Adenocarcinoma Of Distal Esophagus Research Articles

Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

Endoscopic ultrasound performed by surgical approach in a patient with pancreatic lesion and stenosing esophageal adenocarcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) performed in situations of altered anatomy has been described. Thus, in cases of Roux-en-Y gastric by-pass, several approaches have been documented for performing ERCP: by enteroscopy, guided by laparoscopic approach through the gastric remnant, and direct transgastric guided by endoscopic ultrasound through a stent between the reservoir or alimentary loop and the gastric remnant. However, there are clinical situations in which the anatomy is not altered, but there may be pancreatic lesions subsidiary to study by endoscopic ultrasound in situations where the endoscope cannot pass through the esophagus. Therefore, we present the clinical case of a patient with a pancreatic lesion subsidiary to study and a distal esophageal adenocarcinoma that prevented the passage of the endoscope.

OGC V05 Robotic intrathoraxic linear stapled anastomosis following Ivor Lewis oesophagectomy

Abstract Background Ivor lewis oesophagectomy (ILO) for oesophageal cancer (OC) is associated with high morbidity with an anastomotic leak (AL) rate of upto 30% been quoted in literature. This can lead to return to intensive care, delayed recovery and mortality. Several techniques have been developed in an attempt to reduce this risk such as, hand sewn technique, circular anastomosis and side to side linear stapled anastomosis (LSA). Recent meta-analysis suggested reduced AL with LSA. We demonstrate our technique for a totally robotic side to side LSA performed for distal OC. Methods We detail the steps involved in the procedure, including trocar placement, necessary robotic instruments, and surgical description. 74 year old male patient with a BMI of 30 and performance status of 1, underwent robotic ILO for a Siewert type 1 T2N1 distal oesophageal adenocarcinoma after neo-adjuvant chemotherapy. Preoperatively staging investigations included endoscopy, endoscopic ultrasound, computerised tomography (CT) and positron emission tomography (PET). Fitness was assessed using cardio-pulmonary exercise testing (CPET). Results Patient was on the high dependency unit as per our routine practice for less than 24 hours and was transferred to our monitored ward bed. Enhanced recovery after surgery (ERAS) protocol was followed. There were no complications and patient was discharged in 8 days following ILO. Conclusions We demonstrate our technique using side to side LSA for robotic ILO.

S505 A Comparison of Presenting Clinical Symptoms Between Patients With Distal Esophageal Adenocarcinoma and Those With Adenocarcinoma of the Gastroesophageal Junction

S505 A Comparison of Presenting Clinical Symptoms Between Patients With Distal Esophageal Adenocarcinoma and Those With Adenocarcinoma of the Gastroesophageal Junction

The impact of refusing esophagectomy for treatment of locally advanced esophageal adenocarcinoma

ObjectivePatients with esophageal cancer may be reluctant to proceed with surgery due to high complication rates. This study aims to compare outcomes between eligible surgical candidates who proceeded with surgery versus those who refused surgery. MethodsCharacteristics and survival of patients with locally advanced (cT3N0M0, cT1-3N+M0) mid-/distal esophageal adenocarcinoma in the National Cancer Database (2006-2019) who either proceeded with or refused surgery after chemoradiotherapy were evaluated with logistic regression, Kaplan–Meier curves, and Cox proportional hazards methods. ResultsOf the 13,594 patients included in the analysis, 595 (4.4%) patients refused esophagectomy. Patients who refused surgery were older, had less distance to travel to their treatment facility, were more likely to have cN0 disease, and were more likely to be treated at a community rather than academic or integrated network program, but did not have significantly different comorbid disease distributions. On multivariable analysis, refusing surgery was independently associated with older age, uninsured, lower income, less distance to a hospital, and treatment in a community program versus an academic/research or integrated network program. Esophagectomy was associated with better survival (5-year survival 40.1% [39.2-41] vs 23.6% [19.9-27.9], P < .001) and was also independently associated with better survival in the Cox model (hazard rate, 0.78 [95% confidence interval, 0.7-0.87], P < .001). ConclusionsThe results of this study can inform selected patients with resectable esophageal adenocarcinoma that their survival will be significantly diminished if surgery is not pursued. Many factors associated with refusing surgery are non-clinical and suggest that access to or support for care could influence patient decisions.

