Cancer of the Oesophagus
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Cancer of the Oesophagus

The oesophagus (US spelling: esophagus) or gullet is a long hollow muscular tube which connects the throat to the stomach. Oesophageal cancer is a disease where malignant (cancerous) cells arise in the tissues of the oesophagus. The most common symptom is difficulty in swallowing. It can also be associated with weight loss and sometimes pain or discomfort behind the breast bone or in the back - these symptoms should be checked by a doctor but not are sure signs of cancer. There are two main types of oesophageal cancer (depending on how the cells appear under the microscope); approximately half are classed as "squamous cell carcinomas" and half as "adenocarcinomas". People with frequent gastric reflux leading to Barrett's Oesophagus have an increased risk of developing oesophageal cancer.

In 2010, 8,477 people in the UK were diagnosed with oesophageal cancer (Source: Cancer Research UK)

This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Cancer of the Oesophagus Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (8 links)

Information for Health Professionals / Researchers (4 links)

  • PubMed search for publications about Esophageal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Esophageal Cancer
    MeSH term: Esophageal Neoplasms
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Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Wang QL, Lagergren J, Xie SH
Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma.
Gastrointest Endosc. 2019; 89(4):726-732.e2 [PubMed] Related Publications
BACKGROUND AND AIMS: This study aimed to develop a prediction model for identifying individuals at high absolute risk of esophageal squamous cell carcinoma (ESCC) for endoscopic screening at a curable stage based on readily identifiable risk factors.
METHODS: This was a nationwide Swedish population-based, case-control study, including 167 new cases of ESCC and 820 randomly selected control participants. Odds ratios with 95% confidence intervals (CI) were assessed by using multivariable unconditional logistic regression. The discriminative accuracy of the model was assessed by the area under the receiver operating characteristic curve (AUC) with leave-1-out cross validation. Models for projecting individuals' absolute 5-year risk of ESCC were developed by incorporating the age-specific and sex-specific incidence rates and competing risk of death from other causes.
RESULTS: A model including the risk factors age, sex, tobacco smoking, alcohol overconsumption, education, duration of living with a partner, and place of residence during childhood generated an AUC of 0.81 (95% CI, 0.77-0.84). A model based only on age, sex, tobacco smoking, and alcohol overconsumption obtained a similar AUC (0.79; 95% CI, 0.75-0.82). A 5-year follow-up of 355 men aged 70 to 74 years with over 35 years' smoking and alcohol overconsumption history is needed to detect 1 ESCC case. The estimated individuals' absolute 5-year risk of ESCC varied according to the combinations of risk factors.
CONCLUSION: This easy-to-use risk prediction model showed a good discriminative accuracy and had the potential to identify individuals at high absolute risk of ESCC who might benefit from tailored endoscopic screening and surveillance.

Sheikh M, Poustchi H, Pourshams A, et al.
Individual and Combined Effects of Environmental Risk Factors for Esophageal Cancer Based on Results From the Golestan Cohort Study.
Gastroenterology. 2019; 156(5):1416-1427 [PubMed] Related Publications
BACKGROUND & AIMS: Northeast Iran has one of the highest reported rates of esophageal squamous cell carcinoma (ESCC) worldwide. Decades of investigations in this region have identified some local habits and environmental exposures that increase risk. We analyzed data from the Golestan Cohort Study to determine the individual and combined effects of the major environmental risk factors of ESCC.
METHODS: We performed a population-based cohort of 50,045 individuals, 40 to 75 years old, from urban and rural areas across Northeast Iran. Detailed data on demographics, diet, lifestyle, socioeconomic status, temperature of drinking beverages, and different exposures were collected using validated methods, questionnaires, and physical examinations, from 2004 through 2008. Participants were followed from the date of enrollment to the date of first diagnosis of esophageal cancer, date of death from other causes, or date of last follow-up, through December 31, 2017. Proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between different exposures and ESCC.
RESULTS: During an average 10 years of follow-up, 317 participants developed ESCC. Opium smoking (HR 1.85; 95% CI 1.18-2.90), drinking hot tea (≥60°C) (HR 1.60; 95% CI 1.15-2.22), low intake of fruits (HR 1.48; 95% CI 1.07-2.05) and vegetables (HR 1.62; 95% CI 1.03-2.56), excessive tooth loss (HR 1.66; 95% CI 1.04-2.64), drinking unpiped water (HR 2.04; 95% CI 1.09-3.81), and exposure to indoor air pollution (HR 1.57; 95% CI 1.08-2.29) were significantly associated with increased risk of ESCC, in a dose-dependent manner. Combined exposure to these risk factors was associated with a stepwise increase in the risk of developing ESCC, reaching a more than 7-fold increase in risk in the highest category. Approximately 75% of the ESCC cases in this region can be attributed to a combination of the identified exposures.
CONCLUSIONS: Analysis of data from the Golestan Cohort Study in Iran identified multiple risk factors for ESCC in this population. Our findings support the hypothesis that the high rates of ESCC are due to a combination of factors, including thermal injury (from hot tea), exposure to polycyclic aromatic hydrocarbons (from opium and indoor air pollution), and nutrient-deficient diets. We also associated ESCC risk with exposure to unpiped water and tooth loss.

