Feasibility of esophageal endoscopic submucosal dissection after radiofrequency ablation treatment in patients with Barrett's esophagus.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is a well-established treatment for Barrett's esophagus (BE) in the United States. Similarly, endoscopic submucosal dissection (ESD) has been widely performed for early esophageal carcinoma. However, conducting ESD after RFA can be technically challenging. The aim of this study was to assess the feasibility and safety of ESD in patients with prior RFA. METHODS: This study was a single-center retrospective analysis of patients who underwent esophageal ESD after undergoing prior RFA treatment for BE. RESULTS: Of 44 esophageal ESD cases, 7 underwent prior RFA. In those 7 cases, the en bloc resection rate was 100%, and the R0 resection rate was 86%. No acute or delayed adverse events or rehospitalizations occurred in any patient. CONCLUSIONS: ESD may be a feasible and safe option for patients with a history of RFA. It could be considered for esophageal neoplasms in patients previously treated with RFA for BE.

A multicenter, retrospective study of a through-the-needle injection-capable electrosurgical knife for endoscopic submucosal dissection.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a technically challenging resection technique for en-bloc removal of dysplastic and early cancerous gastrointestinal (GI) lesions. We conducted a single-arm retrospective study evaluating the safety and efficacy of a new through-the-needle injection-capable electrosurgical knife used in upper and lower ESD procedures performed at 6 US academic centers. METHODS: Data were retrospectively collected on consecutive cases in which the new ESD knife was used. The primary efficacy endpoint was successful ESD (en bloc resection with negative margins). Secondary efficacy endpoints included en-bloc resection rate, curative resection rate, median ESD time, and median dissection speed. The safety endpoint was device- or procedure-related serious adverse events (SAEs). RESULTS: ESD of 581 lesions in 579 patients were reviewed, including 187 (32.2%) upper GI and 394 (67.8%) lower GI lesions. Prior treatment was reported in 283 (48.9%) patients. Successful ESD was achieved in 477 (82.1% of 581) lesions ‒ lower for patients with versus without submucosal fibrosis (73.6% versus 87.0%, respectively, P < 0.001), but similar for those with versus without previous treatment (81.7% versus 82.3%, respectively, P = 0.848). Four hundred and forty-three (76.2% of 581) lesions met criteria for curative resection. Median ESD time was 1.0 (range 0.1-4.5) hour. Median dissection speed was 17.1 (IQR 5.3-29.8) cm2/hour. Related SAEs were reported in 15 (2.6%) patients, including delayed hemorrhage (1.9%), perforation (0.5%), or postpolypectomy syndrome (0.2%). CONCLUSION: A newly developed through-the-needle injection-capable ESD knife showed a good success rate and excellent safety at US centers. (ClinicalTrials.gov number, NCT04580940).

Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

OBJECTIVE: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. SUMMARY BACKGROUND DATA: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. METHODS: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. RESULTS: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. CONCLUSIONS: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Technical feasibility of salvage endoscopic submucosal dissection after chemoradiation for locally advanced rectal adenocarcinoma.

BACKGROUND AND AIMS: The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients. We aimed to evaluate the feasibility and safety of salvage ESD. METHODS: A retrospective chart review of cases of salvage ESD for locally advanced rectal cancer and standard ESD for rectal tumors without prior CRT from July 2018 to August 2020 at our institution was performed. Clinical factors and imaging, procedural, and pathology results were collected and compared. RESULTS: Twelve salvage ESD cases were compared with 27 standard ESD cases. Before CRT, 83.3% of lesions in the salvage ESD group were initially clinically staged as T3. The en-bloc resection rates were 92.7% and 91.7% (P = 1.00) and R0 resection rates 66.7% and 75.0% (P = .55) for the standard and salvage groups, respectively. In the salvage ESD group, no adverse events were observed, and 75.0% of the adenocarcinomas in the salvage ESD group had morphologically changed to hyperplasia or adenoma after CRT, with no identifiable lesions greater than T1 tumor depth. CONCLUSIONS: Salvage ESD for locally advanced rectal cancer is technically feasible with low adverse event rates. There may be a diagnostic role in salvage ESD in assessing pathologic response to CRT and a possible therapeutic role in resection of residual lesions with the potential to avoid surgery.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Longitudinal Analysis of Quality-of-Life Recovery After Gastrectomy for Cancer.