Ten-year follow-up of endoscopic mucosal resection versus esophagectomy for esophageal intramucosal adenocarcinoma in the setting of Barrett's esophagus: a Canadian experience.

Endoscopic mucosal resection (EMR) is an effective treatment for esophageal intramucosal adenocarcinoma (IMC), with similar recurrence and mortality rates versus esophagectomy in up to 5years of follow-up. Long-term outcomes to 10years have not been studied. This retrospective study investigates IMC eradication, recurrence, morbidity and mortality at 10years following EMR versus esophagectomy in a single Canadian institution. Patients with IMC treated via esophagectomy or EMR from 2006 to 2015 were included. Post-EMR endoscopic follow-up occurred every 3months for 1year, every 6months for 2years and every 12months thereafter. Categorical variables were expressed as percentages and continuous variables as mean with standard deviation or median and interquartile range. The student's t-test and Fischer's exact test were used for comparisons. Survival analysis utilized the Kaplan-Meier estimator and log-rank test. Twenty-four patients were included. Patient and tumor characteristics were similar between groups. Median follow-up for EMR and esophagectomy were 85.2months [IQR 64.8] and 126months [IQR 54] respectively. A mean of 1.3 EMR (SD 1.1) were required for eradication, which was seen in 12 patients (12/14, 86%). No EMR-related complications occurred. Disease progression was seen in two patients (2/14, 14%); local recurrence was seen in 1 patient (1/14, 7%). Esophagectomy eradicated IMC in 10 patients (10/10, 100%); recurrence was seen in 2 (2/10, 20%, metastatic). Major, early esophagectomy-related morbidity affected 3 patients (3/10, 30%), and late morbidity was documented for 9 (9/10, 90%). Esophagectomy and EMR had similar recurrence rates (p = 0.554). Esophagectomy was associated with significantly more procedure-related morbidity (p < 0.001). There was no difference in mortality (p = 0.442) or disease-free survival (p = 0.512) between treatment groups. EMR and esophagectomy for the treatment of IMC are associated with comparable recurrence rates and disease-free survival in 10-year follow-up. EMR is associated with significantly lower procedure-associated morbidity. EMR can be used to treat T1a distal esophageal adenocarcinoma with minimal procedure-related morbidity, and acceptable oncologic outcomes in long-term follow-up.

Facing adenocarcinoma of distal esophagus and esophagogastric junction: a CROSS versus FLOT propensity score-matched analysis of oncological outcomes in a high-volume institution.

Multimodality treatments are the gold standard for advanced resectable gastroesophageal cancer. Neoadjuvant CROSS and perioperative FLOT regimens are adopted for distal esophageal and esophagogastric junction adenocarcinoma (DE/EGJ AC). At present, none of the approaches is clearly superior in the context of a curative-intent multimodal treatment. We analyzed consecutive patients treated with CROSS or FLOT and surgery for DE/EGJ AC between August 2017 and October 2021. Propensity score matching was performed to balance baseline characteristics of patients. The primary endpoint was disease-free survival. Secondary endpoints included overall survival, 90-day morbidity/mortality rates, pathological complete response, margin-negative resection, and pattern of recurrence. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. The 2-year DFS rate was 54.2% versus 64.1% in the CROSS and FLOT group, respectively (p = 0.182). Patients in the CROSS group showed a lower number of harvested LN when compared to the FLOT group (29.5 versus 39.0 respectively, p = 0.005). A higher rate of distal nodal recurrence was found in the CROSS group (23.8% versus 4.8%, p = 0.026). Although not significant, the CROSS group showed a trend toward higher rate of isolated distant recurrence (33.3% versus 21.4% respectively, p = 0.328), together with a higher rate of early recurrence (23.8% versus 9.5% respectively, p = 0.062). FLOT and CROSS regimens for DE/EGJ AC offer similar DFS and OS, together with comparable morbidity/mortality rates. CROSS regimen was associated with a higher distant nodal recurrence rate. Results of ongoing randomized clinical trials are awaited.

Patients with esophageal adenocarcinoma had significantly better outcomes than patients with adenocarcinoma of the gastroesophageal junction.

