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Background: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated., Methods: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months., Results: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009)., Conclusions: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development., Clinical Trials Registry Number: UMIN000001676., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The definition and classification of regional nodes are not standardized for perihilar cholangiocarcinoma. This study aimed to clarify the rational extent of regional lymphadenectomy and to elucidate the impact of number-based regional nodal classification on survival of patients with this disease., Methods: Data of 136 patients with perihilar cholangiocarcinoma who underwent surgery were reviewed. The incidence of metastasis and the survival of patients with metastasis were calculated for each node group., Results: The incidence of metastasis for the node groups in the hepatoduodenal ligament (denoted as no. 12) ranged from 3.7% to 25.4%, with 5-year disease-specific survival of 12.9% to 33.3% for patients with metastasis. The incidences of metastasis in the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups were 14.4% and 11.2%, respectively, with 5-year disease-specific survival rates of 16.7% and 20.0% for the patients with metastasis. When these node groups were defined as regional nodes, the 5-year disease-specific survival rates for the patients with pN0 (n = 80), pN1 (1-3 positive nodes, n = 38), and pN2 (≥ 4 positive nodes, n = 18) were 61.4%, 22.9%, and 17.6%, respectively (p < 0.001). The pN classification was independently associated with disease-specific survival (p < 0.001). When only the no. 12 node groups were regarded as regional nodes, pN classification failed to stratify the patients prognostically., Conclusions: No. 8 and no. 13a node groups should be considered regional nodes in addition to no. 12 node groups and should be dissected. The number-based regional nodal classification allows patients with this disease to be stratified prognostically., (© 2023. Society of Surgical Oncology.)

Background: Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers., Methods: We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4 months for the first 3 years and every 6 months thereafter., Results: Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC., Conclusion: CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Objectives: Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation., Methods: The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated., Results: There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred., Conclusion: Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Backgound: Cold snare polypectomy (CSP) can minimize the risk of adverse events and has become a standard treatment for small colorectal polyps. CSP might also be suitable for small superficial non-ampullary duodenal epithelial tumors (SNADETs). This study aimed to evaluate the safety of CSP for SNADETs., Methods: The major indication criteria were as follows: (1) endoscopically diagnosed SNADET, (2) ≤ 10 mm, and (3) a single primary lesion. CSP was performed using an electrosurgical snare without electrocautery. Follow-up endoscopy and scar biopsy were performed 3 months after CSP. The primary endpoint was the delayed adverse events rate., Results: In total, 21 patients were enrolled. Two and 19 lesions were located in the duodenal bulb and 2nd portion, respectively; the median lesion size was 8 mm. CSP was attempted for all lesions; three lesions could not be resected without electrocautery and were removed by conventional endoscopic mucosal resection (EMR). The rate of spurting bleeding after CSP was 0%. The median procedure time was 12 min, the median resected specimen size was 12 mm, and the rate of en bloc resection was 81% (17/21). No adverse events were observed intraoperatively, with no delayed adverse events after CSP. Histopathology revealed 15 adenomas, 4 cancers (intramucosal), and 2 non-neoplastic lesions. The horizontal margins were negative/positive/undetermined in 9, 1, and 11 cases, respectively. All vertical margins were negative. Only one recurrence was detected by follow-up endoscopy 3 months after CSP., Conclusions: CSP can be performed safely for small SNADETs., Clinical Trial Registration: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm ), and the registration number is UMIN000019157., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In endoscopic retrograde cholangiopancreatography (ERCP), reduction of pressure inside of the bile duct by bile aspiration is a well-known method to lower the rate of adverse events (AEs) including cholangitis. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been introduced as an alternative to ERCP. The use of self-expandable metallic stents is recommended in EUS-HGS to reduce bile leak; however, other methods to reduce the rate of AEs including bile leak, abdominal pain, fever, and sepsis, have not been elucidated yet. This study investigated whether bile aspiration during EUS-HGS decreased the rate of postprocedural AEs., Methods: Consecutive patients who underwent EUS-HGS between July 2016 and April 2020 were retrospectively evaluated in this study. EUS-HGS was performed at a tertiary cancer center. Patient characteristics, site of biliary obstruction, the quantity of bile aspirated during EUS-HGS, type of stent, whether or not antegrade stenting (AS) was performed, procedure time, and AEs were assessed based on a prospectively recorded institutional endoscopy database. Logistic regression analysis was performed to identify factors affecting postprocedural AEs., Results: Ninety-six patients were included in the study. EUS-guided HGS with and without AS was performed in 45 and 51 patients, respectively. Bile was aspirated in 71 patients (74%). The quantity of bile aspirated was 0-10 mL and > 10 mL in 40 and 56 patients, respectively. AEs including fever, abdominal pain, postprocedural cholangitis, sepsis, acute pancreatitis, and bleeding occurred in 45 patients (47%). The AE rates were 65% (26/40) and 34% (19/56), for 0-10 mL and > 10 mL bile, respectively (p = 0.004). Using multivariate analysis, the only independent factor affecting the occurrence of AEs was found to be an aspirated bile amount of 0-10 mL (odds ratio: 4.16; 95% CI 1.6-10.8)., Conclusions: Bile aspiration of more than 10 mL during EUS-HGS contributes to reducing the rate of postprocedural AEs., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic ultrasonography (EUS) is reportedly the reliable modality to predict the depth of esophageal squamous cell carcinoma (ESCC), however, most previous studies are retrospective or single-centered. We aimed to evaluate the diagnostic ability of conventional endoscopy and EUS using the data from a multicenter prospective study of endoscopic resection (ER) followed by chemoradiotherapy for cSM1-2N0M0 ESCC (JCOG0508)., Methods: All lesions were evaluated as cSM cancer with both conventional endoscopy and EUS before enrollment and judged as cSM1 or cSM2 in real time. We compared the clinical and pathological diagnoses for tumor depth and assessed the positive predictive value (PPV) for pSM (pSM/cSM) as the primary endpoint. We also investigated the clinical factors affecting the pathological depth of SM., Results: 175 lesions were examined, and clinical diagnosis was SM1 in 114 and SM2 in 61 lesions. The pathological diagnoses of the epithelium, lamina propria mucosa, muscularis mucosae, SM1, and SM2 were 3, 31, 55, 17, and 69. The PPV for pSM was 49.1% (86/175) in all lesions, 34.2% (39/114) in cSM1 lesions, and 77.0% (47/61) in cSM2 lesions. Multivariable analysis demonstrated that cSM2 (vs. cSM1, OR 6.79) was an independent clinical factor associated with pSM., Conclusions: While the accurate depth diagnosis in cSM ESCC was difficult to make, the clinical diagnosis of SM2 with both conventional endoscopy and EUS was significantly associated with pSM. Furthermore, diagnostic ER could be recommended to confirm the pathological diagnosis especially in cSM1 lesions with both conventional endoscopy and EUS.

