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.

Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers.

INTRODUCTION: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. METHODS: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 µm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. RESULTS: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. CONCLUSION: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.

Repeated steroid injection and polyglycolic acid shielding for prevention of refractory esophageal stricture.

BACKGROUND: Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. METHODS: This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019. RESULTS: The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029). CONCLUSION: Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

[Collision Tumor Involving Primary Ascending Colon Cancer and Malignant Lymphoma].

A 78-year-old male was diagnosed with a primary gastric B-cell malignant lymphoma and metastatic lung tumor 10 years ago. He underwent chemotherapy at another hospital, achieved complete remission, and was actively undergoing follow- up. He presented to our hospital with a 1-month history of a bulge in his right lower abdomen. CT revealed thickening of the ascending colon and dilatation of the oral intestine. He was diagnosed with ascending colon cancer and underwent right hemicolectomy. The subsequent pathological examination revealed a collision tumor involving diffuse, large B-cell lymphoma and well-differentiated adenocarcinoma. He was discharged from our hospital and received chemotherapy at another institution. Unfortunately, the patient died of interstitial pneumonia 31 months postoperatively. This report describes the resection of a collision tumor involving ascending colon cancer and malignant lymphoma. Surgical treatment combined with postoperative chemotherapy improved this patient's long-term survival.

[Laparoscopic Tumor Resection for Asymptomatic Paraganglioma-A Case Study].

A 55-year-old man was referred for the close examination of an abdominal mass noted on abdominal ultrasonography during a physical examination. A contrast-enhanced computed tomography(CT)scan of his abdomen revealed a 36-mm heterogeneously contrast-enhanced mass on the left side of the aorta. He was referred for laparoscopic tumor resection without preoperative histological examination. The tumor was identified from the dorsal aspect of the mesentery of the transverse colon and was resected only because it was detachable from the duodenum. A temporary abnormal hypertension was observed intraoperatively. However, he exhibited a favorable postoperative course and was discharged on the 8th postoperative day. Grossly, it was a nodular tumor with a diameter of 38 mm. Histopathological examination revealed that the tumor cells having abundant cytoplasm formed large foci and were surrounded by sinusoidal vessels. Immunohistochemistry results were positive for chromogranin A, synaptophysin, and neural cell adhesion molecule; thus, paraganglioma was diagnosed. Herein, we report a case of laparoscopic resection of an asymptomatic paraganglioma.

Risk factors for gastric cancer in Japan in the 2010s: a large, long-term observational study.

BACKGROUND: The numbers of Helicobacter pylori (HP)-infected individuals and deaths due to gastric cancer are decreasing in Japan. We aimed to determine whether the serological test for chronic gastritis (the ABC method) is still useful for gastric cancer risk stratification in the 2010s and to analyze risk factors for developing gastric cancer in Japan. METHODS: In this prospective study, we monitored 20773 individuals for the incidence of gastric cancer from 2010 to 2019. The relationships between blood sampling results, physical examination, and lifestyle in 2010 and the cumulative incidence of gastric cancer were analyzed. RESULTS: A total of 19343 participants who met the study criteria were analyzed. Overall, 0.08% of participants in group A (9/11717), 0.63% in group B (28/4452), 2.05% in group C (43/2098), 1.52% in group D (1/66), and 0.30% in group E (3/1010) developed gastric cancer. Cox hazard analysis showed that age ≥ 50 years; groups B, C, and D according to the ABC method; and current smoking habits were independent risk factors for gastric cancer. The hazard ratios (HRs) of the incidence of gastric cancer were 6.7 in group B and 21.7 in groups C and D, while the HRs of group E was 2.8, which was not significantly different from that of group A. The incidence of gastric cancer was not statistically significantly different between those with and without successful HP eradication in groups B, C, and D during follow-up. CONCLUSIONS: The ABC method was still useful for gastric cancer risk stratification in the 2010s.

