Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Development and validation of a preoperative difficulty scoring system for endoscopic resection of gastric gastrointestinal stromal tumor: a multi-center study.

BACKGROUND: Endoscopic resection (ER) is a promising technique for resecting gastric gastrointestinal stromal tumors (gGISTs); however, ER is technically challenging. This study aimed to develop and validate a difficulty scoring system (DSS) to determine the difficulty for ER of a gGIST. METHODS: This retrospective study enrolled 555 patients with gGISTs in multi-centers from December 2010 to December 2022. Data on patients, lesions, and outcomes of ER were collected and analyzed. A difficult case was defined as an operative time ≥ 90 min, or the occurrence of severe intraoperative bleeding, or conversion to laparoscopic resection. The DSS was developed in the training cohort (TC) and validated in the internal validation cohort (IVC) and external validation cohort (EVC). RESULTS: The difficulty occurred in 97 cases (17.5%). The DSS comprised the following: tumor size ≥ 3.0 cm (3 points) or 2.0-3.0 cm (1 point); location in the upper third of the stomach (2 points); invasion depth beyond the muscularis propria (2 points); lack of experience (1 point). The area under the curve (AUC) of DSS in IVC and EVC was 0.838 and 0.864, respectively, and the negative predictive value (NPV) was 0.923 and 0.972, respectively. The proportions of difficult operation in easy (score 0-3), intermediate (score 4-5), and difficult (score 6-8) categories were 6.5%, 29.4%, and 88.2% in the TC, 7.7%, 45.8%, and 85.7% in the IVC, and 7.0%, 29.4%, and 85.7% in the EVC, respectively. CONCLUSIONS: We developed and validated a preoperative DSS for ER of gGISTs based on tumor size, location, invasion depth, and endoscopists' experience. This DSS can be used to grade the technical difficulty before surgery.

Risk factors for postoperative complications in endoscopic resection of gastric gastrointestinal stromal tumors: a multi-center analysis.

BACKGROUND: Endoscopic resection (ER) is widely used in treating gastric gastrointestinal stromal tumors (gGISTs); however, complications occur frequently after resection. We aimed to determine factors associated with postoperative complications for ER of gGISTs. METHODS: This was a retrospective, multi-center, observational study. Consecutive patients who underwent ER of gGISTs at five institutes from January 2013 to December 2022 were analyzed. The risk factors for delayed bleeding and postoperative infection were assessed. RESULTS: A total of 513 cases were finally analyzed. Of 513 patients, 27 (5.3%) had delayed bleeding and 69 (13.4%) had a postoperative infection. Multivariate analysis indicated that risk factors for delayed bleeding were long operative time (OR = 50.655; 95% CI, 13.777-186.252; P < 0.001) and severe intraoperative bleeding (OR = 4.731, 95% CI, 1.139-19.658; P = 0.032), and risk factors for postoperative infection were long operative time (OR = 13.749, 95% CI, 6.884-27.461; P < 0.001) and perforation (OR = 4.339, 95% CI, 2.178-8.644; P < 0.001). CONCLUSIONS: Our study indicated the risk factors for postoperative complications in ER of gGISTs. Long operation time is a common risk factor for delayed bleeding and postoperative infection. Patients with these risk factors should be given careful observation postoperatively.

Learning curve for endoscopic resection of gastric gastrointestinal stromal tumors: a single-center experience.

