Esophageal Tumors Research Articles

Oncoguía de carcinoma esofágico y unión esofagogástrica 2023

Cancer of the esophagus and gastroesophageal junction (GEJ) is among the top ten tumors in incidence and mortality worldwide. Mexico is not the exception; the incidence is increasing, especially for adenocarcinoma, so we must be aware of this disease. In the Department of Gastrointestinal Tumors from Instituto Nacional de Cancerología, we have developed these onco-guidelines through multidisciplinary management. We review epidemiological aspects, criteria for diagnosis, staging, correct differentiation of an esophageal tumor and EGJ, and the multiple treatment options by stage clinic with the most recent evidence including the nutritional approach that is very important in these patients.

Large esophageal gastrointestinal stromal tumors resected thoracoscopically after oral imatinib therapy: a report of two cases

Esophageal gastrointestinal stromal tumors (GISTs) are very rare, accounting for 2–5% of all GISTs. As with other GISTs, the principle of surgical treatment is complete resection with negative margins. In addition to biological grades of GISTs itselves, local recurrence due to capsular damage is a known risk. We describe two cases of massive esophageal GISTs that were successfully resected thoracoscopically after 2 months administration of 400 mg imatinib, with some discussion of the literature. Case 1, the patient was a 51-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtMtAeG, 110 × 95 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 11 months postoperatively. Case 2, the patient was a 70-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtAeG, 90 × 52 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 9 months postoperatively.

Clinicopathological features of verrucous type dysplasia of esophagus

Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.

Meta-analysis on the epidemiology of gastroesophageal reflux disease in China.

No large-scale epidemiological survey on the prevalence of gastroesophageal reflux disease (GERD) in China has been conducted. China has a large population and a complex geographical environment. It is important to understand the prevalence and spatial distribution of GERD in China. To explore the prevalence and the spatial, temporal, and population distributions of GERD in the natural Chinese population. We searched Chinese and English databases for literature on the prevalence of GERD in the natural Chinese population. The prevalence of GERD was pooled using a random-effects meta-analysis model. Subgroup analysis was performed according to time, region, and population. We used ArcGIS software to draw statistical maps and trend analysis charts. Spatial autocorrelation analysis was carried out using Geoda software. Spearman correlation analysis was used to assess the spatial distribution relationship between GERD and upper digestive tract tumours. Altogether, 70 studies involving 276014 individuals from 24 provinces of China were included. The overall pooled prevalence of GERD was 8.7% (95%CI: 7.5%-9.9%) in mainland China. Over the past two decades, the prevalence of GERD in China has increased from 6.0% to 10.6%. GERD was more common in people aged 40-60, with body mass index ≥ 24, and of Uygur ethnicity. The prevalence was higher in the west and east than in the centre, and there may be a local spatial autocorrelation between the Qinghai-Tibet Plateau and the southeast. GERD was correlated with gastric (r = 0.421, P = 0.041) and oesophageal tumours (r = 0.511, P = 0.011) in spatial distribution. GERD is becoming common in China. The prevalence differs by region and population. The development of appropriate strategies for the prevention and treatment of GERD is needed.

OGC P32 Prognostic impact of clinicopathological features following metastectomy for metachronous pulmonary metastasis from oesophageal cancer: a systematic review and meta-analysis

