Esophageal Tumors Research Articles

Clinical outcomes of endoscopic resection for the treatment of esophageal gastrointestinal stromal tumors: a ten-year experience from a large tertiary center in China.

Esophageal gastrointestinal stromal tumors (E-GISTs) are extremely rare and surgical resection is the recommended approach. However, surgical resection usually causes severe trauma that may result in significant postoperative morbidity. Endoscopic resection (ER) has developed rapidly in recent years and has been widely used in gastrointestinal lesions. Nevertheless, the feasibility and efficacy of ER in the management of E-GISTs are unknown. Retrospective data were collected from January 2011 to December 2020 in a large tertiary center of China. Twenty-eight patients with E-GISTs treated by ER were included in the study. Of the 28 patients, there were 21 males and 7 females, with a median age of 55years (40-70years). The median tumor size was 15mm (5-80mm). The technical success rate was 100% (28/28), while the en bloc resection rate was 96.4% (27/28). The median operation time was 35min (10-410min). Sixteen (57.2%) tumors were categorized into very low risk group, six (21.4%) into low risk group, and six (21.4%) into high risk group. Pathologists carefully examined margins of each lesion. There were 11 lesions (39.3%) determined as R0 resection and 17 lesions (60.7%) as R1 resection with positive margins. The median hospital stay was 2days (range, 1-8days). One patient suffered from hydrothorax and required drainage, leading to a major adverse event rate of 3.6% (1/28). There was no conversion to surgery, and no death occurred within 30days after the procedure. Imatinib was given to two patients after ER under multidisciplinary team surveillance. During follow-up (median of 54months, 9-122months), no recurrences or metastasis were observed. ER is safe and effective for E-GISTs and might become an optional choice in the future. Multicenter, prospective, large samples with long-term follow-up studies are still needed.

Two traction methods that can facilitate esophageal endoscopic submucosal dissection.

Different traction devices that can provide a visual field and attain appropriate tension at the dissection plane during endoscopic submucosal dissection (ESD) have been developed. Clip-with-line (CWL) is a classic traction device that can offer per-oral traction toward the direction where the line is drawn. A multicenter randomized controlled trial (CONNECT-E trial) comparing the conventional ESD and CWL-assisted ESD (CWL-ESD) for large esophageal tumors was conducted in Japan. This study showed that CWL-ESD was associated with a shorter procedure time (defined as the time from initiating submucosal injection to completing tumor removal) without increasing the risk of adverse events. Multivariate analysis revealed that whole-circumferential lesion and abdominal esophageal lesion were independent risk factors for technical difficulties, which were defined as a procedure time of > 120 min, perforation, piecemeal resection, inadvertent incision (any accidental incision caused by the electrosurgical knife within the marked area), or handover to another operator. Therefore, techniques other than CWL should be considered for these lesions. Several studies have shown the usefulness of endoscopic submucosal tunnel dissection (ESTD) for such lesions. A randomized controlled trial conducted at five Chinese institutions showed that compared with the conventional ESD, ESTD had a significantly reduced median procedure time for lesions covering ≥ 1/2 of the esophageal circumference. In addition, a propensity score matching analysis conducted at a single Chinese institution showed that compared with the conventional ESD, ESTD had a shorter mean resection time for lesions at the esophagogastric junction. With the appropriate use of CWL-ESD and ESTD, esophageal ESD can be performed more efficiently and safely. Moreover, the combination of these two methods may be effective.

