of an arteriovenous fistula (AVF) associated with an aortoiliac aneurysm, such as a pulsatile abdominal mass, continuous bruit, thrill, and high output heart failure. Multidetector row computed tomography (MDCT) confirmed the presence of an AVF between the right common iliac artery aneurysm and vein. We subjected the patient to surgical repair of the AVF combined with graft replacement, which proved successful.

We present the case of a 53-year-old man who underwent a total arch replacement for descending thoracic aortic aneurysm of distal anastomosis site after bypass grafting for coarctation of the aorta at 26 years of age.

A 48-year-old man presented with typical features of Ehlers-Danlos syndrome, such as soft and hyperextensible skin, subcutaneous nodules, clubbed feet, and a mild degree of pigeon chest. In addition, his past history revealed congenital dislocation of the hip joint, retinal detachment, and repeated episodes of congestive heart failure due to severe mitral regurgitation and atrial fibrillation. We subjected the patient to surgical repair of the mitral valve combined with the maze procedure, which proved successful.

Fig. 1. (a) Coronary computed tomographic angiography showing clusters of new vessels supply to the mass (white arrows). (b) Volume rendering image of a mass with an abnormal feeding artery (black arrows) that is located at the leftposterior wall of the left atrium. (c) Virtual angioscopy image showing a mass attached to the posterior wall of the left atrium (black arrows). LAD: left descending artery; PL: postero-lateral branch; AC: left atrial circumflex branch; LA: left atrium; LV: left ventricle; LUPV: left upper pulmonary vein; LLPV: left lower pulmonary vein; LAA: left atrial appendage; MV: mitral valve.

SummaryWe report a case of a 68-year-old woman with sudden onset of position-dependant hypoxemia after recovering from pulmonary embolism. Transesophageal echocardiography (TEE) and cardiac catheterization revealed the presence of patent foramen ovale (PFO) and right-to-left shunting with no evidence of the right-to-left pressure gradient especially in the right lateral decubitus position. Surgical closure of the PFO was performed because the right-to-left shunting caused position-dependent severe hypoxemia. At operation, it was noted that the patient's enlarged aortic root pressed the heart inferiorly and compressed the upper part of the right atrium. A large Eustachian valve, which is an embryonic remnant of the right valve of the sinus venosus, was observed in the right atrium. Preceding pulmonary embolism could lead to a temporal elevation of the right heart and pulmonary arterial pressures and it caused the reopening of the closed foramen ovale. To the best of our knowledge, this is the first case of reopening of the foramen ovale causing sudden onset of position-dependent hypoxemia.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is highly prevalent in Asia. Alcohol and its metabolite, acetaldehyde, are considered definite carcinogens for the esophagus. Polymorphisms in the aldehyde dehydrogenase 2 gene, which encodes an enzyme that eliminates acetaldehyde, have been associated with esophageal carcinogenesis. Studies of the mutagenic and carcinogenic effects of acetaldehyde support this observation. Several recent large-scale comprehensive analyses of the genomic alterations in ESCC have shown a high frequency of mutations in genes such as TP53 and others that regulate the cell cycle or cell differentiation. Moreover, whole genome and whole exome sequencing studies have frequently detected somatic mutations, such as G:C→A:T transitions or G:C→C:G transversions, in ESCC tissues. Genomic instability, caused by abnormalities in the Fanconi anemia DNA repair pathway, is also considered a pathogenic mechanism of ESCC. Advances in diagnostic techniques such as magnifying endoscopy with narrow band imaging or positron emission tomography have increased the accuracy of diagnosis of ESCC. Updated guidelines from the National Comprehensive Cancer Network standardize the practice for the diagnosis and treatment of esophageal cancer. Patients with ESCC are treated endoscopically or with surgery, chemotherapy, or radiotherapy, based on tumor stage. Minimally invasive treatments help improve the quality of life of patients who undergo such treatments. We review recent developments in the diagnosis and treatment of ESCC and advances gained from basic and clinical research.