M2-like tumor-associated macrophages promote epithelial-mesenchymal transition through the transforming growth factor ß/Smad/zinc finger e-box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma.

Epithelial-mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor-associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1-like and M2-like TAM distribution and EMT by E-cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC-1) and a human monocyte cell line (THP-1) were used for in vitro experiments. M2-like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E-cadherin-positive and 44 (19.9%) were vimentin-positive. M2-like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF-ß1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF-ß1 secretion from TAMs was confirmed by ELISA. TAM-co-cultured H226 and EBC-1 cells exhibited EMT (decreased E-cadherin, increased vimentin). Regarding EMT-activating transcriptional factors, phosphorylated Smad3 and ZEB-family proteins were higher in TAM-co-cultured LUSC cells than in parental cells. TAM-co-cultured H226 and EBC-1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.

Large Inflammatory Myofibroblastic Tumor of the Esophagus: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of myofibroblasts with inflammatory blood cell infiltration. It commonly occurs in the lungs and rarely in the esophagus. We herein report a valuable case of IMT originating in the esophagus. A 60-year-old Japanese woman with dysphagia had a large subepithelial lesion in the cervical esophagus, which was 15 cm in length. Surgical resection was performed to confirm the pathological diagnosis and improve the symptoms. The postoperative diagnosis was IMT composed of multiple nodules. There was no recurrence or metastasis within one year after surgery.

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease.

BACKGROUND: Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. METHODS: Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. RESULTS: The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. CONCLUSIONS: Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.

Aluminium Gauze Reduces SARS-CoV-2 Viral Load in Non-Woven Masks Worn by Patients with COVID-19.

BACKGROUND: Aluminium reduces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) survival in experimental settings. It is unknown whether adding an aluminium gauze to a mask reduces the SARS-CoV-2 RNA load in the mask and whether SARS-CoV-2 is detectable in the breath that permeates through such a mask in clinical settings. METHODS: Patients admitted to Kishiwada City Hospital, Osaka, Japan, between July 2021 and September 2021 were enrolled in the study. Non-woven masks comprising filters with 99% viral filtration efficacy and aluminium and cotton gauzes attached to plastic collection cases were developed. All participants wore the experimental mask models for three hours. RESULTS: Twenty-nine patients who wore the final model masks were analysed in this study. The Ct values of the nucleocapsid gene and envelope gene of SARS-CoV-2 were significantly higher in the aluminium gauze than in the cotton gauze. SARS-CoV-2 RNA was detected in the masks of 8 out of 12 vaccinated patients (66.7%). Although breath condensates were collected behind both aluminium and cotton gauzes, SARS-CoV-2 RNA was not detected in these condensates. CONCLUSIONS: Our study indicated that non-woven masks with an aluminium gauze may obstruct SARS-CoV-2 transmission in clinical settings better than non-woven masks with cotton gauzes.

Efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic adults with COVID-19: A retrospective study.

BACKGROUND: Remdesivir with dexamethasone and remdesivir with baricitinib are effective in coronavirus disease 2019 (COVID-19) patients. However, there has been few evidence regarding the efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic COVID-19 patients. METHODS: Consecutive patients who required oxygen therapy at the time of admission and received remdesivir and dexamethasone at Kishiwada City Hospital between March 1, 2021 and May 31, 2021 were retrospectively analyzed. RESULTS: A total of 90 patients were investigated, including 30 receiving a combination of remdesivir, dexamethasone, and baricitinib (baricitinib group) and 60 receiving remdesivir and dexamethasone (control group). The use of direct oral anticoagulants, the level of C-reactive protein, and chest X-ray abnormalities were significantly higher in the baricitinib group than in the control group. Patients in the baricitinib group recovered a median of four days faster than those in the control group (median, 7 days vs. 11 days; Gray's test, p < 0.001). The recovery rate was 90.0% in the baricitinib group and 63.3% in the control group (p = 0.011). Fine and Gray regression analysis showed that adjusted rate ratio for recovery with the baricitinib combination therapy was 5.26 (95% confidential interval, 1.99-13.9; p < 0.001). The incidence of new onset of bacterial infection was 6.7% in the baricitinib group and 16.7% in the control group (p = 0.324). CONCLUSIONS: Our study suggests that the combination of baricitinib, dexamethasone, and remdesivir is effective and tolerable in hypoxic patients with COVID-19.