van den Berg JW, Luketich JD, Cheong E
Oesophagectomy: The expanding role of minimally invasive surgery in oesophageal cancer.
Best Pract Res Clin Gastroenterol. 2018 Oct - Dec; 36-37:75-80 [PubMed] Related Publications
Historically, open oesophagectomy was the gold standard for oesophageal cancer surgery. This was associated with a relatively higher morbidity. In the last two decades, we have seen significant improvements in short and long term outcomes due to centralisation of oesophagectomy, multidisciplinary approach, enhanced recovery after surgery programmes, neoadjuvant treatments and advances in minimally invasive oesophagectomy (MIO) techniques. MIO has significantly reduced postoperative morbidity and improved functional recovery, while maintaining comparable long-term oncological outcomes. MIO is technically demanding, and requires a long learning curve. However, it has been proven to be safe and successful in expert centres. This is a review on the current role of MIO in the management of oesophageal cancer.

Xie SH, Lagergren J
Risk factors for oesophageal cancer.
Best Pract Res Clin Gastroenterol. 2018 Oct - Dec; 36-37:3-8 [PubMed] Related Publications
The two main histological subtypes of oesophageal cancer, squamous cell carcinoma and adenocarcinoma, have distinct risk factor profiles. For oesophageal squamous cell carcinoma, tobacco smoking and excess alcohol use are the main risk factors. For adenocarcinoma, gastro-oesophageal reflux disease and obesity are main risk factors, whereas tobacco smoking is a moderately strong risk factor and infection with Helicobacter pylori decreases the risk. Dietary factors may influence the risk of both types of oesophageal cancer. Genetic factors are involved in the aetiology, but their influence is generally low. The striking male predominance in oesophageal adenocarcinoma is unexplained, although sex hormones may play a role. Risk prediction models combining information on multiple risk factors have shown promising potential in identifying high-risk individuals for targeted prevention and early detection, which should prompt further studies. More high-quality research efforts are warranted for better understanding of the aetiology of oesophageal cancer, particularly in developing countries.

Duits LC, Lao-Sirieix P, Wolf WA, et al.
A biomarker panel predicts progression of Barrett's esophagus to esophageal adenocarcinoma.
Dis Esophagus. 2019; 32(1) [PubMed] Article available free on PMC after 28/11/2019 Related Publications
Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.

Graham D, Sever N, Magee C, et al.
Risk of lymph node metastases in patients with T1b oesophageal adenocarcinoma: A retrospective single centre experience.
World J Gastroenterol. 2018; 24(41):4698-4707 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
AIM: To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.
METHODS: Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymph-node metastases, disease-specific mortality and overall survival.
RESULTS: A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with high-risk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (
CONCLUSION: T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good out-comes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.

Edwards P, Davidson M, Calamai V, et al.
Third line treatment of advanced oesophagogastric cancer: A critical review of current evidence and evolving trends.
Cancer Treat Rev. 2018; 71:32-38 [PubMed] Related Publications
There is increasing evidence that treatment beyond second line provides significant survival benefit for selected advanced oesophageal and gastric adenocarcinoma patients, and important randomised controlled trials of both chemotherapy, targeted therapy and immunotherapy have recently been reported in this space. Despite this growing evidence base there are presently no formal guidelines for third line treatment available to clinicians, and as these agents move into routine clinical practice patient selection and rational sequencing of treatment will become an increasingly relevant clinical challenge. This review critically appraises the current evidence base for third line treatment and discusses patient selection, potential predictive biomarkers and future directions for third line treatment in this challenging condition.