Fluorescence-based sentinel lymph node mapping and lymphography evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

The identification of metastatic lymph nodes is one of the most important prognostic factors in gastrointestinal (GI) cancers. Near-infrared fluorescence (NIRF) imaging has been successfully used in GI tumors to detect the lymphatic pathway and the sentinel lymph node (SLN), facilitating fluorescence image-guided surgery (FIGS) with the purpose to achieve a correct nodal staging. The aim of this study was to analyze the current results of NIRF SLN navigation and lymphography through data collected in the EURO-FIGS registry. Prospectively collected data regarding patients and ICG-guided lymphadenectomies were analyzed. Additional analyses were performed to identify predictors of metastatic SLN and determinants of fluorescence positivity and nodal metastases outside the boundaries of standard lymphadenectomies. Overall, 188 patients were included by 18 surgeons from 10 different centers. Colorectal cancer was the most reported pathology (77.7%), followed by gastric (19.1%) and esophageal tumors (3.2%). ICG was injected with higher doses (p < 0.001) via extraparietal side (63.3%), and with higher volumes (p < 0.001) via endoluminal side (36.7%). Overall, NIRF SLN navigation was positive in 75.5% of all cases and 95.5% of positive SLNs were retrieved, with a metastatic rate of 14.7%. NIRF identification of lymph nodes outside standard lymphatic stations occurred in 52.1% of all cases, 43.8% of which were positive for metastatic involvement. Positive NIRF SLN identification was an independent predictor of metastasis outside standard lymphatic stations (OR = 4.392, p = 0.029), while BMI independently predicted metastasis in retrieved SLNs (OR = 1.187, p = 0.013). Lower doses of ICG were protective against NIRF identification outside standard of care lymphadenectomy (OR = 0.596, p = 0.006), while higher volumes of ICG were predictive of metastatic involvement outside standard of care lymphadenectomy (OR = 1.597, p = 0.001). SLN mapping helps identifying potentially metastatic lymph nodes outside the boundaries of standard lymphadenectomies. The EURO-FIGS registry is a valuable tool to share and analyze European surgeons' practices.

Abstract 5910: Prospective platform to define microbiome correlates of metastasis and therapy resistance in early onset and average onset gastrointestinal cancers

Abstract Background: The incidence of early onset (EO) gastrointestinal (GI) cancers prior to age 50 is rising, and the etiology is unknown. The gut microbiome may contribute to GI cancer pathogenesis, though how bacteria drive metastasis and treatment resistance is not known. Purpose: To define the microbiome contribution to EO-GI cancers and metastasis by analyzing longitudinal samples from previously untreated patients with GI cancers. Methods: We designed a prospective biospecimen collection platform. We selected patients with newly diagnosed, previously untreated colorectal cancer (CRC) and esophagogastric cancer (EGC). We collected stool, biopsy or surgical tissue, and peripheral blood mononuclear cells (PBMCs) at baseline prior to treatment and at each restaging scan for patients with metastatic disease. For those with locally advanced disease, we collected samples at baseline and after each treatment phase (surgery, radiation, chemotherapy). Stool samples were analyzed using shotgun sequencing. Tissue samples were banked for further analysis. Clinical data was manually curated. Relative abundances of bacteria at the species level were compared between groups. Alpha diversity was calculated using the inverse Simpson index and compared between groups using the Wilcoxon signed-rank test. Beta diversity was analyzed using the Bray-Curtis dissimilarity matrix and compared using PERMANOVA. Multivariate association between species abundance and clinical covariates was performed using MaAsLin2 R package. Results: We analyzed a total of 150 stool samples from 76 patients (colorectal n=53, esophagogastric n=23), including up to 6 samples from a single patient over time. Mean alpha diversity did not differ significantly by primary site or age at diagnosis in patients with CRC but was higher in stage IV compared with stage I disease (P=0.054). Beta diversity was significantly different between samples from patients with right- compared with left-sided CRC (P=0.005) but did not differ significantly by diagnosis age (&amp;lt;50 vs. &amp;gt; 50). Among those with EGC, mean alpha diversity was not significantly different in samples from patients with esophagus or gastroesophageal junction (proximal) tumors compared with gastric (distal) tumors and did not differ significantly by age group. Beta diversity was significantly different between patients with EGC over 50 compared with those under 50 (P=0.002). When CRC baseline samples were examined, several bacterial species were associated with age &amp;lt;50 at diagnosis, including Streptococcus anginosus group (P=0.001), Solobacterium moorei (P=0.013), and Firmicutes bacterium CAG83 (P=0.016). Conclusions/Future Directions: Microbiome composition may cluster by primary tumor site and age at diagnosis in patients with previously untreated GI cancers. Functional analysis and is ongoing and will be presented. Citation Format: Melissa A. Lumish, Asha R. Saxena, Nicholas Waters, Anqi Dai, Saskia Hartner, Teng Fei, Matthew Drescher, Jonathan Bermeo, Dorina Ismailgeci, Maggie Fox, Yelena Y. Janjigian, Luis A. Diaz, Martin R. Weiser, Jonathan Peled, Marcel van den Brink, Karuna Ganesh. Prospective platform to define microbiome correlates of metastasis and therapy resistance in early onset and average onset gastrointestinal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5910.