Abstract Background Disease recurrence following treatment for oesophageal cancer (OC) remains common despite incremental gains from receipt of neoadjuvant chemotherapy. The lung is a common site of distant metastasis following definitive OC treatment. Clinicopathological features of the primary oesophageal tumour have implications on the development of metastatic disease and overall survival. This systematic review sought to identify the prognostic impact of clinicopathological features of the primary oesophageal tumour following treatment of metachronous pulmonary metastasis from OC. Methods A search of the major reference databases (PubMed, Medline, Cochrane) was performed with no time limits up to March 2022. Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting on the clinical and pathological features of the primary OC tumour among patients undergoing treatment for metachronous pulmonary metastasis were included. A random effects meta-analysis model was used to compare the impact of gender (male vs female), primary OC pathological T-stage (pT1/2 vs pT3/4) and pathological N-stage (N0 vs N1+), on 5-year survival following pulmonary metastectomy. Results Seven non-randomised studies comprising 110 patients undergoing pulmonary metastectomy for metastatic OC were included. Gender did not have an impact upon 5-year survival (Risk Ratio (RR) =0.65; 95% confidence interval(CI):0.37–1.15; p=0.14). A lower primary OC T-stage (T1/2) was associated with improved 5-year survival following pulmonary metastectomy compared to advanced T-stages (T3/4), though this did not reach statistical significance (RR= 1.76; 95% CI:0.96–3.20; p=0.07). The absence of nodal disease (N0) in the primary disease did not confer a survival benefit over those patients with nodal involvement (N1+) proceeding to pulmonary metastectomy (RR= 1.45; 95% CI:0.86–2.46; p=0.18). Conclusions Patient gender and pathological T- and N-stages of the primary tumour do not impact upon prognosis following metastectomy for metachronous pulmonary metastasis from OC. However, current evidence from smaller non-randomised studies remains weak owing to variation in the treatment of the primary oesophageal tumour, limiting outcome assessment.

Circ_0058063 regulates the development of esophageal cancer through miR-377-3p/HOXA1 axis.

Esophageal cancer is one of the deadliest cancers. Circular RNA (CircRNA) can be used as a tumor marker. Therefore, this provides an important idea for our research. Real-time quantitative PCR (RT-qPCR) was used to analyze the expression of circ_0058063, miR-377-3p and homeobox protein Hox-A1 (HOXA1), western blot was used to analyze the protein levels of HOXA1 and cyclinD1, B cell leukemia/lymphoma 2 associated X (Bax). Cell Counting Kit-8 (CCK-8) assay, colony formation assay and wound healing assay were used to analyze cell proliferation and migration; apoptosis was analyzed by flow cytometry. Dual-luciferase reporter assays were performed to analyze the luciferase activities. Transwell assay was used to analyze the cell invasion. A glycolysis metabolism assay was used to analyze cell glycolysis ability. Xenograft models were used to validate the effect of circ_0009035 in the growth of esophageal cancer in vivo . Circ_0009035 and HOXA1 were upregulated, while miR-377 was downregulated in esophageal cancer.. Circ_0058063 targeted miR-377-3p, and HOX4 was a target of miR-377-3p. Knockdown of circ_0058063 inhibited migration, invasion and proliferation and promoted apoptosis of esophageal cancer cells. MiR-377-3p inhibition or HOXA1 overexpression could restore the effect of si-circ_0058063 on esophageal cancer cells. Knockdown of circ_0058063 repressed the growth of esophageal cancer tumors in vivo. Our study found that circ_0058063 could regulate the expression of HOXA1 by targeting miR-377-3p, thereby affecting the progress of esophageal cancer.

Esophageal Tumor Length – An Underestimated Predictor of Survival After Esophageal Cancer Resection

Abstract Introduction. Esophageal cancer is one of the most aggressive visceral tumors with increasing frequency and poor prognosis. Differences in survival between patients in the same clinical tumor stage necessitate searching for additional prognostic markers to help identify patients at high risk of recurrence, metastasis or death. The aim of the study was to assess prognostic significance of tumor length on survival after esophageal cancer resection in patients operated at a center for esophageal surgery. Materials and methods. This was a prospective cohort study including 117 patients who had undergone surgical resection with curative intent for esophageal cancer. The study was conducted at the First Surgical Clinic of UMHATEM “N. I. Pirogov”, Sofia, Bulgaria. The inclusion period was between 1st January 2013 and 31st December 2015 and the patients were followed – up until 10 April 2022. The patients were divided into two groups according to the tumor length – under 3 cm (group 1) and over 3 cm (group 2). The prognostic impact of tumor length on survival was analyzed with Cox regression analysis. Overall survival was presented by the Kaplan-Meier method with log-rank tests. Results. The 5-year survival rate was 11.1%. Median survival rate was 26.0 months (95% CI 18.3-33.7 months) for the patients in the first group and 13.0 months (95% CI 10.3-15.7 months) for the second group patients. Tumor length over 3 cm was a negative prognostic factor (HR 2.36 95% CI 1.06-5.25; p = 0,03). Conclusion. Length of esophageal cancer is a powerful independent predictor of survival in addition to the TNM stage.