BACKGROUND: endoscopic resection (ER) is widely used in the treatment of gastric gastrointestinal stromal tumors (gGISTs). However, no studies have previously described the learning curve (LC) for ER of gGISTs. This study aimed to evaluate the LC based on multifarious operative outcomes. METHODS: one hundred consecutive patients who underwent ER of gGISTs by a single endoscopist from January 2017 to December 2022 were included. Patients were analyzed in groups of ten to minimize demographic differences, and operative time (OT), conversion rate, intraoperative and postoperative complication were assessed to evaluate the LC. Meanwhile, for the OT, the LC was further analyzed using the cumulative sum (CUSUM) method and patients were organized chronologically in three phases. RESULT: there was a statistically significant decrease in OT, conversion to laparoscopic surgery, and postoperative complication after 30 cases (median 80.0 min vs 56.0 min, p < 0.001; 10.0 % vs 0 %, p = 0.025; 33.3 % vs 10.0 %, p = 0.004), rate of intraoperative complications after 20 cases (15.0 % vs 1.3 %, p = 0.025). CUSUM chart demonstrated that OT increased dramatically before around 30 cases (phase 1) and decreased after 60 cases (phase 3), with a plateau phase in the middle 30 cases (phase 2). Among the three phases, the R0 resection and conversion rate were not significantly different. However, OT, intraoperative and postoperative complications were gradually decreased (p < 0.05). CONCLUSIONS: the LC of ER of gGISTs is approximately 60 cases. However, about 30 cases were sufficient to acquire skills to reduce complications and conversion rate during the ER procedure.

An evaluation of the use of double-curved endoscopes for gastric gastrointestinal stromal tumors.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is a standard treatment method for gastric gastrointestinal stromal tumors (gGISTs). Evidence of the safety and efficacy of a double-curved endoscope (DCE) in EFTR of gGISTs is limited. We aimed to compare the operative outcomes of DCE versus single-curved endoscopes (SCE) in EFTR of gGISTs. MATERIAL AND METHODS: This retrospective observational study was conducted at four Chinese tertiary institutes. From January 2019 to November 2021, 104 patients who underwent EFTR by SCE (n = 57) or DCE (n = 47) were enrolled. One-to-one propensity score matching (PSM) was performed between the two groups to compare the demographics and operative outcomes. RESULTS: All gGISTs were resected successfully with no recurrence during follow-up. The median (range) tumor size was 1.2 (0.5, 3.5) cm in DCE and 2.0 (0.6, 4.8) cm in SCE (p < .001), and the procedure time was shorter in the DCE group than in the SCE group (50.0 min vs. 62.0 min, p < .05). After PSM, 41 pairs were selected, and no difference was noted in demographics. The procedure time was also shorter in the DCE group than in the SCE group (50.0 min vs. 55.0 min, p < .05). Subgroup analysis showed that the DCE group had a shorter procedure time in the gastric fundus than the SCE group (47.0 min vs. 55.0 min, p < .05). In multiple linear regression analysis, significant factors related to prolonged procedure time were the type of endoscope of SCE and larger tumor size (p < .05). CONCLUSIONS: EFTR of gGISTs using DCE is safe and effective. Compared with SCE, DCE had an advantage in terms of operative time, especially in the gastric fundus.

Snare-assisted endoscopic resection of gastric subepithelial tumors originating from the muscularis propria layer: a multicenter study.

BACKGROUND AND AIM: Although successful endoscopic resection of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer has been frequently reported, it requires a relatively complicated technique and has a high perforation rate. In this retrospective study, we evaluated the efficacy and safety of the snare-assisted endoscopic resection (SAER) method which is performed using a snare and insulated-tip (IT) knife via a single-channel endoscope to reduce the perforation rate. METHODS: In this study, fifty-six patients with gastric SETs originating from the MP layer treated by the SAER method at three institutions between July 2017 and December 2017 were reviewed. The procedure involved multiple steps as shown in Fig. 2. Data were obtained on demographics, SET features, histopathological diagnoses, procedure time, en bloc resection rate, R0 resection (negative margins) status, and adverse events. RESULTS: Endoscopic resection was successfully performed in all patients. The median overall procedure time was 43.5 min (range 26-106 min). The mean size of resected specimens was 19.73 mm (range 10-33 mm). The overall rate of en bloc resection was 96.4% (54/56). In addition, the perforation rate was 7.1% (4/56), and defects in the stomach wall were very small and easily closed using metallic clips. No postprocedural bleeding occurred in any case. CONCLUSIONS: The SAER method is an effective, safe, less costly technique for the removal of some gastric SETs originating from the MP layer with an appropriate size.