OBJECTIVE: The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy. METHODS: Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0-1.5 months (early), > 1.5-6 months (intermediate), and > 6-18 months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection. RESULTS: Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (- 15.1 pts, p < 0.001) and intermediate (- 3.6 pts, p = 0.02) time points, but recovered by the late time point (+ 1.2 pts, p = 0.411). Relative to distal/subtotal gastrectomy, proximal/total gastrectomy was associated with worse recovery in both the early and late time points. Surgical complications were associated with worse early recovery. Patients who presented with locally advanced tumors (T3-T4) had lower preoperative quality-of-life scores, and more readily recovered to baseline after surgery. A minimally invasive approach was not associated with postoperative recovery. CONCLUSIONS: Most patients recover to baseline within 1 year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.

Comparison of Long- and Short-term Outcomes in 845 Open and Minimally Invasive Gastrectomies for Gastric Cancer in the United States.

BACKGROUND: Few Western studies have evaluated the long-term oncologic outcomes of minimally invasive surgery (MIS) approaches to gastrectomy for gastric cancer. This study aimed to compare the outcomes between minimally invasive and open gastrectomies and between laparoscopic and robotic gastrectomies at a high-volume cancer center in the United States. METHODS: The study analyzed data for all patients undergoing curative gastrectomy for gastric adenocarcinoma from January 2007 to June 2017. Postoperative complications and disease-specific survival (DSS) were compared between surgical approaches. RESULTS: The median follow-up period for the 845 patients in this study was 38.5 months. The stage-stratified 5-year DSS did not differ significantly between open surgery (n = 534) and MIS (n = 311). The MIS approach resulted in significantly fewer complications, as confirmed by adjusted comparison (odds ratio [OR], 0.70; range, 0.49-1.00; p = 0.049). After adjustment, the two groups did not differ in terms of DSS (hazard ratio [HR], 0.83; range, 0.55-1.25; p = 0.362). The robotic operations (n = 190) had fewer conversions to open procedure (p = 0.010), a shorter operative time (212 vs 240 min; p < 0.001), more dissected nodes (27 vs 22; p < 0.001), fewer Clavien-Dindo grade ≥3 complications (5.8% vs 13.2%; p = 0.023), and a shorter postoperative stay (5 vs 6 days; p = 0.045) than the laparoscopic operations (n = 121). The DSS rate did not differ between the laparoscopic and robotic groups. CONCLUSION: The study findings demonstrated the long-term survival and oncologic equivalency of MIS gastrectomy and the open approach in a Western cohort, supporting the use of MIS at centers that have adequate experience with appropriately selected patients.

Pathology definitions and resection strategies for early colorectal neoplasia: Eastern versus Western approaches in the post-Vienna era.

There is a well-known discrepancy between East and West classifications of colorectal neoplasm, especially "intramucosal carcinoma," categorized as subgroup 4.4 in the Vienna classification, usually recognized as high-grade dysplasia in the United States and as carcinoma in situ in Japan. Focusing on management, in the current National Comprehensive Cancer Network algorithm, high-grade dysplasia, carcinoma in situ, and intramucosal carcinoma are managed similarly, whereas submucosal invasion by carcinoma requires en bloc resection. To bridge the differences with regard to these conceptual problems in the definition and management of carcinoma in situ and intramucosal carcinoma, endoscopists and pathologists from Japan and the United States gathered and discussed from their perspectives how to accurately assess specimens of en bloc/piecemeal resection and to effectively predict lymph node metastasis risk.

