Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer?

OPINION STATEMENT: This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area.

Pre-operative psoas muscle index, a surrogate for sarcopenia; as a predictor of post-esophagectomy complications.

BACKGROUND: Esophagectomy is the standard of care for curative esophageal cancer. However, it is associated with significant morbidity and mortality. Esophageal cancer is known to negatively affect the nutritional status of patients and many manifest cancer sarcopenia. At present, measures of sarcopenia involve complex and often subjective measurements. We assess whether the Psoas Muscle Index (PMI); an inexpensive, simple, validated method used to diagnose sarcopenia, can be used to predict adverse outcomes in patients after curative esophagectomy. METHODS: Multi-centre, retrospective cohort between 2010-2020, involving all consecutive patients undergoing curative esophagectomy for esophageal cancer in University Malaya Medical Centre, Sungai Buloh Hospital, and Sultanah Aminah Hospital. The cut-off value differentiating low and normal PMI is defined as 443mm2/m2 in males and 326326 mm2/m2 in females. Complications were recorded using the Clavien-Dindo Scale. RESULTS: There was no statistical correlation between PMI and major post-esophagectomy complications (p-value: 0.495). However, complication profile was different, and patients with low PMIs had higher 30-day mortality (21.7%) when compared with patients with normal PMI (8.1%) (p-value: 0.048). CONCLUSIONS: Although PMI did not significantly predict post-esophagectomy complications, low PMI correlates with higher 30-day mortality, reflecting a lower tolerance for complications among these patients. PMI is a useful, inexpensive tool to identify sarcopenia and aids the patient selection process. This alerts healthcare professionals to institute intensive physiotherapy and nutritional optimization prior to esophagectomy.

Impact of aspirin use on rates of metastasis in patients with esophageal cancer: insights from the National Inpatient Sample.

Despite advancing treatment methods, esophageal cancer (EC) maintains a high mortality rate and poor prognosis. Through various mechanisms, aspirin has been suggested to have a chemopreventive effect on EC. However, the long-term impact, particularly regarding the rate of metastasis, needs to be further elucidated. NIS 2016-2020 was used to identify adult patients (age > 18 years) with EC using ICD-10 codes. Patients with missing demographics and mortality were excluded. Patients were stratified into two groups based on aspirin use. Data were collected on patient demographics, Elixhauser Comorbidity Index (ECI), and comorbidities (hypertension, chronic pulmonary disease, coronary artery disease (CAD), chronic kidney disease (CKD), congestive heart failure (CHF), coagulopathy, alcohol use, smoking, and obesity). The outcomes studied were rates of total metastasis, gastrointestinal (GI) metastasis, non-GI metastasis, and lymphoid metastasis. Multivariate logistic regression analysis was performed to evaluate the impact of aspirin use on various metastases after adjusting for patient demographics, comorbidities, and ECI. Out of 190,655 patients, 20,650 (10.8%) patients were aspirin users. Majority of the patients in the aspirin group were aged > 65 years (74.7%), males (82.1%), White race (84%), and had medicare insurance (71%). There was a higher incidence of diabetes, hypertension, chronic pulmonary disease, CAD, CKD, CHF, and smoking in aspirin users than non-aspirin users. Patients with aspirin users had a lower incidence of metastasis (28.9% vs. 38.7%, P < 0.001), GI metastasis (14.2% vs. 20.6%, P < 0.001), non-GI metastasis (15.1% vs. 22%, P < 0.001), and lymphoid metastasis (8.9% vs. 11.3%, P < 0.001) than non-aspirin users. After adjusting for confounding factors, patients with aspirin use had lower odds of having metastasis (aOR-0.73, 95% CI-0.70-0.77, P < 0.001). Our study noted that aspirin use is associated with a reduction in the rate of metastasis in patients with EC. These studies support the use of aspirin in patients with EC and suggest the need for further studies to understand the mechanism by which aspirin use reduces metastasis in patients with EC.

Performance of radiomics-based artificial intelligence systems in the diagnosis and prediction of treatment response and survival in esophageal cancer: a systematic review and meta-analysis of diagnostic accuracy.