Background: As the predictive role of many risk factors for parasagittal meningioma (PM) recurrence remains unclear, the objective of the meta-analysis was to make a comprehensive assessment of the predictive value of selected risk factors in these lesions., Methods: Studies including data on selected risk factors, such as histology, tumor and sinus resection, sinus invasion, tumor localization, and immediate postoperative radiotherapy for PMs recurrence, were searched in the NCBI/NLM PubMed/MEDLINE, EBM Reviews/Cochrane Central, ProQuest, and Scopus databases, and analyzed using random effects modeling., Results: Thirteen observational studies involving 1243 patients met the criteria for inclusion in the meta-analysis. WHO grading of meningiomas was identified as the most powerful risk factor for recurrence. WHO grade II meningiomas (OR 11.61; 95% CI 4.43-30.43; P < .01; I 2  = 31%) or composite group of WHO grades II and III (OR 14.84; 95% CI 5.10-43.19; P < .01; I 2  = 48%) had a significantly higher risk of recurrence than benign lesions. Moreover, an advanced sinus involvement (types IV-VI according to the Sindou classification) (OR 3.49; 95% CI 1.30-9.33; P = .01; I 2  = 0%) and partial tumor resection (Simpson grades III-V) (OR 2.73; 95% CI 1.41-5.30; P = .03; I 2  = 52%) were associated with a significantly higher risk of recurrence than their counterparts., Conclusion: Among the selected risk factors, high-grade WHO lesions, advanced sinus invasion, and partial tumor resection were associated with a higher risk of PM recurrence, with WHO grading system being the most powerful risk factor.

Background: Renal hypoplasia (RH) is the most common cause of chronic kidney disease in children. In cases of RH, proteinuria is often induced by glomerular hypertrophy and hyperfiltration that is commonly associated with focal segmental glomerulosclerosis. This study reports the first case series of a possible association between RH and membranous nephropathy (MN)., Methods: Of the 168 children with RH who visited our department between 1999 and 2017, five with overt proteinuria (≥ 1 g/gCr) underwent renal biopsy. We retrospectively reviewed the medical charts and analyzed biopsy specimens using light microscopy (LM), immunofluorescence (IF), and electron microscopy., Results: The five children (four boys and one girl) had a median age of 5.5 years at the time of renal biopsy. The median proteinuria was 4.23 g/gCr (range 1.46-14.25), median serum albumin, 2.9 g/dL (range 2.3-3.7), and median estimated glomerular filtration rate, 59.7 mL/min/1.73 m 2 (range 36.7-103.6). LM showed segmental spike formation and mesangial hypercellularity and IF study showed segmental granular immunoglobulin G (IgG) staining (IgG1 and IgG3 dominant) along the capillary loops in all five patients. Electron-dense deposits were observed in the subepithelial and mesangial areas. Thus, the pathological studies showed MN-like lesions in all patients., Conclusion: Our study suggests that RH can be the cause of MN-like lesions.

Background: Macrocytosis is associated with an increased risk of squamous cell carcinoma (SCC) arising in the esophagus in men. The aim of this study was to evaluate the association between macrocytosis and metachronous SCC of the esophagus after endoscopic resection (ER) of early esophageal SCC in men., Methods: The study group comprised 278 men with early esophageal SCC after ER. The main study variables were as follows: (1) cumulative incidence and total number of metachronous SCC of the esophagus according to the presence or absence of macrocytosis (mean corpuscular volume ≥ 106 fl) and (2) predictors of metachronous SCC of the esophagus as assessed with a multivariate Cox proportional-hazards model., Results: The median follow-up was 50.3 months. Macrocytosis was associated with a higher 2-year cumulative incidence of metachronous SCC of the esophagus (without macrocytosis vs. with macrocytosis: 11.4% vs. 38.1%, p = 0.002). Macrocytosis was also associated with a higher total number of metachronous SCC of the esophagus per 100 person-years (without macrocytosis vs. with macrocytosis: 7.7 vs. 31.5 per 100 person-years, p < 0.0001). In addition, macrocytosis was a significant predictor of metachronous SCC of the esophagus on multivariate Cox proportional-hazards analysis (relative risk 2.23)., Conclusion: Macrocytosis is a useful predictor of the risk of metachronous SCC of the esophagus after ER of early esophageal SCC in men.

