Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.

BACKGROUND: Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. METHODS: This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. RESULTS: ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%). CONCLUSIONS: ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

Endoscopic resection as an independent predictive factor of local control in patients with T1bN0M0 esophageal squamous cell carcinoma treated with chemoradiotherapy: a retrospective study.

BACKGROUND: Although chemoradiotherapy (CRT) is one of the curative treatments for thoracic esophageal squamous cell carcinoma (ESCC) with submucosal invasion, the risk of local recurrence after CRT remains a clinical problem. This retrospective study aimed to analyze the predictive factors for local recurrence after CRT. METHODS: Ninety-one patients with clinical or pathological (c/p) T1bN0M0 thoracic ESCC who underwent CRT from 2004 to 2017 in our institution were analyzed retrospectively. Sixty-three patients were diagnosed with pathological T1b after undergoing initial endoscopic resection (ER) and treated with additional CRT; meanwhile, 28 patients were clinically diagnosed with T1b and underwent definitive CRT. We investigated the predictors of disease-specific survival (DSS) and local recurrence-free survival (LRFS) by performing univariate and multivariate analyses. RESULTS: The median observation period was 59.8 months. The 5-year DSS and LRFS rates were 84.3% (95% confidence interval [CI]: 76.1-92.5) and 87.1% (95% CI: 79.1-95.1), respectively. The multivariate analysis revealed no significant predictors associated with DSS. On the contrary, ER (hazard ratio [HR]: 0.11, 95% CI: 0.02-0.48, p = 0.003) and tumor length (HR: 6.78, 95% CI: 1.28-36.05, p = 0.025) were recognized as independent predictive factors for LRFS. During follow-up, recurrence was observed in 18 patients (19.8%). With regard to the patterns of relapse, local recurrence was the most common in 11 patients, and salvage ER was performed in 9 of 11 patients. CONCLUSIONS: ER and tumor length were independent predictive factors for LRFS. Our study suggested that performance of ER prior to CRT improved the local control in patients with c/p T1bN0M0 ESCC. In addition, most of the patients who experienced local recurrence were treated with salvage ER, which contributed to preserving the organs.

Occupational Health Physiotherapy (OHP) Practice: A Comparison between Japan and Australia.

OBJECTIVE: This study aimed to adapt a pre-existing cross-country comparison (CCC) model to Occupational Health Physiotherapy (OHP) practice as a basis for locating and examining contextual factors that may influence OHP practice in Japan and Australia. METHOD: A secondary analysis was conducted of existing publicly-available data on OHP and related influential factors, following the five components of the CCC model: work-related legislation; labor market characteristics; culture; physiotherapy practice norms; and organization of OHP practice. RESULTS: Legislation in both countries promotes safe work and rehabilitation of work injured/ill workers. 2019 unemployment was lower in Japan with higher employment protection than Australia. Both countries have an ageing workforce and rising retirement age. Cultural differences relate to higher long-term orientation and uncertainty avoidance in Japan. Australia has higher individualism and physiotherapists are autonomous practitioners with direct access, which differs from Japan. Both countries have a national OHP subgroup, to date only Australia has OHP professional practice standards. DISCUSSION: This study is the first to compare OHP practice in Japan and Australia. Contextual similarities and differences observed may underpin OHP practitioner role and its enhancement in work-related musculoskeletal disorder prevention and management strategies, the return-to-work process, and development of this physiotherapy discipline nationally. CONCLUSION: Adapting the CCC model to OHP practice enabled a structured exploration of resources and data, from which to extract and compare contextual factors that may shape OHP practice in Japan and Australia. This in turn may provide a useful springboard for further discussion about OHP practice internationally.

Evaluation and treatment results of trimodality therapy for advanced esophageal squamous cell carcinoma.

OBJECTIVES: The prognosis for highly advanced esophageal squamous cell carcinoma (ESCC) remains poor, and there is currently no standard treatment. The purpose of this study was to examine the benefits of trimodality therapy [chemoradiation plus surgery, (CRT + S)] by evaluating the surgical outcomes of patients with ESCC in Keiyukai Sapporo Hospital, Japan. We assessed the preoperative and postoperative adverse events, treatment effects of preoperative CRT, metastatic diagnosis of the dissected lymph nodes, and survival. PATIENTS AND METHODS: Between 2012 and 2018, 148 patients with highly advanced ESCC who underwent preoperative CRT + S were analyzed for diagnosis and staging, preoperative complications, clinical and histopathological effects of CRT in the resected specimens, survival rates, and recurrences. RESULTS: The grade 3 and higher complications of preoperative CRT were neutropenia in 3 cases and thrombocytopenia in 1 case. Among the postoperative complications, there were 2 cases (1.4%) of direct surgical death, only tracheobronchial bleeding and liver failure. Using the 11th edition of the classification of esophageal cancer by the Japanese Esophageal Society, 60 patients (40.5%) were classified as grade 3 (negative for cancer cells, pathological complete response). However, 20 of them (33.3%) had metastatic tumor cells in the lymph nodes. The overall 5-year survival rate was 58.5%. Including references to the pathological findings and recurrence patterns, there is no effective diagnostic method for selecting the subsequent approach based on the effectiveness of CRT. CONCLUSION: Planned surgery following CRT was the only solution for achieving better treatment results. CRT + S is a promising treatment with low direct surgical mortality.