Current status of gastrectomy and reconstruction types for patients with proximal gastric cancer in Japan

BackgroundSurgical procedures for proximal gastric cancer remain a highly debated topic. Total gastrectomy (TG) is widely accepted as a standard radical surgery. However, subtotal esophagectomy, proximal gastrectomy (PG) or even subtotal gastrectomy, when a small upper portion of the stomach can technically be preserved, are alternatives in current clinical practice. MethodsUsing a cohort of the PGSAS NEXT trial, consisting of 1909 patients responding to a questionnaire sent to 70 institutions between July 2018 and December 2019, gastrectomy type, reconstruction method, and furthermore the remnant stomach size and the anti-reflux procedures for PG were evaluated. ResultsTG was the procedure most commonly performed (63.0%), followed by PG (33.4%). Roux-en-Y was preferentially employed following TG irrespective of esophageal tumor invasion, while jejunal pouch was adopted in 8.5% of cases with an abdominal esophageal stump. Esophagogastrostomy was most commonly selected after PG, followed by the double-tract method. The former was preferentially employed for larger remnant stomachs (≧3/4), while being used slightly less often for tumors with as compared to those without esophageal invasion in cases with a remnant stomach 2/3 the size of the original stomach. Application of the double-tract method gradually increased as the remnant stomach size decreased. Anti-reflux procedures following esophagogastrostomy varied markedly. ConclusionsTG is the mainstream and PG remains an alternative in current Japanese clinical practice for proximal gastric cancer. Remnant stomach size and esophageal stump location appear to influence the choice of reconstruction method following PG.

Diagnostic potential of endosonography in primary and secondary esophageal tumors: retrospective study

Aim. To determine the diagnostic value of endosonography in primary and secondary esophageal tumors.
 Materials and methods. Between 2018 and 2022, 118 patients with primary and secondary esophageal changes were managed at the Blokhin National Medical Research Center for Oncology. Primary changes imply invasion of the esophagus directly by a tumor, secondary changes mean invasion of the esophageal wall by a tumor from outside, and the transition of a tumor from the stomach to the esophagus.
 Results. All patients had esophagogastroduodenoscopy combined with endoscopic ultrasound performed. Besides estimating the tumor invasion depth in the esophageal wall and the possible involvement of other structures at a distance up to 5 cm from the esophagus, the proximal margin of the tumor was examined. According to esophagogastroduodenoscopy and endoscopic ultrasound examination, the difference in the proximal margin was not more than 1.0 cm. The difference in results may be due to the submucosal nature of tumor growth.
 Conclusion. Endoscopic ultrasound examination is the most important diagnostic method to determine the proximal margin of the primary and secondary esophageal tumors and evaluate the degree of invasion into the esophageal wall, which is an essential factor for the treatment choice.

Automatic segmentation of esophageal gross tumor volume in 18F-FDG PET/CT images via GloD-LoATUNet

Background and objectiveFor esophageal squamous cell carcinoma, radiotherapy is one of the primary treatments. During the planning before radiotherapy, the intractable task is to precisely delineate the esophageal gross tumor volume (GTV) on medical images. In current clinical practice, the manual delineation suffers from high intra- and inter-rater variability, while also exhausting the oncologists on a treadmill. There is an urgent demand for effective computer-aided automatic segmentation methods. To this end, we designed a novel deep network, dubbed as GloD-LoATUNet. MethodsGloD-LoATUNet follows the effective U-shape structure. On the contractile path, the global deformable dense attention transformer (GloDAT), local attention transformer (LoAT), and convolution blocks are integrated to model long-range dependencies and localized information. On the center bridge and the expanding path, convolution blocks are adopted to upsample the extracted representations for pixel-wise semantic prediction. Between the peer-to-peer counterparts, enhanced skip connections are built to compensate for the lost spatial information and dependencies. By exploiting complementary strengths of the GloDAT, LoAT, and convolution, GloD-LoATUNet has remarkable representation learning capabilities, performing well in the prediction of the small and variable esophageal GTV. ResultsThe proposed approach was validated in the clinical positron emission tomography/computed tomography (PET/CT) cohort. For 4 different data partitions, we report the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Mean surface distance (MSD) as: 0.83±0.13, 4.88±9.16 mm, and 1.40±4.11 mm; 0.84±0.12, 6.89±12.04 mm, and 1.18±3.02 mm; 0.84±0.13, 3.89±7.64 mm, and 1.28±3.68 mm; 0.86±0.09, 3.71±4.79 mm, and 0.90±0.37 mm; respectively. The predicted contours present a desirable consistency with the ground truth. ConclusionsThe inspiring results confirm the accuracy and generalizability of the proposed model, demonstrating the potential for automatic segmentation of esophageal GTV in clinical practice.