Radiomics can interpret radiological images with more detail and in less time compared to the human eye. Some challenges in managing esophageal cancer can be addressed by incorporating radiomics into image interpretation, treatment planning, and predicting response and survival. This systematic review and meta-analysis provides a summary of the evidence of radiomics in esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE, and Ovid EMBASE databases-articles describing radiomics in esophageal cancer were included. A meta-analysis was also performed; 50 studies were included. For the assessment of treatment response using 18F-FDG PET/computed tomography (CT) scans, seven studies (443 patients) were included in the meta-analysis. The pooled sensitivity and specificity were 86.5% (81.1-90.6) and 87.1% (78.0-92.8). For the assessment of treatment response using CT scans, five studies (625 patients) were included in the meta-analysis, with a pooled sensitivity and specificity of 86.7% (81.4-90.7) and 76.1% (69.9-81.4). The remaining 37 studies formed the qualitative review, discussing radiomics in diagnosis, radiotherapy planning, and survival prediction. This review explores the wide-ranging possibilities of radiomics in esophageal cancer management. The sensitivities of 18F-FDG PET/CT scans and CT scans are comparable, but 18F-FDG PET/CT scans have improved specificity for AI-based prediction of treatment response. Models integrating clinical and radiomic features facilitate diagnosis and survival prediction. More research is required into comparing models and conducting large-scale studies to build a robust evidence base.

The role of artificial intelligence in the endoscopic diagnosis of esophageal cancer: a systematic review and meta-analysis.

Early detection of esophageal cancer is limited by accurate endoscopic diagnosis of subtle macroscopic lesions. Endoscopic interpretation is subject to expertise, diagnostic skill, and thus human error. Artificial intelligence (AI) in endoscopy is increasingly bridging this gap. This systematic review and meta-analysis consolidate the evidence on the use of AI in the endoscopic diagnosis of esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE and Ovid EMBASE databases and articles on the role of AI in the endoscopic diagnosis of esophageal cancer management were included. A meta-analysis was also performed. Fourteen studies (1590 patients) assessed the use of AI in endoscopic diagnosis of esophageal squamous cell carcinoma-the pooled sensitivity and specificity were 91.2% (84.3-95.2%) and 80% (64.3-89.9%). Nine studies (478 patients) assessed AI capabilities of diagnosing esophageal adenocarcinoma with the pooled sensitivity and specificity of 93.1% (86.8-96.4) and 86.9% (81.7-90.7). The remaining studies formed the qualitative summary. AI technology, as an adjunct to endoscopy, can assist in accurate, early detection of esophageal malignancy. It has shown superior results to endoscopists alone in identifying early cancer and assessing depth of tumor invasion, with the added benefit of not requiring a specialized skill set. Despite promising results, the application in real-time endoscopy is limited, and further multicenter trials are required to accurately assess its use in routine practice.

Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study.

Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

Contemporary outcomes of esophageal and gastroesophageal junction neuroendocrine tumors.

Adenocarcinoma and squamous cell esophageal cancers have been extensively studied in the literature. Esophageal neuroendocrine (NET)/carcinoid tumors are less commonly studied and have only been described in small series. The purpose of this study was to describe the demographics and natural history of esophageal NETs, as well as optimal treatments. We hypothesized that surgical resection would be the best treatment of esophageal NETs. The National Cancer Database was used to identify adult patients with esophageal or gastroesophageal junction (GEJ) cancer from 2004 to 2018. Patients were characterized as carcinoid/NET, adenocarcinoma, or squamous cell cancer. Clinical and demographic characteristics were compared between the histology groups. The primary outcome was overall survival, which was assessed by multivariable Cox analysis. Multivariable Cox analysis was also used to analyze factors associated with survival among NET patients who underwent surgery. Among 206,321 patients with esophageal cancer, 1,563 were NETs (<0.01%). Relative to the other two histologies, NETs were associated with younger age, female sex, and advanced clinical stage at diagnosis. Multivariate analysis suggested that NETs were less likely to be treated with surgical resection (OR 0.51, P < 0.001). Nonetheless, surgical resection was associated with improved survival (HR 0.64, P = 0.003). Among patients with NETs who received surgery, neoadjuvant therapy was associated with improved overall survival (HR 0.38, P = 0.013). NET of the esophagus presents with more advanced disease than other common histologies. Among patients with nonmetastatic cancer, surgical resection appears to be the best treatment. Neoadjuvant systemic therapy may offer survival benefit, but future studies are necessary.

Clinical predictors of special type of esophageal cancer.