A rare case of Helicobacter pylori-uninfected intramucosal poorly differentiated adenocarcinoma that occurred in the gastric fornix.

We report a rare case of undifferentiated-type intramucosal gastric cancer that occurred in the fornix of the stomach without Helicobacter pylori infection, which consisted mainly of poorly differentiated adenocarcinoma. A 49-year-old man visited our hospital for a follow-up endoscopic examination of a small depressed lesion of the gastric fornix detected by surveillance esophagogastroduodenoscopy. On magnifying endoscopy with blue laser imaging, the depressed lesion (approximately 10 mm in diameter) was regarded as undifferentiated-type early gastric cancer that proved to be a poorly differentiated adenocarcinoma by histological examination of biopsied specimens. The cancerous lesion was successfully treated with endoscopic submucosal dissection and microscopically showed an intramucosal cancer that invaded the whole mucosal layer with predominant growth of a poorly differentiated adenocarcinoma component. The patient status was verified as Helicobacter pylori-naïve according to the strict diagnostic criteria, thereby confirming this case as an undifferentiated-type Helicobacter pylori-uninfected gastric cancer. Helicobacter pylori-uninfected intramucosal poorly differentiated adenocarcinoma occurring in the gastric fornix has not been previously reported.

Relationship between the duration and trunk inclination and hip angle during car transfer in individuals with tetraplegia.

[Purpose] The purpose of the present study was to investigate the relationship between the duration of the car transfer (CT) movement and trunk inclination and hip angles during this movement in individuals with tetraplegia. [Subjects and Methods] Eleven adult males with C6 tetraplegia participated in this study. The CT movement was recorded from the passenger side of the car using a digital video camera. From the video, the duration and trunk inclination and hip joint angle were recorded, and correlation coefficients were calculated. [Results] No correlation was found between the trunk inclination angle and the duration of the CT movement. However, a significant correlation was found between the hip angle and the duration of the CT movement: when the duration was short, the hip flexion angle was substantial. [Conclusion] The trunk inclination angle probably showed no effect on the duration of the CT movement because the movement was performed in a limited space and because the trunk muscles of the subjects were paralyzed. In contrast, C6 tetraplegia enabled smooth CT by allowing for control of trunk inclination, such as placing the lower extremities in the car, whereby the pelvis backward tilt angle increased.

Muscle activity and mood state during simulated plant factory work in individuals with cervical spinal cord injury.

[Purpose] The present study investigated the physical and mental effects of plant factory work in individuals with cervical spinal cord injury and the use of a newly developed agricultural working environment. [Subjects] Six males with C5-C8 spinal cord injuries and 10 healthy volunteers participated. [Methods] Plant factory work involved three simulated repetitive tasks: sowing, transplantation, and harvesting. Surface electromyography was performed in the dominant upper arm, upper trapezius, anterior deltoid, and biceps brachii muscles. Subjects' moods were monitored using the Profile of Mood States. [Results] Five males with C6-C8 injuries performed the same tasks as healthy persons; a male with a C5 injury performed fewer repetitions of tasks because it took longer. Regarding muscle activity during transplantation and harvesting, subjects with spinal cord injury had higher values for the upper trapezius and anterior deltoid muscles compared with healthy persons. The Profile of Mood States vigor scores were significantly higher after tasks in subjects with spinal cord injury. [Conclusion] Individuals with cervical spinal cord injury completed the plant factory work, though it required increased time and muscle activity. For individuals with C5-C8 injuries, it is necessary to develop an appropriate environment and assistive devices to facilitate their work.

Malignant Potential of Gastrointestinal Cancers Assessed by Structural Equation Modeling.

BACKGROUND: Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling. MATERIALS AND METHODS: We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis. RESULTS: Because latent variables were disparate except for their number, 'three' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others. CONCLUSION: These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers.

A randomized controlled trial of endoscopic steroid injection for prophylaxis of esophageal stenoses after extensive endoscopic submucosal dissection.

