Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non-drinker and non-smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. METHODS: The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. RESULTS: Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. CONCLUSION: Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Clinical factors associated with stable treatment of chronic constipation in Japanese patients.

BACKGROUND/AIMS: Chronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients. METHODS: A retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC. RESULTS: A total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12-7.08, p = 0.03). CONCLUSION: Administration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.

Predictive factors for esophageal stenosis in patients receiving prophylactic steroid therapy after endoscopic submucosal dissection for esophageal squamous cell carcinoma.

BACKGROUND: Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC. METHODS: Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. RESULTS: Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. CONCLUSIONS: Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Endoscopic findings suggestive of a high risk of non-radical cure after definitive chemoradiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (DCRT) is a curative treatment option for cT1bN0M0 esophageal squamous cell carcinoma (ESCC); however, local residual disease and recurrence after complete remission may occur. We aimed to identify endoscopic findings associated with the risk of non-radical cure (local remnant or recurrence) after DCRT for cT1bN0M0 ESCC. METHODS: We retrospectively analyzed 40 consecutive patients with cT1bN0M0 ESCC who had undergone DCRT between January 2007 and December 2017. We examined the endoscopic findings in patients with residual or recurrent (RR) disease (RR group) and those without RR disease [non-RR (NRR) group] after DCRT. We also evaluated outcomes after DCRT for each endoscopic finding. RESULTS: There were 10 patients in the RR group and 30 patients in the NRR group. The RR group had a significantly larger tumor size and a higher proportion of lesions with type 0-I. The 5-year relapse-free survival rate was significantly lower in type 0-I and in the presence of B3 vessels. Endoscopic findings in 15 patients with cT1bN0M0 ESCC, type 0-I, who underwent DCRT revealed significantly more reddish lesions in the RR group compared to the NRR group. CONCLUSIONS: cT1bN0M0 ESCC large size, with B3 vessels, and type 0-I has a high risk of non-radical cure after DCRT, especially the reddish type 0-I, which may need to be considered for treatment similar to advanced cancer, including surgery with preoperative DCRT.

Proportion of Neutrophils in White Blood Cells as a Useful Marker for Predicting Bacteremic Acute Cholangitis.

Objective A positive hemoculture in acute cholangitis is serious, but a blood culture result cannot be obtained at the initial diagnosis and so cannot be used for the severity assessment and decision-making concerning urgent/early biliary drainage. Accordingly, a predictor for bacteremia at the initial diagnosis of acute cholangitis would be particularly useful. We investigated the association between neutrophil proportions in white blood cell counts (%Neutro) and bacteremic acute cholangitis. Methods Of 166 patients with acute cholangitis who were diagnosed with the Tokyo Guidelines 2018/2013 from April 2015 to March 2017, a total of 94 underwent blood culture assessments and were divided into those with a positive hemoculture (n=48) and a negative hemoculture (n=46) and then compared. A receiver operating characteristic curve analysis was used to evaluate the predictive ability of %Neutro and other inflammatory markers. Results The %Neutro values were significantly higher in the positive hemoculture group than in the negative hemoculture group (91.7±4.0% vs. 82.5±9.0%, p<0.0001). A cut-off %Neutro value of 89.7% was strongly associated with bacteremia (area under the curve 0.86, sensitivity 77.1%, specificity 80.4%). A %Neutro of ≥89.7% was a predictor of a positive hemoculture in univariate (p<0.0001) and multivariate analyses (p<0.001). Patients with a %Neutro ≥89.7% needed early biliary drainage more frequently than others (30/46, 65.2% vs. 18/48, 37.5%, p=0.0063). Conclusion %Neutro is an independent predictor of bacteremia in patients with acute cholangitis and may contribute to decision-making concerning early biliary drainage.

A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). CASE PRESENTATION: We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. CONCLUSION: ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

Newly developed self-expandable Niti-S MD colonic metal stent for malignant colonic obstruction.

BACKGROUND: Colonic stents are increasingly used to treat acute malignant colonic obstructions. The WallFlex and Niti-S D type stents are the commonly used self-expandable metallic stents available in Japan since 2012. WallFlex stent has a risk of stent-related perforation because of its axial force, while the Niti-S D type stent has a risk of obstructive colitis because of its weaker radial force. Niti-S MD type stents not only overcome these limitations but also permit delivery through highly flexible-tipped smaller-caliber colonoscopes. AIM: To compare the efficacy and safety of the newly developed Niti-S MD type colonic stents. METHODS: This single-center retrospective observational study included 110 patients with endoscopic self-expandable metallic stents placed between November 2011 and December 2018: WallFlex (Group W, n = 37), Niti-S D type (Group N, n = 53), and Niti-S MD type (Group MD, n = 20). The primary outcome was clinical success, defined as a resolution of obstructive colonic symptoms, confirmed by clinical and radiological assessment within 48 h. The secondary outcome was technical success, defined as accurate stent placement with adequate stricture coverage on the first attempt without complications. RESULTS: The technical success rate was 100% in Groups W, N, and MD, and the overall clinical success rate was 89.2% (33/37), 96.2% (51/53), and 100% (20/20) in Groups W, N, and MD, respectively. Early adverse events included pain (3/37, 8.1%), poor expansion (1/37, 2.7%), and fever (1/37, 2.6%) in Group W and perforation due to obstructive colitis (2/53, 3.8%) in Group N (likely due to poor expansion). Late adverse events (after 7 d) included stent-related perforations (4/36, 11.1%) and stent occlusion (1/36, 2.8%) in Group W and stent occlusion (2/51, 3.9%) in Group N. The stent-related perforation rate in Group W was significantly higher than that in Group N (P < 0.05). No adverse event was observed in Group MD. CONCLUSION: In our early and limited experience, the newly developed Niti-S MD type colonic stent was effective and safe for treating acute malignant colonic obstruction.

BDNF as a possible modulator of EEG oscillatory response at the parietal cortex during visuo-tactile integration processes using a rubber hand.

Multisensory integration of visuo-tactile information presented on the body or a dummy body has a strong impact on body image. Previous researches show that alteration of body image induced by visuo-tactile integration is closely related to the activation of the parietal cortex, a sensory association area. The expression of brain-derived neurotrophic factor (BDNF) in the parietal area of macaque monkeys is thought to modulate the activation of the parietal cortex and alter the extension of body image during tool-use learning. However, the relationship between parietal cortex activation related to body image alterations and BDNF levels in humans remains unclear. We investigated the relationship between human serum BDNF levels and electroencephalography responses during a visuo-tactile integration task involving a rubber hand. We found cortical oscillatory components in the high frequency (gamma) band in the left parietal cortex. Moreover, the power values of these oscillations were positively correlated (p<0.05) with serum BDNF levels. Our results suggest that serum BDNF could play a role in modulating the cortical activity in response to visuo-tactile integration processes related to body image alteration in humans.