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.

Split-dose low-volume polyethylene glycol is non-inferior but less preferred compared with same-day bowel preparation for afternoon colonoscopy.

Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in western countries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan.This was a single-blinded, non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the same-day regimen or the split regimen using a web-based registry system. The same-day group was instructed to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy, followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the Boston Bowel Preparation Scale.A total of 153 patients were randomized to either the same-day group (n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates of successful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%-97.0%) in the split group, P=0.10). No serious adverse events occurred in the study population. However, more patients in the same-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients preferred the same-day regimen.

Successful treatment with metronidazole and paromomycin for fulminant amoebic colitis during cytotoxic chemotherapy in a patient with small-cell lung cancer.

We report the case of a 64-year-old man with advanced small-cell lung cancer who developed fulminant amoebic colitis during cytotoxic chemotherapy. During the first cycle of carboplatin/etoposide treatment, febrile neutropenia and grade 4 neutropenia developed. Because diarrhea, abdominal pain, and bloody stool were observed, abdominal computed tomography was performed, showing intussusception, and extensive colectomy and colostomy were performed. Histopathology of the colon revealed gastrointestinal necrosis and perforation due to Entamoeba histolytica infection. Amoebiasis improved after treatment with metronidazole and paromomycin. The second cycle of carboplatin/etoposide with dose reduction was completed, resulting in a partial response to small-cell lung cancer. The results of this case suggest that paromomycin is an additional option for amoebiasis during cytotoxic chemotherapy, and persistent diarrhea during cytotoxic chemotherapy should alert clinicians to consider the development of amoebiasis.

Identification of Blood-Based Biomarkers for the Prediction of the Response to Neoadjuvant Chemoradiation in Rectal Cancer.

The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision surgery. However, the response to nCRT varies among patients and only about 20% of LARC patients achieve a pathologic complete response (pCR) at the time of surgery. Therefore, there is an unmet need for biomarkers that could predict the response to nCRT at an early time point, allowing for the selection of LARC patients who would or would not benefit from nCRT. To identify blood-based biomarkers for prediction of nCRT response, we performed in-depth quantitative proteomic analysis of pretreatment plasma from mice bearing rectal tumors treated with concurrent chemoradiation, resulting in the quantification of 567 proteins. Among the plasma proteins that increased in mice with residual rectal tumor after chemoradiation compared to mice that achieved regression, we selected three proteins (Vascular endothelial growth factor receptor 3 [VEGFR3], Insulin like growth factor binding protein 4 [IGFBP4], and Cathepsin B [CTSB]) for validation in human plasma samples. In addition, we explored whether four tissue protein biomarkers previously shown to predict response to nCRT (Epidermal growth factor receptor [EGFR], Ki-67, E-cadherin, and Prostaglandin G/H synthase 2 [COX2]) also act as potential blood biomarkers. Using immunoassays for these seven biomarker candidates as well as Carcinoembryonic antigen [CEA] levels on plasma collected before nCRT from 34 patients with LARC (6 pCR and 28 non-pCR), we observed that levels of VEGFR3 (p = 0.0451, AUC = 0.720), EGFR (p = 0.0128, AUC = 0.679), and COX2 (p = 0.0397, AUC = 0.679) were significantly increased in the plasma of non-pCR LARC patients compared to those of pCR LARC patients. The performance of the logistic regression model combining VEGFR3, EGFR, and COX2 was significantly improved compared with the performance of each biomarker, yielding an AUC of 0.869 (sensitivity 43% at 95% specificity). Levels of VEGFR3 and EGFR were significantly decreased 5 to 7 months after tumor resection in plasma from 18 surgically resected rectal cancer patients, suggesting that VEGFR3 and EGFR may emanate from tumors. These findings suggest that circulating VEGFR3 can contribute to the prediction of the nCRT response in LARC patients together with circulating EGFR and COX2.

A rare case of neonatal colonic obstruction caused by a solitary intestinal tumor.