Background: Endoscopic submucosal dissection (ESD) is the standard treatment for superficial esophageal cancer (SEC); however, it is sometimes technically difficult. Our aim was to identify the predictors of technical difficulty during ESD for SEC., Methods: We reviewed the records of patients who underwent ESD for superficial esophageal squamous cell carcinomas at a tertiary cancer center between April 2008 and March 2016. Patients undergoing ESD after esophagectomy or for residual/recurrent lesions were excluded. Preoperative factors such as tumor subsite, localization, preoperative size, macroscopic type, endoscopic depth of invasion, and treatment for synchronous multiple SECs or previous history of radiation therapy were analyzed. Logistic regression analysis was performed to identify the predictors of technical difficulty, defined as (1) long procedure time (≥ 120 min), (2) adverse events (perforation, pneumomediastinum), or (3) incomplete resection (piecemeal resection, positive or indeterminate vertical margin)., Results: A total of 679 lesions in 511 patients were analyzed. Difficultly was experienced in 60 cases. The procedure time was > 120 min in 43 (6.3%) patients, adverse events occurred in 16 (2.8%), and incomplete resection occurred in 17 (2.5%). Multivariate logistic regression revealed that tumors in the left esophageal wall (OR 2.15; 95% CI 1.17-3.91; p = 0.014) and those encompassing ≥ 1/2 its circumference (OR 5.06; 95% CI 2.40-11.34; p < 0.001) were independently associated with difficulty., Conclusions: Tumors in the left esophageal wall and tumors measuring > 1/2 of the esophageal circumference are predictors of difficult esophageal ESD. These results may contribute to better patient selection according to each endoscopist's skill.

Background and Aim: Endoscopic salvage treatment for recurrent or residual neoplasms is sometimes technically challenging, and information in choice of treatment methods is lacking. This study aimed to clarify the appropriate treatment strategy for local recurrence after endoscopic resection (ER)., Methods: Seventy-four patients with 74 lesions who received endoscopic treatment for local recurrence after ER for colorectal epithelial neoplasms between January 2010 and December 2016 were enrolled. Patients with hyperplastic polyp, sessile-serrated adenoma/polyp, and submucosal invasive cancer in their initial ER were excluded. Treatment methods, treatment outcomes, and recurrence rate were evaluated for each recurrence based on the preoperative endoscopic diagnosis (adenomatous or cancerous)., Results: Forty-nine of the 74 patients diagnosed with adenomatous recurrence were treated using cold polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) in 15, 26, and 8 patients, respectively. Cold polypectomy was applied only to diminutive lesions. EMR and ESD en bloc resection rates were 53.8 and 100%, respectively (p = 0.030). Two patients (7.7%) in the EMR group developed local recurrence, but an additional ER achieved complete resection. Meanwhile, the remaining 25 patients diagnosed with cancerous recurrence were treated via EMR and ESD for 7 and 18 patients, respectively. EMR and ESD en bloc resection rates were 28.6 and 83.3%, respectively (p = 0.017). Three patients (42.9%) in the EMR group developed recurrence., Conclusions: Selecting appropriate treatment methods for adenomatous recurrence could be decided based on estimated pathology and lesion size. ESD was effective for cancerous recurrence to achieve complete disease control.

The rate constants of OH radicals with CF 3 CF=CCl 2 , CF 3 CH=CF 2 , CF 3 CF=CH 2 , CF 3 CH=CH 2 , and (CF 3 ) 2 C=CH 2 have been measured over the temperature range 250-430 K. Kinetic measurements have been carried out using flash photolysis and laser photolysis methods combined respectively with laser-induced fluorescence technique. The Arrhenius rate parameters have been determined as k(CF 3 CF=CCl 2 ) = (6.50 ± 0.22) × 10 -13 ∙exp[(200 ± 10)/T], k(CF 3 CH=CF 2 ) = (4.85 ± 0.14) × 10 -13 ∙exp[(120 ± 10)/T], k(CF 3 CF=CH 2 ) = (1.54 ± 0.03) × 10 -12 ∙exp[- (100 ± 10)/T], k(CF 3 CH=CH 2 ) = (1.06 ± 0.02) × 10 -12 ∙exp[(80 ± 10)/T], and k((CF 3 ) 2 C=CH 2 ) = (8.75 ± 0.23) × 10 -13 ∙exp[- (20 ± 10)/T] cm 3  molecule -1  s -1 . Infrared absorption spectra of the halogenated alkenes have been measured at room temperature. The atmospheric lifetime, global warming potential, ozone depleting potential, and photochemical ozone creation potential have been estimated. The change in the reactivity of halogenated alkenes by the substitution has been examined by considering the structure containing the atoms or atomic groups attached to the carbons on both sides of the double bond.

