Early-stage Esophageal Cancer Research Articles

Injury to the Muscle Layer and Risk of Non-cardiac Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer.

Non-cardiac chest pain (NCCP) is a frequent complication of endoscopic submucosal dissection (ESD) for early-stage esophageal cancer. However, little is known about relationships between ESD findings and NCCP. This study aims to evaluate the risk factors for NCCP, including ESD findings related to injury to the muscle layer. We enrolled a total of 296 lesions from 270 patients with esophageal squamous cell carcinoma (ESCC), who underwent ESD in our center. The grade of injury to the muscle layer caused by ESD was categorized as follows: grade 0: no exposure of muscularis propria; grade 1: muscularis propria exposure and/or whitish color change by the electrocoagulation; grade 2: torn muscularis propria with whitish color change by the electrocoagulation; and grade 3, esophageal perforation. The risk factors for NCCP, including ESD findings, were analyzed by univariate and multivariate analyses. NCCP occurred in 89 patients (33.0%) after esophageal ESD. Multivariate analysis demonstrated that younger age [odds ratio (OR) 0.95, 95% confidence interval (95%CI) 0.92-0.98, p=0.003), postoperative fever (>= 38°C) (OR=25.9, 95%CI: 2.89-232.10, p=0.004), ESD findings (grade 1: OR=3.99, 95%CI: 1.63-9.75, p=0.003 and grade 2: OR=3.18, 95%CI: 1.54-6.57, p=0.002) were independently associated with the incidence of post ESD NCCP. ESD findings relate to slight Injury to the muscle layer, such as muscularis propria exposure and whitish color change by the electrocoagulation were identified as risk factor for post ESD NCCP. We should therefore perform esophageal ESD carefully to avoid injuring the muscle layers.

Treatment strategy for early-stage esophageal cancer.

Approximately 90% of esophageal cancers in Japan are squamous cell carcinomas, and they are often detected at earlier stages in Japan than in Western countries; superficial esophageal cancer without lymph node or distant metastasis comprises one-third of all esophageal cancers in Japan. Endoscopic resection is a minimally invasive treatment for superficial esophageal cancer; however, the risk of regional lymph node recurrence is negligible when it invades the submucosal layer or lymphovasculature. In such cases, surgical treatment is necessary to control regional lymph node recurrences, although the physical burdens and potential complications cannot be overlooked. Recently, clinical trials in Japan have shown promising clinical outcomes of organ preservation strategies. One strategy is initially performing endoscopic resection for superficial esophageal cancer, assessing the risk of lymph node metastasis based on pathological diagnosis for endoscopically resected specimens, and subsequently considering additional therapy (e.g., observation or prophylactic chemoradiotherapy)-another strategy aimed to cure superficial esophageal cancer through definitive chemoradiotherapy alone. The safety and efficacy of the two strategies have been evaluated in clinical trials, which showed that both organ preservation strategies are comparable to surgery in terms of overall survival. However, challenges include improving the accuracy of pretreatment endoscopic diagnosis and decreasing the local-regional recurrence after chemoradiotherapy. This review provides an overview of the latest standard treatment for early-stage esophageal cancer and its future perspectives.

Similar survival after endoscopic submucosal dissection and esophagectomy in early esophageal cancer and synchronous or metachronous head and neck cancer.

Early-stage esophageal cancer is treated using endoscopic submucosal dissection and esophagectomy. Field cancerization in patients with early-stage esophageal cancer affects treatment outcomes and causes synchronous or metachronous head and neck cancers. We hypothesized that esophagectomy could provide better overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer. We retrospectively identified patients with early esophageal squamous cell carcinoma and synchronous or metachronous head and neck cancers. We separated the patients into endoscopic submucosal dissection and esophagectomy groups to compare overall and relapse-free survivals. The study included 106 patients, 25 of whom underwent endoscopic submucosal dissection and 81 underwent esophagectomy. Overall and relapse-free survivals did not show significant differences between the two groups for both synchronous and metachronous head and neck cancers. Endoscopic submucosal dissection could provide similar overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer.

Fecal Microbiota Transplantation Alleviates Severe PD-1 Inhibitor-Associated Colitis Caused by Neoadjuvant Therapy for Esophageal Cancer: A Case Report.