The impact of sarcopenia on adverse events associated with gastric endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is one of the main methods of treatments for early gastric cancer. Sarcopenia is a known risk factor for postoperative adverse events; however, the effect of sarcopenia on gastric ESD is unclear. We investigated the impact of sarcopenia on short-term prognosis after gastric ESD. METHODS: This was a retrospective cohort study. We reviewed 832 patients who underwent gastric ESD between January 2015 and December 2019 and classified them into two groups: sarcopenia and non-sarcopenia groups. The curative resection rate, adverse events, and lengths of hospital stay were evaluated. We also evaluated risk factors associated with adverse events. RESULTS: 700 patients were analyzed (239 in the sarcopenia group and 461 in the non-sarcopenia group). The curative resection rates were similar in both groups. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 (17% vs. 10%) were significantly more common, and the length of hospital stay was longer (8 vs. 7 days) in the sarcopenia group. Univariate analysis identified age ≥ 75 years, antithrombotic medication, history of gastric surgery, submucosal (SM) invasion, and sarcopenia as risk factors for CTCAE grade ≥ 2. Multivariate analysis showed that sarcopenia [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-2.89, p = 0.016], history of gastric surgery (OR 9.32, 95% CI 1.97-44.05, p = 0.005), and SM invasion (OR 2.14, 95% CI 1.24-3.70, p = 0.006) were significant independent risk factors. CONCLUSIONS: Sarcopenia significantly affected short-term prognosis and is a novel risk factor for gastric ESD.

Highly accurate artificial intelligence systems to predict the invasion depth of gastric cancer: efficacy of conventional white-light imaging, nonmagnifying narrow-band imaging, and indigo-carmine dye contrast imaging.

BACKGROUND AND AIMS: Diagnosing the invasion depth of gastric cancer (GC) is necessary to determine the optimal method of treatment. Although the efficacy of evaluating macroscopic features and EUS has been reported, there is a need for more accurate and objective methods. The primary aim of this study was to test the efficacy of novel artificial intelligence (AI) systems in predicting the invasion depth of GC. METHODS: A total of 16,557 images from 1084 cases of GC for which endoscopic resection or surgery was performed between January 2013 and June 2019 were extracted. Cases were randomly assigned to training and test datasets at a ratio of 4:1. Through transfer learning leveraging a convolutional neural network architecture, ResNet50, 3 independent AI systems were developed. Each system was trained to predict the invasion depth of GC using conventional white-light imaging (WLI), nonmagnifying narrow-band imaging (NBI), and indigo-carmine dye contrast imaging (Indigo). RESULTS: The area under the curve of the WLI AI system was .9590. The lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the WLI AI system were 84.4%, 99.4%, 94.5%, 98.5%, and 92.9%, respectively. The lesion-based accuracies of the WLI, NBI, and Indigo AI systems were 94.5%, 94.3%, and 95.5%, respectively, with no significant difference. CONCLUSIONS: These new AI systems trained with multiple images from different angles and distances could predict the invasion depth of GC with high accuracy. The lesion-based accuracy of the WLI, NBI, and Indigo AI systems was not significantly different.

[A Case of Advanced Gastric Cancer with Ptosis Caused by Orbital Metastasis].

Orbital metastasis of gastric cancer occurs very rarely.A 76-year-old woman, who consulted another doctor with the chief complaints of palpitation, shortness of breath, and anorexia 1 month previously, was referred to our clinic for workup and treatment.Workup revealed type III advanced gastric cancer at the lesser curvature of the gastric antrum.Biopsy revealed a diagnosis of poorly differentiated adenocarcinoma.As computed tomography suggested periaortic lymph node metastasis, a diagnosis of T4a(SE)N3aM1(LYM), cStage IV was made.Two weeks later, ptosis was observed in the right eye, and positron emission tomography-computed tomography(PET-CT)revealed metastasis to the right superior rectus muscle.No intracranial tumor progression was observed.The Cyberknife system(20 Gy/1 Fr)was used for treating the orbital tumor. Increased LYM was observed even after 2 courses of S-1 plus oxaliplatin(SOX)therapy.Therefore, weekly combination therapy of paclitaxel and ramucirumab(wPTX plus Rmab)was administered as second-line therapy.No new distal metastasis has been detected in the 10 months since the orbital metastasis development, and the patient is still alive.

[Carcinosarcoma of the Esophagus That Presented as Esophageal Stenosis].

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.

Laparoscopic and luminal endoscopic cooperative surgery can be a standard treatment for submucosal tumors of the stomach: a retrospective multicenter study.