A multicenter retrospective study of endoscopic submucosal tunnel dissection for large lesser gastric curvature superficial neoplasms.

BACKGROUND AND AIM: Endoscopic submucosal tunnel dissection (ESTD) has been used for dissection of esophageal and gastric lesions. However, outcomes of ESTD for large lesions in the lesser gastric curvature had not been acknowledged because previous reports had the limitations of being single-center studies. We aimed to clarify the outcomes of ESTD for large lesser gastric curvature superficial neoplasms and provide our experience to accelerate its application. METHODS: Between July 2014 and July 2016, 87 patients with early cancer in the lesser gastric curvature treated at six Chinese institutions were enrolled. Our primary outcome was dissection speed. Moreover, both efficacy and safety clinical data were collected and analyzed retrospectively. RESULTS: All of the 87 patients were found to successfully undergo ESTD or ESD. Of these, 32 underwent ESTD and 55 underwent endoscopic submucosal dissection (ESD). The ESTD group had a higher dissection speed (18.0 mm2/min vs. 7.8 mm2/min, p < 0.01) and was associated with higher en bloc resection rate (100% vs. 87.3%, p = 0.035) and curative resection rate (100% vs. 85.5%, p = 0.024) compared with the ESD group. No perforation or muscular injury occurred in the ESTD group and its intraprocedural bleeding rate was lower (59.4% vs. 100%, p < 0.01) than that of the ESD group. CONCLUSIONS: In this multicenter retrospective study, outcomes of ESTD were excellent with a higher dissection speed and radical curative rate compared with ESD.

Analysis of Endoscopy Intervention in Postesophagectomy Anastomotic Leak: A Retrospective Study.

BACKGROUND: Anastomotic leak after esophagectomy is one of the most challenging complications resulting in a high morbidity and mortality and prolonged hospitalization. The aim of this retrospective study was to access the impact of endoscopy intervention in anastomotic leak. METHODS: A retrospective review was conducted at our hospital from January 2008 to December 2016. In total, 263 patients who were diagnosed with an anastomotic leak after esophagectomy and underwent endoscopy examination were included in this study. First, all patients were divided into two groups based on a single criteria-whether they received endoscopy intervention or not-and comparisons were conducted between the two groups. Second, we categorized all patients into three groups based on the diameter of the anastomotic leak (group I: <5 mm; group II: 5-15 mm; group III: >15 mm). Detailed analyses were made for each group. Factors we considered included demographic factors, the length of postoperative hospital stay, the amount of medical expenditure, limited days of oral intake, and the incurrence of complications. Data relating to those factors were collected and then analyzed using standard statistic tools. RESULTS: In general, the difference between endoscopy intervention and conservative measure was significant. Moreover, the hospital stay (p < 0.001; p = 0.018), medical expenditure (p < 0.001; p = 0.003), limited days of oral intake (p < 0.001; p = 0.019), and postoperative complications such as hemorrhage (p < 0.001; p = 0.036), tracheoesophageal fistula (p = 0.002; p = 0.017), and anastomosis stricture (p = 0.03; p = 0.026) were significantly lower among patients who received endoscopy intervention in groups II and III. However, no significant difference was identified between endoscopy intervention and conservative measure in group I. CONCLUSIONS: Endoscopy intervention is safe and effective in the diagnosis and treatment of postesophagectomy anastomotic leak. Especially for patients with a diameter of anastomotic leaks greater than 5 mm, the advantages of endoscopy intervention should not be neglected.

Transcriptomes reveal genes involved in covering and sheltering behaviors of the sea urchin Strongylocentrotus intermedius exposed to UV-B radiation.