Background: Stenosis is a troublesome complication after wide endoscopic submucosal dissection (ESD). As steroids are known to prevent post-ESD esophageal stenosis, this study aimed to clarify the gastric effects., Methods: This was a retrospective single-institution study. Between September 2002 and June 2015, 132 patients with a post-ESD mucosal defect exceeding three-fourths of the circumference were identified. Among them, 107 patients who did not undergo additional surgery for non-curative resection were reviewed. Steroid treatment (local injection and/or systemic) for stenosis prevention was administered to 28 patients within 10 days after ESD (steroid group). The incidence of stenosis and course of therapeutic endoscopic balloon dilation (EBD) were analyzed between the steroid and non-steroid group., Results: Stenosis occurred in 31% (33/107) of patients. Full circumferential defect and defect extending to the pyloric ring were significantly related with stenosis. The proportion of patients with a full circumferential defect was relatively higher in the steroid group (14%) compared to the non-steroid group (5%) (p = 0.111). There was no significant relationship between the incidence of stenosis and the use of steroids (steroid group 39%, non-steroid group 28%, p = 0.260). However, the interval from ESD to stenosis was significantly delayed among steroid-treated patients with a near-circumferential to three-fourth mucosal defect (p = 0.001) and among patients with ESD in the lower stomach (p = 0.002). The number of therapeutic EBDs and treatment duration did not differ significantly between the groups. Steroid treatment did not increase the incidence of ESD- and EBD-related complications., Conclusion: Despite the retardation of the occurrence of stenosis in some subgroups, early steroid treatment did not a show a significant effect on stenosis prevention after wide gastric ESD. Further evaluation is needed to determine the dose and timing of steroid treatment for stenosis after wide gastric ESD.

Background: Although endoscopic submucosal dissection (ESD) represents a significant progress in therapeutic endoscopy, little is known about how trainees attain its technical proficiency. The aims of this study were to evaluate the learning curve and clinical outcomes of gastric ESD performed by trainee endoscopists., Methods: Between April 2009 and March 2014, 334 gastric ESD procedures were performed by seven trainees (42-50 consecutive cases per trainee). The learning curve for gastric ESD was evaluated using the cumulative sum (CUSUM) method. Long-term outcomes were also analyzed., Results: The calculated CUSUM learning curve comprised three phases: Phase I (the initial 15 cases), Phase II (the middle 15 cases), and Phase III (the final 20 cases). The resection speed was 5.7 ± 3.2 min/cm 2 in Phase I, 4.7 ± 2.7 min/cm 2 in Phase II, and 4.3 ± 2.2 min/cm 2 in Phase III. The resection speed was significantly faster in Phase II than in Phase I (p = 0.019). The rate of self-completion reached more than 95% in Phases II and III. The overall complete resection rate was 95%, showing no significant differences between the three phases. Local recurrence was diagnosed in none of the patients during a median follow-up of 38 months., Conclusions: For the trainees, 30 cases were required to attain a higher technical level of competence in gastric ESD. After the learning curve phase, trainee operators could be expected to complete the procedure successfully with favorable long-term outcomes.

Background: This study was designed to evaluate the prognostic value of positive posterior superior pancreaticoduodenal lymph nodes to clarify the need for dissection of these nodes., Methods: A total of 148 patients with gallbladder carcinoma who underwent radical resection including dissection of the posterior superior pancreaticoduodenal nodes were enrolled. The incidence of metastasis and the survival rates among patients with metastasis to each lymph node group were calculated., Results: Of the 148 patients, 70 (47%) had nodal disease. The incidences of metastasis in the cystic duct, pericholedochal, retroportal, and hepatic artery node groups, defined as regional nodes in the UICC TNM staging system, ranged from 8.3 to 24.3% with 5-year survival rates of 12.5-46.4% in patients with positive nodes. The incidence of metastasis to the posterior superior pancreaticoduodenal nodes was 12.8% with a 5-year survival rate of 31.6% in patients with positive nodes. Survival after resection was significantly better in patients with distant nodal disease affecting only the posterior superior pancreaticoduodenal nodes (5-year survival, 55.6%) than in patients with distant nodal disease beyond these nodes (5-year survival, 15.0%; p = 0.046), whereas survival after resection was comparable between the former group and patients with regional nodal disease alone (5-year survival, 40.7%; p = 0.426)., Conclusions: In gallbladder carcinoma, involvement of the posterior superior pancreaticoduodenal nodes is similar to that of regional nodes in terms of both the incidence of metastasis and the impact on survival. Inclusion of the posterior superior pancreaticoduodenal nodes among the regional nodes should be considered.

Background: The management of antithrombotic therapy in the patients undergoing gastric endoscopic submucosal dissection (ESD) is of concern. This study aimed to assess delayed bleeding rate after gastric ESD in the patients receiving antithrombotic therapy., Methods: This study was a retrospective observational study held in a single institute. The patients undergoing gastric ESD from January 2009 to October 2014 were reviewed. Delayed bleeding rate in the patients receiving antithrombotic therapy was compared with that in matched controls. We also compared delayed bleeding rate in the patients continuing antithrombotic therapy with that in the patients with heparin bridging or cessation of antithrombotic therapy. Among 2388 lesions resected by gastric ESD, 367 lesions were resected in the patients with antithrombotic therapy, and 722 lesions were selected as controls. The lesions in the patients receiving antithrombotic therapy were divided into three subgroups: 54 lesions without preoperative cessation (continuation group), 37 lesions with heparin bridging (heparin group), and 276 lesions with cessation of antithrombotic therapy (cessation group)., Results: The incidence of delayed bleeding was significantly higher in the patients receiving antithrombotic therapy (9.5 % [35/367] vs. 4.2 % [30/722]; p < 0.01). Delayed bleeding rate in continuation group, heparin group, and cessation group was 9.2 % (5/54), 10.8 % (4/37), and 9.4 % (26/276), respectively, and no significant difference was observed. Thrombosis occurred only in cessation group (1.6 %)., Conclusions: Delayed bleeding rate associated with gastric ESD is significantly higher in the patients receiving antithrombotic therapy. No significant difference in delayed bleeding rate was observed among patients with and without cessation of antithrombotic therapy. To prevent thrombosis, gastric ESD without cessation may be feasible.