BACKGROUND: Intestinal obstruction caused by a tumor is very rare in newborns, and the preoperative diagnosis is difficult. We herein report a rare case of neonatal colonic obstruction due to solitary intestinal myofibroma with characteristic findings on gastrografin enema and the surgical strategy. CASE PRESENTATION: A 4-day-old female infant presented to our neonatal intensive-care unit with abdominal distention and bilious vomiting after feeding. A gastrografin enema showed that the transverse colon near the hepatic flexure was not delineated at the oral side. When pressure was applied, a small amount of contrast material moved into the mouth in the form of threads. Microcolon was not observed, and stenosis of the transverse colon was found 9 cm from the Bauhin valve. Partial resection and end-to-end anastomosis were performed. A pathological examination of the resected specimen suggested gastrointestinal stromal tumor (GIST). After obtaining a second opinion, the histology and immunohistological markers were deemed characteristic of infantile myofibroma. CONCLUSION: If string sign and a napkin ring appearance are found in a case of neonatal intestinal obstruction, surgery should be performed with a tumor in mind. In cases of neonatal intestinal obstruction caused by a tumor, the lesion should be resected with a sufficient surgical margin before the pathological examination.

Across-Site Differences in the Mechanism of Alcohol-Induced Digestive Tract Carcinogenesis: An Evaluation by Mediation Analysis.

A genetic variant on aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the ALDH2 Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior). Alcohol was associated with an increased risk of most digestive tract cancers, but significant direct effects were observed only for upper gastrointestinal tract cancer risk, and varied substantially by site, with ORs (95% confidence interval) of 1.83 (1.43-2.36) for head and neck cancer, 21.15 (9.11-49.12) for esophageal cancer, and 1.65 (1.38-1.96) for stomach cancer. In contrast, a significant protective indirect effect was observed on risk for all cancers, except small intestine cancer. These findings suggest that alcohol is a major risk factor for digestive tract cancers, but its impact as a surrogate for acetaldehyde exposure appears heterogeneous by site. Meanwhile, the behavior-related effect of the ALDH2 Lys allele results in a decreased risk of most digestive tract cancers. SIGNIFICANCE: These findings support that genetic alcohol avoidance is a factor against alcohol-induced cancers.

A Case of a Two-Month-Old Boy Diagnosed with Infantile Crohn's Disease Based on an Atypical Perianal Lesion.

Inflammatory bowel disease is rare in infants, and the early diagnosis is very important. We herein report an infant who received an early diagnosis of infantile Crohn's disease (CD). A two-month-old boy presented with bloody stool. He developed a poor sucking tendency and a painful perianal lesion at three months of age. He was suspected of having infantile CD because of his atypical perianal lesion. Colonoscopy revealed that his perianal lesion had induced rectal longitudinal ulcers. Histology showed no granulomas but patchy inflammation reaching the submucosal layer. He was diagnosed with infantile CD based on the Japanese criteria. CD should be suspected in infants with atypical perianal lesions, irrespective of their age. Early colonoscopy with histology should be considered in these cases in order to prevent adverse outcomes in children.

Bronchoscopic Surgery for a Solitary Tracheal Tumor of Tracheobronchopathia Osteochondroplastica.

Tracheobronchopathia osteochondroplastica is a rare benign condition in which multiple cartilaginous or bony submucosal nodules project into the trachea or bronchi. A 71-year-old man complained of cough for 3 months. Computed tomography scanning revealed a calcified tracheal tumor near the tracheal bifurcation. Pulmonary function testing indicated airflow limitation, and bronchoscopic examination confirmed a solitary rigid tumor. Bronchoscopic resection was performed under general anesthesia, and the tumor was detached by cauterizing its stem with high-frequency coagulation. The tumor was pathologically indicative of tracheobronchopathia osteochondroplastica. After surgery, the clinical signs of cough and dyspnea resolved and pulmonary function normalized.

Risk of second primary malignancies after definitive treatment for esophageal cancer: A competing risk analysis.