Kunzmann AT, Cañadas Garre M, Thrift AP, et al.
Information on Genetic Variants Does Not Increase Identification of Individuals at Risk of Esophageal Adenocarcinoma Compared to Clinical Risk Factors.
Gastroenterology. 2019; 156(1):43-45 [PubMed] Related Publications
We previously developed a tool that identified individuals who later developed esophageal adenocarcinoma (based on age, sex, body mass index, smoking status, and prior esophageal conditions) with an area under the curve of 0.80. In this study, we collected data from 329,463 individuals in the UK Biobank cohort who were tested for genetic susceptibility to esophageal adenocarcinoma (a polygenic risk score based on 18 recognized genetic variants). We found that after inclusion of this genetic information, the area under the curve for identification of individuals who developed esophageal adenocarcinoma remained at 0.80. Testing for genetic variants associated with esophageal adenocarcinoma therefore seems unlikely to improve identification of individuals at risk of esophageal adenocarcinoma.

Cartwright E, Keane FK, Enzinger PC, et al.
Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?
Am Soc Clin Oncol Educ Book. 2018; 38:280-291 [PubMed] Related Publications
Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

Pouw RE, Beyna T, Belghazi K, et al.
A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett's esophagus.
Gastrointest Endosc. 2018; 88(4):647-654 [PubMed] Related Publications
BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices.
METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time.
RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0).
CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).

Fransen L, Berkelmans G, Asti E, et al.
Dis Esophagus. 2018; 31(13):1 [PubMed] Related Publications
Background: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated.
Methods: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses.
Results: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found.
Conclusion: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients.
Disclosure: All authors have declared no conflicts of interest.

Sawas T, Killcoyne S, Iyer PG, et al.
Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts.
Gastroenterology. 2018; 155(6):1720-1728.e4 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis.
METHODS: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM).
RESULTS: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34-0.57; P<.001). In a multivariable analysis, BE with IM was associated with longer survival independent of patient age or sex, tumor stage or location, and BE length (adjusted HR, 0.66; 95% CI, 0.5-0.88; P=.005). In the United Kingdom cohort, patients BE and IM had a reduced risk of death compared with those without (HR, 0.59; 95% CI, 0.5-0.69; P<.001), with continued significance in multivariable analysis that included patient age and sex and tumor stage and tumor location (adjusted HR, 0.77; 95% CI, 0.64-0.93; P=.006).
CONCLUSION: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Peerally MF, Bhandari P, Ragunath K, et al.
Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett's esophagus: a randomized pilot study (BRIDE).
Gastrointest Endosc. 2019; 89(4):680-689 [PubMed] Related Publications
BACKGROUND AND AIMS: Endoscopic resection (ER) is safe and effective for Barrett's esophagus (BE) containing high-grade dysplasia (HGD) or mucosal adenocarcinoma (T1A). The risk of metachronous neoplasia is reduced by ablation of residual BE by using radiofrequency ablation (RFA) or argon plasma coagulation (APC). These have not been compared directly. We aimed to recruit up to 100 patients with BE and HGD or T1A confirmed by ER over 1 year in 6 centers in a randomized pilot study.
METHODS: Randomization was 1:1 to RFA or APC (4 treatments allowed at 2-month intervals). Recruitment, retention, dysplasia clearance, clearance of benign BE, adverse events, healthcare costs, and quality of life by using EQ-5D, EORTC QLQ-C30, or OES18 were assessed up to the end of the trial at 12 months.
RESULTS: Of 171 patients screened, 76 were randomized to RFA (n = 36) or APC (n = 40). The mean age was 69.7 years, and 82% were male. BE was <5 cm (n = 27), 5 to 10 cm (n = 45), and >10 cm (n = 4). Sixty-five patients completed the trial. At 12 months, dysplasia clearance was RFA 79.4% and APC 83.8% (odds ratio [OR] 0.7; 95% confidence interval [CI], 0.2-2.6); BE clearance was RFA 55.8%, and APC 48.3% (OR 1.4; 95% CI, 0.5-3.6). A total of 6.1% (RFA) and 13.3% (APC) had buried BE glands. Adverse events (including stricture rate after starting RFA 3/36 [8.3%] and APC 3/37 [8.1%]) and quality of life scores were similar, but RFA cost $27491 more per case than APC.
CONCLUSION: This pilot study suggests similar efficacy and safety but a cost difference favoring APC. A fully powered non-inferiority trial is appropriate to confirm these findings. (Clinical trial registration number: NCT01733719.).