Background: The long-term outcomes after non-curative gastric endoscopic submucosal dissection (ESD) are still unknown. We aimed to clarify the pathological risk factors for lymph node metastasis (LNM) of early gastric cancer (EGC) and the long-term outcomes among patients who were judged to have had non-curative ESD., Methods: From September 2002 to December 2012, 506 patients who were judged to have had non-curative gastric ESD were enrolled and classified into two groups: (1) those who subsequently underwent additional surgical resection (surgical group, n = 323) and (2) those followed up without additional surgical resection (nonsurgical group, n = 183). We analyzed pathological risk factors for LNM of EGC in the surgical group. Additionally, we compared long-term outcomes in the two groups., Results: LNM was found pathologically in 9.3 % of the surgical group (30/323) at the additional surgical resection after non-curative ESD. In the multivariate logistic regression analysis, lymphovascular invasion (LVI) was an independent risk factor for LNM in the surgical group (odds ratio 8.57, 95 % confidence interval 2.76-38.14, P < 0.0001). The 5-year cause-specific survival rate was similar in the surgical and nonsurgical groups (98.7 and 96.5 %, respectively; log-rank test, P = 0.07). In contrast, the 5-year cause-specific survival rate of patients with LVI in the surgical group was better than that in the nonsurgical group (98.2 and 79.1 %, respectively; log-rank test, P < 0.0001)., Conclusions: A detailed assessment of LVI is essential to the pathological evaluation of endoscopically resected specimens. An additional surgical resection should be strongly recommended for patients with LVI.

Background: Although a high incidence of bacteremia after esophageal endoscopic procedures has been reported, the incidence of bacteremia associated with esophageal endoscopic submucosal dissection (ESD) remains unknown. Therefore, we investigated the incidence of bacteremia associated with esophageal ESD., Methods: From April 2013 to March 2014, patients who underwent esophageal ESD were enrolled prospectively. Two sets of blood cultures were collected from patients at the following time points: (1) immediately after ESD; (2) the next morning; and (3) when fever ≥38 °C was present after ESD., Results: A total of 424 blood culture sets were collected from 101 patients. Six patients had positive blood cultures immediately after ESD (4 %, 7/202 sets). Another patient had a positive blood culture the next morning (0.5 %, 1/202 sets). Ten patients (10 %) developed a post-ESD fever ≥38 °C, and blood cultures from these patients were all negative (0/20 sets). The seven patients with positive blood cultures had no post-ESD fever or infectious symptoms. Growth of Bacteroides thetaiotaomicron was only observed in one patient (1 %) with positive blood cultures immediately after ESD, and this patient was diagnosed with transient bacteremia. The other six patients were considered to have contaminants in their blood cultures. Thus, the incidence of bacteremia after esophageal ESD was 1 % [95 % confidence interval (CI) 0-5 %]. No patient had infectious symptoms, and none required antibiotics after ESD., Conclusions: The incidence of bacteremia after esophageal ESD was low and post-ESD fever was not associated with bacteremia. We conclude that use of routine prophylactic antibiotics to patients undergoing esophageal ESD is unnecessary., Clinical Trial Registry Number: UMIN000012908.

Background: Endoscopic resection has been used to treat small rectal neuroendocrine tumors (NETs). However, the indication for additional surgery after endoscopic resection is unclear. The aim of this study was to identify risk factors for rectal NET metastasis and to determine the indication for additional surgery., Methods: Fifty-five patients with a total of 57 rectal NETs, treated between October 2003 and January 2013, were retrospectively divided into metastatic (11 lesions) and non-metastatic (46 lesions) groups. Tumor size, central depression, invasion depth, lymphatic and venous permeation, mitotic activity, nuclear abnormality, Ki-67 labeling index, and World Health Organization grading classification (G1 or G2) were compared between the groups. Patients underwent endoscopic submucosal resection with a ligation device, transanal full-thickness surgical resection, or radical surgery., Results: By univariate analysis, the odds ratios (OR) for a Ki-67 labeling index >3.0 %, positive lymphatic or venous permeation, World Health Organization grading classification G2, tumor size >10 mm, submucosal invasion >4000 μm, and central depression were 120 (P < 0.001), 67.6 (P < 0.001), 58.7 (P < 0.001), 9.8 (P = 0.0037), 6.8 (P = 0.012), and 5.7 (P = 0.018), respectively. Multivariate logistic regression analyses showed that vascular permeation (OR 111; P = 0.006) and a Ki-67 labeling index >3.0 % (OR 88; P = 0.012) were independent risk factors for metastasis., Conclusions: The Ki-67 labeling index and lymphatic/venous permeation were reliable predictors of rectal NET metastases.