BACKGROUND: Esophageal cancer is associated with synchronous or metachronous cancer at other primary sites. However, few studies have evaluated the second malignancies after the treatment of esophageal cancer. The present study aimed to clarify the frequency of and risk factors for the second malignancies after definitive therapy for esophageal cancer. PATIENTS AND METHODS: We included patients with esophageal cancer who received definitive therapy between 2000 and 2010. Exclusion criteria were synchronous cancer or a past history of cancer. Standardized incidence rate (SIR) was calculated using age- and sex-specific incidence rates from the cancer registry data. To conduct risk analyses, we used the competing risk regression model, which defined death and the development of second malignancies as competing risks. RESULTS: A total of 758 patients were included, with 131 second malignancies occurring in 106 patients (14%), over a median follow-up of 3.7 years. Cumulative incidences of second malignancies after 3, 5, and 8 years were 4.0%, 7.6%, and 13.8%, respectively. The risk of second malignancy was significantly elevated [SIR = 1.83, 95% confidence interval (CI): 1.50-2.22]. The most common sites of primary tumor were the head and neck (20%), followed by the lung (17%), stomach (16%), colon and rectum (11%), and urinary tract (9%). Risk analyses revealed that age ≥ 65 years [subdistribution hazard ratio (sHR): 1.51, 95% CI: 1.01-2.24, vs age < 65] and clinical stages 0-I (sHR: 2.48, 95% CI: 1.46-4.22, vs stage III and IV) and II (sHR: 2.10, 95% CI: 1.23-3.58, vs stage III and IV) were significantly associated with second malignancies. CONCLUSIONS: Compared with the general population, an increased incidence of second malignancies was observed in the patients with esophageal cancer in the present study even after definitive treatment. Careful follow-up is required, especially in patients at a higher risk of second malignancies.

Risk factor analysis for adverse events and stent dysfunction of endoscopic ultrasound-guided choledochoduodenostomy.

BACKGROUND AND AIMS: Although the technique of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is becoming standardized, its safety issues have not been sufficiently investigated. Therefore, we aimed to identify factors associated with adverse events and stent patency in EUS-CDS. METHODS: Consecutive patients who underwent EUS-CDS between September 2003 and July 2017 were included. Technical/clinical success, adverse events and stent dysfunctions were analyzed retrospectively. RESULTS: A total of 151 patients underwent EUS-CDS. In nine patients, procedures were discontinued before puncture. Technical and clinical success rates were 96.5% (137/142) and 98.5% (135/137), respectively. The adverse event rate was 20.4% (29/142). As a risk factor for peritonitis, plastic stents (PS) showed a significantly high odds ratio (OR) compared with covered self-expandable metal stents (CSEMS; OR, 4.31; P = 0.030). CSEMS cases showed a significantly longer patency period than PS cases (329 vs 89 days; HR, 0.35; P < 0.001). As a risk factor for early stent dysfunction (within 14 days), stent direction to the oral side showed a significantly high OR (OR, 43.47; P < 0.001). In cases with oblique-viewing EUS, double penetration of the duodenum occurred at significantly higher frequency than in cases with forward-viewing EUS (7.0 vs 0.0%; P = 0.024). CONCLUSIONS: Plastic stents and stent direction to the oral side were risk factors for peritonitis and early stent dysfunction, respectively. Using covered self-expandable metal stents and changing stent direction to the anal side seemed appropriate to prevent peritonitis and early stent dysfunction.

Clinical relevance of fluorodeoxyglucose positron emission tomography/computed tomography and magnifying endoscopy with narrow band imaging in decision-making regarding the treatment strategy for esophageal squamous cell carcinoma.

BACKGROUND: Recent advances in endoscopic technology, especially magnifying endoscopy with narrow band imaging (ME-NBI) enable us to detect superficial esophageal squamous cell carcinoma (ESCC), but determining the appropriate method of resection, endoscopic resection (ER) vs surgical resection, is often challenging. Recently, several studies have reported that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful indicator for decision-making regarding treatment for superficial ESCC. Although, there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC. And, there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC. This study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for ESCC. AIM: To investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC. METHODS: A database of all patients with superficial ESCC who had undergone both ME-NBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed. FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background, or not. The invasion depth of ESCC was classified according to the Japan Esophageal Society. Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC. Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC. RESULTS: A total of 82 lesions in 82 patients were included. FDG-PET showed positive uptake in 29 (35.4%) lesions. Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension (P = 0.014), pathological depth of tumor invasion (P < 0.001), infiltrative growth pattern (P < 0.001), histological grade (P = 0.002), vascular invasion (P = 0.001), and lymphatic invasion (P < 0.001). On multivariate analysis, only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility (P = 0.018). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae and T1b upper submucosal layer were 68.4%/79.4%/50.0%/89.3%/76.8%, respectively, and those of Type B3 for the depth of T1b middle and deeper submucosal layers (SM2 and SM3) were 46.7%/100%/100%/89.3%/90.2%, respectively. On the other hand, those of FDG-PET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%, respectively, whereas, if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy, the sensitivity, specificity, PPV, NPV, and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%, respectively. CONCLUSION: FDG uptake was correlated with the invasion depth of superficial ESCC. Combined use of FDG-PET and ME-NBI, especially with the microvascular findings of Type B2 and B3, is useful to determine whether ER is indicated for the lesion.

Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer.

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04-2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.

Long-term outcomes of metachronous neoplasms in the ileal pouch and rectum after surgical treatment in patients with familial adenomatous polyposis.

Background and study aims Restorative proctocolectomy has become the most common surgical option for patients with familial adenomatous polyposis (FAP). However, adenomas and even carcinomas may develop in the ileal pouch over time. The aim of this study was to evaluate the long-term incidence and nature of ileal pouch or distal ileal adenomas and carcinomas in patients with FAP. Patients and methods This was a retrospective study of 47 FAP patients with Kock's continent ileostomy (Kock) (n = 8), ileorectal anastomosis (IRA) (n = 13), and ileal pouch-anal anastomosis (IPAA) (n = 26). Patients were followed with a standardized protocol including chromoendoscopy and biopsies of visible polyps in the ileal pouch, distal ileum, and rectum every 6 to 12 months. Results Median follow-up was 21.0 years. Overall risk of adenoma development was significantly higher in IRA patients, with incidence rates of 85 % and 100 % at 5 and 10 years' follow-up, respectively, compared to pouch patients (Kock + IPAA) ( P  < 0.001). However, there was also a high frequency of adenomas in the ileal pouch mucosa, with rates of 12 %, 33 %, and 68 %, at 5, 10, and 20 years of follow-up, respectively. Maximum size of ileal pouch adenomas was significantly related to time since surgery ( P  = 0.0214). Six cases of advanced adenomas including two cases of adenocarcinomas developed in the ileal pouch mucosa. Conclusions There is a significant incidence of adenoma(s) in the ileal pouch of FAP patients on long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA patients, but also in pouch patients after proctocolectomy.

Usefulness of septal thickness measurement on endoscopic ultrasound as a predictor of malignancy of branched-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND AND AIM: Septal thickness (ST) can predict a malignant branch-duct (BD) and mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but its cut-off value has not been established. The aim of the present study was to determine the optimal ST cut-off value to predict malignancy using endoscopic ultrasound (EUS). METHODS: We retrospectively identified 200 patients with IPMN, including 132 with BD- and mixed-IPMN, who underwent surgical resection between 1989 and 2017. ST was defined as the septum or lesion wall with the maximum diameter in BD- and mixed-IPMN. The possibility of ST as a malignant predictor was examined, as well as the diagnostic ability of ST combined with mural nodule (MN) height for malignant IPMN. RESULTS: Among the 132 IPMN patients, pathological diagnosis was benign in 81 (61.4%) and malignant in 51 (38.6%). Area under the curve for the diagnosis of malignancy using ST was 0.74 for pathological specimens, 0.70 for EUS and 0.56 for computed tomography. Multivariate analysis showed that the odds ratios for ST ≥2.5 mm and MN height ≥5 mm were 3.51 [95% confidence interval (CI), 1.55-7.97, P = 0.003] and 3.36 (95% CI, 1.52-7.45, P = 0.003), respectively. CONCLUSIONS: Septal thickness was an independent predictive factor similar to MN height for malignant IPMN in a multivariate analysis. The ST on EUS appeared to be the thickness of a fibrotic septum associated with the malignant transformation of IPMN. An ST cut-off value of 2.5 mm might provide an accurate prediction of malignant IPMN.

A thin layer of sucrose octasulfate protects the oesophageal mucosal epithelium in reflux oesophagitis.

Sucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 µm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.