Although the potential link exists between behavioral responses to UV-B radiation and the maximization of fitness, molecular mechanisms of these UV-B induced behaviors remain poorly understood. For the first time, we investigated the transcriptomes of covered (CB), sheltered (SB) and non-protected (NA) sea urchins Strongylocentrotus intermedius exposed to UV-B radiation. A total of 330 differentially expressed genes were revealed by transcriptome comparisons. By comparing with the group NA, we found 79 up-regulated and 118 down-regulated genes in SB group, as well as 26 up-regulated and 67 down-regulated genes in group CB. There were 34 up-regulated genes and 52 down-regulated genes in group SB, compared with group CB. These differentially expressed genes failed to enrich either Gene Ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG), only except an enrichment in KEGG. We highlighted TRPA1 and Opsin as key neurobiological genes involved in the molecular mechanisms of covering and sheltering behaviors of sea urchins exposed to UV-B radiation. What's more, other identified genes provide valuable resources for future investigations on the molecular basis of covering and sheltering behaviors of sea urchins.

Carryover effects of short-term UV-B radiation on fitness related traits of the sea urchin Strongylocentrotus intermedius.

Carryover effects of UV-B radiation are largely unknown in marine invertebrates, despite the ecological importance. For the first time, we investigated fitness related traits of the sea urchin Strongylocentrotus intermedius 8 weeks after short-term (1 h) UV-B radiations (0, 10 and 20 µW cm-2). Short-term UV-B radiations had significant negative effects on survival, food consumption, test diameter, test height, test height:test diameter, gonad weight and crude protein of gonads of S. intermedius, despite of the absence of UV-B radiation for 8 weeks. Survival, food consumption and crude protein of gonads were significantly lowest in S. intermedius exposed to UV-B radiation at 20 µW cm-2, highlighting that 20 µW cm-2 is a dangerous UV-B radiation intensity for the fitness of sea urchins (at least S. intermedius). Gonads were significantly more sensitive to UV-B radiation than the gut. The present study increases our understanding of carryover effects of UV-B radiations on sea urchins and provides valuable information into marine environmental safety.

Transgenerational effects of ocean warming on the sea urchin Strongylocentrotus intermedius.

Transgenerational effects, which involve both selection and plasticity, are important for the evolutionary adaptation of echinoderms in the changing ocean. Here, we investigated the effects of breeding design and water temperature for offspring on fertilization, hatchability, larval survival, size, abnormality and metamorphosis of the sea urchin Strongylocentrotus intermedius, whose dams and sires were exposed to long-term (~15 months) elevated temperature (~3°C above ambient) or ambient temperature. There was no transgenerational effect on fertilization and metamorphosis of S. intermedius, while negative transgenerational effects were found in hatchability and most traits of larval size. Dam and sire effects were highly trait and developmental stage dependent. Interestingly, we found S. intermedius probably cannot achieve transgenerational acclimation to long-term elevated temperature for survival provided their offspring were exposed to an elevated temperature. The present study enriches our understanding of transgenerational effects of ocean warming on sea urchins.

Application of novel endoloops to close the defects resulted from endoscopic full-thickness resection with single-channel gastroscope: a multicenter study.

BACKGROUND: The key step of the endoscopic full-thickness resection (EFTR) procedure is the successful closure of any gastric wall defect which ultimately avoids surgical intervention. This report presents a new method of closing large gastric defects left after EFTR, using metallic clips and novel endoloops by means of single-channel endoscope. METHODS: We retrospectively analyzed 68 patients who were treated for gastric fundus gastrointestinal stromal tumors originating from the muscularis propria layer at four institutes between April 2014 and February 2015 and consequently underwent EFTR. The large gastric post-EFTR defects were completely closed with metallic clips and novel endoloops using single-channel endoscope, and all the patients were discharged with subsequent endoscopic and clinical follow-up. Patient characteristics, tumor size, en bloc resection rate, closure operation time, and postoperative adverse events were evaluated. RESULTS: EFTR was successfully performed on 68 patients [41 male (60 %), 27 female (40 %); median age 61 years, range 38-73], and the en bloc resection rate was 100 %. Complete closure of all the gastric post-EFTR defects was achieved (success rate 100 %). The mean closure operation time was 13 min (range 9-21 min). The mean maximum size of the lesions was 2.6 cm (range 2.0-3.5 cm). One Mallory-Weiss syndrome and one delayed bleeding were resolved with nonsurgical treatment. The wounds were healed in all cases 1 month after the procedure. CONCLUSIONS: The use of metallic clips and novel endoloops with single-channel endoscope is a relatively safe, easy, and feasible method for repairing large gastric post-EFTR defects.

