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Background: Though laparoscopic gastrectomy (LG) has become the gold standard for gastric cancer treatment according to the Japanese treatment guidelines, its learning curve remains steep. Decreasing numbers of surgeons and transitions in the work environment have changed LG training recently. We analyzed LG training over the last decade to identify factors affecting the learning curve. Study Design: Laparoscopic distal and pylorus‐preserving gastrectomies conducted between 2010 and 2020 were included. We assessed learning curves based on the standard operation time (SOT) defined by analysis of covariance. Then we divided the trainees into two groups based on the length of the learning curve and examined the factors affecting the learning curve with linear regression analysis. Results: Among 2335 LGs, 960 cases treated by 27 trainees and 1301 cases treated by six attending surgeons were analyzed. The operation time was prolonged (p = 0.009) and postoperative morbidity rates were lower (p = 0.0003) for cases treated by trainees. Trainees experienced 38 (range, 9–81) cases as scopists and nine (range, 0–41) cases as first assistants to the first operator. The learning curve was approximately 30 cases. The SOT was calculated based on gender, body mass index, tumor location, reconstruction, and lymph node dissection. Trainees who had shorter learning curves had more experience (51–100 cases) with any laparoscopic surgery before LG training than the others (11–50 cases, p = 0.017). Conclusion: Sufficient experience with laparoscopic surgery before starting LG training might contribute to the efficiency of LG training and shorten the learning curve. [ABSTRACT FROM AUTHOR]

Background: Reports on the factors predicting long‐term survival of CRT‐D cases from Western countries are increasing, however, those from Asia including Japan are still sparse. We aimed to clarify the factors predicting long‐term survival of Japanese CRT‐D cases. Methods: We retrospectively analyzed consecutive 133 patients who underwent CRT‐D implantation between 2006 and 2021. We compared clinical factors between patients who died within 5 years after implantation (short‐survival group: n = 31) and who had survived for more than 5 years (long‐survival group: n = 36) after implantation. Results: Major underlying heart diseases were dilated cardiomyopathy (45%) and ischemic heart disease (12%). There was no difference between the short‐survival group and the long‐survival group in incidence of CLBBB (32% vs. 30%), whereas CRBBB was more common in the short‐survival group (26% vs. 0%, p =.004). Mechanical dyssynchrony at implantation was more frequent in the long‐survival group (48% vs. 78%, p =.02). The incidence of response to CRT at 1 year after implantation was higher in long‐survival group (19% vs. 50%, p =.02). Multiple logistic regression analysis identified NYHA class, mechanical dyssynchrony at implantation, and response at one year as predictors of long‐term survival. Conclusions: In Japanese CRT‐D cases, lower NHYA class, preexisting mechanical dyssynchrony, and 1‐year response to CRT predict long‐term survival. [ABSTRACT FROM AUTHOR]

A T‐shaped Pt0 complex with a diphosphine‐borane (DPB) ligand was prepared. The Pt→B interaction enhances the electrophilicity of the metal and triggers the addition of Lewis bases to give the corresponding tetracoordinate complexes. For the first time, anionic Pt0 complexes are isolated and structurally authenticated. X‐ray diffraction analyses show the anionic complexes [(DPB)PtX]− (X=CN, Cl, Br, I) to be square‐planar. The d10 configuration and Pt0 oxidation state of the metal were unambiguously established by X‐ray photoelectron spectroscopy and DFT calculations. The coordination of Lewis acids as Z‐type ligands is a powerful mean to stabilize elusive electron‐rich metal complexes and achieve uncommon geometry. [ABSTRACT FROM AUTHOR]

A T‐shaped Pt0 complex with a diphosphine‐borane (DPB) ligand was prepared. The Pt→B interaction enhances the electrophilicity of the metal and triggers the addition of Lewis bases to give the corresponding tetracoordinate complexes. For the first time, anionic Pt0 complexes are isolated and structurally authenticated. X‐ray diffraction analyses show the anionic complexes [(DPB)PtX]− (X=CN, Cl, Br, I) to be square‐planar. The d10 configuration and Pt0 oxidation state of the metal were unambiguously established by X‐ray photoelectron spectroscopy and DFT calculations. The coordination of Lewis acids as Z‐type ligands is a powerful mean to stabilize elusive electron‐rich metal complexes and achieve uncommon geometry. [ABSTRACT FROM AUTHOR]

Background: The incidence of electrical storm (ES) is significantly higher during the daytime. However, the association between nocturnal ventricular tachyarrythmias during ES and prognosis remains unclear. Therefore, this study aimed to investigate the clinical characteristics and outcomes of ES with midnight ventricular tachyarrythmias. Methods: We included 48 consecutive patients who had an implantable cardioverter‐defibrillator or cardiac resynchronization therapy defibrillator implanted between 2010 and 2020 and those who had experienced the onset of an out‐of‐hospital ES episode. According to the midnight (0:00 a.m.–6:00 a.m.) occurrence of ventricular arrythmia events consisting of ventricular tachycardia (VT) and ventricular fibrillation (VF), we divided them into two groups (with‐midnight group: n = 27, without‐midnight group: n = 21). The clinical characteristics and outcomes of the two groups were compared. Results: The patients in the with‐midnight group were mostly males, had longer QRS duration, and longer corrected QT‐interval than those in the without‐midnight group (p <.05). The incidence of all‐cause death, especially heart failure death, was higher in the with‐midnight group than in the without‐midnight group (p <.01). Multivariate analysis showed that the presence of midnight VT/VF during ES was the only independent risk factors for heart failure death (HR = 18.9, 95%CI = 1.98−181, p =.011). Conclusions: The presence of midnight VT/VF during ES might be associated with the poor prognosis. The loss of a sympathetic circadian pattern of VT/VF distribution during ES might suggest advanced stages of the cardiac disease. [ABSTRACT FROM AUTHOR]