Davidson M, Cafferkey C, Goode EF, et al.
Survival in Advanced Esophagogastric Adenocarcinoma Improves With Use of Multiple Lines of Therapy: Results From an Analysis of More Than 500 Patients.
Clin Colorectal Cancer. 2018; 17(3):223-230 [PubMed] Related Publications
BACKGROUND: Although progress has been made in the molecular stratification of esophagogastric adenocarcinoma, the outlook for advanced disease remains poor. The present evaluation of over 500 patients treated at a single European high-volume tertiary center during a 6-year period gives important information on current and developing "real-world" treatment patterns and outcomes.
RESULTS: The overall survival for the whole cohort was 11.5 months, with a range of treatments used in first-, second-, and third-line settings. Treatment with sequential lines of therapy was associated with better outcomes, although only 39% and 14% of patients subsequently received treatment in the second- and third-line setting, respectively. Treatment within a therapeutic clinical trial was associated with significantly improved survival.
CONCLUSION: At present, a substantial proportion of patients with advanced esophagogastric adenocarcinoma will not proceed beyond first-line therapy, and for this group refinement of initial systemic therapies are required to improve outcomes. Although a number of established first- and second-line treatment options are now available, the therapeutic landscape of the disease continues to change, most notably in the application of immunotherapy and increasing interest in establishing evidence-based interventions in the third-line setting and beyond. A small but growing proportion of patients will benefit from sequential treatment approaches incorporating multiple lines of therapy, and improved selection of such patients will be a key challenge for clinicians moving forwards. Data such as these provide an overview of current treatment patterns and outcomes which can be used to inform planning of future research effectively within existing treatment frameworks.

van Munster SN, Overwater A, Haidry R, et al.
Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett's esophagus: impact on treatment response and postprocedural pain.
Gastrointest Endosc. 2018; 88(5):795-803.e2 [PubMed] Related Publications
BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) but is associated with significant postprocedural pain. Alternatively, balloon-based focal cryoablation (CRYO) has recently been developed, which preserves the extracellular matrix and might therefore be less painful. Although data for CRYO are still limited, uncontrolled studies suggest comparable safety and efficacy to RFA in eradicating limited BE areas. Therefore, secondary endpoints such as pain might become decisive for treatment selection. We aimed to compare efficacy and tolerability between focal CRYO and RFA.
METHODS: We identified BE patients undergoing focal ablation (either RFA or CRYO) of all visible BE from our prospective cohort in 2 Dutch referral centers. After ablation, patients completed a 14-day digital diary to assess chest pain (0-10), dysphagia (0-4), and analgesics use. A follow-up endoscopy was scheduled after 3 months to assess the BE surface regression (blindly scored by 2 independent BE expert endoscopists). Outcomes were BE surface regression; 14-day cumulative scores (area under the curves [AUCs]) for pain, dysphagia, analgesics, and peak pain.
RESULTS: We identified 46 patients (20 CRYO, 26 RFA) with similar baseline characteristics. The BE regression was comparable (88% vs 90%, P = .62). AUCs for pain, dysphagia, and analgesics were significantly smaller after CRYO versus RFA (all P < .01). Peak pain was lower after CRYO (visual analog scale 2 vs 4, P < .01), and the duration of pain was also shorter after CRYO (2 vs 4 days, P < .01). CRYO patients used analgesics for 2 days versus 4 days for RFA (P < .01).
CONCLUSIONS: In this multicenter, nonrandomized cohort study, we found no differences in efficacy after a single treatment with CRYO and RFA for short-segment BE. Patients reported less pain after CRYO as compared with RFA. Moreover, CRYO patients used fewer analgesics. Our results suggest a different pain course favoring CRYO over RFA, but a randomized trial is needed for definitive conclusions. (Clinical trial registration number: NCT02249975.).