ESD and Pit Pattern Diagnosis: Lessons from a Japanese Endoscopist Working in the United States.

Endoscopic submucosal dissection (ESD) was developed in 2000s to overcome the limitations of endoscopic mucosal resection (EMR), especially to accomplish en-bloc resection, and it has been accepted worldwide in the past decades. Many ESD devices and diagnosis modalities are currently available, which include pit pattern and narrow band imaging (NBI) diagnoses to evaluate the depth of the tumor preoperatively with sensitivities of 70 to 90%. Depending on the Japanese colorectal guideline, the intramucosal cancer and shallow invasion of the submucosal layer are the main good indications of ESD; however, the ESD practices between Japan and Western countries still vary, including pathologic definition of cancer, tumor/node/metastasis classification, and handling of ESD specimen. In the United States, despite the large demand for treatment of colorectal neoplasm, pit pattern and magnified NBI diagnoses are not widely accepted yet, and piecemeal EMR is still the major method in most of the institutions. Moreover, the specific guideline of ESD is also not available yet. More new technologies are being developed other than conventional ESD methods in Eastern and Western countries, and ESD is now expected to change in the next generation. It is recommended that not only gastroenterologists but also colorectal surgeons have appropriate knowledge of colorectal lesions and their management to ensure current treatments is applied to patients.

Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells.

BACKGROUND: Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples. RESULTS: In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens. CONCLUSIONS: Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.

Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer.

BACKGROUND AND AIMS: Carbohydrate sulfotransferase 15 (CHST15) promotes tumor growth and invasion and is considered to be an emergent therapeutic target for pancreatic cancer. The aim of this study was to evaluate the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, the double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. METHODS: Six patients with unresectable pancreatic cancer, treated at Tokyo Metropolitan Geriatric Hospital, were used in this open-labeled, investigator-initiated trial. A total of 16 mL STNM01 (250 nM) was injected into the tumor through EUS-FNI. The study's primary endpoint was safety, with a secondary endpoint of tumor response 4 weeks after the initial injection. Some patients received a series of infusions as extensions. The local expression of CHST15 and overall survival (OS) were also evaluated. RESULTS: There were no adverse events. The mean tumor diameter changed from 30.7 to 29.3 mm 4 weeks after injection. Four patients exhibited necrosis of tumor in biopsy specimens. CHST15 was highly expressed at baseline, with 2 patients showing large reductions of CHST15 at week 4. The mean OS of these 2 patients was 15 months, whereas it was 5.7 months for the other 4 patients. CONCLUSIONS: EUS-FNI of STNM01 in pancreatic cancer is safe and feasible. The CHST15 reduction could predict tumor progression and OS. Injections of STNM01 during the beginning of treatment may reduce CHST15 and warrants further investigation.

Nonextraction treatment with temporary skeletal anchorage devices to correct a Class II Division 2 malocclusion with excessive gingival display.

The patient was a 22-year-old Japanese woman who complained of a gummy smile. She had several other orthodontic problems, including crowding of the maxillary anterior teeth, retroclination of the maxillary central incisors, excessive maxillary incisor display, a deep overbite, Class II dental relationships, a Class II profile, and a long face. Two options for the correction of these problems were proposed. The first option was to extract the maxillary first premolars to correct the Class II relationship and implant a miniscrew to correct the gingival display; the second option was to place 2 miniplates for distalization of the maxillary molars and a miniscrew to correct the gingival smile without premolar extractions. The patient chose the second option. After placing a preadjusted bracketed system, 2 miniplates were placed in the zygomatic buttresses bilaterally with monocortical screws, and 1 miniscrew was fixed between the root apices of the maxillary central incisors. Distalization and intrusion of the maxillary molars and intrusion of the maxillary incisors were simultaneously started with those temporary skeletal anchorage devices functioning as absolute orthodontic anchors. The total treatment period was approximately 22 months. Her orthodontic problems were corrected. According to the cephalometric evaluation, the entire maxillary dentition was significantly distalized, and her maxillary incisors were successfully intruded, with the mandible showing a slight counterclockwise rotation. Thanks to the temporary anchorage devices combined with miniplates and a miniscrew, we were able to predictably achieve her treatment goals without premolar extractions, orthognathic surgery, and the need for patient compliance.