Background: Preoperative malnutrition is believed to contribute to increased postoperative complications. Preoperative serum prealbumin level was reported to be a predictor of nutritional status and postoperative complications after gastrointestinal surgery, including gastrectomy. Gastric outlet obstruction caused by gastric cancer leads to insufficient nutritional status. However, the impact of preoperative enteral nutrition using naso-jejunal feeding tubes for patients with gastric outlet obstruction is not fully understood. Methods: From July 2010 to June 2020, 50 patients with gastric cancer-induced outlet obstruction who underwent gastrectomy following preoperative enteral nutrition via feeding tube were included. We investigated the relationship between changes in nutritional status after preoperative enteral nutrition and postoperative complications. Postoperative complications were defined as grade ≥II based on the Clavien–Dindo classification. Results: The median period of preoperative enteral nutrition was 10 days. The median increase rate of the serum prealbumin level was 10.5% (interquartile range, 0.63–38.2%), and patients with an increase rate ≥ 10% were defined as the elevated group. Postoperative morbidity was significantly higher in the non-elevated group (P = 0.0031). Univariate and multivariate analyses showed that an increased rate of the serum prealbumin level was an independent risk factor of postoperative complications for patients with gastric outlet obstruction caused by gastric cancer (P = 0.0025 and P = 0.009, respectively). Conclusions: Preoperative enteral nutrition improved the serum prealbumin level of patients with gastric cancer-induced outlet obstruction, and an increased rate of prealbumin can be an indicator of sufficient preoperative enteral nutrition and decreased postoperative morbidity. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis. Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts. Results: We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79–0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69–0.91]; and n = 165, AUC:0.89 [95%CI:0.83–0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87–0.96]); and (n = 188, AUC:0.93, [95%CI:0.88–0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001). Conclusions: We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts. [ABSTRACT FROM AUTHOR]

Sporadic foveolar-type gastric adenoma (FGA) has been described as an extremely rare polyp that is whitish and flatly elevated. However, we recently found that sporadic FGA with a raspberry-like appearance (FGA-RA) is not rare in Helicobacter pylori (H. pylori)–naïve gastric mucosa. We endoscopically or surgically treated 647 patients with gastric epithelial neoplasms in the last 5 years, with 7.7% (50/647) being H. pylori–naïve. Among these, 43 FGA-RAs were diagnosed based on histologic and endoscopic features in 34 patients, who were all enrolled in this retrospective study. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We subsequently analyzed their endoscopic and microscopic features and patient characteristics. The patients were 22 males and 12 females aged 57±23 years (mean±2SD). WLE showed raspberry-like small polyps mimicking gastric hyperplastic polyps in the oxyntic gastric compartment (body/fundus). Multiple growths were confirmed in 20.6% (7/34) of the patients. NBIME revealed irregularly shaped papillary/gyrus-like microstructures with abnormal capillaries. Histologically, all lesions were intraepithelial neoplasms, and most of lesions (62.8%, 27/43) exhibited low-grade dysplasia. Immunohistochemically, neoplastic cells featured strong and diffuse MUC5AC expression, negative or very low MUC6 expression, and negative MUC2/CD10 expression. They also showed Ki-67 hyperexpression with a mean labeling index of 59.4±48.7%. The coexistence of fundic gland polyps in the background mucosa was significantly higher in multiple FGA-RA cases than in solitary cases (100% vs. 55.5%, P< 0.05). FGA-RA is a newly suggested histologic variant of sporadic FGA whose occurrence is not rare in daily endoscopic practice. [ABSTRACT FROM AUTHOR]

Background: Remote monitoring (RM) has been shown to reduce all‐cause mortality in patients with implantable cardioverter‐defibrillators or cardiac resynchronization therapy defibrillators (ICD/CRT‐D). Not all devices transmit an alert for antitachycardia pacing (ATP) therapy, and it is unknown whether differences of RM alert affect the outcomes of electrical storm (ES). Methods: We enrolled 42 patients with ICD/CRT‐D whose out‐of‐hospital ES were detected by RM between 2013 and 2020. We divided their 54 episodes into two groups (ATP‐alert‐on; 22, ATP‐alert‐off; 32), and clinical outcomes were compared between the two groups. Results: In 35 of 54 episodes of ES, ventricular tachycardia (VT) could be terminated within 24 h of ES onset just by ATP (ATP‐alert‐on: 14, ATP‐alert‐off: 21); however, many patients subsequently received shock delivery for VT. Among the 35 episodes, only in ATP‐alert‐on group, seven patients were prompted to visit our hospital without ICD shock through confirmation of ES by ATP‐alert. Episodes that led to shock delivery 24 h or longer after the ES onset were significantly less common in the ATP‐alert‐on group (ATP‐alert‐on: 1/14, ATP‐alert‐off: 9/21, p =.03). Although there were no significant differences in the number of shock deliveries between episodes in the two groups, the number of ATP deliveries were significantly fewer in the ATP‐alert‐on group (12[7‐26] vs. 29[16‐53] in ATP‐alert‐off group, p =.03). Multivariate logistic regression analyses showed that the only ATP‐alert significantly reduced ATP deliveries (HR = 0.14, 95%CI = 0.04‐0.57, p =.003). Conclusion: Remote monitoring with an ATP‐alert function during electrical storm may reduce appropriate ICD therapy through prompting early review. [ABSTRACT FROM AUTHOR]