Surgical resection is the preferred treatment for early-stage esophageal cancer. But most patients with esophageal cancer are diagnosed at advanced stages, making them ineligible for surgery. Therefore, preoperative neoadjuvant therapy has been introduced to help them meet surgical requirements. However, this therapy has been associated with serious complications, such as diarrhea, preventing patients from surgery. During neoadjuvant therapy combined with chemoradiotherapy, a 58-year-old male patient with esophageal cancer was diagnosed with severe immune-related colitis, which seriously affected both cancer treatment and the patient's quality of life. Despite conventional antidiarrheal therapy, the patient remained refractory to treatment. However, after undergoing fecal microbiota transplantation, the frequency of diarrhea was significantly reduced. During e-colonoscopy, no significant ulcers were found in the sigmoid colon. Additionally, successful radical resection of esophageal cancer was performed, resulting in a favorable outcome for the patient. Regular follow-up appointments were scheduled to monitor the patient's progress. Fecal microbiota transplantation effectively relieved severe immune-related diarrhea in a patient undergoing neoadjuvant immunotherapy and chemoradiotherapy for esophageal cancer. This successful treatment ultimately enabled the patient to meet the surgical requirements for radical esophagectomy.

Esophageal cancer: Does inaccuracy in clinical staging affect our ability to reach optimal outcomes?

BackgroundPretreatment clinical staging is used to decide the course of treatment in early-stage esophageal cancer. Few studies assess the effect of inaccurate clinical staging on oncologic outcomes. MethodsWe queried the National Cancer Database to identify patients undergoing esophagectomy for clinical stage cT1bN0 esophageal carcinoma between 2010 and 2019. Patients were categorized as being upstaged if, on final pathology, they had histopathologic disease that would have warranted treatment with neoadjuvant therapy. The textbook oncologic outcome was defined as margin-negative resection, 15 lymph nodes examined, a hospital stay of <21 days, no unplanned 30-day readmission or mortality, and stage-appropriate use of neoadjuvant therapy. ResultsIn total, 916 patients met inclusion criteria; 378 (41.2%) had a pathologic stage that differed from their pretreatment clinical stage. By multivariable regression, factors associated upstaging included: presentation between 2015 and 2019 (odds ratio 1.92 95% confidence interval [1.19, 3.13]), delay to esophagectomy of >30 days (odds ratio 2.38 95% confidence interval [1.13, 5.57]), larger tumor size (>2 cm relative to <2 cm, odds ratio 2.73 95% confidence interval [1.72, 4.39]), and poorly differentiated histology (odds ratio 2.79 95% confidence interval [1.75, 4.49]). The rate of textbook oncologic outcome assuming reliable clinical staging was 43.8%; accounting for upstaging, the rate of textbook oncologic outcome was 22.5% (P < .001). ConclusionIn patients with cT1bN0 esophageal cancer, tumor size and histology are associated with the risk of inaccurate pretreatment clinical staging. Inaccuracies in clinical staging impact the rate at which providers achieve optimal oncologic outcomes.

Screening for Esophageal Squamous Cell Carcinoma: A Review

Esophageal cancer is amongst the most common types of cancer in Asia. It is a deadly disease where incidence almost parallels mortality. It is of 2 major subtypes, adenocarcinoma being more common in the global north and squamous cell carcinoma being more common in the global south. China, Japan, India, Iran, and other Asian countries contribute to roughly 80% of the global disease burden. Fortunately, esophageal squamous cell cancers (ESCC) are also amenable for screening. Natural history studies have shown that severe dysplasia carries the highest risk of progression to ESCC. Early detection has shown to be extremely beneficial, with cure rates above 90% for precursor lesions and early-stage esophageal cancer. There are various modalities available for screening—Chinese balloon cytology is a low cost technique that can be applied for mass screening but has only moderate sensitivity (39%-62%). Recent studies have demonstrated that using methylated DNA markers and applying artificial intelligence technology can significantly improve the yield of cytology. Lugol’s chromo-endoscopy has been demonstrated to have good sensitivity and specificity (&gt;85%), but is an invasive technique and requires operator expertise. Other image enhancing techniques such as narrow-band imaging, autofluorescence, endocytoscopy and micro-endoscopy are promising, but currently not cost effective for mass screening. There are 3 large randomized trials underway in China, initial published results have demonstrated a detection rate between 0.7% to 1.2% for ESCC and 4% to 6% for pre cursor lesions. These trials, with some of them involving &gt;100 000 patients have demonstrated the feasibility of endoscopic screening, but long term results are awaited.

Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

Neoadjuvant and adjuvant therapy in esophageal cancer.

Esophageal cancer is an aggressive malignancy that carries a high mortality rate. The treatment of locally advanced resectable esophageal cancer requires a multimodal approach involving chemotherapy, radiation therapy, and surgical resection. Optimal treatment combinations and sequences for squamous cell carcinoma (SCC) versus adenocarcinoma (AC) histological subtypes are still being determined. For very early stage esophageal cancers, endoscopic therapies or surgical resection without chemotherapy and radiation are preferred. Neoadjuvant chemoradiation followed by surgical resection has been the standard in locally advanced resectable esophageal cancer based on the landmark CROSS trial. Definitive chemoradiation is recommended for patients who are not surgical candidates or decline surgery. Perioperative chemotherapy without radiation can be considered for lower esophageal AC and gastroesophageal (GE)-junction AC based on landmark MAGIC and FLOT4 trials. Additional trials are underway to compare preoperative chemoradiation to perioperative chemotherapy in esophageal and GE-junction ACs. Thus far, targeted therapies against vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor 2 (HER2) have not been successful in the neoadjuvant/adjuvant setting. The roll of immunotherapy in perioperative/adjuvant setting is promising. Based on the CheckMate 577 trial, adjuvant nivolumab should be considered for all patients following neoadjuvant chemoradiation and R0 resection with residual pathologic disease. Additional trials involving various immunotherapy agents are underway.

Long-term survival in esophagectomy for early-stage esophageal cancer versus endoscopic resection plus additional chemoradiotherapy: a systematic review and meta-analysis.

Esophagectomy is still advised as an additional treatment for patients with superficial esophageal cancer (EC, T1a-T1b) after endoscopic resection (ER). However, esophagectomy often deteriorates the general condition of EC patients. In recent years, adjuvant chemoradiotherapy (CRT) has been recognized as a reliable, non-surgical treatment that can improve the prognosis. How to combine ER with adjuvant therapy to bring maximal benefits to patients has become a hot clinical research hot topic. However, the current studies have mostly been conducted retrospectively, in single centers, and with small clinical samples; there have been few prospective and large sample size randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to compare the outcomes of adjuvant CRT versus esophagectomy in the treatment of early EC, and to provide a reference for clinical research and practice. A comprehensive and extensive literature search was performed via the databases of PubMed, Cochrane Library, Embase, and Web of Science online and all randomized cohort studies and retrospective cohort studies were collected. The quality of research was evaluated according to Cochrane's quality standards, and statistical analysis was conducted with Stata 13.0 and RevMan 5.3 software and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). A total of 9 cohort studies, including 790 patients, were included for meta-analysis. The long term effects of the esophagectomy group were better than those of the CRT after ER group [odds ratio (OR) =6.08, 95% confidence interval (CI): 1.96 to 18.84, P=0.002] in disease-free survival (DFS) [hazard ratio (HR) =0.24, 95% CI: 0.07 to 0.85, P=0.03] and overall survival (OS) (HR =1.02, 95% CI: 0.57 to 1.82, P=0.94). Other survival indicators showed no significant difference (P>0.05). The 2 groups showed no significant results in OS. Although we found that CRT may be suitable for patients with high-risk of relapse or unable to tolerate surgery, it cannot totally replace surgical treatment; further randomized trials are required to verify this view.

Optimizing management for early-stage esophageal adenocarcinoma: longitudinal results from a multidisciplinary program.