Robust deep learning-based forward dose calculations for VMAT on the 1.5T MR-linac

In this work we present a framework for robust deep learning-based VMAT forward dose calculations for the 1.5T MR-linac. A convolutional neural network was trained on the dose of individual multi-leaf-collimator VMAT segments and was used to predict the dose per segment for a set of MR-linac-deliverable VMAT test plans. The training set consisted of prostate, rectal, lung and esophageal tumour data. All patients were previously treated in our clinic with VMAT on a conventional linac. The clinical data were converted to an MR-linac environment prior to training. During training time, gantry and collimator angles were randomized for each training sample, while the multi-leaf-collimator shapes were rigidly shifted to ensure robust learning. A Monte Carlo dose engine was used for the generation of the ground truth data at 1% statistical uncertainty per control point. For a set of 17 MR-linac-deliverable VMAT test plans, generated on a research treatment planning system, our method predicted highly accurate dose distributions, reporting 99.7% ± 0.5% for the full plan prediction at the 3%/3 mm gamma criterion. Additional evaluation on previously unseen IMRT patients passed all clinical requirements resulting in 99.0% ± 0.6% for the 3%/3 mm analysis. The overall performance of our method makes it a promising plan validation solution for IMRT and VMAT workflows, robust to tumour anatomies and tissue density variations.

Combination conventional endoscopy and endoscopic ultrasound can differentiate between esophageal granular cell tumors and leiomyomas.

Esophageal leiomyomas and granular cell tumors (GCTs) are the 2 most common subepithelial tumors found in the esophagus. We attempted to differentiate the 2 tumors using endoscopic findings and endoscopic ultrasound (EUS) features. Between December 2008 and June 2021, a total of 38 esophageal GCTs and 11 esophageal leiomyomas originating from the muscularis mucosa were selected. Clinical characteristics and endoscopic features were retrospectively reviewed. Although esophageal GCTs are mainly located in the lower third of the esophagus (81.6%), esophageal leiomyomas are mainly located in the upper third of the esophagus (45.5%). Broad-based (84.2%, P = .002) and whitish-to-yellowish color changes (97.4%, P < .001) are significant endoscopic features of esophageal GCTs. The echogenicity of esophageal leiomyoma was similar to that of proper muscle echogenicity. However, the echogenicity of esophageal GCTs was hyperechoic compared to that of the proper muscle layer (90.0% vs 9.1%, respectively, P < .001). EUS revealed a clearer hyperechoic epithelial lining in the esophageal leiomyoma than in esophageal GCTs (100% vs 26.7%, respectively, P < .001). The 5 endoscopic factors (location of the lower third, broad base, whitish-to-yellowish color, hyper-echogenic, and unclear demarcated hyperechoic epithelial line) were counted to differentiate esophageal GCTs from esophageal leiomyomas. Tumors with 3 or more endoscopic factors were all esophageal GCTs. The characteristic endoscopic and EUS features of esophageal GCTs were broad-based, whitish-to-yellowish colored subepithelial tumors located in the lower third of the esophagus and hyperechoic tumor with an unclear demarcated hyperechoic epithelial line. A combination of these features can predict esophageal GCTs before endoscopic resection.