Abstract 2636: Amanitin-based ADCs targeting Guanylyl cyclase C (GCC) as novel therapeutic modality for treatment of colorectal cancer

Abstract Background: Amatoxin-based antibody drug conjugates (so called ATAC®s) constitute a new class of antibody-drug conjugates (ADCs) which utilize amanitin as toxic payload. Amanitin binds to the RNA pol II and thereby efficiently inhibits cellular transcription. In the current study, in vitro and in vivo data of an ATAC® targeting GCC (guanylyl cyclase C) are presented. GCC is a cell surface receptor expressed in &amp;gt;95% of colorectal cancer, and in approximately 65% of esophageal, gastric, and pancreatic tumors. In healthy conditions GCC expression is restricted to the gastrointestinal tract, and more specific to the apical brush border of the intestinal epithelium (luminal site). Thus, GCC in healthy tissue is not exposed to the circulation but upon tumor progression in GI malignancies it becomes accessible for i.v. injected targeted therapeutics. This tumor-specific accessibility for drugs in circulation makes GCC a highly attractive target for ATAC®s. Material and Methods: ATAC®s: Cysteine-reactive amanitin-linker constructs were synthesized at Heidelberg Pharma and conjugated site-specifically to engineered cysteine residues of a proprietary anti-GCC antibody yielding ATAC®s with a DAR of 2.0. Animal models: Subcutaneous (s.c.) mouse xenograft models with the GCC overexpressing cell line HEK293-GUCY2C mono2 or colon cancer PDX models (Charles River) were performed in single-dose and multiple-dosing experiments. Tolerability was assessed in NMRI nude mice and non-human primates (NHP). Results: All anti-GCC ATAC®s with amanitin-linker derivatives, optimized for use in solid tumors, showed favorable in vitro cytotoxicity with picomolar activity on GCC+ cell lines and no cytotoxic activity on target-negative cells. In mouse xenograft models, the optimized anti-GCC ATAC®s caused dose-dependent tumor regression in HEK293-GUCY2C mono2 s.c. xenografts. Even in colorectal cancer PDX models, anti- GCC ATAC®s led to a substantial anti-tumor effect. Multiple dosing improved this anti-tumor efficacy even further without negative impact on toxicity. The MTD of the ATAC®s tested in mice differed between 7.5 and 50 mg/kg depending on linker chemistry. Safety profiling in cynomolgus monkeys revealed good tolerability for all selected ATAC®s. Hematology and clinical chemistry parameters were unaffected apart from a moderate and transient increase in liver enzymes. Conclusions: Targeted cytotoxic drug delivery to GCC+ cell lines was achieved by using anti-GCC ATAC®s optimized for the use in solid tumors. The mode of action of the payload amanitin led to a pronounced anti-tumor effect in vitro and in vivo in PDX models with good tolerability in non-human primates. The use of anti-GCC ATAC®s with their novel mode of action in the therapy of GCC positive cancers, such as colorectal cancer represents a promising approach in cancer therapy. Citation Format: Alexandra Braun, Andreas Pelz, Franziska Ebeling, Kristin Decker, Anikó Pálfi, Michael Kulke, Andreas Pahl, Torsten Hechler. Amanitin-based ADCs targeting Guanylyl cyclase C (GCC) as novel therapeutic modality for treatment of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2636.