Here, heptacoordinate and hexacoordinate triorganotin compounds [o‐{(Ph2)(O)P}C6H4]3SnX (X=F (2 a), Cl (2 b), Me (2 f)) featuring three O→Sn interactions were synthesized. Chloro (2 b) and methyl (2 f) compounds were obtained from the oxygenation of the heptacoordinate triorganotin compounds {o‐(Ph2P)C6H4}3SnX (X=Cl (1 b), Me (1 f)) bearing three P donors. The fluorination of 2 b using tetrabutylammonium fluoride (TBAF) yielded the fluoro analogue 2 a. Structural studies were performed on a series of hypercoordinate triorganotin compounds, 2. The chloro analogue (2 b) exhibited a hexacoordinate geometry attributed to the Sn−Cl bond cleavage, where the highly electrophilic stannyl cation was stabilized by three O donors. In contrast, both the fluoro (2 a) and methyl (2 f) analogues exhibited heptacoordinate structures. Although 2 f adopted a tricapped tetrahedral geometry, 2 b is classified to adopt a distinctly rare bicapped trigonal pyramidal geometry featuring one strong LP(O)→σ*(Sn−F) interaction and two weak LP(O)→σ*(Sn−C) interactions (LP: lone pair electrons). The origin of the structural alternations depending on the substituent is discussed using density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Introduction: The local conduction delay has been deemed to play an important role in the perpetuation of ventricular fibrillation (VF) in Brugada syndrome (BrS). We evaluated the relationship between the activation delay during programmed stimulation and cardiac events in BrS patients. Methods: This study included 47 consecutive BrS patients who underwent an electrophysiological study and received implantable cardiac defibrillator therapy. We divided the patients into two groups based on whether they had developed VF (11 patients) or not (36 patients) during the follow‐up period of 89 ± 53 months. The activation delay was assessed using the interval between the stimulus and the QRS onset during programmed stimulation. The mean increase in delay (MID) was used to characterize the conduction curves. Results: The MID at the right ventricular outflow tract (RVOT) was significantly greater in patients with VF (4.5 ± 1.2 ms) than in those without VF (2.2 ± 0.9 ms) (p <.001). A receiver operating characteristics curve analysis indicated that the optimal cut‐off point for discriminating VF occurrence was 3.3 with 88.9% sensitivity and 91.3% specificity. Furthermore, patients with an MID at the RVOT ≥ 3.3 ms showed significantly higher rates of VF recurrence than those with an MID at the RVOT < 3.3 ms (p <.001). The clinical characteristics, including the signal‐averaged electrocardiogram measurement and VF inducibility were similar between the two groups. Conclusion: A prolonged MID at the RVOT was associated with VF and maybe an additional electrophysiological risk factor for VF in BrS patients. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) for extensive esophageal cancer is sometimes associated with post-ESD stenosis, despite preventative steroid therapy. In this retrospective multicenter analysis, we evaluated the factors associated with therapy resistance. We enrolled 73 patients with 75 extensive esophageal cancers treated with ESD. Stenosis prevention was performed using two esophageal triamcinolone acetonide (TA)-fillings, and repeated if stenosis was found on follow-up. Therapy-resistance factors associated with incidence of severe stenosis requiring endoscopic balloon dilation (EBD) were evaluated, including age, gender, previous treatment history, tumor location, morphology, resection size, histologic type, invasion depth, and horizontal resection grade (HR-grade 1, ≥ 9/12 and <10/12 of the circumference; grade 2, ≥ 10/12 and <11/12; grade 3, ≥ 11/12 but not circumferential; and grade 4, entirely circumferential). Severe stenosis occurred in 17.3%(13/75) of cases, with a median of two EBDs (range, 1–6 times). Severe stenosis was significantly associated with HR-grade elevation and previous treatment history (p <.05); multivariate analysis showed both as independent therapy-resistance factors (p <.05). Patients without previous treatment history demonstrated severe stenosis at 12.9%(9/70): 0%(0/26) HR-grade 1, 18.8%(3/16) grade 2, 17.6%(3/17) grade 3, and 27.3%(3/11) grade 4, showing a risk of HR-grade 2 or more resection but an acceptable stenosis prevention even after entirely circumferential resection. Conversely, patients with previous treatment history demonstrated severe stenosis at a high frequency of 80%(4/5). Esophageal TA-filling is a promising stenosis-preventive steroid therapy, even in entirely circumferential ESD cases. However, HR-grade 2 or more elevation and previous treatment history were independently associated with therapy resistance. [ABSTRACT FROM AUTHOR]

Introduction: The significance of high precordial electrocardiograms in idiopathic ventricular fibrillation (IVF) is unknown.Method: This study included 50 consecutive patients (48 men; age, 42 ± 18 years) who had spontaneous ventricular fibrillation not linked to structural heart disease and received implantable cardiac defibrillator therapy. IVF was diagnosed in 35 patients and Brugada syndrome was diagnosed in other 15 patients. Electrocardiograms in high intercostal space were compared between 35 patients with IVF and 105 age- and sex-matched healthy controls (patient: control ratio, 1:3).Results: The frequency of J point elevation ≥ 0.1 mV in the 4th intercostal spaces was similar between patients with IVF (14%) and healthy controls (7%). However, the frequency of J point elevation ≥ 0.1 mV in the 3rd intercostal space was higher in patients with IVF (40%) than controls (11%) (p < .01). J point elevation was present only in the 3rd intercostal space but not in the 4th intercostal space in 30% of patients with IVF but only in 6% of controls (p < .01). During follow-up, the recurrence of ventricular fibrillation was higher in patients with IVF who had J point elevation in the 3rd intercostal space (36%) and Brugada syndrome(40%) than those with IVF who did not have J point elevation in the 3rd intercostal space(11%) (p < .05 for both).Conclusion: J point elevation in the 3rd intercostal space was associated with IVF and recurrences of ventricular fibrillation. Electrocardiogram recordings in the high intercostal space may be useful to identify risk of sudden death. [ABSTRACT FROM AUTHOR]

Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as "non-responders". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the β-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients. [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12‐chemokine (CCL2, ‐3, ‐4, ‐5, ‐8, ‐18, ‐19, ‐21, CXCL9, ‐10, ‐11, ‐13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12‐chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12‐chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12‐chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12‐chemokine signature status had a significant shorter relapse‐free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087). High 12‐chemokine signature status had significant associations with right‐sided tumor, high tumor‐localized TLS expression, BRAF mutant, CIMP‐high status and MSI‐high status. Furthermore, RNA‐seq based analysis showed that high 12‐chemokine signature status was strongly associated with inflammation‐related, immune cells‐related and apoptosis pathways (using gene set enrichment analysis), and more tumor‐infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP‐counter analysis). We investigated a promising effect of 12‐chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC. What's new? Chronic inflammation at tumor sites is linked to the emergence of ectopic formations known as tertiary lymphoid structures (TLSs), which combat tumor progression. Here, analyses of human colorectal cancer (CRC) tissue show that high expression of a previously identified 12‐chemokine signature predicts high TLS expression at tumor sites and is associated with increased presence of tumor infiltrating immune cells and reduced CRC recurrence rate. High 12‐chemokine signature status was further linked to key clinicopathological and molecular features of CRC. The findings indicate that the 12‐chemokine signature is informative for host immune status and may have a prognostic role in CRC. [ABSTRACT FROM AUTHOR]