Unique Epidemiologic Features of Esophageal Squamous Dysplasia: A Retrospective Single Institution Study

Abstract Introduction/Objective Squamous cell carcinoma (SCC) is the most common esophageal primary tumor worldwide. On the contrary, SCC and its precursor lesion, esophageal squamous dysplasia (ESD), are uncommon in western countries and North America, with smoking and heavy alcohol (EtOH) use being the significant risk factors. Given the influence of geography on the prevalence of SCC, we hypothesize that there may be unique risk factors in the Northeastern United States population compared to worldwide factors. Our retrospective study focuses on ESD, the premalignant condition, examining known risk factors at our institution. Methods/Case Report Patients diagnosed/followed with ESD during 2006-19 were identified from pathology database. Among patients who had an initial esophagogastroduodenoscopy (EGD) finding suspicious for SCC and confirmed by histology were excluded. Demographics, social and medical history (hx), EGD reports, and pathology reports were reviewed. We evaluated subgroups of risk factors. Results (if a Case Study enter NA) Study included 37 patients. Mean age at initial EGD biopsy was 66.8 years (range: 42-94 years); 56.8% (21/37) were female. By endoscopy, the most common finding was erythema followed by friability and nodularity. 45.9% had at least one recurrent ESD in subsequent biopsies, and 35.1% were eventually diagnosed with SCC. 83.3% showed high grade ESD on initial biopsy. Smoking [current, former, or never (NS)] and EtOH hx [heavy, light/moderate, or no] showed no significant association (p=0.38). Majority were either former or NS (72.9%); 34.3% were NS. In NS, 91.7% (11/12) were female, 50.0% did not consume EtOH, and 50.0% had concurrent Barrett esophagus. 33.3% later developed SCC. Also in NS, 50% had a personal hx of cancer and reported no family hx of GI/esophageal cancer. Conclusion In our institution, while some data is consistent with population data (i.e. EGD distribution, appearance), our study cohort is mostly women and within it is a unique subgroup lacking classical strong risk factors. This subset of NS is mostly women with no to moderate alcohol intake and lacking a strong family hx of GI/esophageal cancer. Our data emphasizes that not all predisposing factors have been elucidated in ESD. Our findings may offer a unique opportunity to further the understanding of SCC pathogenesis.

Endoscopic Findings in Patient with Dyspepsia in Al- Ramadi General Hospital

This study including upper gastro - intestinal endoscopic findings of 1998 patients complaining from dyspepsia, 803 (40%) of them were found to have normal endoscopic findings and 1195 (60%) found to have upper gastro - intestinal abnormalities. Duodenal ulcer represents the highest frequency (24%) of these abnormalities followed by gastritis (13%), duodenitis (7%), gastro duodenitis (4.4%), hiatus hernia &amp; prolapse gastropathy (3.9%), reflux esophagitis (3.1%), gastric tumor (1.7%), gastric ulcer (1.3%), gastric outlet obstruction (1.2%) while tumor of esophagus found to be the lowest value (0.4%).Of the all examined cases as well as cases with abnormal endoscopy (1195 case), the highest number of referred cases were from the age group 21-30year, and the lowest was from the age group 81-90years. Also, we found that when the age is more than 60years of age, more than 79% of their endoscopic findings were abnormal.There were no significant sex differences among all studied cases except for tumor of esophagus and hiatus hernia as showed male predominance.

A case of undifferentiated pleomorphic sarcoma in esophagus after multiple cancer treatments of surgery and chemoradiotherapy

BackgroundUndifferentiated pleomorphic sarcoma (UPS) in the esophagus is extremely rare. Therefore, there are few reports of UPS in the esophagus (UPSE). We present a case of UPSE after multiple cancer treatments.Case presentationA 73-year-old man with a history of cancer treatment, including distal gastrectomy, transverse colectomy, and chemoradiotherapy, was diagnosed with an elevated lesion such as a submucosal tumor in the lower esophagus by regular endoscopy. A boring biopsy was performed, and the specimen showed features of sarcoma. The patient underwent a partial esophagectomy without lymph node dissection. Histopathological findings confirmed an undifferentiated pleomorphic sarcoma. Adjuvant therapy was not administered, and the patient survived without recurrence 1 year after surgery.ConclusionsCurrently, complete resection is the only treatment option for UPSE. An optimal treatment strategy using chemotherapy or radiotherapy should be established.