Association of RASSF1A promoter methylation with gastric cancer risk: a meta-analysis.

Ras-association domain family 1A (RASSF1A), a candidate tumor suppressor gene, is frequently silenced and inactivated by hypermethylation of its promoter region in several human tumors. However, the association between RASSF1A promoter methylation and gastric cancer risk remains conflicting. The aim of this study was to assess the association of RASSF1A promoter methylation with gastric cancer risk by a comprehensive meta-analysis. Relevant studies were identified by searches of PubMed and Web of Science databases with no restrictions. Combined odds ratio (OR) and 95 % confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and gastric cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test the between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant association was observed between RASSF1A promoter methylation and gastric cancer risk (OR, 12.67; 95 % CI, 8.12-19.78; p < 0.001) with no between-study heterogeneity. Subgroup analyses further revealed that gastric cancer risk was increased for individuals carrying the methylated RASSF1A compared with those with unmethylated RASSF1A. In addition, no publication bias was detected in the overall and subgroup analyses. This study identified a strong association between RASSF1A promoter methylation and risk of gastric cancer and highlighted a promising potential for RASSF1A promoter methylation in gastric cancer risk prediction.

Assessment of a Real-world Learning Curve for the Endoscopic Resection of Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Endoscopic resection (ER) is a proven treatment for gastric gastrointestinal stromal tumors (gGISTs). We aimed to assess the learning curve (LC) associated with ER for gGISTs and identify determinants. METHODS: We conducted an analysis of 289 patients who underwent the ER of gGISTs by an experienced endoscopist. To characterize the LC, we employed cumulative sum analysis of the duration of surgery. The participants were divided into an early phase (cases 1-50) and a later phase (case 51-289), which were compared. Furthermore, we identified risk factors for the conversion from endoscopic to laparoscopic resection (LR). RESULTS: The durations of surgery and hospitalization were shorter, and there were fewer complications and fasting days in the later phase. The conversion rates to LR were 6.0% and 2.5% in the early and later phases, respectively. The tumor diameter (≥3.0 cm) and invasion beyond the muscularis propria were significant risk factors for conversion to LR (odds ratio 17.92, 95% confidence interval 2.66-120.87; and 58.03, 6.40-525.84; respectively). CONCLUSIONS: The LC for ER of gGISTs lasts for approximately 50 cases. In addition, tumors ≥3.0 cm in diameter and those that invade beyond the muscularis propria are more likely to require conversion to LR.

Risk factors for conversion from endoscopic resection to laparoscopic resection for gastric gastrointestinal stromal tumors.

OBJECTIVE: Endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) is a commonly used treatment; however, it is associated with a risk of conversion to laparoscopic resection (LR). This study was performed to identify factors influencing conversion from ER to LR and the effects of conversion on outcomes. METHODS: The clinicopathological features of patients treated for gGISTs from March 2010 to May 2021 were retrospectively collected. Endpoints included the determination of risk factors associated with LR conversion, with comparisons of surgical outcomes with and without conversion. Propensity score matching was performed to compare the two groups. RESULTS: In total, 371 gGISTs were analyzed. Sixteen patients required conversion from ER to LR. Propensity score matching demonstrated that invasion depth (muscularis propria with exophytic growth) and gGIST size (≥3 cm) were independent risk factors for conversion to LR. The procedure duration (median, 160.5 vs. 60.0 minutes), postoperative hospitalization duration (median, 8 vs. 6 days), and postoperative fasting duration (median, 5 vs. 3 days) were significantly longer in patients who underwent conversion to LR. CONCLUSIONS: Accurate preoperative measurements of tumor size and invasion depth may help determine more appropriate surgical approaches for patients with gGISTs.