Abstract 6300: Therapeutic potential of EO-3021/SYSA1801, a Claudin18.2 antibody-drug conjugate, for the treatment of CLDN18.2-expressing cancers

Abstract Background: Claudin18.2 (CLDN18.2), a tight junction protein normally expressed only on gastric mucosa, is overexpressed in gastric, pancreatic, esophageal, ovarian, lung and other solid tumors. Unlike in normal tissue, CLDN18.2 is exposed on epithelial surfaces in malignancy. There are no approved targeted therapies for CLDN18.2-expressing cancers. An antibody-drug conjugate (ADC) composed of a monoclonal antibody (mAb) targeting CLDN18.2 with a monomethyl auristatin E (MMAE) payload site-specifically conjugated via a cleavable linker at a drug-antibody ratio (DAR) of 2, EO-3021/SYSA1801, was developed to target CLDN18.2-expressing cancer cells, minimize toxicities and maximize therapeutic index. Methods: HEK293-CLDN18.2 cells were used to evaluate CLDN18.2-dependent EO-3021 endocytosis, MMAE payload release, inhibition of proliferation and antibody dependent cellular cytotoxicity (ADCC). Cell cycle distribution and caspase-3/7 activity were measured 24 hours after treating BxPC3-CLDN18.2 pancreatic cells with EO-3021 or the unconjugated antibody, EO-3021 mAb. Inhibition of proliferation by EO-3021 was measured on cell lines ectopically expressing medium to high CLDN18.2 and on cell lines with endogenous low to medium CLDN18.2 expression. Xenograft studies evaluating tumor growth inhibition by EO-3021, EO3021 mAb, and cisplatin or gemcitabine were done in gastric (NUGC4; NUGC4-CLDN18.2), pancreatic (Patu8988S; BxPC3-CLDN18.2), and lung (NCI-H460) cancer models. Results: EO-3021 binding to cancer cells, endocytosis, MMAE release, and inhibition of proliferation were dependent on CLDN18.2 expression. EO-3021 (EC50: 172 ng/ml) and EO-3021 mAb (EC50: 130 ng/ml) demonstrated similar levels of ADCC. EO-3021 but not EO-3021 mAb promoted G2/M cell cycle arrest and apoptosis and exhibited potent activity across cell lines with low, medium, and high CLDN18.2 expression (IC50: 7-456 ng/mL). EO-3021 induced tumor regressions with a single dose across low, medium, and high CLDN18.2-expressing in vivo models derived from pancreatic (2-10 mg/kg), gastric (0.5-10 mg/kg), and lung cancers (4 mg/kg), respectively. In contrast, standard of care (SOC) chemotherapies and EO-3021 mAb did not induce tumor regressions across in vivo models. Conclusions: EO-3021 demonstrated profound in vivo antitumor activity and outperformed SOC in gastric, pancreatic, and lung cancer models. Results from in vitro and in vivo studies highlight the promising therapeutic potential of EO-3021/SYSA1801 for patients with CLDN18.2-expressing cancers. A Phase 1 study is ongoing to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of SYSA1801 in patients with CLDN18.2 positive advanced solid tumors (NCT05009966). Citation Format: Mo Dan, Xiwu Hui, Yancui Wang, Can Yuan, Thomas O'Hare, Valerie Malyvanh Jansen, Shawn M. Leland, Yang Zhang, David Dornan, Xiaoyan Wang. Therapeutic potential of EO-3021/SYSA1801, a Claudin18.2 antibody-drug conjugate, for the treatment of CLDN18.2-expressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6300.