Background and Aim: The esophageal triamcinolone acetonide (TA)‐filling method is a novel local approach for stenosis prevention after extensive esophageal endoscopic submucosal dissection (ESD). We evaluated this method after subcircumferential ESD. Methods: We enrolled 20 patients with esophageal cancer requiring subcircumferential ESD in a prospective multicenter study. Esophageal TA filling was carried out 1 day and 1 week after ESD, with follow‐up endoscopy every 2 weeks. We treated severe stenosis preventing endoscope passage with endoscopic balloon dilatation (EBD) and additional TA filling, and mild stenosis allowing endoscope passage with additional TA filling only. Primary endpoint was incidence of severe stenosis; secondary endpoints were total number of EBD, rate of additional TA filling, time to stenosis and complete re‐epithelialization, dysphagia score, and adverse events. Horizontal resection grade was divided into grades 1 (≥ 9/12 and <10/12 of the circumference), 2 (≥ 10/12 and <11/12), and 3 (≥ 11/12 but not circumferential) and analyzed statistically for correlation with endpoints. Results: Incidence of severe stenosis was 5.0% (1/20; 0.1–24.8%) and was treated with three EBD. Six patients showed mild stenosis. Additional TA filling was carried out in these seven patients: 0% (0/9) for grade 1 resection, 40% (2/5) for grade 2, and 83% (5/6) for grade 3 (P < 0.05). Median time to stenosis and re‐epithelialization was 3 and 7 weeks, respectively. Dysphagia score deteriorated in one patient. No adverse events occurred. Conclusions: The esophageal TA‐filling method prevented stenosis after subcircumferential ESD. Grade ≥2 resection showed a high risk for stenosis, but additional TA filling for mild stenosis inhibited stenosis progression (UMIN000024384). [ABSTRACT FROM AUTHOR]

Background: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly that results in high mortality if left untreated. Our aim was to extend our knowledge of the histological, angiographic, and clinical characteristics of ALCAPA in order to deepen our understanding of this rare entity.Case Presentation: We were involved in the assessment, treatment, and pathological evaluation of two adult ALCAPA patients who were rescued from ventricular fibrillation and then surgically treated to establish a dual coronary artery system. Histological studies indicated various chronic ischemic changes in the myocardium, patchy fibrosis, and severely thickened arteriolar walls in both ventricles. The first patient is alive and well 11.5 years after surgical correction without any implantable cardioverter defibrillator (ICD) activations. The second patient required re-do surgery 9 months after the initial operation but subsequently died. Histologically, chronic ischemic alteration of the myocardium and thickened arteriolar walls persisted even after surgical correction, and coronary angiography (CAG) showed an extremely slow flow phenomenon even after surgical correction in both patients. The average postoperative opacification rate in the first case was 7.36 + 1.12 (n = 2) in the RCA, 3.81 + 0.51 (n = 3) in the left anterior descending (LAD) artery, and 4.08 + 0.27 (n = 4) in the left circumflex (LCx) artery. The slow flow phenomenon may represent persistent high arteriolar resistance in both ventricles.Conclusions: Seldom reported or new findings in adult ALCAPA were identified in two cases. More frequent diagnosis of adult ALCAPA can be expected because of the widespread availability of resuscitation and more advanced diagnostic modalities. Accumulation of pathological and clinical findings and confirmation of the long-term follow-up results after treatment may contribute to expanding our knowledge of this rare entity and establishing optimal treatment. [ABSTRACT FROM AUTHOR]

Introduction: Early repolarization syndrome is a recently proposed condition characterized by an early repolarization pattern in the electrocardiogram (ECG) and ventricular fibrillation in the absence of structural heart abnormalities. Although some studies have suggested that early repolarization is associated with frequency of atrial fibrillation, the association of early repolarization with atrial fibrillation is not well known. Hypothesis: Early repolarization indicates the substrate for atrial fibrillation in addition to that for ventricular fibrillation. Method: This study included 79 patients (57 men [72%]; age, 45 ± 12 years) aged less than 60 years who had paroxysmal lone atrial fibrillation and 395 age‐ and sex‐matched healthy controls (patient:control ratio, 1:5). Patients who had structural heart disease, hypertension, diabetes, hyperthyroidism, history of successful resuscitation, or the Brugada type ECG were excluded. ECGs recorded during sinus rhythm were compared between patients with atrial fibrillation and healthy controls. Results: Early repolarization in the inferior and/or lateral leads was more common in patients with atrial fibrillation (25%) than controls (10%; P = 0.001). The location and magnitude of early repolarization were similar between the two groups. Other electrocardiographic measurements were not different between the two groups. Among patients with atrial fibrillation, there was no difference in clinical characteristics including age at atrial fibrillation development, sex, and body mass index between patients with early repolarization and those without early repolarization. Electrocardiographic measurements were not different between patients with early repolarization and those without early repolarization. Conclusion: Early repolarization was associated with lone atrial fibrillation. Early repolarization may indicate increased susceptibility to atrial fibrillation. [ABSTRACT FROM AUTHOR]

The adenoma‑carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well‑established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma‑carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma‑carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non‑cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki‑67 (Ki‑67), cyclin‑dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin‑fixed paraffin‑embedded blocks and reverse transcription‑quantitative polymerase chain reaction analysis of these genes was performed. Ki‑67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki‑67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21. [ABSTRACT FROM AUTHOR]

Abstract: RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. Here, we investigated the clinical significance of RNF43 mutations in a large Japanese cohort and the role of RNF43 at various stages of colorectal cancer development and progression. Mutation analysis of the RNF43 gene locus with pyrosequencing technology detected RNF43 hotspot mutations in one (0.88%) of 113 colorectal polyp cases and in 30 (6.45%) of 465 colorectal cancer cases. Moreover, patients with colorectal cancer harbouring mutated RNF43 experienced a higher recurrence rate than those harbouring non‐mutated RNF43. In addition, the growth of RNF43 wild‐type colorectal cancer cell lines was significantly increased by RNF43 silencing. We generated Rnf43 knockout mice in a C57BL/6 N background by using the CRISPR–Cas9 system. Although intestinal organoids from Rnf43 knockout mice did not show continuous growth in the absence of R‐spondin, an azoxymethane/dextran sodium sulphate mouse model demonstrated that tumours were markedly larger in Rnf43 knockout mice than in wild‐type mice. These findings provide evidence that Wnt signalling activation by RNF43 mutations during the tumourigenic stage enhances tumour growth and promotes a high recurrence rate in colorectal cancer patients. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients’ prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy.Methods: We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT ≧ 2 or CONUT < 2).Results: The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT ≧ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) (p = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4-6.8; p = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien-Dindo classification ≧ III or more).Conclusions: CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy. [ABSTRACT FROM AUTHOR]