The management of early-stage esophageal cancer is nuanced. A multidisciplinary approach may optimize management through selection of candidates for surgical or endoscopic therapies. The objective of this research was to examine long-term outcomes of patients with early-stage esophageal cancer who undergo treatment with endoscopic resection or surgery. Data on patient demographics, co-morbidities, pathology results, OS and RFS were obtained for both the endoscopic resection group and esophagectomy group. Univariate analysis of OS and RFS were conducted using the Kaplan-Meier method with calculation of the log-rank test. Multivariate cox-proportional hazards models were created for OS and RFS using a hypothesis-driven approach. A multivariate logistic regression model was created to identify predictors of esophagectomy among patients undergoing initial endoscopic resection. A total of 111 patients were included. The median OS for the surgery group was 67.0months compared to 74.0months in the endoscopic resection group (log-rank p = 0.93). The median RFS for the surgery group was 109.4months compared to 63.3months in the endoscopic resection group (log-rank p = 0.0127). On multivariable analysis, patients undergoing endoscopic resection had significantly worse RFS (HR 2.55, 95% CI 1.09-6.00; p = 0.032), but equivalent OS (HR 1.03, 95% CI 0.46-2.32; p = 0.941), compared to patients undergoing esophagectomy. High-grade disease (OR 5.43, 95% CI 1.13-26.10; p = 0.035) and submucosal involvement (OR 7.75, 95% CI 1.90-31.40; p = 0.004) were identified as significant predictors of proceeding to esophagectomy. Through a multidisciplinary approach, patients with early-stage esophageal cancer achieve excellent RFS and OS. Submucosal involvement and high-grade disease place patients at increased risk for local disease recurrence; these patients may undergo endoscopic resection safely if treated with a multidisciplinary approach incorporating endoscopic surveillance and surgical consultation. Further risk-stratification models may enable better patient selection and optimization of long-term outcomes.

Mechanisms of esophageal cancer metastasis and treatment progress.

Esophageal cancer is a prevalent tumor of the digestive tract worldwide. The detection rate of early-stage esophageal cancer is very low, and most patients are diagnosed with metastasis. Metastasis of esophageal cancer mainly includes direct diffusion metastasis, hematogenous metastasis, and lymphatic metastasis. This article reviews the metabolic process of esophageal cancer metastasis and the mechanisms by which M2 macrophages, CAF, regulatory T cells, and their released cytokines, including chemokines, interleukins, and growth factors, form an immune barrier to the anti-tumor immune response mediated by CD8+ T cells, impeding their ability to kill tumor cells during tumor immune escape. The effect of Ferroptosis on the metastasis of esophageal cancer is briefly mentioned. Moreover, the paper also summarizes common drugs and research directions in chemotherapy, immunotherapy, and targeted therapy for advanced metastatic esophageal cancer. This review aims to serve as a foundation for further investigations into the mechanism and management of esophageal cancer metastasis.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

Fusobacterium nucleatum promotes the early occurrence of esophageal cancer through upregulation of IL-32/PRTN3 expression.

Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.

Frailty Assessed by the Clinical Frailty Scale is Associated with Prognosis After Esophagectomy

The Clinical Frailty Scale (CFS) is a simple and validated tool for assessing frailty, and higher CFS scores are correlated with worse perioperative outcomes after cardiovascular surgery. However, the relationship between the CFS scores and postoperative outcomes after esophagectomy remain unclear. We retrospectively analyzed data from 561 patients with esophageal cancer (EC) who underwent resection from August 2010 to August 2020. We defined a CFS score of ≥4 as indicative of frailty; thus, patients were classified into frail patients (CFS scores of ≥4) and non-frail patients (CFS scores of ≤3). The Kaplan-Meier method was used to describe the overall survival (OS) distributions with the log-rank test. Of the 561 patients, 90 (16%) had frailty and 471 (84%) did not. Frail patients had a significantly older age, lower body mass index, higher American Society of Anesthesiologists physical status classification, and greater cancer progression than non-frail patients. The 5-year survival rate was 68% in non-frail patients and 52% in frail patients. OS was significantly shorter in frail than non-frail patients (p=0.017 by log-rank test). In particular, OS was significantly shorter in frail patients with clinical stage I-II EC (p=0.0024 by log-rank test) but was not correlated with frailty in patients with clinical stage III-IV EC (p=0.87 by log-rank test). Preoperative frailty was associated with shorter OS after resection of EC. The CFS score may be a prognostic biomarker for patients with EC, especially early-stage EC.