Background: Providing appropriate tension to the lesion and securing a stable view of the submucosal layer is important for accomplishing successful endoscopic submucosal dissection (ESD) in gastric cancer. Dental floss clip traction (DFC), a new traction method, is proposed to reduce the difficulty of ESD. The objective of this pilot study was to investigate the efficacy of DFC for gastric ESD., Methods: From August to November 2014, a total of 95 patients with 104 gastric epithelial neoplasms underwent DFC-ESD (DFC group). Historical controls treated by conventional ESD (control group) were individually matched to cases at a 1:1 ratio by lesion location, ulcer findings, resected specimen size, and the proficiency of the operator (trainee/expert). The outcomes of the procedure in the two groups were then compared., Results: The mean ± SD procedure time was 43 ± 24 min in the DFC group and 52 ± 30 min in the control group (P < 0.01). Fewer lesions in the DFC group needed >80 min compared with the control group (3-vs-16 cases, P = 0.01). There were no significant differences in adverse events between the groups. Perforation and delayed bleeding occurred in one and four lesions, respectively, in the DFC group, and three and nine in the control group. En bloc resection was achieved in all cases. No significant differences were found regarding curability of ESD between the groups., Conclusions: DFC effectively reduced ESD procedure time without increasing adverse events. DFC is helpful for rapid, safe ESD.

Background: Gastric stenosis is a major problem after endoscopic submucosal dissection (ESD) for large early gastric cancer, but little is known about the incidence of adverse events associated with endoscopic dilation (ED) for stenosis caused by gastric ESD. The aims of this study were to determine the incidence and risk of bleeding and perforation associated with ED for gastric stenosis after ESD., Methods: This was a single-center, retrospective cohort study conducted at a specialized center for treating cancer. A total of 342 procedures of wire-guided balloon ED were performed for stenosis after gastric ESD in 64 patients. The incidence of adverse events and related clinical characteristics was analyzed., Results: The incidence of bleeding was 3.1% (2/64) per patient and 0.6% (2/342) per procedure. One bleeding case with incomplete cessation of antithrombotics before ED required blood transfusion. The incidence of perforation was 7.8% (5/64) per patient and 1.5% (5/342) per procedure. All perforations occurred in the lower part of the stomach. Two of the five perforation cases were inappropriate for nonoperative therapy, and thus, emergency surgery was performed. Among the other three perforation cases, one case required surgery for refractory stenosis and ED was continued in one case after nonoperative therapy., Conclusions: The incidence of bleeding caused by ED for gastric stenosis after ESD was small. Although not significant, ED in the lower stomach presents a substantial risk of perforation.

We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions., (© The Author(s) 2015.)

Background: Endoscopic dilation (ED) is used for the treatment of benign strictures caused by reflux esophagitis or anastomotic stenosis after esophagectomy. Esophageal stenosis is a major complication after endoscopic submucosal dissection (ESD) of large superficial esophageal cancer, but little is known regarding the incidence of complications of ED for stenosis caused by esophageal ESD., Methods: This was a retrospective study conducted at a single institution. From September 2002 to December 2012, a total of 1,337 ED procedures were performed for stenosis after esophageal ESD in 121 patients. The incidence of complications of ED and related clinical characteristics were analyzed., Results: The incidence of bleeding was 0.8 % (1/121) per patient and 0.07 % (1/1,337) per procedure. The incidence of perforation was 4.1 % (5/121) per patient and 0.37 % (5/1,337) per procedure. Perforation occurred at a median of third time of ED procedures (range 2-9 procedures) and at a median of 18 days (range 8-29 days) after ESD. There were no significant characteristics correlated to perforation, such as location, circumferential extent, or diameter of mucosal defect after ESD. The total number of ED procedures was significantly larger among perforation cases (37, range 6-57) compared with those without perforation (7, range 1-70) (p = 0.01), and the treatment duration tended to be longer (190 vs. 69 days, respectively)., Conclusions: The incidence of bleeding caused by ED for esophageal stenosis after ESD was very low. Relevant risk of perforation should be considered for patients requiring multiple ED procedures.

Background: In cases of synchronous gastric cancers (SGC) that include one for surgical indication and another for endoscopic resection (ER) in two different regions of the stomach, patients can avoid total gastrectomy and undergo subtotal gastrectomy following successful pre-emptive ER. The aim of this study was to evaluate the feasibility and efficacy of pre-emptive endoscopic resection and surgery (PRES) with curative intent for such SGCs., Methods: Between September 2002 and December 2012, 34 patients with SGCs (72 lesions) underwent PRES. Our institutional principals of PRES ensure the following: (1) treatment with curative intent, (2) multiple lesions indicated for ER and surgery, (3) evasion of TG following successful pre-emptive ER, (4) exclusion of type 4 and large type 3 (>80 mm) tumors, and (5) nonemergent cases such as hemorrhage, perforation, and obstruction. Clinicopathological characteristics and technical data were evaluated for all patients, and long-term outcomes were analyzed in patients who obtained curative ER and underwent subtotal gastrectomy., Results: Curative ER was obtained in 31 patients (91.1 %), and subtotal gastrectomy was performed a median of 44 days after ER. Final stages were as follows: stage I, 25 patients (80.6 %); stage II, four patients (12.9 %); stage III, one patient (3.2 %); and stage IV, one patient (3.2 %). The 5-year overall and cause-specific survival rates were 96.3 % (95 % confidence interval 89.4-100 %) and 100 %, respectively., Conclusions: PRES was feasible and effective as the first treatment of choice for multiple SGCs. PRES enables minimally invasive surgery with promising oncological outcomes.