Garalla HM, Lertkowit N, Tiszlavicz L, et al.
Matrix metalloproteinase (MMP)-7 in Barrett's esophagus and esophageal adenocarcinoma: expression, metabolism, and functional significance.
Physiol Rep. 2018; 6(10):e13683 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
Matrix metalloproteinase (MMP)-7, unlike many MMPs, is typically expressed in epithelial cells. It has been linked to epithelial responses to infection, injury, and tissue remodeling including the progression of a number of cancers. We have now examined how MMP-7 expression changes in the progression to esophageal adenocarcinoma (EAC), and have studied mechanisms regulating its expression and its functional significance. Immunohistochemistry revealed that MMP-7 was weakly expressed in normal squamous epithelium adjacent to EAC but was abundant in epithelial cells in both preneoplastic lesions of Barrett's esophagus and EAC particularly at the invasive front. In the stroma, putative myofibroblasts expressing MMP-7 were abundant at the invasive front but were scarce or absent in adjacent tissue. Western blot and ELISA revealed high constitutive secretion of proMMP-7 in an EAC cell line (OE33) that was inhibited by the phosphatidylinositol (PI) 3-kinase inhibitor LY294002 but not by inhibitors of protein kinase C, or MAP kinase activation. There was detectable proMMP-7 in cultured esophageal myofibroblasts but it was undetectable in media. Possible metabolism of MMP-7 by myofibroblasts studied by proteomic analysis indicated degradation via extensive endopeptidase, followed by amino- and carboxpeptidase, cleavages. Myofibroblasts exhibited increased migration and invasion in response to conditioned media from OE33 cells that was reduced by MMP-7 knockdown and immunoneutralization. Thus, MMP-7 expression increases at the invasive front in EAC which may be partly attributable to activation of PI 3-kinase. Secreted MMP-7 may modify the tumor microenvironment by stimulating stromal cell migration and invasion.

de Jong RGPJ, Peeters PJHL, Burden AM, et al.
Gastrointestinal cancer incidence in type 2 diabetes mellitus; results from a large population-based cohort study in the UK.
Cancer Epidemiol. 2018; 54:104-111 [PubMed] Related Publications
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have been shown to have higher incidences of liver, pancreatic, and colorectal cancer compared to non-diabetic individuals. Current evidence is conflicting for other gastrointestinal (GI) cancers. Therefore, we aimed to determine incidence rates (IRs) of all GI cancers in patients with and without T2DM.
METHODS: A cohort study was performed using the UK Clinical Practice Research Datalink (1988-2012). A cohort of antidiabetic drug users was matched at baseline to a non-diabetic cohort, by age, sex, and practice. Crude IRs and 95% confidence intervals (95% CI) of GI cancers per 100,000 person-years were calculated stratified by age, sex, and calendar year.
RESULTS: 333,438 T2DM and 333,438 non-diabetic individuals were analyzed. IRs of liver (IR 26, 95% CI 24-28 vs. 8.9, 95% CI 7.7-10), pancreatic (IR 65, 95% CI 62-69 vs. 31, 95% CI 28-34), and colon cancer (IR 119, 95% CI 114-124 vs. 109, 95% CI 104-114) were significantly higher in the diabetic compared to the non-diabetic cohort, whereas the IR of oesophageal cancer was significantly lower (IR 41, 95% CI 39-44 vs. 47, 95% CI 44-51). Sex-specific IRs of colon cancer remained significantly higher in men with T2DM, and IRs of esophageal cancer remained significantly lower in women with T2DM.
CONCLUSION: In this study, T2DM patients were shown to have higher crude IRs of liver, pancreatic and colon cancer, but not of gastric, biliary, and rectal cancer. Moreover, the lower observed IRs of oesophageal cancer in diabetic patients warrants further investigation.

Kuwai T, Yamaguchi T, Imagawa H, et al.
Endoscopic submucosal dissection for early esophageal neoplasms using the stag beetle knife.
World J Gastroenterol. 2018; 24(15):1632-1640 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
AIM: To determine short- and long-term outcomes of endoscopic submucosal dissection (ESD) using the stag beetle (SB) knife, a scissor-shaped device.
METHODS: Seventy consecutive patients with 96 early esophageal neoplasms, who underwent ESD using a SB knife at Kure Medical Center and Chugoku Cancer Center, Japan, between April 2010 and August 2016, were retrospectively evaluated. Clinicopathological characteristics of lesions and procedural adverse events were assessed. Therapeutic success was evaluated on the basis of
RESULTS: Eligible patients had dysplasia/intraepithelial neoplasia (22%) or early cancers (squamous cell carcinoma, 78%). The median procedural time was 60 min and on average, the lesions measured 24 mm in diameter, yielding 33-mm tissue defects. The
CONCLUSION: ESD procedures using the SB knife are feasible, safe, and effective for treating early esophageal neoplasms, yielding favorable short- and long-term outcomes.