Recent genomic studies by the Cancer Genome Atlas show much simpler genomic profiles in distal esophageal adenocarcinoma (EAC) than in adenocarcinoma of the gastroesophageal junction (AGEJ). However, the prognostic significance of categorizing patients in these two cancer groups remains unknown. We studied clinicopathologic and prognostic features of both cancers in 303 consecutive patients treated at the Veterans Affairs Boston Healthcare System over a 20-year period. Using uniform criteria and standardized routines, we studied and statistically compared the clinicopathologic and prognostic features between EAC and AGEJ. In this cohort, over 99% of patients were white men with mean age of 69.1 years and an average body mass index of 28.0. No significant difference was detected in age, gender, ethnicity, body mass index, and history of tobacco abuse between the two groups. Compared to AGEJ patients, a significantly higher proportion of EAC patients had gastroesophageal reflux disease, long-segment Barrett's esophagus, common adenocarcinoma type, smaller tumor size, better differentiation, more stages I/II but fewer stages III/IV diseases, scarcer lymphovascular invasion, fewer nodal and distant metastases, and better overall, disease-free, and relapse-free survival. The 5-year overall survival rate was significantly higher in EAC patients (41.3%) than in AGEJ patients (17.2%) (p<0.001). This improved survival among EAC patients remained significant after censoring all cases discovered during surveillance, suggesting different pathogenesis mechanisms between EAC and AGEJ. Our findings suggest that EAC patients showed significantly better outcomes than AGEJ patients. Our results require validation in other patient populations.

Facing adenocarcinoma of distal esophagus and esophago-gastric junction: A CROSS versus FLOT propensity score matching analysis of survival in a single-center institution

Facing adenocarcinoma of distal esophagus and esophago-gastric junction: A CROSS versus FLOT propensity score matching analysis of survival in a single-center institution

186. RECURRENT DISEASE AFTER ESOPHAGEAL CANCER SURGERY; A SUBSTUDY OF THE DUTCH NATIONWIDE IVORY STUDY

Abstract Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. This study investigated the predictors, patterns and survival of recurrent disease following esophageal cancer surgery. This nationwide cohort study included patients with resectable distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma undergoing curatively intended esophagectomy from January 2007 until December 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site (locoregional or distant) and treatment intent (none, palliative, curative) with post-recurrence survival. Among 4626 patients, 45.1% developed recurrent disease at a median of 11 months postoperatively, of whom most had distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Young age (≤65 years), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, non-radical resection, higher T-stage, and (y)pN+ stage were significantly associated with disease recurrence. Overall, median post-recurrence survival was 4 months (95%CI 3.6–4.4). Median survival after locoregional recurrence was 7 months (95%CI 5.7–8.4) and favorable compared to distant recurrence (HR = 0.74, 95%CI 0.65–0.84). For 127 patients that underwent curatively intended treatment for recurrence, median survival was 20 months (95%CI 16.4–23.7). This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half of included patients developed recurrent disease, and risk of recurrence was higher in patients with, amongst others, higher tumor stage, non-radical resection and tumor positive lymph nodes. Overall, patients with recurrent disease had limited prospects of survival, although median survival after curatively intended treatment reached 20 months.

187. ADENOCARCINOMA OF DISTAL ESOPHAGUS AND ESOPHAGO-GASTRIC JUNCTION: CROSS VERSUS FLOT PROPENSITY SCORE MATCHING ANALYSIS OF SURVIVAL IN A SINGLE-CENTER INSTITUTION

Abstract Multimodal treatments are the gold standard for advanced resectable gastroesophageal cancer. The exclusive neoadjuvant, chemoradiation-based CROSS regimen and the perioperative chemotherapy-based FLOT regimen are commonly adopted for adenocarcinoma of distal esophagus and esophago-gastric junction (EGJ). At present, there is no clear evidence of the superiority of either of these two approaches on survival. An intention-to-treat analysis was performed on a cohort of consecutive patients who underwent neoadjuvant CROSS or FLOT regimen and subsequently confirmed to curative-intent surgery for adenocarcinoma of distal oesophagus and EGJ between August 2017 and October 2021. Propensity Score Matching (PSM) was performed in order to balance baseline characteristics of patients undergoing CROSS and FLOT neoadjuvant regimen. The primary endpoint was Overall Survival (OS). Secondary endpoints included Disease-Free Survival (DFS), 90-day morbidity rate, margin status, incidence and pattern of recurrence. Subgroup analyses were performed according to the specific neoadjuvant regimen adopted. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. CROSS and FLOT patients showed similar 1-year OS rate (85.3% and 85.4% respectively, p = 0.189) and 1-year DFS rate (73.3% and 81.3% respectively, p = 0.267). When compared to FLOT patients, CROSS patients reported lower but not significant rates of post-operative severe complications (4.8% vs 11.9%, p = 0.433) and negative margins of resection (95.2% vs 97.6%, p = 1.000). In the CROSS group, 89% of recurrences occurred outside the radiation field. In FLOT group, 69% of patients completed all the 8 expected perioperative cycles. FLOT and CROSS offer similar OS and DFS, together with comparable 90-day morbidity/mortality rates and pathological findings. Both regimens are affected by specific limitations that have to be kept in mind during treatment assessment. The results of ongoing Randomized Controlled Trials are urgently awaited.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