BACKGROUND: Esophageal cancers with a histological type other than the two major types, squamous cell carcinoma (SCC) and adenocarcinoma, are referred to as "special type of esophageal cancer" (STEC). STEC is rare and difficult to diagnose preoperatively. Therefore, we aimed to clarify the clinicopathological findings of STEC, including magnifying endoscopy with narrow band imaging (ME-NBI). METHODS: We reviewed 1133 lesions in 936 consecutive cases who underwent endoscopic resection or surgical resection for primary esophageal cancer. Patients were classified into the SCC group and the STEC group, respectively. Factors that predict STEC endoscopically, as well as clinicopathologic features of STEC compared to SCC, were examined. RESULTS: Twenty-eight STECs were diagnosed in 28 patients: 15 with basaloid squamous cell carcinoma, 6 with adenosquamous carcinoma, 4 with mucoepidermoid carcinoma, 1 with carcinosarcoma, 1 with salivary duct-type carcinoma, and 1 with neuroendocrine cell carcinoma. There was significantly more pT1b or deeper cancer (60.7% vs. 12.8%), lymphovascular invasion (50.0% vs. 11.1%) and elevated type (53.6% vs. 16.1%) in the STEC group. The proportion of lesions with type R vessels on ME-NBI was significantly higher in the STEC group (46.4% vs. 3.9%). The STEC group had significantly lower accuracy of ME-NBI for prediction of depth (64.3% vs. 83.5%) and a greater proportion of underestimated lesions (32.1% vs. 9.3%). In the multivariate analysis, the histopathology of STEC was associated with type R vessels on ME-NBI. CONCLUSION: Type R vessels and submucosal tumor-like elevation might be the clinical predictors of STEC.

Pre-existing and new-onset depression among patients undergoing esophageal cancer surgery: a nationwide cohort study in South Korea.

BACKGROUND: Esophageal cancer is believed to be related to psychological stress. This study aimed to examine the prevalence and risk factors for new-onset depression after esophageal cancer surgery among patients who had no pre-existing depression. In addition, we examined whether pre-existing depression affected postoperative 1-year mortality. METHODS: The National Health Insurance Service database in South Korea was used for data extraction in this population-based cohort study. This study included all adult patients diagnosed with esophageal cancer who underwent esophageal surgery between January 1, 2011, and December 31, 2018. RESULTS: A total of 7039 adult patients who underwent esophageal cancer surgery at 95 South Korean hospitals were included in the analyses. Of the total, 608 patients (8.6%) were diagnosed with new-onset depression within 1 year after esophageal cancer surgery. Female sex, adjuvant chemotherapy, increased Charlson comorbidity index, pre-existing anxiety disorder, and pre-existing insomnia disorder were potential risk factors for new-onset depression. In multivariable Cox regression analysis, the pre-existing depression group showed a 1.27-fold (hazard ratio: 1.27; 95% confidence interval: 1.08-1.48; P = 0.004) higher risk of 1-year all-cause mortality than those who had no pre-existing depression. CONCLUSION: In South Korea, 8.6% of patients are newly diagnosed with depression after esophageal cancer surgery, and some potential risk factors have been identified. Moreover, pre-existing depression was associated with increased 1-year all-cause mortality. Patients with esophageal cancer and pre-existing depression may be at high risk, requiring interventions after esophageal cancer surgery.

Impact of standardized clinical pathways on esophagectomy: a systematic review and meta-analysis.

Esophageal surgery is historically associated with adverse postoperative outcomes. Selected high-volume centers have previously reported the effect on clinical outcomes following the adoption of a standardized clinical pathway (SCP). This meta-analysis aims to evaluate the current literature to document the effect of SCP and enhanced recovery after surgery (ERAS) on esophagectomy outcomes. A literature search was conducted through the main search engines (PubMed, Embase, Medline, and Cochrane database) in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. All eligible comparative studies (randomized control trial, prospective, retrospective, and combined) were identified and assessed based on Methodological Index for Non-Randomized Studies and Jadad quality criteria. Data concerning overall morbidity, early mortality, and length of stay (LOS) were primarily collected and compared. Secondary outcomes included anastomotic leaks, pulmonary complications, and readmission rate. Twenty-six articles (including five randomized controlled trials and six prospective trials) were included in the analysis. Overall study quality was moderate and the included studies utilized a variable approach to SCP. No statistically significant differences were found between groups in terms of overall morbidity, postoperative mortality, anastomotic leak, and readmission rates. Significant improvements included pulmonary complications (odds ratios [OR] 0.66, 95% confidence interval [CI] 0.49-0.94) and hospital LOS (OR -3.68, 95% CI -4.49 to -2.87). Previous reports of SCP within esophagectomy programs have demonstrated clinical improvements in postoperative pulmonary complications and LOS. Given the high heterogeneity historically demonstrated within SCPs, further improvement in outcomes should be expected following the adoption of standardized ERAS guidelines.