Zupčić M, Korušić A, Barišin S, et al.
Gastrostomy Under Paravertebral Block in High-Risk Patients with Esophageal Cancer - Two Case Reports.
Acta Clin Croat. 2017; 56(4):803-807 [PubMed] Related Publications
Here we present two cases of gastrostomy insertion via laparotomy in patients with malignant esophageal disease. Patients were ASA (American Society of Anesthesiologists) physical status III and IV. The patients presented as very high risk for general anesthesia, so we decided to use unilateral left sided paravertebral block (PVB) on four thoracic levels along with contralateral local infiltration at the gastrostomy insertion site. We present two cases, one of them a 57-year-old male ASA III patient scheduled for a gastrostomy procedure due to esophageal cancer with infiltration of the trachea. We also present a case of a 59-year-old male patient, ASA IV status, scheduled for the same procedure due to advanced esophageal cancer with a fistula between the left main bronchus and the esophagus and metastases in the left lung. The paravertebral space was identified with the use of an 8 Hertz (Hz) linear ultrasound probe and a nerve stimulator. Paravertebral block was successfully used for insertion of a gastrostomy, thereby enabling adequate anesthesia and perioperative analgesia without hemodynamic or respiratory complications.

Brusselaers N, Engstrand L, Lagergren J
Maintenance proton pump inhibition therapy and risk of oesophageal cancer.
Cancer Epidemiol. 2018; 53:172-177 [PubMed] Related Publications
BACKGROUND: The association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication.
METHODS: This population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005-2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population. The different indications for maintenance PPI therapy were analysed separately.
RESULTS: Among all individuals using maintenance PPI therapy, the overall SIR of oesophageal adenocarcinoma was 3.93 (95% CI 3.63-4.24). The SIRs of adenocarcinoma were increased also among individuals without gastro-oesophageal reflux disease who used PPIs for indications not associated with any increased risk of oesophageal adenocarcinoma. For example, the SIRs among participants using maintenance PPI therapy because of maintenance treatment with non-steroidal anti-inflammatory drugs and aspirin were 2.74 (95% CI 1.96-3.71) and 2.06 (95% CI 1.60-2.60), respectively. The SIRs of oesophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for oesophageal adenocarcinoma.
CONCLUSION: In conclusion, the long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution.

Yu C, Tang H, Guo Y, et al.
Hot Tea Consumption and Its Interactions With Alcohol and Tobacco Use on the Risk for Esophageal Cancer: A Population-Based Cohort Study.
Ann Intern Med. 2018; 168(7):489-497 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
This article has been corrected. The original version (PDF) is appended to this article as a Supplement.
Background: Although consumption of tea at high temperatures has been suggested as a risk factor for esophageal cancer, an association has not been observed consistently, and whether any relationship is independent of alcohol and tobacco exposure has not been evaluated.
Objective: To examine whether high-temperature tea drinking, along with the established risk factors of alcohol consumption and smoking, is associated with esophageal cancer risk.
Design: China Kadoorie Biobank, a prospective cohort study established during 2004 to 2008.
Setting: 10 areas across China.
Participants: 456 155 persons aged 30 to 79 years. Those who had cancer at baseline or who reduced consumption of tea, alcohol, or tobacco before baseline were excluded.
Measurements: The usual temperature at which tea was consumed, other tea consumption metrics, and lifestyle behaviors were self-reported once, at baseline. Outcome was esophageal cancer incidence up to 2015.
Results: During a median follow-up of 9.2 years, 1731 incident esophageal cancer cases were documented. High-temperature tea drinking combined with either alcohol consumption or smoking was associated with a greater risk for esophageal cancer than hot tea drinking alone. Compared with participants who drank tea less than weekly and consumed fewer than 15 g of alcohol daily, those who drank burning-hot tea and 15 g or more of alcohol daily had the greatest risk for esophageal cancer (hazard ratio [HR], 5.00 [95% CI, 3.64 to 6.88]). Likewise, the HR for current smokers who drank burning-hot tea daily was 2.03 (CI, 1.55 to 2.67).
Limitation: Tea consumption was self-reported once, at baseline, leading to potential nondifferential misclassification and attenuation of the association.
Conclusion: Drinking tea at high temperatures is associated with an increased risk for esophageal cancer when combined with excessive alcohol or tobacco use.
Primary Funding Source: National Natural Science Foundation of China and National Key Research and Development Program.