Background: Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease.Methods: Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests.Results: Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings.Conclusion: The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms. [ABSTRACT FROM AUTHOR]

Background: A variety of endoscopic findings are considered useful for the diagnosis of eosinophilic esophagitis (EoE). However, the diagnostic consistency among Japanese endoscopists for those findings has not been fully examined. The aim of this study was to investigate the inter- and intra-observer agreement for endoscopic findings suggesting EoE. Methods: Forty endoscopists, including 20 with board certification from the Japan Gastroenterological Endoscopy Society (JGES), participated in this study. Initially, they examined 50 randomized white-light endoscopic images from 30 patients with EoE and 20 without EoE. Four weeks later, the same 50 endoscopic images were re-examined in a different random order. Inter- and intra-observer agreement was calculated using kappa statistics for multiple observers. Results: The kappa coefficient of reliability [95% confidence interval (CI)] for all 40 endoscopists for diagnosis of EoE was 0.34 (0.33-0.35), indicating poor level of inter-observer agreement, while intra-observer agreement showed a moderate value of 0.52 (0.47-0.57). Among 4 possible endoscopic findings (linear furrows, concentric rings, edema, white exudates) for EoE, acceptable levels (kappa value >0.4) of inter- and intra-observer agreement were seen only for linear furrows. When the JGES board-certified and non-certified endoscopists were compared for successful diagnosis of EoE, the value was significantly higher for the board-certified group. However, the level of inter-observer agreement remained poor level. Conclusion: We concluded that inter-observer agreement on the endoscopic diagnosis of EoE among Japanese endoscopists did not reach a clinically acceptable level. [ABSTRACT FROM AUTHOR]

The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. Chugai previously established an LGR5+ human colorectal cancer (CRC) stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant noncycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs. The c-Myc expression alterations were mediated by upregulation of F-box/WD repeat-containing protein 7 (FBXW7), as evidenced through FBXW7-small interfering RNA knockdown experiments that resulted in enhanced cell sensitivity to anticancer agents. Upregulation of FBXW7 following drug treatment was not evident in commercially available cancer cell lines. Colorectal CSCs were induced to differentiation by Matrigel and fetal bovine serum. Differentiated CSCs treated with anticancer agents did not show upregulation of FBXW7 and were more sensitive to irinotecan (CPT-11), highlighting the potential CSC-specific nature of our data. The FBXW7 over-expression was further validated in resected liver metastatic sites in CRC patients after chemotherapy. In conclusion, our study revealed that a CSC-specific FBXW7-regulatory mechanism is strongly associated with resistance to chemotherapeutic agents. Inhibition of FBXW7-upregulation in CSCs following chemotherapy may enhance the response to anticancer agents and represents an attractive strategy for the elimination of colorectal CSCs. S tem C ells 2017;35:2027-2036 [ABSTRACT FROM AUTHOR]

Background: Various systemic inflammatory and nutritional scores have been reported to predict postoperative outcomes. This study aimed to investigate the best systemic inflammatory and nutritional scores in colorectal cancer (CRC) patients who underwent potentially curative resection. Method: We evaluated 468 consecutive CRC patients in this study. Comparisons of systemic inflammatory and nutritional scores, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), were performed using univariate/multivariate analyses for patient survival. Results: The PNI and mGPS, but not the NLR, PLR, and PI, were significantly associated with overall and relapse-free survival. The mGPS, but not the PNI, was strongly correlated with TNM stage ( P < 0.001). Cox multivariate analysis showed that both the PNI and mGPS were exclusive independent prognostic factors for both overall and relapse-free survival ( P < 0.001). Furthermore, the PNI status predicted patient survival more clearly than the mGPS in combination with TNM stage. Conclusions: This study suggests that the PNI and mGPS are useful predictive scores in CRC patients who undergo potentially curative resection, especially the PNI in combination with TNM stage. Routine evaluation of the host status using the scores may be useful in CRC treatment. [ABSTRACT FROM AUTHOR]

A diphosphine-borane ligand (DPB) enables the straightforward synthesis of unique examples of square-planar anionic Pt SP 0 sp complexes [(DPB)PtX] SP - sp , as reported by Hajime Kameo, Didier Bourissou et al. in their Communication (e202301509). Keywords: Anionic Complexes; Photoelectron Spectroscopy; Platinum; X-Ray Diffraction EN Anionic Complexes Photoelectron Spectroscopy Platinum X-Ray Diffraction 1 1 1 05/05/23 20230508 NES 230508 B Coordination Compounds b . Frontispiece: Square-Planar Anionic Pt0 Complexes. [Extracted from the article]

Keywords: Anionic Complexes; Photoelectron Spectroscopy; Platinum; X-Ray Diffraction EN Anionic Complexes Photoelectron Spectroscopy Platinum X-Ray Diffraction 1 1 1 05/05/23 20230508 NES 230508 B Coordination Compounds b . Anionic Complexes, Photoelectron Spectroscopy, Platinum, X-Ray Diffraction A diphosphine-borane ligand (DPB) enables the straightforward synthesis of unique examples of square-planar anionic Pt SP 0 sp complexes [(DPB)PtX] SP - sp , as reported by Hajime Kameo, Didier Bourissou et al. in their Communication (e202301509). [Extracted from the article]