Laparoscopic transhiatal esophagectomy in esophageal cancer patients with high-risk post-operative complications.

Surgical treatment of esophageal cancer is challenging, due to considerable morbidity, especially in high surgical risk patients. While transhiatal esophagectomy leads to good oncological outcomes and reduced postoperative complications, less invasive techniques might further improve outcomes. Our goal was to compare results of laparoscopic transhiatal esophagectomy (LTE) with open transhiatal esophagectomy (OTE) in esophageal cancer patients at high surgical risk. From 2014 to 2020, 128 patients were identified. Seventy received OTE while 51 received LTE. After propensity score matching (1:1), postoperative complications, analysis of overall and disease-free survival, and survival-related prognostic factors were assessed in two groups of 48 patients. Ninety-one (77%) patients were men with a mean age of 65 ± 10.3 years. Those who underwent OTE experienced more clinical and surgical complications. In LTE patients, the number of mean resected lymph nodes was 25.9, and in patients who had OTE, it was 17.4 (P < 0.001). Overall survival was 56.0% in the LTE group and 33.6% (P = 0.023) in the OTE group. In multivariable analysis of overall survival, open surgery and incomplete pathological response were seen as worse negative factors. In multivariable analysis, metastatic lymph nodes, incomplete pathologic response, surgical complications, and a Charlson's index > 2 (P = 0.014) were associated with poor prognosis. Both surgical methods are safe with similar morbidity and mortality; however, LTE was associated with fewer complications, a higher number of resected lymph nodes, better overall survival, and more prognostic factors related to global and disease-free overall survival in high-risk patients.

Quantitative perfusion assessment of gastric conduit with indocyanine green dye to predict anastomotic leak after esophagectomy.

Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green fluorescence angiography as a predictor for cervical esophagogastric anastomotic leak after esophagectomy. Indocyanine green fluorescence angiography using the SPY Elite system was performed in patients undergoing a transhiatal or McKeown esophagectomy from July 2015 through December 2020. Ingress (dye uptake) and Egress (dye exit) at two anatomic landmarks (the tip of a conduit and 5 cm from the tip) were assessed. The collected data in the leak group and no leak group were compared by univariate and multivariable analyses. Of 304 patients who were evaluated, 70 patients developed anastomotic leak (23.0%). There was no significant difference in patients' demographic between the groups. Ingress Index, which represents a proportion of blood inflow, at both the tip and 5 cm of the conduit was significantly lower in the leak group (17.9 vs. 25.4% [P = 0.011] and 35.9 vs. 44.6% [P = 0.019], respectively). Ingress Time, which represents an estimated time of blood inflow, at 5 cm of the conduit was significantly higher in the leak group (69.9 vs. 57.1 seconds, P = 0.006). Multivariable analysis suggested that these three variables can be used to predict future leak. Variables of gastric conduit perfusion correlated with the incidence of cervical esophagogastric anastomotic leak. Intraoperative measurement of gastric conduit perfusion can be predictive for anastomotic leak following esophagectomy.

Learning curve for robot-assisted Ivor Lewis esophagectomy.

This study aimed to demonstrate the learning curve of robot-assisted minimally invasive esophagectomy (RAMIE). A retrospective analysis of the first 124 consecutive patients who underwent RAMIE with intrathoracic anastomosis (Ivor Lewis) by a single surgeon between May 2015 and August 2020 was performed. An risk-adjusted cumulative sum (RA-CUSUM) analysis was applied to generate a learning curve of RAMIE considering the major complication rate, which reflected the technical proficiency. The overall 30-day morbidity rate was 38.7%, while the major complication rate was 25.8%. The learning curve was divided into two phases based on the RA-CUSUM analysis: phase I, the initial learning phase (cases 1-51) and phase II, the proficiency phase (cases 52-124). As we compared the proficiency phase with the initial learning phase, significantly decreased trends were observed in relation to the major complication rate (37.3% vs. 18.7%, P = 0.017), total operation time (330.9 ± 55.6 vs. 267.3 ± 39.1 minutes, P < 0.001), and length of hospitalization (10 [IQR, 9-14] days vs. 9 [IQR, 8-11] days, P = 0.034). In conclusion, the learning curve of RAMIE consisted of two phases, and at least 51 cases were required to gain technical proficiency.