Abstract PL03-01: New insights into carcinogenesis from normal esophagus

Abstract All normal tissues studied to date carry somatic mutant clones, the burden of which increases with age. This talk considers how insights into the biology of mutants in normal tissues can inform our understanding of the earliest stages of carcinogenesis. The esophagus becomes a patchwork of mutant clones. As they expand, these clones compete for the limited space available, resulting in selection of the fittest mutant genes. The ability to out compete other mutants in normal tissue does not correlate with carcinogenic potential. For example, NOTCH1 mutant clones colonize most of the esophagus by middle age but NOTCH1 mutations are comparatively rare in squamous cancers. In mouse models Notch pathway mutant clones eliminate microscopic intraepithelial neoplasms and loss of Notch1 markedly slows esophageal tumor growth. In contrast, mutant TP53 is less effective than NOTCH1 at driving clonal expansion but is found in almost all human squamous esophageal cancers and contributes to carcinogenesis in mice. The normal tissue mutational landscape of the esophagus is shaped by environmental factors. For example, body metabolism alters the behavior of mutant PIK3CA which drives clonal expansions in the esophagus of overweight humans and mice. The mutation causes cells to switch their metabolism to aerobic glycolysis, giving the mutants a proliferative advantage. One way to reduce the competitive advantage of mutants is to increase the fitness of the neighboring cells. Treating cells or mice with metformin, a drug used to treat type 2 diabetes, induces aerobic glycolysis throughout the tissue. This eliminates the growth advantage of Pik3ca mutant clones, showing it may be possible to halt the expansion of oncogenic mutant populations. Beyond the esophagus, these findings suggest the need to consider the relative prevalence of mutations in normal tissue and the corresponding cancer(s) before deciding if a mutant gene is a cancer driver or not. Variation in cancer risk between different human populations may depend on the proportion of pro- and anti-oncogenic mutants in normal tissue. Understanding how certain mutations can impede cancer development and how environmental factors alter selection of oncogenic mutants in normal tissue may guide new approaches to cancer prevention. Citation Format: Phil H. Jones. New insights into carcinogenesis from normal esophagus. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-01.

MiR-132-3p promotes heat stimulation-induced esophageal squamous cell carcinoma tumorigenesis by targeting KCNK2.

Epidemiological evidence supports that consumption of high-temperature food and beverages is an important risk factor for esophageal squamous cell carcinoma (ESCC);however, the underlying mechanism still remains unclear. Here, we established a series of animal models and found that drinking 65°C water can promote esophageal tumor progression from preneoplastic lesions to ESCC. RNA sequencing data showed that miR-132-3p was highly expressed in the heat stimulation group compared with controls. Further study verified that miR-132-3p were upregulated in human premalignant lesion tissues of the esophagus, ESCC tissues, and cells. Overexpression of miR-132-3p could promote ESCC cell proliferation and colony formation, whereas knockdown of miR-132-3p could inhibit ESCC progression in vitro and in vivo. Importantly, dual-luciferase reporter assays showed that miR-132-3p could bind with the 3'-untranslated regionof KCNK2 and inhibit KCNK2 gene expression. Knockdown or overexpression of KCNK2 could promote or suppress ESCC progression in vitro. These data suggest that heat stimulation can promote ESCC progression and miR-132-3p mediated this process by directly targeting KCNK2.

Intrafraction motion analysis in online adaptive radiotherapy for esophageal cancer.

Intrafraction motion during magnetic resonance (MR)-guided dose delivery of esophageal cancer tumors was retrospectively analyzed. Deformable image registration of cine-MR series resulted in gross tumor volume motion profiles in all directions, which were subsequently filtered to isolate respiratory and drift motion. A large variability in intrafraction motion patterns was observed between patients. Median 95% peak-to-peak motion was 7.7 (3.7 - 18.3) mm, 2.1 (0.7 - 5.7) mm and 2.4 (0.5 - 5.6) mm in cranio-caudal, left-right and anterior-posterior directions, relatively. Furthermore, intrafraction drift was generally modest (<5mm). A patient specific approach could lead to very small margins (<3mm) for most patients.

Rectal and esophageal gastrointestinal stromal tumors—how to deal with it?—technical approach and role of neoadjuvant treatment

Rectal and esophageal gastrointestinal stromal tumors—how to deal with it?—technical approach and role of neoadjuvant treatment

Abscopal effect of radiation in metastatic esophageal carcinoma: fourth reported case.