ODP552 Hypercalcemic Crisis Due to PTH Secretion From a Poorly Differentiated Esophageal Neuroendocrine Tumor

Abstract Background Paraneoplastic secretion of PTH is described in a number of solid organ tumors. Hypercalcemia occurs in up to 30% of patients with malignancy. The most common cause of this phenomenon is PTHrP production. We present a rare case of PTH mediated hypercalcemic crisis from a tumor of presumed esophageal lineage. Clinical Case A 54-year-old man presented with several days of fatigue, lethargy and polyuria. Initial calcium was markedly elevated at 18.4 (8.3-10.1mg/dL). Past medical history included Barrett's esophagus, history of gastric bypass, and prior alcohol abuse. He also had progressive dysphagia and 30lb weight loss over the prior month. On examination, he had tachycardia, cachexia, and encephalopathy. Laboratory testing revealed an elevated PTH of 281 (nl 18.4-80.1pg/mL), creatinine 1.34mg/dL, and low phosphorus at 2.8 (nl 2.7-4.5mg/mL). Hypercalcemia was treated with IV fluids, calcitonin, and pamidronate. The calcium normalized but PTH remained 210pg/mL. Subsequent PTHrP and 1,25 di-hydroxy vitamin D levels were normal. Esophagogastroduodenoscopy (EGD) revealed a friable esophageal mass and biopsy identified a poorly differentiated carcinoma with neuroendocrine features, immunoreactive to synaptophysin and high Ki-67 index of 90%. Immunostains for chromogranin and PTH were negative. A CT of the chest, abdomen, and pelvis revealed diffuse metastases in the liver, lungs, and enlarged mediastinal lymph nodes. The source of primary tumor could not be fully identified from pathology but suspected to be esophageal. Parathyroid scan showed a subtle persistent uptake posterior to right side of trachea suspicious for a parathyroid adenoma, but that could not account for the severity of PTH elevation. He was readmitted in 1 month with recurrent symptomatic severe hypercalcemia to 18mg/dL and PTH to 619.4pg/mL. Again, he received IV fluids, calcitonin, and zoledronic acid. He received 3 cycles of platinum and etoposide based chemotherapy. After chemotherapy, PTH decreased to 123pg/mL and calcium to 9.7mg/dL but he continued to have rapid disease progression including jaundice, pathological bone fractures and orbital metastases. He elected hospice care and passed away in about 4 months from initial diagnosis. Final PTH was 916.8pg/mL. Conclusion PTH is a normally secreted by parathyroid gland chief cells, which are part of the embryonic neural crest cells found in various neuroendocrine tissues. It is plausible that malignancies with neuroendocrine features may secrete neuropeptides including PTHrP and PTH. Few case reports exist describing PTH secretion by neuroendocrine tumors, though most common are tumors of gastroenteropancreatic origin. PTH stain and focal chromogranin tends to be negative with poorly differentiated neuroendocrine tumors. PTH gene is usually intact and upregulation of the regulator sequence of PTH gene promotor is suspected to be the mechanism of elevated PTH levels and hypercalcemia. This case demonstrates the potential for poorly differentiated neuroendocrine malignancies to cause hypercalcemic crises from paraneoplastic secretion of PTH. Presentation: No date and time listed

ODP278 A rare case of Ectopic ACTH secretion associated with Primary Gastric Choriocarcinoma