Spence AD, Busby J, Murchie P, et al.
Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases.
Int J Cancer. 2018; 143(1):22-31 [PubMed] Related Publications
Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation.

Petrick JL, Falk RT, Hyland PL, et al.
Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study.
PLoS One. 2018; 13(1):e0190325 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
BACKGROUND: Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association.
METHODS: Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA.
RESULTS: Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered.
CONCLUSIONS: This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

Warren S, Hurt CN, Crosby T, et al.
Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer.
Int J Radiat Oncol Biol Phys. 2017; 99(3):729-737 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
PURPOSE: Radiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors.
METHODS AND MATERIALS: Twenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient.
RESULTS: The 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V
CONCLUSIONS: The results of the present study have shown that proton therapy can reduced bone marrow toxicity.

Dong J, Buas MF, Gharahkhani P, et al.
Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants.
Gastroenterology. 2018; 154(5):1273-1281.e3 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
BACKGROUND & AIMS: We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors.
METHODS: We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett's and EAC consortium as well as the United Kingdom's BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations of non-genetic factors and the PRS were compared for their accuracy in identifying patients with BE or EAC using the area under the receiver operating characteristic curve (AUC) analysis.
RESULTS: Individuals in the highest quartile of risk, based on genetic factors (PRS), had a 2-fold higher risk of BE (odds ratio, 2.22; 95% confidence interval, 1.89-2.60) or EAC (odds ratio, 2.46; 95% confidence interval, 2.07-2.92) than individual in the lowest quartile of risk based on PRS. Risk models developed based on only demographic or lifestyle factors or GERD symptoms identified patients with BE or EAC with AUC values ranging from 0.637 to 0.667. Combining data on demographic or lifestyle factors with data on GERD symptoms identified patients with BE with an AUC of 0.793 and patients with EAC with an AUC of 0.745. Including PRSs with these data only minimally increased the AUC values for BE (to 0.799) and EAC (to 0.754). Including the PRSs in the model developed based on non-genetic factors resulted in a net reclassification improvement for BE of 3.0% and for EAC of 5.6%.
CONCLUSIONS: We used data from 3 large databases of patients from studies of BE or EAC to develop a risk prediction model based on genetic, clinical, and demographic/lifestyle factors. We identified a PRS that increases discrimination and net reclassification of individuals with vs without BE and EAC. However, the absolute magnitude of improvement is not sufficient to justify its clinical use.

Subramaniam S, Kandiah K, Chedgy F, et al.
The safety and efficacy of radiofrequency ablation following endoscopic submucosal dissection for Barrett's neoplasia.
Dis Esophagus. 2018; 31(3) [PubMed] Related Publications
The current standard of treating early Barrett's neoplasia is resection of visible lesions using endoscopic mucosal resection (EMR) followed by ablative therapy to the Barrett's segment. There is increasing evidence to support the use of endoscopic submucosal dissection (ESD) where en-bloc resection and lower recurrence rates may be achieved. However, ESD is associated with deep submucosal dissection when compared to EMR. This may increase the risk of complications including stricture formation with subsequent radiofrequency ablation (RFA) therapy. The aim of this study is to compare the safety and efficacy of RFA following EMR and ESD as well as when RFA was used without prior endoscopic resection. The primary outcome measure was complication rates. Clearance of dysplasia (CRD) and clearance of intestinal metaplasia (CRIM) were secondary outcomes. A retrospective analysis of a cohort of 91 patients referred for RFA from a single academic tertiary center was performed. The choice of endoscopic resection method was tailored according to the lesion type and morphology. Focal and circumferential ablation was performed after initial follow up endoscopy postresection. Patients proceeded straight to RFA in the absence of any visible lesions. In this study, the ESD group had a higher proportion of cancers compared to the EMR cohort (74.1% vs. 30.2%, P < 0.01) prior to RFA. All complications post RFA occurred in the groups with previous endoscopic resection. There was no significant difference in the total complication rate (7.4% vs. 9.3%, P = 0.78) and stricture formation rate (3.7% vs. 9.3%, P = 0.38) between the ESD and EMR groups. CRD was achieved in 96.3% in the ESD group, 88.4% in the EMR group, and all patients in the RFA alone group. CRIM rates were similar in the EMR and ESD groups (81.4% vs. 85.2%) but higher in the RFA alone group (90.5%). In conclusion, RFA following ESD is very effective and not associated with an increased risk of complications compared to EMR. This supports the application of RFA in the treatment algorithm of patients undergoing ESD for Barrett's neoplasia.