We report here a case of esophageal perforation made by an endoscope while treating cicatrical stenosis that developed after wide circumferential dissection of superficial esophageal carcinoma. Perforation closure with a conventional endoclip was difficult as the perforation was large and the surrounding tissue was fragile as a result of steroids administration for stenosis prevention. To avoid surgical intervention, we employed the over-the-scope-clip system and successfully closed the perforation. The favorable outcome suggests the utility of the over-the-scope-clip system for closing perforations when conventional methods are ineffective.

Background: Currently, granular-type laterally spreading tumors (LST-G) have been classified into uniform [LST-G (UNI)] and nodular mixed [LST-G (MIX)] subtypes. However, the progression pattern of each subtype has not been evaluated in detail. The present study was designed to assign adequate treatment strategies to each LST-G subtype, based on the progression pattern., Methods: This retrospective study included 457 consecutive patients with 482 LST-Gs that had been removed endoscopically or surgically in a tertiary cancer center between September 2002 and December 2011. We classified the tumors as LST-G (UNI) or LST-G (MIX) subtypes. We analyzed clinicopathological characteristics and submucosal invasion rates for both subtypes, and we determined the incidence of submucosal invasions associated with the largest nodules for each subtype., Results: We evaluated the histopathological data from 136 LST-G (UNI) and 316 LST-G (MIX) lesions with diameters of 10-19 mm (14%), 20-29 mm (26%), 30-39 mm (25%), or >40 mm (35%). Submucosal invasions were observed in 3 (1.8%) LST-G (UNI) and 49 (15.5%) LST-G (MIX) lesions. In LST-G (MIX) lesions, the submucosal invasion incidences (within a tumor-size category) were as follows: 5.8% (10-19 mm), 11.1% (20-29 mm), 14.7% (30-39 mm), and 19.1% (>40 mm), respectively. In LST-G (MIX) lesions that showed submucosal invasions, the invasive cancers were located under the largest nodule (69%; 34/49), outside the largest nodule (25%; 12/49), or in both sites (6%; 3/49)., Conclusions: Our results indicated that, for LST-G (UNI) lesions, piecemeal resections would be acceptable due to the low risk of submucosal invasion. For LST-G (MIX) lesions, particularly those with diameters ≥20 mm, en bloc removal in an endoscopic resection is preferable for sufficient histological evaluation.

A 75-year-old hemodialysis patient with right critical limb ischemia received endovascular therapy for a chronic total occlusion (CTO) in a diffusely calcified superficial femoral artery (SFA). During a retrograde approach, a Brockenbrough needle (BN) was able to penetrate the calcified hard plaque formed in the middle segment of the CTO. Moreover, bougie dilatation with the BN allowed balloon crossing and stent deployment, even after failure to pass a 2.0-mm monorail balloon across the plaque. These results suggest that the BN offers a new therapeutic option in the penetration and modification of severely calcified CTO in SFA.

Background: We developed a technique, submucosal endoscopy with mucosal resection (SEMR) intended to make endoscopic submucosal dissection easier and safer. With this technique, the submucosal layer is balloon dissected in lieu of electrosurgical knife dissection. The aim of this study was to further evaluate SEMR in the porcine rectum and colon., Methods: Targeted sites in the rectum and the distal colon were marked by spot coagulation. Submucosal fluid cushions (SFC) were created followed by a circumferential mucosal incision. After isolation of the targeted mucosa, balloon dissection was initiated. The balloon catheter was inserted deep into SFC and the inflated balloon repeatedly pulled back toward the endoscope tip to disrupt the submucosa. Residual strands of submucosa were cut. Dissection difficulty scores (DDS) were used using a visual analogue scale ranging from 0 to 5 (failed). The entire study period was divided into three periods (first period, pigs 1-10; second period, pigs 11-20; third period, pigs 21-30)., Results: Sixty lesions in 30 pigs were resected using SEMR. The en block resection rate was 95%. There were three incomplete resections, two as a result of an errant site location and one as a result of a floppy prototype balloon catheter tip. The median resected size, procedure time, and DDS were 6.0 cm, 25 min, and 1. All three failed cases occurred in first period. The procedure time in third period was significantly shorter than the second period (P = 0.0017). The DDS in first period was significantly higher than the second (P = 0.0024) and third (P = 0.0155) periods. Two perforations, one muscularis propria catheter perforation, and one mucosal perforation were observed (3.3%)., Conclusions: Large mucosal target sites in the rectum and distal colon could be safely removed en bloc by means of a hybrid technique, SEMR, with blunt submucosal balloon dissection.

Background: A few studies have shown promising results with endoscopic submucosal dissection (ESD) for adenocarcinoma at the esophagogastric junction (EGJAC). However, curative criteria on the histology of EGJAC have not been developed, and long-term clinical results are lacking. The purpose of this study was to validate the application of the Japanese curative criteria to EGJAC after ESD., Methods: Between September 2002 and March 2009, 1,350 superficial gastric neoplasms in 1,181 patients were treated by ESD at a single tertiary cancer center. For this retrospective cohort study, 49 patients with 50 superficial EGJACs were extracted from our database. Complications, en bloc resection rate, curative resection rate, overall survival, and cause-specific survival were evaluated in all patients. For assessment of curability, curative criteria proposed by the Japanese Gastric Cancer Association for early gastric carcinoma after endoscopic resection were used., Results: Delayed bleeding and postoperative stenosis each occurred in three (6 %) patients but were managed endoscopically. No other major complications were observed related to ESD. The en bloc resection rate was 98 % (49/50), and the curative resection rate was 72 % (36/50). With a median follow-up period of 47 (range 22-97) months, the overall survival rates and cause-specific survival rates at 5 years were 86.2 % [95 % confidence interval (CI) 76-97] and 100 % (95 % CI 91-100), respectively., Conclusions: Endoscopic submucosal dissection with application of the Japanese curative criteria may be a feasible and effective treatment for curative intent in patients with superficial EGJAC.