A phase II study of perioperative mFOLFOX plus pembrolizumab combination in patients with potentially resectable adenocarcinoma of the esophageal, gastroesophageal junction (GEJ) and stomach.

4047 Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach. The primary objective is pathological response rate (ypRR with tumor regression score, TRS ≤ 2). Methods: Newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m2, Leucovorin 400mg/m2, 5-FU bolus 400mg/m2, and 5-FU 2400mg/m2 infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Up to 2/10/2021, all 37 patients eligible for the study finished preoperative treatment. 27 had curative intended operations, and all had R0 resection. 5 of 27 (19%) achieved ypCR and 6/27 (22 %) with regression score of 0 in the primary cancer. All except 2 patients (25/27, 93%) had shown pathologic response to the treatment with TRS ≤ 2. 21 patients completed all planned treatment with an average follow-up of 27 months. 2 patients had recurrence/metastatic disease (at 9 and 10 months from the enrollment) with 1 died at 23 months, and the other is still alive at 20 month. The rest patients (19/21) are all free of disease. G3/4 toxicities were reported in 21 of all 37 treated patients. There were no unexpected toxicities. Conclusions: The combination of mFOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe. The preliminary benefit data are very encouraging with ypRR of 93%, ypCR of 19 %, and the long-time survival. The data support the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. In addition, the data supports the staging laparoscopy for peritoneal disease assessment as the standard in resctacbility evaluation. Clinical trial information: NCT03488667.

A phase II study of perioperative mFOLFOX chemotherapy plus pembrolizumab combination in patients with potentially resectable adenocarcinoma of the esophageal, gastroesophageal junction (GEJ), and stomach.

329 Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach with the primary objectives of pathological response rate (ypRR with tumor regression score, TRS ≤ 2). We are reporting the preliminary analyses while the study nears completion. Methods: Patients with newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m2, Leucovorin 400mg/m2, 5-FU bolus 400mg/m2, and 5-FU 2400mg/m2 infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Of 35 patients enrolled (age range 44-86, mean of 65 years; with male:female of 28:7), 33 finished preoperative treatment, 26 had curative intended operations with R0 resection for all, 1 is pending for surgery, and 2 are still on pre-operative treatment. 5 of 26 pts achieved ypCR (19% regression score of 0). All except 2 patients (24/26, 92%) had shown pathologic response to the treatment with TRS ≤ 2. 23/26 (88%) finished post-operative treatment. 20 patients completed all planned treatment with an average follow-up of 22.7 months. Amount them, 2 patients had recurrence/ metastatic disease (at 9 and 10 months, respectively) with 1 died 23.3 months from enrollment, and the rest are all free of disease. G3/4 toxicities were reported in 19 of all 35 treated patients. There were no unexpected toxicities. Conclusions: The combination of FOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe and preliminary benefit data are very encouraging with ypRR of 92% and ypCR of 19% and supporting the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. Clinical trial information: NCT03488667.