Abstract Background Ectopic ACTH production contributes to 10-15% of cases of Cushing's syndrome. Most cases are caused by neuroendocrine tumors of the lung, pancreas, or thymus. Other rare tumors causing ectopic ACTH secretion include esophageal tumor, gastric carcinoid tumor and squamous cell carcinoma of the larynx (1). We present a rare case of ectopic ACTH production causing Cushing syndrome due to primary gastric choriocarcinoma. Case Presentation A 27-year-old lady, not known to have any chronic illnesses, presented with two days history of epigastric pain. The patient also reported facial puffiness, leg swelling, generalized weakness and oligomenorrhea for the last four months. There was no history of easy bruisability or weight. She was not taking any medications. The patient did not smoke or use alcohol. Physical examination revealed conjunctival pallor, facial acne, wide striae on her thighs and hepatomegaly. The rest of the examination was normal. Lab tests showed microcytic anemia with hemoglobin of 7 gm/dl (12-15 gm/dl), hypokalemia (2.5 mmol/L; normal 3.5-5.3 mmol/L), AST 38 U/L (0-40 U/L) and ALT 45 U/L (0-41 U/L). β HCG was 1,506 mIU/mL (0 -5 mIU/ml). An abdominal ultrasound showed hepatomegaly with multiple echogenic solid mass lesions suspicious of metastatic origin. A CT abdomen showed a solid lesion in the fundal region of the stomach with multiple liver metastases and moderate ascites. An esophagogastroduodenoscopy showed fungating mass originating from the stomach fundus. Biopsy of the gastric mass revealed primary gastric adenocarcinoma, which was positive forCK 7, CK 19, beta hCG, CDX2 and CEA, consistent with the diagnosis of primary gastric choriocarcinoma. Due to widespread metastasis, the patient was started on palliative chemotherapy with dexamethasone 2 mg injection once daily along with capecitabine, cisplatin and pembrolizumab. In view of persistent hypokalemia and physical examination findings, a workup for Cushing's syndrome was performed. Early-morning serum cortisol was 1054 nmol/L (138–689 nmol/L), and plasma ACTH was 174 pg/ml (7.2-63.3 pg/ml) despite the patient being on intravenous 2 mg dexamethasone once daily for more than ten days. An MRI of the brain showed a normal pituitary gland. Based on these findings, the patient was diagnosed with Cushing's syndrome due to ectopic ACTH secretion. Unfortunately, her hospital course was complicated by massive upper gastrointestinal bleeding from the tumor, leading to her demise. Conclusion Gastric choriocarcinoma is a rare tumor associated with ectopic ACTH secretion leading to Cushing's syndrome. Reference: Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer. 1975 May;35(5): 1430-7 Presentation: No date and time listed

Robotic-Assisted Thoracoscopic (RATS) Enucleation of Esophageal Mesenchymal Tumors and Foregut Cysts.

Background: Esophageal mesenchymal tumors and foregut cysts are mostly benign lesions of the esophagus. Tumor enucleation is recommended for lesions with a risk of malignancy, or for the relief of clinical symptoms. Although robotic-assisted thoracoscopic enucleation of esophageal tumors and cysts has been demonstrated in sporadic case reports, its clinical role is yet to be elucidated. Methods: This study aimed to present the first case series in the literature for the perioperative and long-term clinical outcomes of robotic-assisted thoracoscopic enucleation. Results: A total of 19 patients who underwent robotic-assisted thoracoscopic enucleation of esophageal tumors and cysts from 2012 to 2019 were included in the study. The mean tumor/cyst size was 5.5 cm (1.5-22 cm). There were two cases shifting to minimally invasive esophagectomy (10.5%) due to intraoperative pathological confirmation of malignant gastrointestinal stromal tumors with mucosal invasion. Perioperative complication was detected in three (15.8%) cases, without 30-day or surgical mortality. There was no recurrence of tumor or symptoms in all patients during the clinical follow-up period (mean = 35 months). Conclusions: Robotic-assisted thoracoscopic enucleation of esophageal submucosal benign tumors is technically feasible and effective. Given its advantage in overcoming spatial limitations, it can become a widely accepted surgical option for such diseases.

Feasibility of Pretreatment FDG PET Radiomics in Predicting Complete Pathological Response after Neoadjuvant Concurrent Chemoradiotherapy for Esophageal Cancer