A 77-year-old woman underwent percutaneous closure of post-infarction ventricular septal defect. The defect was successfully closed with a 20-mm Amplatzer septal occluder with a small residual shunt and Qp/Qs improved from 3.38 to 1.48. She was discharged 30 days after procedure. To our knowledge, this is the first case reported in Japan.

Purpose: The aim of this study was to evaluate the efficacy and safety of redistributed subclavian arterial infusion chemotherapy (RESAIC). We have focused on the local response, quality of life (QOL), and complications. We have also investigated factors that influence the local response of RESAIC., Materials and Methods: The subjects were patients with locally advanced breast cancer whose tumors were resistant to standard systemic chemotherapy (at least more than two regimens), those who were physically unable to tolerate systemic chemotherapy, and patients with locally recurrent breast cancer. The registration period was between April 2006 and May 2009., Results: A total of 24 cases in 22 patients (mean age 59.5 years, range 36-82 years) were entered in the study. The local response rate of RESAIC was 77.3% (17/22). The QOL score showed improvement on average. There were no serious complications during catheter port implantation, and there was hematological toxicity over grade 3 in 27.3% (6/22) of patients. A significant difference between responders and nonresponders was seen in patients with a replaced type tumor (on imaging, diffuse contrast enhancement was seen in whole quadrants) (P = 0.043), and the patients underwent radiotherapy (P = 0.043)., Conclusion: RESAIC is an effective, safe treatment for locally advanced breast cancer. Because it was reviewed in only a few cases, however, large-scale studies are warranted.

The ASTM Method D4994-89 has been used in the United States for almost two decades to assess the virological quality of biosolids. However, the efficiency of this method for recovery of different enteric viruses has never been determined. The method was found to recover several different enteroviruses and adenovirus 2 with an efficiency ranging from 18.1 ± 5.5 to 24.6 ± 7.8%., (© 2011. Springer Science + Business Media, LLC.)

Chlamydomonas raudensis Ettl UWO241, a natural variant of C. raudensis, is deficient in state transitions. Its habitat, the deepest layer of Lake Bonney in Antarctica, features low irradiance, low temperature, and high salinity. Although psychrophily and low-light acclimation of this green alga has been described, very little information is available on the effect of salinity. Here, we demonstrate that this psychrophile is halotolerant, not halophilic, and it shows energy redistribution between photosystem I and II based on energy spillover under low-salt conditions. Furthermore, we revealed that C. raudensis exhibits higher non-photochemical quenching in comparison with the mesophile Chlamydomonas reinhardtii, when grown with low-salt, which is due to the lower proton conductivity across the thylakoid membrane. Significance of the C. raudensis UWO241 traits found in the low salinity culture are implicated with their natural habitats, including the high salinity and extremely stable light environments.

In a screen searching for new bioactive agents, a new indoloditerpene, penijanthine A (1), was isolated from Penicillium janthinellum IFM 55557. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison with the spectroscopic and physico-chemical data of paxilline (2), which was isolated along with 1.

Background: D2-40 monoclonal antibody immunoreactivity is specific for lymphatic endothelium and therefore provides a marker of lymphatic invasion. We hypothesized that intrahepatic lymphatic invasion reflects the nodal status of colorectal carcinoma liver metastases and may function as an adverse prognostic factor., Methods: A retrospective analysis of 105 consecutive patients who underwent resection for colorectal carcinoma liver metastases was conducted. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity for D2-40 monoclonal antibody. The median follow-up time was 124 months., Results: Of 105 patients, 13 were classified as having intrahepatic lymphatic invasion. All tumor foci of intrahepatic lymphatic invasion were detected within the portal tracts. Intrahepatic lymphatic invasion was significantly associated with hepatic lymph node involvement (P = 0.039). Survival after resection was significantly worse in patients with intrahepatic lymphatic invasion (median survival time of 13 months; cumulative five-year survival rate of 0%) than in patients without (median survival time of 40 months; cumulative five-year survival rate of 41%; P < 0.0001). Patients with intrahepatic lymphatic invasion also showed decreased disease-free survival rates (P < 0.0001). Intrahepatic lymphatic invasion thus independently affected both survival (relative risk, 7.666; 95% confidence interval, 3.732-15.748; P < 0.001) and disease-free survival (relative risk, 4.112; 95% confidence interval, 2.185-7.738; P < 0.001)., Conclusions: Intrahepatic lymphatic invasion is associated with hepatic lymph node involvement and is an adverse prognostic factor in patients with colorectal carcinoma liver metastases.

We describe a giant aneurysm of the anterior communicating artery (ACoA) which was treated with a STA-RA graft-A3 bonnet bypass and A3-A3 side-to-side anastomosis. A giant and partially thrombosed ACoA aneurysm was partially coated 3 years before his current presentation, its gradual increase producing visual field disturbances. An A3-A3 side-to-side anastomosis and STA-RA graft-A3 bonnet bypass were performed. The aneurysm was dissected, and the thrombus removed under transient parent-artery occlusion. The aneurysmal neck was successfully clipped without encountering ischemic changes. This strategy may be useful for treating giant or thrombosed aneurysms in the region of the ACoA.