Chinese expert consensus on early diagnosis and treatment of esophageal cancer

Although the incidence rate of esophageal cancer in China is on the decline, China is still a high-incidence country of esophageal cancer with great regional variation. In recent years, the five-year survival of esophageal cancer in China has improved significantly. However, due to the absence of typical symptoms in early stage, there still exists a large esophageal cancer diagnostic yield gap between China and developed countries. At present, there are no international guidelines defining the target population for esophageal squamous cell carcinoma (ESCC) screening. Exploring and implementing effective esophageal cancer screening together with early diagnosis and early treatment are the keys to reducing the mortality and improving the survival rate and life quality. Endoscopic therapies, such as endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and radiofrequency ablation (RFA), are used to treat early-stage esophageal cancer. If the tumor invasion is deep or lymph node metastasis is suspected, surgery is needed, meanwhile radiation therapy could also be an optional treatment. Regular follow-up and surveillance are required for any strategy above to deal with relapse and metachronous primary cancers. The Early Diagnosis and Treatment Group of the Chinese Medical Association Oncology Branch has reached an expert consensus on screening and diagnostic protocols for esophageal cancer, on endoscopic and surgical treatment of early esophageal cancer and precancerous lesions, as well as on postoperative monitoring and adjuvant therapy. This consensus follows the evidence-based medicine at both domestic and international levels, combines the current clinical practice and application experience in the treatment of esophageal cancer in China, is based on a multidisciplinary treatment model, and can be used as a reference for clinicians.

S1125 Utility and Role of Endoscopic Ultrasound for Suspected Early Esophageal Cancer

Introduction: Accurate clinical staging of esophageal cancer is vital in selecting appropriate treatment options. Endoscopic ultrasound (EUS) has been determined to be an accurate imaging modality for esophageal cancer staging, differentiating superficial lesions from deep lesions. Despite being accurate, utilization of EUS in apparent early-stage cancer remains controversial. The current study aims to assess the utility of EUS for early-stage esophageal cancer and whether endoscopic features of esophageal malignancy can help direct the optimal management of the cancer. Methods: This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center. 50 patients met inclusion criteria for this study. Patient clinical data, initial EGD/biopsy, EUS, and final resection pathology reports were extracted from chart review and statistical analysis was performed to determine the accuracy of EUS and associations of endoscopic findings with deeper invasion. Results: EUS T stage was concordant with histological T stage in 74% of patients (37/50). In determining sub-mucosal involvement (T1a vs T1b), EUS had a specificity of 85% and sensitivity of 53.8%. EUS had an overall accuracy of 72.7% in identifying sub-mucosal invasion in T1 cancers. Prominent lymph nodes on EUS and tumor size >2 cm on visual inspection were significantly associated with deeper invasion of cancer on histology with p-values < 0.01. Barrett’s morphology was significantly associated with superficial cancers with a p-value < 0.01. EUS affected management from EMR/ESD to esophagectomy in 9.4% of patient with Barrett’s morphology and 6.7% of patients with tumor size < 2cm. In patients without any endoscopic findings suggestive of deep invasion, EUS identified deeper cancer and changed management in < 7% of cases. Conclusion: For assessing deeper invasion (T2, T3 and T4), EUS has been substantiated as a significantly effective tool. In staging T1b lesions, EUS was reasonably specific in ruling out sub-mucosal invasion; however, it had relatively poor sensitivity in identifying sub-mucosal invasion. Additionally, data validated endoscopic features suggesting superficial cancers including a tumor size < 2cm and the presence of Barrett’s morphology. In patients with these findings suggesting superficial cancer, EUS rarely identified a deep cancer that warranted a change in management.

En-face polarization-sensitive optical coherence tomography to characterize early-stage esophageal cancer and determine tumor margin.

Current imaging tools are insufficiently sensitive to the early diagnosis of esophageal squamous cell carcinoma (ESCC). The application of polarization-sensitive optical coherence tomography (PS-OCT) to detect tumor-stroma interaction is an interesting issue in cancer diagnosis. In this translational study, we found that en-face PS-OCT effectively characterizes protruding, flat, and depressive type ESCC regardless of animal or human specimens. In addition, the tumor contour and margin could also be drawn and determined on a broad en-face view. The determined tumor margin could be in the proximity of 2 mm to the actual tumor margin, which was proved directly using histology.

Long-Term Clinical Outcomes and Safety Analysis of Superficial Esophageal Cancer Patients Treated with Definitive or Adjuvant Radiotherapy.