BACKGROUND: Esophageal stenosis following endoscopic submucosal dissection (ESD) is a serious adverse event that makes subsequent management more difficult. METHODS: This parallel, randomized, controlled, open-label study was designed to examine whether local steroid injection is an effective prophylactic treatment for esophageal stenoses following extensive ESD. This single center trial was conducted at the Keiyukai Hospital, a tertiary care center for gastrointestinal disease in Japan [University Hospital Medical Network Clinical Trial Registry (UMIN-CTR) on 15 September 2011 (UMIN000006327)]. Thirty-two patients with mucosal defects involving ≥75% of the esophageal circumference were randomized to receive a single dose of triamcinolone acetonide injections (n = 16) or be treated conventionally (n = 16). The primary outcome was the frequency of stricture requiring endoscopic dilatation; the surrogate primary endpoint was the number of dilatation sessions needed. Secondary outcomes included adverse event rates, the minimum diameter of the stenotic area and the duration of the course of dilatation treatments. RESULTS: The frequency of stricture was not significantly different between the groups because of insufficient statistical power, but the number of dilatation sessions required was significantly less in the steroid group (6.1 sessions [95% confidence interval, CI 2.8-9.4] versus 12.5 [95% CI 7.1-17.9] sessions in the control group; P = 0.04). The perforation rate was similar in both groups. The minimum diameter of stenotic lumens was significantly greater in the treatment group than controls (11.0 mm versus 7.1 mm, respectively; P = 0.01). The perforation rate was not significantly different between the groups (1.0% versus 0.5% in the treatment and control group, respectively). Steroid injection was effective in cases of mucosal defects encompassing the entire esophageal circumference. CONCLUSIONS: Prophylactic endoscopic steroid injection appears to be a safe means of relieving the severity of esophageal stenoses following extensive ESD.

Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors.

Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs.

Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) was originally developed in Japan for en bloc resection of gastric neoplasms. OBJECTIVE: To clarify whether the novel ESD procedure is feasible and gives results that justify the pursuit of integrated minimally invasive procedures aimed at curing early squamous cell carcinoma of the esophagus (SCCE). DESIGN: Retrospective cohort study. SETTING: A single-institution trial by experienced endoscopists. PATIENTS: This study involved 300 consecutively enrolled patients with SCCE (Tumor, Nodes, Metastasis classification T1, N0) who underwent either EMR (n = 184) or ESD (n = 116) from March 1994 to July 2007. INTERVENTION: The patients underwent endoscopic resection and then were followed by periodic endoscopy for 8 to 174 months (mean 65 months). MAIN OUTCOME MEASUREMENTS: Resectability, cure rates, complications, disease-free survival of the two groups, and risk factors for local recurrence were explored. RESULTS: En bloc resection and the local recurrence rate were significantly better in the ESD group (P = .0009 and .065, respectively). The frequency of perforation was not significantly different between the two groups (P = .68). Four independent risk factors for local recurrence were identified by the Cox regression model: EMR, deep cancer invasion, upper esophagus location, and family history of esophageal cancer. Radical cure is mostly obtained by successful endoscopic retreatment of local recurrence after previous endoscopic resection. Disease-free survival was significantly better with ESD. LIMITATIONS: The study's retrospective nature prevents definitive conclusions. CONCLUSIONS: We provide evidence that ESD gives a higher cure rate and is safer than conventional endoscopic resection when applied to early SCCE. ESD warrants prospective comparative studies with conventional endoscopic resection.

Phase I/II study of docetaxel/cisplatin/fluorouracil combination chemotherapy against metastatic esophageal squamous cell carcinoma.

INTRODUCTION: More effective regimens are urgently needed for squamous cell carcinoma of esophagus (SCCE), therefore, we conducted a phase I/II trial of a combination of docetaxel, platinum, and fluorouracil (TPF) for treating metastatic SCCE. METHODS: This phase I/II trial (n = 12/39) was conducted in our institute from April 2005 to June 2008. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method. RESULTS: The recommended dose of docetaxel was determined to be 50 mg/m in phase I. In phase II with a mean follow-up period of 13.3 months, the objective response rate was 66.6%, a median survival period of 13 months and PFS of 7 months was achieved, and the 1-year survival and PFS rates were 52.9% and 19.6%, respectively. Grade 3/4 toxicities of leukopenia, neutropenia, and anorexia were observed in 53.8%, 43.6%, and 25.6%, respectively. CONCLUSIONS: A TPF regimen against metastatic SCCE was well tolerated and achieved a favorable objective response rate and survival benefit compared with other recently reported regimens. Randomized phase III trials of the TPF regimen are warranted and urgently required.