Abscopal or bystander effect of radiotherapy is a rare and unpredictable outcome encountered during treatment of metastatic cancer where tumor regression is observed distant from irradiated volume. While it has been more frequently reported with malignancies like melanoma, lymphoma, and renal cell carcinoma, data regarding metastatic esophageal cancers are sparse. We describe a case of abscopal regression of distant mediastinal and upper abdominal lymph nodes in a 65-year-old gentleman whose primary esophageal tumor was irradiated with hypo-fractionated radiotherapy in an attempt to achieve local palliation. Our case study emphasizes the systemic benefit of local radiotherapy and the need for future research to investigate its utility as this clinical event poses widespread response in an otherwise dismal Stage-IV cancer with minimal treatment-related side effects.

Enteral Access: A Review of Technique, Complications, and Management Strategies

AbstractPercutaneous enteral access for nutritional support may be required for a wide host of comorbid conditions, including processes such as obstructive head and neck tumors, esophageal tumors, neurologic/neuromuscular disorders such as amyotrophic lateral sclerosis, multiple sclerosis, or stroke, chronic gastric outlet obstruction, small bowel obstruction, and motility disorders. Given this demand, it is important for providers to be aware of the complications associated with percutaneous radiologic enteral access and how to manage them. We herein provide a brief overview of complications related to enteral access, including anatomic, technical, preventative, and management considerations.

Recent Advances in the Systemic Treatment of Localized Gastroesophageal Cancer.

The overall survival expectancy of localized gastroesophageal cancer patients still remains under 5 years despite advances in neoadjuvant and adjuvant treatment strategies in recent years. For almost a decade, immunotherapy has been successfully implemented as a first-line treatment for various oncological diseases in advanced stages. In the case of advanced gastroesophageal cancer, 2021 witnessed several approvals of immune checkpoint inhibitor therapies by different authorities. Although it is still a debate whether this treatment should be restricted to a certain subgroup of patients based on biomarker selection, immunotherapy agents are making remarkable steps in resectable settings as well. The Checkmate-577 study demonstrated significant benefits of nivolumab as an adjuvant treatment for resectable esophageal and gastroesophageal junction tumors and thereby obtained approvals both from U.S. American and European authorities. First results of further potential practice-changing clinical trials are expected in 2023, which might change the treatment armamentarium for resectable gastroesophageal cancers significantly. This review aims to demonstrate the advances of immunotherapy and targeted therapies in treatment of localized gastric, gastroesophageal junction and esophageal tumors and gives a short summary on promising ongoing clinical trials.

Coronary CT angiography for preoperative evaluation of non-cardiac surgery in patients with thoracic tumors: preliminary exploratory analysis in a retrospective cohort

PurposeNoninvasive coronary CT angiography (CCTA) was used to retrospectively analyze the characteristics of coronary artery disease (CAD) in patients with thoracic tumors and the impact of the results on clinical surgery decision-making, thus increasing the understanding of perioperative cardiac risk evaluation.MethodA total of 779 patients (age 68.6 ± 6.6 years) with thoracic tumor (lung, esophageal, and mediastinal tumor) scheduled for non-cardiac surgery were retrospectively enrolled. Patients were divided into two groups: accepted or canceled surgery. Clinical data and CCTA results were compared between the two groups, and multivariate logistic regression analysis was performed to determine predictors of the events of cancellations of scheduled surgeries.Results634 patients (81.4%) had non-significant CAD and 145 patients (18.6%) had significant CAD. Single‑, 2‑, and 3‑ vessel disease was found in 173 (22.2%), 93 (11.9%) and 50 (6.4%) patients, respectively. 500 (64.2%), 96 (12.3%), 96 (12.3%), 56 (7.2%) and 31 (4.0%) patients were rated as CACS 0, 1–99, 100–399, 400–999 and > 1000, respectively. Cancellations of scheduled procedures continue to increase based on the severity of the stenosis and the number of major coronary artery stenosis. The degree of stenosis and the number of vascular stenosis were independent predictors of cancelling scheduled surgery.ConclusionsFor patients with thoracic tumors scheduled for non-cardiac surgery, the results suggested by CCTA significantly influenced surgery planning and facilitated to reduce perioperative cardiovascular events.