Background: Esophageal eosinophilia is classified as either eosinophilic esophagitis (EoE) or proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE), depending on the response to PPI treatment. The aim of this study was to compare the clinical, endoscopic, and histopathological findings of EoE and PPI-REE in Japanese patients. In addition, the characteristics of these cases were compared with those of reflux esophagitis (RE) cases.Methods: Eleven patients diagnosed with EoE, 16 with PPI-REE, and 39 with RE, who were all consecutively examined from 2005 to 2015 at Shimane University Hospital, were enrolled. Clinical, endoscopic, and histopathological esophageal findings in these groups were retrospectively examined and compared.Results: The differences in the clinical characteristics of EoE and PPI-REE were not remarkable, though patients with EoE and PPI-REE were younger, presented a higher prevalence of allergic comorbidities, and complained of symptoms of dysphagia more frequently than those with RE. The only noteworthy differences between EoE and PPI-REE were more frequent reports of asthma (36.4 vs. 2.6 %) and food allergy (27.3 vs. 0 %) by patients with EoE (P < 0.05, P < 0.05, respectively). Endoscopic findings in patients with EoE and PPI-REE were similar, with the presence of esophageal erosions in a small percentage of PPI-REE cases being the only difference. There were no histopathological differences between EoE and PPI-REE.Conclusions: Comparisons of clinical, endoscopic, and histopathological findings between EoE and PPI-REE showed that these two types have similar characteristics, though EoE patients showed a higher atopic background. Predicting PPI responsiveness in cases with esophageal eosinophilia is difficult and requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection. Methods: Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined. Results: CONUT score correlated significantly with age ( P < 0.001), body mass index ( P = 0.005), carcinoembryonic antigen ( P = 0.002), and carbohydrate antigen 19-9 ( P = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30-14.92; P < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89-10.74; P < 0.001). Conclusions: CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status. [ABSTRACT FROM AUTHOR]

Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra-esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases. [ABSTRACT FROM AUTHOR]

Our objective was to clarify whether thrombogenic problems with stent struts are resolved at 3 months after 2nd-generation drug-eluting stent implantation. Twenty-one patients with stable angina pectoris having 28 (22 zotarolimus-eluting, 6 everolimus-eluting) stents with optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) were evaluated. Stent strut coverage and malapposition were evaluated by OCT immediately after PCI and at 3-month follow-up. Acute strut malapposition was observed in 26 out of 28 analyzed stents (92.9 %). At 3-month follow-up, 7 (26.9 %) of those 26 stents with strut malapposition were completely resolved, and the mean percentages of uncovered struts and malapposed struts were 8.3 and 2.0 % when analyzed by each individual stent. When analyzing a total of 30,060 struts, 807 struts (2.7 %) demonstrated acute strut malapposition. Among these, 219 struts (27.1 %) demonstrated persistent strut malapposition. On the basis of receiver-operating characteristic curve analysis, a strut-to-vessel (S-V) distance ≤160 µm on post-stenting OCT images was the corresponding cutoff point for resolved malapposed struts (sensitivity 78.1 %, specificity 62.8 %, area under the curve 0.758). The S-V distance of persistent malapposed struts on post-stenting OCT images was longer than that of resolved malapposed struts (235 ± 112 vs. 176 ± 93 µm, p < 0.01). At 3 months after PCI, the prevalence rates of uncovered and malapposed struts were relatively low in 2nd-generation drug-eluting stent. Our results suggest that OCT-guide PCI with an S-V distance ≤160 µm may be recommended especially in patients with planed short-term DAPT. [ABSTRACT FROM AUTHOR]

Purpose: As cancer advances, changes in the systemic inflammatory response alter the relative levels of circulating white blood cell types and may contribute to the progression and outcomes of cancer. The aim of the current study is to clarify the impact of the preoperative neutrophil/lymphocyte ratio (NLR) on the prognosis and whether clinical and pathological features modify the influence of the NLR on the prognosis of esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively analyzed the mortality hazard ratios (HRs), including the preoperative NLR, obtained from data for 283 ESCC patients undergoing resection in the period from 2005 to 2011, adjusting for clinical and pathological features. Results: A high NLR was associated with a significantly shorter overall survival ( p = 0.0018) and cancer-specific survival ( p = 0.0097). In the multivariate Cox model, we confirmed that the NLR was an independent prognostic marker for both overall survival ( p = 0.0081) and cancer-specific survival ( p = 0.028). The outcomes were not significantly modified by other diagnostic factors, including the tumor stage, in the survival analysis. Conclusions: The preoperative NLR is significantly associated with a poor prognosis in patients with ESCC, suggesting the utility of NLR as a cost-effective and broadly available independent prognostic marker of ESCC. [ABSTRACT FROM AUTHOR]

Acquired genetic and epigenetic alterations in normal cells give rise to transformed cells, which lead to tumor development. Elucidation of the precise mechanisms underlying primary and metastatic tumor formation is required. MicroRNAs (miRNAs) are small noncoding RNAs that play a major role in post-transcriptional gene regulation during various biological processes. Accumulating evidence suggests that dysregulation of miRNAs is intimately involved in the carcinogenesis, progression and metastasis of many cancers, including gastric cancers (GCs), while the alteration of certain miRNAs provides biomarkers to detect early GCs. This review summarizes the most recent findings into the mechanisms of miRNA-mediated regulation of GCs, which will support the development of diagnostic biomarkers and novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are reportedly involved in invasion and metastasis in several types of cancer, including gastric cancer (GC), through the stimulation of CXCL12/CXCR4 signaling. However, the mechanisms underlying these tumor-promoting effects are not well understood, which limits the potential to develop therapeutic targets against CAF-mediated CXCL12/CXCR4 signaling. CXCL12 expression was analyzed in resected GC tissues from 110 patients by immunohistochemistry (IHC). We established primary cultures of normal fibroblasts (NFs) and CAFs from the GC tissues and examined the functional differences between these primary fibroblasts using co-culture assays with GC cell lines. We evaluated the efficacy of a CXCR4 antagonist (AMD3100) and a FAK inhibitor (PF-573,228) on the invasive ability of GC cells. High CXCL12 expression levels were significantly associated with larger tumor size, increased tumor depth, lymphatic invasion and poor prognosis in GC. CXCL12/CXCR4 activation by CAFs mediated integrin ß1 clustering at the cell surface and promoted the invasive ability of GC cells. Notably, AMD3100 was more efficient than PF-573,228 at inhibiting GC cell invasion through the suppression of integrin ß1/FAK signaling. These results suggest that CXCL12 derived from CAFs promotes GC cell invasion by enhancing the clustering of integrin ß1 in GC cells, resulting in GC progression. Taken together, the inhibition of CXCL12/CXCR4 signaling in GC cells may be a promising therapeutic strategy against GC cell invasion. [ABSTRACT FROM AUTHOR]