The Value of Paratracheal Lymphadenectomy in Esophagectomy for Adenocarcinoma of the Esophagus or Gastroesophageal Junction: A Systematic Review of the Literature

BackgroundThe role of upper mediastinal lymphadenectomy for distal esophageal or gastroesophageal junction (GEJ) adenocarcinomas remains a matter of debate. This systematic review aims to provide a comprehensive overview of evidence on the incidence of nodal metastases in the upper mediastinum following transthoracic esophagectomy for distal esophageal or GEJ adenocarcinoma.MethodsA literature search was performed using Medline, Embase and Cochrane databases up to November 2020 to include studies on patients who underwent transthoracic esophagectomy with upper mediastinal lymphadenectomy for distal esophageal and/or GEJ adenocarcinoma. The primary endpoint was the incidence of metastatic nodes in the upper mediastinum based on pathological examination. Secondary endpoints were the definition of upper mediastinal lymphadenectomy, recurrent laryngeal nerve (RLN) palsy rate and survival.ResultsA total of 17 studies were included and the sample sizes ranged from 10-634 patients. Overall, the median incidence of upper mediastinal lymph node metastases was 10.0% (IQR 4.7-16.7). The incidences of upper mediastinal lymph node metastases were 8.3% in the 7 studies that included patients undergoing primary resection (IQR 2.0-16.6), 4,4% in the 1 study that provided neoadjuvant therapy to the full cohort, and 10.6% in the 9 studies that included patients undergoing esophagectomy either with or without neoadjuvant therapy (IQR 8.9-15.8%). Data on survival and RLN palsy rates were scarce and inconclusive.ConclusionsThe incidence of upper mediastinal lymph node metastases in distal esophageal adenocarcinoma is up to 10%. Morbidity should be weighed against potential impact on survival.

Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery

BackgroundGastric and esophageal cancers are malignant diseases with rising importance in Western countries. To improve oncologic outcome after surgery, it is essential to understand the relevance of germline mutations. The aim of the study was to identify and distinguish clinically relevant single-nucleotide polymorphisms (SNPs).Patients and MethodsIn total, 190 patients with curative oncological resections of gastric and distal esophageal adenocarcinomas at Heidelberg University Hospital were eligible for this study. Outcome differences were determined for each SNP by analysis of clinical variables, survival, and mRNA expression levels.ResultsSignificant survival differences were found on univariate analysis for usual prognostic variables (such as pTNM) and for six SNPs. On multivariate survival analysis, the SNPs rs12268840 (intron variant of MGMT, p = 0.045) and rs9972882 (intron variant of STARD3 and eQTL of PGAP3, p = 0.030) were independent and significant survival predictors along with R status and pT/pN category. Group TT of rs12268840 had the highest rate of second primary carcinoma (30.4%, p = 0.0003), lowest expression of MGMT based on cis-eQTL analysis in normal gastroesophageal tissue (p = 1.99 × 10−17), and worst oncologic outcome. Group AA of rs9972882 had the highest rate of distant metastases pM1 (42.9%, p = 0.0117), highest expression of PGAP3 (p = 1.29 × 10−15), and worst oncologic outcome.ConclusionsTwo intron variant SNPs of MGMT and STARD3 were identified that were significant survival predictors and may influence tumor biology. The data indicate that DNA methylation (MGMT) and malfunction of GPI anchoring (PGAP3) are distinct mechanisms that are relevant for tumor progression and relapse.

Combined Therapy of Locally Advanced Oesophageal and Gastro-Oesophageal Junction Adenocarcinomas: State of the Art and Aspects of Predictive Factors.

Simple SummaryThe optimal treatment strategy for locally advanced distal oesophageal and gastrooesophageal junction (GOJ) adenocarcinoma is currently not clear. Surgery as a main curative modality is usually combined with either preoperative chemoradiotherapy or perioperative chemotherapy. The aim of the review is to provide an overview of current treatment options in locally advanced oesophageal and GOJ adenocarcinomas based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

The value of 18F-FDG-PET testing in the management of esophageal and gastroesophageal junction adenocarcinoma - review.