<h3>Purpose/Objective(s)</h3> To investigate the feasibility in predicting the pathological complete pathological response (pCR) of esophageal tumors after neoadjuvant concurrent chemoradiotherapy (CCRT) using pretreatment 18-fluorodeoxyglucose positron emission tomography (FDG PET) images. <h3>Materials/Methods</h3> This study retrospectively included 60 esophageal tumors of 59 patients from November 2012 to August 2021. All patients received neoadjuvant CCRT followed by radical surgery. The FDG PET examination before CCRT was used for evaluation. First, the maximum standardized uptake value (SUVmax) within a tumor was identified and then utilized to form a metabolic tumor volume (MTV) by grouping a set of voxels connecting to the SUVmax and with SUV not less than SUVmax * 0.5. Next, the texture indices were further calculated to describe the heterogeneity of the FDG uptakes discretized as gray level (GL) within MTV. Finally, receiver operating characteristic (ROC) curves analysis assessed the predictive performance of each index. In the analysis, pCR was defined as a positive event. <h3>Results</h3> Fifty-seven out of 59 patients were men (57/59, 96.6%). The number of tumors located at the upper, middle, and lower third of the esophagus were 9, 12, and 39, respectively. Ninety-five percent of the tumors were squamous cell carcinomas (57/60, 95%). Seventeen tumors of 17 patients were proved as pCR (17/60, 28.3%). The Chi-square test demonstrated that the associations between treatment response (pCR and non-pCR) and tumor location, clinical T, and N stage were insignificant (p=.16, .193, and .254). The SUVmax demonstrated a significant ability in identifying pCR tumors (AUC=.694, p=.013), whereas MTV was nonsignificant. The tumors with high metabolic uptake corresponded to a high probability of pCR. The texture indices, including GL nonuniformity normalized, low GL zone emphasis, and small area low GL emphasis of zones, GL nonuniformity normalized, long run low GL emphasis, low GL run emphasis, and short run low GL emphasis of runs, and low GL emphasis and small dependence low GL emphasis of GL dependencies, exhibited a significant ability to differentiate pCR from non-pCR tumors (AUC=.331, .289, .298, .339, .311, .311, .316, .312, and .302). These texture indices reflected that a low evaluation corresponded to a high likelihood of pCR. The tumors with a low or low uptake associated with small areas demonstrated a high probability of non-pCR. <h3>Conclusion</h3> This study revealed that pCR for esophageal cancer tumors could be predicted using metabolic and texture indices. Future studies are warranted for clinical application.

Brain Metastases in Stage IV Esophageal Cancer: Incidence, Risk Factors and Radiation Utilization

<h3>Purpose/Objective(s)</h3> Limited studies indicate that brain metastases from esophageal cancer are uncommon and associated with poor prognosis. This National Cancer Database (NCDB) study investigated the incidence and risk factors associated with brain metastases at diagnosis for Stage IV esophageal cancer patients, as well as radiation utilization and outcomes. <h3>Materials/Methods</h3> The NCDB was used to identify newly diagnosed Stage IV esophageal cancer patients with brain metastases between 2010-2017. A multivariate logistic regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for brain metastases at diagnosis. Survival analysis was performed using the Kaplan-Meier method and Cox regression modeling. The multivariate model included age, gender, race, insurance status, income, facility type, Charlson-Deyo comorbidity score, histology, and tumor location. <h3>Results</h3> Of 23,930 patients diagnosed with Stage IV esophageal cancer, 1,532 (6.4%) patients had brain metastases. There was no significant change in the incidence of brain metastases over time with 6.1% in 2010 to 6.6% in 2017 (range: 5.7-7.4%; p=0.27). Patients who were older (aOR 0.98 [95% CI 0.98-0.99]; p<0.0001), female (aOR 0.81 [0.69-0.96]; p=0.015), or Black (aOR 0.77 [0.60-0.99]; p=0.045) were less likely to present with brain metastases. Mid esophageal tumors had higher probability of brain metastases vs. lower esophageal location (aOR 1.55 [1.27-1.89]; p<0.0001). Adenocarcinoma histology was strongly associated with increased risk of brain metastases vs. squamous cell carcinoma (aOR 2.41 [1.97-2.95]; p<0.0001). Of 679 patients with brain metastases who received brain radiotherapy as part of their primary treatment, 504 (74.2%) received whole-brain radiotherapy (WBRT) and 175 (25.8%) received stereotactic radiosurgery (SRS). The use of WBRT decreased over time from 86.4% in 2010 to 72.7% in 2017, while the use of SRS increased from 13.6% in 2010 to 27.3% in 2017 (p=0.035). For patients who received brain radiotherapy, median follow-up was 5.1 months and median survival was 5.2 months. Median survival for patients who received WBRT was 4.5 months vs. 7.8 months for SRS patients (p=0.0001). On multivariate analysis, SRS was associated with improved survival vs. WBRT (hazard ratio [HR] 0.72 [0.59-0.89]; p=0.002). <h3>Conclusion</h3> Approximately 6% of patients with Stage IV esophageal cancer present with brain metastases, with no change in incidence from 2010 to 2017. Older, female, or Black patients were less likely to present with brain metastases, while adenocarcinoma histology and mid esophagus location were significant risk factors for synchronous brain metastases. While survival rates remain dismal, SRS is associated with improved survival vs. WBRT, and its utilization in this population is increasing over time.