APOBEC3B belongs to the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family of enzymes and induces C to T transitions of target DNA by cytidine deamination. Recently, several mutations in various cancers have been linked to APOBEC3B, suggesting a crucial role for this protein in carcinogenesis and cancer development. However, the significance of APOBEC3B in esophageal squamous cell carcinoma (ESCC) remains uncertain. In addition, the APOBEC3B immunoreactivity in cancer tissues is uncertain. Recently, we have demonstrated that PIK3CA mutation and the methylation level of long interspersed nucleotide element 1 (LINE-1) (a surrogate marker of global DNA methylation level) are prognostic markers and have crucial role on malignancy in ESCC patients. This study aims to clarify the impact of APOBEC3B on the clinical, pathological, and molecular features of ESCC. We evaluated APOBEC3B expression in ESCC and investigated the relationships among the immunoreactivity of APOBEC3B, clinical and pathological features, and the molecular features of ESCC ( PIK3CA mutation, p53 expression, and LINE-1 methylation level). The immunoreactivity and mRNA level of APOBEC3B were significantly higher in cancer tissues than in noncancerous esophageal mucosae ( P = 0.050). APOBEC3B expression was significantly correlated with PIK3CA mutation ( P = 0.013), particularly with C to T transitions of PIK3CA ( P = 0.041). Moreover, a high expression of APOBEC3B was significantly associated with LINE-1 hypomethylation ( P = 0.027). Given the crucial roles of PIK3CA mutation and LINE-1 methylation levels, our findings might provide new insights into the biological mechanisms of ESCC tumorigenesis and progression. [ABSTRACT FROM AUTHOR]

Background: Jumonji-domain containing 3 (JMJD3) affects transcriptional regulation by demethylating lysine 27 residue of histone 3. We investigated its function and prognostic significance in colorectal cancer (CRC). Methods: The influence of JMJD3 on cell proliferation was assessed using quantitative RT-PCR and western blot on the downstream target gene of JMJD3, in knock-down (KD) experiments and clinical samples from 151 CRC patients. Results: Cells with KD JMJD3 significantly increased proliferation through cell cycle progression and apoptosis suppression. Expression of P15INK4B was remarkably decreased in KD JMJD3 cells; and JMJD3 expression strongly correlated with p15INK4B expression in clinical CRC samples ( P < 0.001, r = 0.566). Low JMJD3 also was an independent predictor of poor prognosis ( P = 0.042) in surgically resected CRC patients. Conclusions: JMJD3 has prognostic significance in CRC and mediates p15INK4B expression. These results imply that elucidation of the JMJD3 role may lead to a new therapeutic approach for CRC patients. [ABSTRACT FROM AUTHOR]

Background: Smoking is one of the risk factors for postoperative morbidity. There were no studies on the correlation between the duration of smoking cessation and the incidence of morbidities after esophagectomy. Methods: A total of 246 patients undergoing elective esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and February 2015 were retrospectively analyzed. Patients were divided into five groups according to the duration of smoking cessation [no smoking cessation (including cessation for a few days), cessation for 7-30, 31-90, ≥91 days, never smoker]. Results: Any morbidity of Clavien-Dindo classification (CDc) ≥II, pneumonia, any pulmonary morbidity, surgical site infection, cardiovascular morbidity, and severe morbidities of CDc ≥IIIb frequently occurred in patients with no smoking cessation. The incidence of pneumonia and severe morbidities decreased as the duration of smoking cessation became longer. Logistic regression analysis suggested that no smoking cessation was the independent risk factor for any pulmonary morbidity (HR 3.68, 95 % CI 1.152-11.74; p = 0.028). Smoking cessation ≤30 days was also the independent risk factor for pneumonia (HR 2.89, 95 % CI 1.141-7.301; p = 0.025). Smoking cessation ≤90 days was the independent risk factor for severe morbidities of CDc ≥IIIb (HR 2.82, 95 % CI 1.072-7.427; p = 0.036). Conclusions: Preoperative smoking cessation more than 90 days is ideal to reduce morbidities after esophagectomy. When patients with insufficient smoking cessation undergo esophagectomy, careful perioperative management is required. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). Methods: In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Results: Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI ( P < 0.0001; r = 0.63) and BCAA levels ( P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group ( P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. Conclusions: High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Excess visceral adipose tissue may promote cancer development and progression via an obesity-related metabolic derangements, including adipocytokine-related inflammation, insulin resistance, and hypoxia. The relationship between visceral fat content and patient prognosis has been reported in some types of cancers, but not in the upper gastrointestinal cancer. The purpose of this retrospective study was to investigate the relationship between visceral fat status and clinical outcome in patients with upper gastrointestinal cancers (esophageal cancer and gastric cancer) treated by surgical resection. Methods: This retrospective study was conducted in a single, academic hospital in Kumamoto, Japan, and involved 507 patients with upper gastrointestinal cancers between April 2005 and December 2010. Preoperative visceral fat content was quantified by radiologic measures using standard computed tomography scans. Results: Higher visceral fat mount was correlated with male sex, presence of preoperative comorbidity, absence of preoperative therapy, low tumor depth, low tumor stage, and gastric cancer. Compared to high visceral fat cases, low visceral fat cases experienced a higher overall mortality rate [log-rank p = 0.0050; univariate hazard ratio (HR) = 1.73, 95 % confidence interval (CI) 1.16-2.54; p = 0.0075; multivariate HR 1.57; 95 % CI 1.02-2.37; p = 0.031]. Interestingly, the influence of low visceral fat on patient outcome was modified by age at surgery ( p for interaction = 0.036); low visceral fat was associated with a poor prognosis, especially in elderly patients (log-rank p < 0.0001). Conclusion: Visceral fat content in the upper gastrointestinal cancers was associated with a poor prognosis, thus suggesting that it has potential for use as a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Superior mesenteric artery (SMA) dissection without aortic dissection is a rare condition, and its diagnosis is considered to be difficult. Intestinal infarction is a severe complication of the disease, which may require resection of the intestine. We present a case of isolated SMA dissection. A 53-year-old man experienced sudden pain in the abdomen while playing Japanese pinball and was admitted to our hospital due to acute abdominal symptoms of uncertain cause. Enhanced CT revealed a defect of the root of the SMA, while angiography and intravascular ultrasound findings showed dissection of the SMA wall. Conservative treatment was chosen at the time, while a part of the small intestine was eventually resected because of progressive ischemia. Although SMA dissection is a rare occurrence in cases with acute abdominal symptoms, awareness of the condition is important for differential diagnosis. [ABSTRACT FROM AUTHOR]