Automated machine learning to predict the difficulty for endoscopic resection of gastric gastrointestinal stromal tumor.

Background: Accurate preoperative assessment of surgical difficulty is crucial to the success of the surgery and patient safety. This study aimed to evaluate the difficulty for endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) using multiple machine learning (ML) algorithms. Methods: From December 2010 to December 2022, 555 patients with gGISTs in multi-centers were retrospectively studied and assigned to a training, validation, and test cohort. A difficult case was defined as meeting one of the following criteria: an operative time ≥ 90 min, severe intraoperative bleeding, or conversion to laparoscopic resection. Five types of algorithms were employed in building models, including traditional logistic regression (LR) and automated machine learning (AutoML) analysis (gradient boost machine (GBM), deep neural net (DL), generalized linear model (GLM), and default random forest (DRF)). We assessed the performance of the models using the areas under the receiver operating characteristic curves (AUC), the calibration curve, and the decision curve analysis (DCA) based on LR, as well as feature importance, SHapley Additive exPlanation (SHAP) Plots and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML. Results: The GBM model outperformed other models with an AUC of 0.894 in the validation and 0.791 in the test cohorts. Furthermore, the GBM model achieved the highest accuracy among these AutoML models, with 0.935 and 0.911 in the validation and test cohorts, respectively. In addition, it was found that tumor size and endoscopists' experience were the most prominent features that significantly impacted the AutoML model's performance in predicting the difficulty for ER of gGISTs. Conclusion: The AutoML model based on the GBM algorithm can accurately predict the difficulty for ER of gGISTs before surgery.

Transcriptomes reveal the involved genes in the sea urchin Mesocentrotus nudus exposed to high flow velocities.

Despite the importance of flow velocity in marine ecosystems, molecular mechanisms of the water flow induced behavioral and growth changes remain largely unknown in sea urchins. The present study compared the gene expressions of the sea urchin Mesocentrotus nudus at high flow velocities (10 cm/s and 20 cm/s) and low flow velocity (2 cm/s) using transcriptomes. A total of 490 and 470 differentially expressed genes (DEGs) were discovered at 10 cm/s and 20 cm/s, respectively. There were 235 up-regulated and 255 down-regulated genes at 10 cm/s, 213 up-regulated and 257 down-regulated genes at 20 cm/s, compared with sea urchins at 2 cm/s. Further, there were 72 overlapped DEGs involved in regulation at both 10 cm/s and 20 cm/s. Gene Ontology (GO) functional annotation showed that DEGs were mainly enriched to cellular process, cell part, binding, and metabolism process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that DEGs were enriched in three pathways related to amino acid metabolism and lipid metabolism. A number of genes related to growth and metabolism of sea urchins were mobilized in high flow velocity environment. We further highlighted a muscle-associated gene ankyrin-1, which is correlated with the movement of tube feet at different flow velocities. The present study provides valuable information on the molecular mechanisms of changed behaviors and growth when sea urchins are exposed to high flow velocity.

Risk Factors and Timing of Additional Surgery after Noncurative ESD for Early Gastric Cancer.

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery. Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days, n = 11), delayed surgery (>30 days, n = 11) after ESD, and upfront surgery (n = 59) were compared. Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups. Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.

Carryover effects of long-term high water temperatures on fitness-related traits of the offspring of the sea urchin Strongylocentrotus intermedius.