A revamped MIC-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk

BackgroundThe purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery.MethodsThis revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed.ResultsAll patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation.ConclusionsMerit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.

Lymphatic Invasion of Plakoglobin-Dependent Tumor Cell Clusters Drives Formation of Polyclonal Lung Metastases in Colon Cancer

Patients with colon cancer with liver metastases may be cured with surgery, but the presence of additional lung metastases often precludes curative treatment. Little is known about the processes driving lung metastasis. This study aimed to elucidate the mechanisms governing lung vs liver metastasis formation. Patient-derived organoid (PDO) cultures were established from colon tumors with distinct patterns of metastasis. Mouse models recapitulating metastatic organotropism were created by implanting PDOs into the cecum wall. Optical barcoding was applied to trace the origin and clonal composition of liver and lung metastases. RNA sequencing and immunohistochemistry were used to identify candidate determinants of metastatic organotropism. Genetic, pharmacologic, invitro, and invivo modeling strategies identified essential steps in lung metastasis formation. Validation was performed by analyzing patient-derived tissues. Cecum transplantation of 3 distinct PDOs yielded models with distinct metastatic organotropism: liver only, lung only, and liver and lung. Liver metastases were seeded by single cells derived from select clones. Lung metastases were seeded by polyclonal clusters of tumor cells entering the lymphatic vasculature with very limited clonal selection. Lung-specific metastasis was associated with high expression of desmosome markers, including plakoglobin. Plakoglobin deletion abrogated tumor cell cluster formation, lymphatic invasion, and lung metastasis formation. Pharmacologic inhibition of lymphangiogenesis attenuated lung metastasis formation. Primary human colon, rectum, esophagus, and stomach tumors with lung metastases had a higher N-stage and more plakoglobin-expressing intra-lymphatic tumor cell clusters than those without lung metastases. Lung and liver metastasis formation are fundamentally distinct processes with different evolutionary bottlenecks, seeding entities, and anatomic routing. Polyclonal lung metastases originate from plakoglobin-dependent tumor cell clusters entering the lymphatic vasculature at the primary tumor site.

Role of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) in the Diagnosis of Suspicious Malignant Esophageal Strictures.

(1) Background: The accurate diagnosis of esophageal strictures is quite critical for optimizing medical intervention. However, the diagnosis of suspicious malignant esophageal strictures with intact mucosa appearance and negative biopsy results is challenging. This study aimed to evaluate the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of suspicious esophageal strictures. (2) Methods: We retrospectively analyzed the cases with suspicious malignant esophageal strictures that underwent EUS-FNA, with or without rapid on-site evaluation (ROSE), in our hospital from April 2017 to September 2022. Their clinical manifestations, imaging examinations, gastroscopic examinations, EUS-FNA results, and therapeutic strategies were retrospectively recorded and analyzed. (3) Results: A total of 23 patients (15 male and 8 female) were enrolled in this study. Based on EUS-FNA results, 18 patients were diagnosed with malignancies, including 16 cases of primary esophageal cancer (13 squamous carcinomas and 3 adenocarcinomas), 1 case of mediastinal cancer, and 1 case of metastatic esophageal cancer; 1 case of tuberculosis was also confirmed by EUS-FNA. Among 4 cases of ambiguous diagnosis with EUS-FNA, 1 was diagnosed with an esophageal glomus tumor after surgical removal, and 2 patients survived for several years without medical intervention, which hinted at the possibility of benign esophageal strictures. No major complications, including bleeding or perforation, were observed. (4) Conclusions: EUS-FNA may serve as a safe and effective diagnostic tool in suspicious malignant esophageal strictures with accurate specimen acquisition, especially for biopsy-negative cases.

Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner.