Simple SummaryFor superficial esophageal cancer, many tumor features have been identified as risk factors for lymph node metastasis, including depth of invasion, tumor size, the presence of lymphovascular invasion, etc. In such cases, endoscopic resection (ER) alone is not adequate for treatment coverage, and additional radiotherapy (RT)/concurrent chemoradiotherapy (CCRT) merits further investigation. On the other hand, esophagectomy has a high cure rate for early stage esophageal squamous cell cancer (ESCC); however, there are concerns of treatment complications and loss of esophagus preservation. Hence, definitive RT/CCRT may be a promising treatment alternative to esophagectomy, especially for those who are unable or unwilling to receive surgery. We retrospectively analyzed outcomes of patients with T1N0M0 staged ESCC treated with ER + RT/CCRT or RT/CCRT. We conclude that definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.(1) Background: The role of radiotherapy (RT) in superficial esophageal squamous cell cancer (ESCC) remains unclear. The objective of our study was to perform a detailed outcome and safety analysis of RT as a definitive or adjuvant treatment for T1N0M0 staged ESCC patients. (2) Methods: A total of 55 patients treated with endoscopic resection (ER) + RT/concurrent chemoradiotherapy (CCRT) or RT/CCRT from January 2011 to June 2021 were included in this study. Eighteen patients with risk factors received ER + RT/CCRT, and thirty-seven patients solely received RT/CCRT. Kaplan–Meier curves were used to calculate the clinical outcomes, and toxicities were scored. (3) Results: The median follow-up time was 51.9 months. The estimated 5-year local recurrence-free survival (LRFS) and overall survival (OS) were 88.9% and 94.4% in the ER + RT/CCRT group and 91.8% and 91.7% in the RT/CCRT group. The predominant failure pattern was in-field local failure (5.5%, 3/55), with one patient in the ER + RT/CCRT group and two patients in the RT/CCRT group. One patient (1.8%, 1/55) had lung metastasis in the RT/CCRT group. The most common toxicities were Grades 1–2 in all patients, including esophagitis (74.5%, 41/55), myelosuppression (49.1%, 27/55) and esophageal stricture after RT (27.3%, 15/55). Two patients (11.1%, 2/18) and four patients (10.8%, 4/37) had Grade 3 esophageal stricture after RT in the ER + RT/CCRT group and RT/CCRT group, respectively. No patients experienced a Grade 4 or higher toxicity, and there were no treatment-related deaths. (4) Conclusions: Definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.

Considerations for the Surgical Management of Thoracic Cancers During the COVID-19 Pandemic: Rational Strategies for Thoracic Surgeons.

ObjectiveThe novel Coronavirus Disease 2019 (COVID-19) has resulted in a global health crisis since first case was identified in December 2019. As the pandemic continues to strain global public health systems, elective surgeries for thoracic cancer, such as early-stage lung cancer and esophageal cancer (EC), have been postponed due to a shortage of medical resources and the risk of nosocomial transmission. This review is aimed to discuss the influence of COVID-19 on thoracic surgical practice, prevention of nosocomial transmission during the pandemic, and propose modifications to the standard practices in the surgical management of different thoracic cancer.MethodsA literature search of PubMed, Medline, and Google Scholar was performed for articles focusing on COVID-19, early-stage lung cancer, and EC prior to 1 July 2021. The evidence from articles was combined with our data and experience.ResultsWe review the challenges in the management of different thoracic cancer from the perspectives of thoracic surgeons and propose rational strategies for the diagnosis and treatment of early-stage lung cancer and EC during the COVID-19 pandemic.ConclusionsDuring the COVID-19 pandemic, the optimization of hospital systems and medical resources is to fight against COVID-19. Indolent early lung cancers, such as pure ground-glass nodules/opacities (GGOs), can be postponed with a lower risk of progression, while selective surgeries of more biologically aggressive tumors should be prioritized. As for EC, we recommend immediate or prioritized surgeries for patients with stage Ib or more advanced stage and patients after neoadjuvant therapy. Routine COVID-19 screening should be performed preoperatively before thoracic surgeries. Prevention of nosocomial transmission by providing appropriate personal protective equipment (PPE), such as N-95 respirator masks with eye protection to healthcare workers, is necessary.

Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer

BackgroundThe surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer.MethodsIn this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC).ResultsWe identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic.ConclusionWe disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.Graphical