Treatment of esophageal adenocarcinoma in patients with a history of bariatric surgery.

BACKGROUND: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used. METHODS: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery. RESULTS: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m2). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy). CONCLUSION: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible.

Endoscopic advances in the management of gastric cancer and premalignant gastric conditions.

Gastric cancer is the fifth most common cancer and in 2018, it was the third most common cause of cancer-related deaths worldwide. Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions. In this review, we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs late-stage gastric cancer outcomes. We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions. This includes the implementation of different imaging modalities such as narrow-band imaging, chromoendoscopy, confocal laser endomicroscopy, and other experimental techniques. We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer. We then discuss the endoscopic advances made in the treatment of these conditions, including endoscopic mucosal resection, endoscopic submucosal dissection, and hybrid techniques such as laparoscopic endoscopic cooperative surgery. Finally, we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.

Safety of Duodenal Endoscopic Submucosal Dissection for Superficial Non-Ampullary Duodenal Epithelial Tumor: A Single-Center Study in the United States.

Endoscopic submucosal dissection (ESD) of superficial non-ampullary duodenal epithelial tumors (SNADETs) is associated with a high rate of en bloc resection and low rate of recurrence. However, in the United States, SNADETs are predominantly managed using endoscopic mucosal resection (EMR) or surgery because the feasibility and safety of duodenal ESD have not yet been established. In this study, we analyzed the outcomes of duodenal ESD for SNADETs. This single-center retrospective study reviewed the data of patients who underwent ESD for SNADETs between June 2018 and August 2023. Baseline patient characteristics, histopathology of the resected lesions, adverse events, and recurrence rates were evaluated. The primary outcome measures were en bloc resection, complications, and recurrence rate. Thirty ESD procedures were performed on 24 patients. All 30 lesions were adenomas, with no cancerous lesions. The en bloc resection rate and R0 resection rates were both 53%. There were no cases of procedure-associated perforation. Post-ESD bleeding was observed in six cases. No ESD-related mortality was observed. The recurrence rate was 14% in 1 year follow up, and 28% the during all follow-up period. ESD is a safe option for SNADET in the United States; however further comparative studies are necessary to determine the optimal procedure for North American populations.

Esophageal Endoscopic Submucosal Dissection in Older Patients Is Safe and Feasible: A Retrospective Single-Center Cohort Study in the United States.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-established method for treating early esophageal carcinomas. However, data on the safety and efficacy of esophageal ESD in older patients in the United States are limited. METHODS: This retrospective study investigated the outcomes of esophageal ESD in patients aged ≥80 years and included those who underwent esophageal ESD between June 2018 and April 2023 at a single center in the United States. Patients were divided into two age groups for comparison: ≥80 and <80 years. Treatment outcomes and complications were evaluated and compared between these groups. RESULTS: A total of 53 cases of esophageal ESD for malignant neoplasms were included, with 12 patients in the ≥80 years age group. No significant differences were observed in the patients' background and characteristics, except for a prior history of interventions (p = 0.04). The en bloc resection rate was 100% in both groups. The R0 resection rate was lower in the ≥80 years age group (75% vs. 88%). There were no complications requiring additional intervention in the ≥80 years age group, such as post-ESD bleeding, perforation, mediastinal emphysema, or pneumonia. CONCLUSIONS: Esophageal ESD may be a safe and feasible procedure for treating esophageal carcinomas in older patients.

STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial.

Background: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). Methods: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055). Findings: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events. Interpretation: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment. Funding: The present study was supported by the Japan Agency for Medical Research and Development (AMED).