Posttranslational modifications add tremendous complexity to proteomes; however, gaps remain in knowledge regarding the function and regulatory mechanism of newly discovered lysine acylation modifications. Here, we compared a panel of non-histone lysine acylation patterns in metastasis models and clinical samples, and focused on 2-hydroxyisobutyrylation (Khib) due to its significant upregulation in cancer metastases. By the integration of systemic Khib proteome profiling in 20 paired primary esophageal tumor and metastatic tumor tissues with CRISPR/Cas9 functional screening, we identified N-acetyltransferase 10 (NAT10) as a substrate for Khib modification. We further showed that Khib modification at lysine 823 in NAT10 functionally contribute to metastasis. Mechanistically, NAT10 Khib modification enhances its interaction with deubiquitinase USP39, resulting in increased NAT10 protein stability. NAT10 in turn promotes metastasis by increasing NOTCH3 mRNA stability in an N4-acetylcytidine-dependent manner. Furthermore, we discovered a lead compound #7586-3507 that inhibited NAT10 Khib modification and showed efficacy in tumor models in vivo at a low concentration. Together, our findings bridge newly identified lysine acylation modifications with RNA modifications, thus providing novel insights into epigenetic regulation in human cancer. We propose that pharmacological inhibition of NAT10 K823 Khib modification constitutes a potential anti-metastasis strategy.

Efficacy of endoscopic ultrasound and endoscopic resection for esophageal schwannoma

Background Esophageal schwannoma (ES) is a rare submucosal tumor, and its complete and safe resection is a topic that deserves special attention. Aim This study aimed to investigate the clinical value of endoscopic ultrasound (EUS) in the diagnosis of ES and the clinical efficacy of endoscopic resection for ES. Methods The clinical data, endoscopic characteristics, endoscopic treatment, postoperative complications, immunohistochemical results, and follow-up records of patients with ES admitted to the Tianjin Medical University General Hospital from January 2012 to January 2022 were retrospectively analyzed. Results Under white-light endoscopy, 81.8% (9/11) of lesions were submucosal elevations, covering the normal esophageal epithelium. Two of the lesions with redness and erosive surface. Eight lesions (72.7%) appear on EUS originating from the muscularis propria were homogeneous or inhomogeneous hypoechoic signals. Two lesions were inhomogeneous hyperechoic originating from the submucosa or muscularis propria, respectively. One lesion was homogeneous hypoechoic originating from the submucosa. All lesions had no blood flow signals, cystic changes, or calcification, and were completely removed by submucosal tunnel endoscopic resection (STER) or endoscopic submucosal dissection (ESD). All patients did not experience serious adverse events as well as recurrence, metastasis, or cicatricial esophageal stenosis during the follow-up period. Conclusion ES is a rare submucosal lesion, which endoscopic characteristics are difficult to distinguish from other esophageal submucosal tumors. Endoscopic resection can provide a minimally invasive and alternative treatment for ES.

A rare and severe complication after minimally invasive esophagectomy: First case of a left-sided tension pneumothorax caused by intrathoracic perforation of the herniated transverse colon. Case report and literature review

Nowadays, a minimally invasive surgical approach is increasingly being chosen to treat distal esophageal tumors. Here, postoperative hiatal herniation has been identified as a potentially severe complication. In such cases, it is still not known whether surgical or conservative treatment is preferable. In this report, we elaborate the case of a 62-year-old male patient who presented at our emergency department with severe chest pain. This patient had undergone minimally invasive esophagectomy with gastric pull-up 2 years prior to this event. Emergency computed tomography revealed a left-sided tension pneumothorax based on transhiatal herniation of the transverse colon causing an intrathoracic closed-loop obstruction with subsequent perforation. Immediate surgical treatment was initiated and the transverse colon could be successfully repositioned and resected. Nevertheless, the patient died due to postoperative septic shock in the setting of fecal peritonitis, mediastinitis, and pleuritis within 48 hours after surgery. We provide a detailed description of this rare case and provide a review of the literature concerning intrathoracic colonic herniations.