Background and study aims We have developed a combined laparoscopic and luminal endoscopic surgery technique for resection of gastric submucosal tumors (SMTs) that can be performed without excessive resection of the stomach. In a multicenter retrospective study we aimed to evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery (LECS) for gastric SMT resection. Patients and methods Between October 2007 and December 2011, 126 patients with gastric SMTs underwent LECS at 8 institutions. Patient demographics, tumor histopathologic characteristics, and operative and follow-up data were reviewed. Results 16 tumors (12.7 %) were located in the upper third of the stomach, 88 (69.8 %) in the middle third, 5 (4.0 %) in the lower third, and 17 (13.5 %) at the esophagogastric junction. The mean (standard deviation [SD]) operation time for LECS was 190.2 (66.8) min, with a mean estimated blood loss of 15.1 (38.6) mL. In 2 cases (1.6 %), the procedure was converted to open surgery because of intra-abdominal adhesions or stenosis. Morbidity was found in 6 cases (4.8 %), including 2 leakage, 2 gastric stasis, 1 fever, and 1 cystitis. Histologically, a gastrointestinal stromal tumor (GIST) was found in 86 (68.3 %) cases. The median follow-up period was 54.7 months; no local or distant tumor recurrence was observed and all patients were alive. Conclusions LECS proved to be a safe and feasible procedure for the resection of gastric SMTs, with a reasonable operation time, low bleeding, and an acceptable complication rate in this multicenter study in Japan.

Premedication with fast-acting oxycodone hydrochloride hydrate effectively reduced oxaliplatin-induced severe vascular pain.

Oxaliplatin is a platinum-based chemotherapeutic agent that holds a prominent position in the treatment of colorectal and gastric cancers. However, severe oxaliplatin-related vascular pain can be problematic for patients. Here we describe seven patients who experienced severe vascular pain caused by oxaliplatin administration. All seven patients were treated with capecitabine and oxaliplatin or capecitabine plus oxaliplatin with bevacizumab as an adjuvant or a treatment for recurrent colorectal cancer, respectively. Patients experienced intolerable vascular pain during oxaliplatin administration, which continued for several days. Moreover, vascular pain also induced insomnia and appetite loss in all patients. We recommended implantation of a central venous (CV) port to the patients; however, all patients declined this treatment. In addition, various known countermeasures were taken, but were ineffective. Therefore, patients were orally administered oxycodone hydrochloride hydrate (Oxinorm®) 45 min prior to oxaliplatin administration. This pretreatment successfully reduced vascular pain and improved subsequent chemotherapy. Oxinorm® is a fast-acting opioid that can be an effective and practical option for severe vascular pain induced by oxaliplatin. The present report is the first description that emphasizes the usefulness of Oxinorm® to overcome the vascular pain induced by administration of oxaliplatin via a peripheral vein.

Open surgery versus laparoscopic surgery after stent insertion for obstructive colorectal cancer.

PURPOSE: To compare the outcomes of laparoscopic surgery vs. open surgery after insertion of a colonic stent for obstructive colorectal cancer. METHODS: Between April 2005 and August 2013, 58 patients underwent surgery after the insertion of a colonic stent for obstructive colorectal cancer. We analyzed the outcomes of the patients who underwent laparoscopic surgery vs. those who underwent open surgery. RESULTS: We compared blood loss, operative time, hospital stay, and complications in 26 patients who underwent laparoscopic surgery and 32 patients who underwent open surgery. Blood loss was significantly less in the laparoscopic surgery group, but operative time was significantly shorter in the open surgery group. The length of hospital stay was shorter in the laparoscopic surgery group than in the open surgery group, but the difference was not significant. There was no significant difference in postoperative surgical complications between the groups. CONCLUSION: The patients who underwent laparoscopic resection had less blood loss, although no significant difference was found in postoperative morbidity or mortality. Thus, laparoscopic resection after stent insertion is a feasible and safe option for patients with obstructive colorectal cancer.

Self-expanding metallic stent for unresectable obstructive colorectal cancer.

Colon stent self-expanding metallic stents(SEMS) are useful for obstructive colorectal cancers (CRC). SEMS placement has indicated in the palliation of malignant colorectal obstruc- tion, and bridge to elective surgery for resectable colorectal cancers. SEMS can reduce the risk of early complications, mortality, stoma creation rate, and shorten hospital stay. Although SEMS placement was associated with a risk of perforation of the colon and late complications, it also contributed significantly to better long-term quality of life. Perforation might occur with mishandling of guide wire during endoscopic procedure. Therefore, it is better to take careful attention and follow the mini-guide line of Japan colonic stent safe procedure research group during the procedure. SEMS could provide feasible outcomes for patients with obstructive unresectable CRC as palliative treatment.

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.