Importance of long-term surveillance after curative esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: The long-term outcomes after esophagectomy for esophageal cancer remain uncertain and the optimal surveillance strategy after curative surgery remains controversial. METHODS: In this study, the clinicopathological characteristics of patients who underwent curative thoracic esophagectomy between 1991 and 2015 at Toranomon Hospital were retrospectively analyzed and reviewed until December 2020. We evaluated the accumulated data regarding the pattern and rates of recurrence and second malignancy. RESULTS: A total of 1054 patients were eligible for inclusion in the study. Of these, 97% were followed up for 5 years, and the outcomes after 25 years could be determined in 65.5%. Recurrence was diagnosed in 318 patients (30.2%), and the most common pattern was lymph node metastasis (n = 168, 52.8%). Recurrence was diagnosed within 1 year in 174 patients (54.7%) and within 3 years in 289 (90.9%). Second malignancy possibly occurred through the entire study period after esophagectomy even in early-stage cancer, keeping 2%-5% of the incidental risk. There was no significant difference in the prognosis between 3-year survivors with and without a second malignancy. CONCLUSIONS: Most recurrences after resection of esophageal cancer occurred within 3 years regardless of disease stage. However, these patients have an ongoing risk of developing a second malignancy after esophagectomy. Further consideration is required regarding the efficacy of long-term surveillance.

Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy.

Gastroesophageal adenocarcinoma (GEA) and squamous esophageal cancer (ESCC) are responsible for >1 million deaths annually globally. Until now, patients with metastatic GEA and ESCC could anticipate survival of <1 year. Anti- programmed cell death protein 1 (anti-PD-1) monotherapy has demonstrated modest efficacy in previously treated GEA and ESCC. In 2020, four pivotal trials have established anti-PD-1 therapy as a new standard of care for selected GEA and ESCC patients as first-line advanced and adjuvant therapy. In this review, we discuss the recent results of the CheckMate 649, ATTRACTION-4, KEYNOTE-590 and CheckMate 577 trials. We consider these results in the context of current standards of care and historical trials of immune checkpoint blockade in GEA and ESCC. We explore biomarker selection for anti-PD-1 therapy and appraise the future of combination therapies. In CheckMate 649, treatment with oxaliplatin-fluoropyrimidine chemotherapy plus nivolumab in patients with combined positive score ≥5 GEA tumors provided a clinically meaningful and statistically significant improvement in overall survival. The ATTRACTION-4 trial did not see a similar overall survival benefit, despite a clear improvement in progression-free survival. We review potential explanations for this result. KEYNOTE-590 showed profoundly improved survival when pembrolizumab was added to cisplatin-fluoropyrimidine chemotherapy in ESCC patients with combined positive score ≥10 tumors; this benefit was less convincing in unselected ESCC. Finally, CheckMate 577 provides proof-of-concept for the improvement in disease-free survival with adjuvant nivolumab in high-risk resected GEA and ESCC following trimodality therapy. Immune checkpoint blockade has come of age in GEA and ESCC, and will now be integrated into first-line and earlier lines of therapy, providing benefit for a larger proportion of patients. Biomarker standardization will be critical to select the patients most likely to benefit from treatment. For patients with immune evasive tumors, novel combinations under development show promise; however, global trials are needed.

Comparison of Esophagectomy outcomes between a National Center, a National Audit Collaborative, and an International database using the Esophageal Complications Consensus Group (ECCG) standardized definitions.

The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data from the Irish National Center (INC) with both published benchmark studies. All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied, with data recorded prospectively and entered onto a secure online database (Esodata.org). 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%,nrespectively. Anastomotic leak rate was 5.4%, pneumonia 18.2%, respiratory failure 10%, ARDS 2.7%, atrial dysrhythmia 22.8%, recurrent nerve injury 3%, and delirium in 5% of patients. Compared with both ECCG and DUCA, where MIE constituted 47 and 86% of surgical approaches, respectively, overall complications were similar, as were severity of complications; however, anastomotic leak rate was several-fold less, and mortality was significantly lower (P < 0.001). In this consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publications, a low mortality and anastomotic leak rate were the key differential findings. Although not risk stratified, the severity of complications from this 'open' series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.

Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature.

Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 µg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 µg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

Impact of histology classification on pathologic treatment response and overall survival in distal esophageal cancer patients: a propensity matched analysis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has been linked to superior pathologic treatment response compared to esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiation. However, the impact of histology on survival remains unclear. It has been suggested, based on epidemiologic similarities, that distal EAC should be grouped with gastric cancers as an entity distinct from distal ESCC, but there is little data to support this recommendation. We therefore aim to compare pathologic treatment response (PTR) and overall survival (OS) in patients with distal EAC versus distal ESCC. METHODS: This retrospective cohort study included patients who underwent esophagectomy for distal esophageal malignancy. Histologic sub-groups were matched (1:1) using a propensity-score matching approach. Pre-operative clinical parameters, oncologic outcomes and survival were compared between groups. RESULTS: 1031 distal EC patients, with a median age of 64.4 years and a male preponderance (86.5%), underwent esophagectomy at our institution between 1999 and 2019. 939 (91.1%) patients had a diagnosis of EAC and 92 (8.9%) had ESCC. A higher proportion of ESCC patients were female (26.1% vs. 12.1%; P < 0.01) and non-white (12.0% vs. 3.8%; P < 0.01). Propensity-score sub-analysis identified 75 matched pairs. Rates of pathologic complete response (58.0% vs. 48.9%; P = 0.67) and OS (43.0 vs. 52.0 months; P = 0.808) were not significantly different between matched groups. CONCLUSIONS: Although traditionally known to have a better overall PTR compared to EAC, ESCC patients in our large series did not show any improvement in PTR or OS. Treatment recommendations for patients with EAC and ESCC should consider tumor location in addition to histology.

Minimally invasive esophagectomy is associated with superior survival, lymphadenectomy and surgical margins: propensity matched analysis of the National Cancer Database.

Despite excellent short-term outcomes of minimally invasive esophagectomy (MIE), there is minimal data on long-term outcomes compared to open esophagectomy. MIE's superior visualization may have improved lymphadenectomy and complete resection rate and therefore improved long-term outcomes. We hypothesized that MIE would have superior long-term survival. Patients undergoing an esophagectomy for cancer between 2010 and 2016 were identified in the National Cancer Database. MIE included laparoscopic/robotic approach, and conversions were categorized as open. A 1:1 propensity match was performed. Lymphadenectomy and margin status were compared between MIE and open using Stuart Maxwell marginal homogeneity and Wilcoxon matched-pair signed-rank test. Survival was compared using log-rank test. 13,083 patients were identified: 8,906 (68%) open and 4,177 (32%) MIE. Propensity matching identified 3,659 'pairs' of MIE and open esophagectomy patients. Among them, MIE was associated with higher number lymph nodes examined (16 vs. 14, P < 0.001) and similar number of positive lymph nodes (0 vs. 0, P = 0.33). MIE had higher rate of negative pathologic margin (95 vs. 93.5%, P < 0.001). MIE was also associated with shorter hospitalization (9 vs. 10 days, P < 0.001). Survival was improved among MIE patients (46.6 vs. 41.4 months for open, P = 0.003) and among pathologic node-negative patients (71.4 vs. 61.5 months, P = 0.005). These data suggest that MIE has improved short-term outcomes (improved lymphadenectomy, pathologic margins, and length of stay) and also associated improved overall survival. The etiology of superior overall survival is likely secondary to many factors related and unrelated to surgical approach.

The role of home visits by a nurse to improve palliation in patients treated with self-expandable metallic stents due to incurable esophageal cancer.

Self-expandable metallic stent (SEMS) is a preferred option to relieve dysphagia and to palliate patients with incurable esophageal or gastro-esophageal junction (GEJ) cancer. Health Related Quality of Life (QoL) represents a clinically relevant outcome measure in research focused on palliation of patients with advanced GI cancer. In this context, home visits by a nurse carry the potential to offer important advantages. Eighty patients with incurable esophageal or GEJ cancer were randomized to either standard follow up or to an intervention containing regular home visits by a nurse. The primary outcome variable QoL was assessed by EORTC QLQ-C30 and OES-18 before insertion of SEMS, and at 2, 7 and 12 weeks thereafter. Secondary outcomes were; need for re-interventions, number of patients receiving palliative oncological therapy and overall survival. Sixty-six males and 13 females, with a median age of 71, were included. Self-reported overall QoL was significantly higher in the intervention group (P = 0.03). The organ specific module OES-18 revealed a significant reduction in dysphagia by the intervention (P = 0.03) as well as fewer eating disabilities (P = 0.04). No differences were observed in secondary outcomes except for overall survival, where the median survival was increased from 114 to 183 days by the active intervention (P = 0.02). Home visits by a nurse seem to play an important palliative role after placement of SEMS in patients with incurable esophageal or GEJ cancer by improving QoL and may carry the potential to increase overall survival.