It is important to study the fitness of marine invertebrates in exposure to high water temperature. We studied whether the long-term high temperatures work on the fitness-related traits (righting behavior, covering behavior, foraging behavior, Aristotle's lantern reflex, body size) of S. intermedius whose parents (males and females) were exposed to ambient or high temperatures (~3 °C higher than the ambient) for a long period of time. The present study found that test diameter, wet body weight and test weight of offspring were not significantly different between temperature treatments, indicating that the parental sea urchins in exposure to high temperatures develop no carryover effects on the body size of the offspring sea urchins. We found no significant difference in foraging behavior, Aristotle's lantern reflex, lantern length and lantern weight of sea urchins after their parents had experienced long-term high temperatures. In addition, no significant change was found in the righting and covering behaviors of sea urchins whose parents were at long-term high temperatures. These results indicate that no significant lasting effects exhibited in the fitness-related behaviors and tissue size after their parents were exposed to high temperatures for a long time. The crushing force of test and test thickness showed no significant difference in the offspring of S. intermedius, no matter whether their parents were exposed to long-term high temperatures or not. The current results enrich our understanding that the parental sea urchin experiencing long-term high temperatures probably develop no carryover effects on the test of their offspring. We found that sea urchins whose parents were exposed to long-term elevated temperatures showed a significantly higher lantern length/test diameter and a significantly lower test height/test diameter in offspring sea urchins due to the thermal experience of their parents, showing the plasticity of lantern and test of offspring sea urchins in response to the thermal experience of their parents. Together with our previous investigation, the present study indicates that small sea urchins are less susceptible to the carryover effects of high temperatures in comparison with the developmental stages of embryos and larvae.

Transcriptomes shed light on transgenerational and developmental effects of ocean warming on embryos of the sea urchin Strongylocentrotus intermedius.

Ocean warming increasingly endangers the fitness of marine invertebrates. Transgenerational effects (TE) potentially mitigate the impacts of environmental stress on the embryos of marine invertebrates. The molecular mechanisms, however, remain largely unknown. Using high-throughput RNA sequencing technology, we investigated the gene expression patterns of embryos (the gastrula stage) of the sea urchin Strongylocentrotus intermedius at different developmental temperatures, whose parents were exposed to long-term (15 months) elevated temperature (A) or not (B). The temperatures at which adults were held for ~4 weeks prior to the start of the experiment (21 °C for A and 18 °C for B) were also used for the development of offspring (high: 21 °C and ambient (laboratory): 18 °C) resulting in four experimental groups (HA and HB at 21 °C, and LA and LB at 18 °C). The embryos were sampled ~24 h after fertilization. All samples were in the gastrula stage. Twelve mRNA libraries (groups HA, HB, LA, LB, 3 replicates for each group) were established for the following sequencing. Embryos whose parents were exposed to elevated temperatures or not showed 1891 significantly different DEGs (differentially expressed genes) at the ambient developmental temperature (LB vs LA, LB as control) and 2203 significantly different DEGs at the high developmental temperature (HB vs HA, HB as control), respectively. This result indicates complex molecular mechanisms of transgenerational effects of ocean warming, in which a large number of genes are involved. With the TE, we found 904 shared DEGs in both LB vs LA (LB as control) and HB vs HA (HB as control) changed in the same direction of expression (i.e., up- or down-regulated), indicating that parental exposed temperatures affect the expression of these genes in the same manner regardless of the development temperature. With developmental exposure, we found 198 shared DEGs in both HB vs LB (HB as control) and HA vs LA (HA as control) changed in the same direction of expression. Of the 198 DEGs, more genes were up-regulated at high developmental temperature. Interestingly, embryos whose parents were exposed to high temperature showed fewer differently expressed DEGs between high and low developmental temperatures than the individuals whose parents were exposed to ambient temperature. The results indicate that gene expressions are probably depressed by the transgenerational effect of ocean warming. The roles of hsp70 and hnf6 in thermal acclimation are highlighted for future studies. The present study provides new insights into the molecular mechanisms of the transgenerational and developmental effects of ocean warming on the embryos of sea urchins.