Preoperative chemoradiotherapy (CRT) and perioperative chemotherapy (CHMT) are a standard of care for distal esophageal and gastroesophageal junction adenocarcinomas. PET/CT using 18F-fluorodeoxyglucose (18F-FDG-PET/CT) is one of the basic staging examinations with a certain prognostic significance and has recently been studied for the possibility of showing prognostic or predictive results suitable for the individualization of treatment strategy. The aim of this review is to map the role of 18-FDG-PET/CT in predicting the response to CHMT and CRT, which could be a starting point for personalized treatment. The change in metabolic activity in the maximum standardized uptake value is most often used to quantify the treatment response; total lesion glycolysis is a volumetric parameter. A method for standardizing measurements was offered in the PERCIST system. Several studies have been published showing that the decrease in metabolic activity after chemotherapy correlates with a surrogate measure of the treatment outcome, which is the degree of tumor regression in the resected tissue, but also with survival or time to progression. The cut-off value separating sensitive and resistant tumors varied from 33 to 78%, the measurement took place either at the end of neoadjuvant treatment or &#8222;early&#8220;, about 2 weeks after the first cycle of CHMT. However, this value has not yet been validated and the parameters of sensitivity, specificity and negative and positive predictive values for the prediction of treatment outcome fluctuated significantly. In the case of preoperative CRT, PET/CT could not predict the complete response to the treatment with satisfactory accuracy. Studies using early metabolic response to change the treatment strategies in non-responders have not yet shown whether changing the treatment in patients without an early metabolic response to CHMT will improve survival. In the case of randomization, a standard arm with a continuation of the original CHMT was never used. Evaluation of an early PET-based response has the potential to modify the treatment in patients who have not demonstrated an early response to CHMT. However, this is not an approach suitable for routine practice outside of clinical trials. So far, it seems possible to use an early metabolic response for small, exploratory studies evaluating new agents and their combinations in the preoperative treatment of localized esophageal cancer or gastroesophageal junction cancer.

Green synthesis of NiO nanoparticles using Calendula officinalis extract: Chemical charactrization, antioxidant, cytotoxicity, and anti-esophageal carcinoma properties

In this study, nickel nanoparticles (NiONPs) have been successfully synthesized in an aqueous medium using the aqueous extract from the leaves of Calendula officinalis. The synthesized NiONPs were characterized using different techniques. According to the XRD analysis, the mean crystal size for NiONPs was found to be 33.17 nm. In addition, SEM images exhibited a uniform spherical morphology with a size of 60.39 nm for the NiONPs. The anti-esophageal carcinoma potentials of C. officinalis leaf aqueous extract, and NiONPs were assessed by the MTT assay against distal esophageal adenocarcinoma (FLO-1), gastroesophageal junction adenocarcinoma (ESO26), human caucasian esophageal carcinoma (OE33), and human esophageal squamous cell carcinoma (KYSE-270) cell lines. This study showed that NiONPs had excellent cell death and anti-cancer effects against esophageal carcinoma cell lines. The IC50 of NiONPs were 380, 263, 229, and 251 µg/mL against FLO-1, ESO26, OE33, and KYSE-270 cell lines, respectively. Among the studied cell lines, the best anti-esophageal cancer activities of NiONPs were gained in the cell line of OE33. The antioxidant activity of NiONPs was investigated using the DPPH test. In the antioxidant test, NiONPs prevented the oxidation of 50% of the DPPH molecules at a concentration of 204 µg/mL. Considering the obtained results, it can be suggested that NiONPs may be administrated as a chemotherapeutic supplement/drug to treat esophageal carcinoma.

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer.

To compare the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) and continuous infusion 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) protocols administered in distal esophageal and gastroesophageal junction (GEJ) tumors in terms of effectiveness and toxicity. Descriptive study. Ankara Oncology Training and Research Hospital, Turkey between 2015 and 2020. Patients diagnosed with distal esophageal and GEJ squamous cell carcinoma (SCC) or adenocarcinoma (ADC), older than 18 years of age, in localised or locally advanced stage were included. Metastatic stages were excluded. Kaplan-Meier was used for survival analysis, log-rank test was performed for comparisons between groups. A total of 25 patients (44.6%) were treated with CROSS protocol (15 distal esophageal and 10 GEJ tumor), 31 patients (55.4%) with GEJ tumors were treated with the FLOT regimen. Eight of the patients who were administered the CROSS protocol before the operation demonstrated complete pathologicial response, no patients in the FLOT group had complete response to the treatment. In patients with GEJ tumors and ADC histopathology, CROSS and FLOT group had similar second years survival (60% and 59.3%, respectively) (p = 0.803). The frequency of neutropenia was significantly higher in the CROSS group compared to the FLOT group (p = 0.004.) Conclusion: Postoperative pathological response rate in the CROSS group was significantly higher compared to the FLOT group. CROSS and FLOT protocols contributed to survival similarly in patients with GEJ ADC, hematological side effects were more pronounced in patients receiving CRT. Key Words: GEJ cancer, Esophageal cancer, Cross, Flot.