Purposes: Primary mucosal malignant melanoma (PMMM) is a rare and highly lethal neoplasm associated with a poor prognosis. CXC chemokine receptor 4 (CXCR4) is expressed on various tumor cells, including malignant melanoma. Recent data indicate that CXCL12 and CXCR4 play a critical role in the behavior of cancer cells and in the survival of cancer patients. However, there has been no study that has addressed the expression and function of CXCR4/CXCL12 signaling in PMMM. Methods: Immunohistochemical staining for CXCL12 and Ki67 in biopsy tissues from 10 cases of PMMM was performed. We analyzed the correlations between the clinicopathological features and expression levels of CXCL12 and Ki67. Results: Six cases showed a high level of CXCL12 expression, while four cases had a low level of expression. High expression of CXCL12 correlated with a poor prognosis, although statistical significance was not reached ( p = 0.054). Ki67 was highly expressed in five cases, while the expression in the other five cases was low. There was no correlation between the Ki67 expression and prognosis. Conclusions: The findings of this study suggest that CXCL12 expression may play an important role in the biological behavior of PMMM and may be associated with a poor prognosis of PMMM patients. [ABSTRACT FROM AUTHOR]

Background: Infection with Helicobacter pylori is the main risk factor for development of gastric cancer. CD44 overexpression, especially that of variant 9 (CD44v9), has also been implicated in the local inflammatory response and metaplasia-carcinoma sequence in human stomach. We recently identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. The aim of the current study was to determine the relationship between miR-328 and CD44v9 expression in H. pylori-infected gastric mucosa during the development of preneoplastic lesions. Methods: Immunohistochemical staining of myeloperoxidase and CD44v9 was performed using paraffin-embedded tissue sections obtained from 54 patients who underwent gastric resection without preoperative treatment. The levels of miR-328 expression in the gastric mucosa were measured in the same patients using quantitative reverse transcription polymerase chain reaction. Results: Both infiltration of myeloperoxidase-positive inflammatory cells and expression of proinflammatory cytokines closely correlated with H. pylori infection in the cancer-afflicted gastric mucosa. High CD44v9 expression levels, identified in the gastric mucosa in 61 % of samples (33/54), correlated significantly with H. pylori infection in the gastric mucosa. Notably, high CD44v9 expression was significantly associated with low miR-328 expression, whereas low CD44v9 expression was significantly associated with high miR-328 expression. Conclusions: We showed that miR-328 downregulation and de novo expression of CD44v9 occurred in H. pylori-infected gastric mucosa adjacent to gastric cancer compared with gastric mucosa not infected with H. pylori adjacent to gastric cancer. CD44v9-overexpressing cells are known to acquire reactive oxygen species resistance; thus, these cells may avoid cell death caused by various stress inducers, which may be linked to the origin of gastric cancer development. [ABSTRACT FROM AUTHOR]

Lymphangiomas are rare cystic tumors that may be present in the retroperitoneum. Retroperitoneal lymphangiomas account for approximately 1 % of all lymphangiomas. We experienced an adult patient with a retroperitoneal cystic lymphangioma coexisting with an esophageal hiatus hernia. Abdominal ultrasonography showed a cyst in the abdomen of a 76-year-old woman. She was admitted to our clinic because of an enlargement of the cyst and epigastric pain after meals. She had a long history of heartburn after meals and had not undergone any treatment. She had no record of previous illnesses. Computed tomography revealed a single bunch cystic tumor with septations, located from the mediastinum to the retroperitoneal space. The tumor was not enhanced, and there was no solid part. She was diagnosed with a retroperitoneal cyst. Laparoscopic total excision was performed because the cyst was increasing in size and the patient had symptoms. The cyst was successfully removed. Although laparoscopic excision of retroperitoneal cystic lymphangiomas is the treatment of choice, surgical methods should be carefully chosen in selected patients. [ABSTRACT FROM AUTHOR]

Although cancer-associated fibroblasts (CAFs) mainly produce CXCL12 and stimulate CXCL12/CXCR4 signaling in cancer cells, the significance of this interaction in adenocarcinoma of the esophagogastric junction (AEG) was unclear. This study investigated the functional characteristics of CAF-derived CXCL12 in AEG. Immunohistochemical staining for CXCL12 was performed on sections from 123 AEG patients and analyzed against clinicopathological data. Newly isolated CAFs and normal fibroblasts were examined for phenotype. An invasion assay was performed with AEG cells co-cultured with CAFs isolated from AEG. CXCL12 expression was significantly associated with age, depth of invasion, lymphatic invasion, and lymph node metastases. High CXCL12 expression significantly correlated with poor prognosis. Isolated CAFs had abundant α-smooth muscle actin expression and showed various CXCL12 expression patterns. Notably, AEG cells co-cultured with CXCL-expressing CAFs invaded more than when co-cultured with CXCL-expressing CAFs; these invasive properties were impeded by CXCR4 antagonist AMD3100. We demonstrated that AEG cells co-cultured with CXCL12 CAFs were significantly more invasive than those co-cultured with CXCL12 CAFs and that high CXCL12 expression correlates with poor prognosis in AEG patients. CXCL12 derived from CAFs in tumor microenvironment stimulates CXCL12/CXCR4 signaling in AEG cells and promotes their invasive ability, resulting in tumor progression. [ABSTRACT FROM AUTHOR]

The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori ( H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues ( P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals ( P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection ( P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients ( P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori. [ABSTRACT FROM AUTHOR]