Spence AD, Busby J, Johnston BT, et al.
Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer.
Gastroenterology. 2018; 154(4):849-860.e1 [PubMed] Related Publications
BACKGROUND & AIMS: Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer.
METHODS: We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts.
RESULTS: The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32).
CONCLUSIONS: In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Visser E, van Rossum PSN, van Veer H, et al.
A structured training program for minimally invasive esophagectomy for esophageal cancer- a Delphi consensus study in Europe.
Dis Esophagus. 2018; 31(3) [PubMed] Related Publications
Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

Fischer C, Lingsma H, Klazinga N, et al.
Volume-outcome revisited: The effect of hospital and surgeon volumes on multiple outcome measures in oesophago-gastric cancer surgery.
PLoS One. 2017; 12(10):e0183955 [PubMed] Article available free on PMC after 28/11/2019 Related Publications
BACKGROUND: Most studies showing a volume outcome effect in resection surgery for oesophago-gastric cancer were conducted before the centralisation of clinical services. This study evaluated the relation between hospital- and surgeon volume and different risk-adjusted outcomes after oesophago-gastric (OG) cancer surgery in England between 2011 and 2013.
METHODS: In data from the National Oesophago-Gastric Cancer Audit from the UK, multivariable random-effects logistic regression models were used to quantify the effect of surgeon and hospital volume on three outcomes: 30-day and 90-day mortality and anastomotic leakage. The models included patient risk factors to adjust for differences in case-mix among hospitals and surgeons. The between-cluster heterogeneity was estimated with the median odds ratio (MOR).
RESULTS: The study included patients treated at 42 hospitals and 329 surgeons. The median (interquartile range) of the annual hospital and surgeon volumes were 110 patients (82 to 137) and 13 patients (8 to 19), respectively. The overall rates for 30-day and 90-day mortality were 2.3% and 4.4% respectively, and the anastomotic leakage was 6.3%. Higher hospital volume was associated with lower 30-day mortality (OR: 0.94; 95% CI: 0.91-0.98) and lower anastomotic leakage rates (OR: 0.96; 95% CI: 0.93-0.98) but not 90-day mortality. Higher surgeon volume was only associated with lower anastomotic leakage rates (OR: 0.81; 95% CI: 0.72-0.92). Hospital volume explained a part of the between-hospital variation in 30-day mortality whereas surgeon volume explained part of the between-hospital variation in anastomotic leakage.
CONCLUSIONS: In the setting of centralized O-G cancer surgery in England, we could still observe an effect of volume on short-term outcomes. However, the effect is inconsistent, depending on the type of outcome measure under consideration, and much smaller than in previous studies. Efforts to centralise O-G cancer services further should carefully address the effects of both hospital and surgeon volume on the range of outcome measures that are relevant to patients.

Quante M, Graham TA, Jansen M
Insights Into the Pathophysiology of Esophageal Adenocarcinoma.
Gastroenterology. 2018; 154(2):406-420 [PubMed] Related Publications
Although researchers have identified genetic alterations that contribute to development of esophageal adenocarcinoma, we know little about features of patients or environmental factors that mediate progression of chronic acid biliary reflux to Barrett's esophagus and cancer. Increasing our understanding of the mechanisms by which normal squamous epithelium progresses to early-stage invasive cancer will help formulate rational surveillance guidelines and allow us to divest resources away from patients at low risk of malignancy. We review the cellular and genetic alterations that occur during progression of Barrett's esophagus, based on findings from clinical studies and mouse models of disease. We review the features of the luminal and mucosal microenvironment of Barrett's esophagus that promote, in a small proportion of patients, development of esophageal adenocarcinoma. Markers of clonal evolution can be used to determine patient risk for cancer and set surveillance intervals.

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