Surface microdialysis measures local tissue metabolism after Ivor Lewis esophagectomy; an attempt to predict anastomotic defect.

Anastomotic defect (AD) after esophagectomy can lead to severe complications with need for surgical or endoscopic intervention. Early detection enables early treatment and can limit the consequences of the AD. As of today, there are limited methods to predict AD. In this study, we have used microdialysis (MD) to measure local metabolism at the intrathoracic anastomosis. Feasibility and possible diagnostic use were investigated. Sixty patients planned for Ivor Lewis esophagectomy were enrolled. After construction of the anastomosis, surface MD (S-MD) probes were attached to the outer surface of the esophageal remnant and the gastric conduit in close vicinity of the anastomosis and left in place for 7 postoperative days (PODs). Continuous sampling of local tissue concentrations of metabolic substances (glucose, lactate, and pyruvate) was performed postoperatively. Outcome, defined as AD or not according to Esophagectomy Complications Consensus Group definitions, was recorded at discharge or at first postoperative follow up. Difference in concentrations of metabolic substances was analyzed retrospectively between the two groups by means of artificial neural network technique. S-MD probes can be attached and removed from the gastric tube reconstruction without any adverse events. Deviating metabolite concentrations on POD 1 were associated with later development of AD. In subjects who developed AD, no difference in metabolic concentrations between the esophageal and the gastric probe was recorded. The technical failure rate of the MD probes/procedure was high. S-MD can be used in a clinical setting after Ivor Lewis esophagectomy. Deviation in local tissue metabolism on POD 1 seems to be associated with development of AD. Further development of MD probes and procedure is required to reduce technical failure.

Symptoms, problems and quality of life in patients newly diagnosed with oesophageal and gastric cancer - a comparative study of treatment strategy.

BACKGROUND: Patients with oesophageal and gastric cancer have a low likelihood of being cured and suffer from a broad spectrum of symptoms and problems that negatively affect their quality-of-life (QOL). Although the majority (67-75%) of patients at the time of diagnosis suffer from an incurable disease, research has primarily focused on the pre- and postoperative phase among patients treated with curative intent, with little attention to symptoms and problems in the diagnostic phase, especially in those who cannot be offered a cure. METHODS: In this cross-sectional study 158 patients newly diagnosed with oesophageal and gastric cancer visiting the surgical outpatient department for a preplanned care visit were included consecutively during 2018-2020. The validated instruments QLQ-C30 and QLQ-OG25, developed by the European Organization for Research and Treatment of Cancer (EORTC), and selected items from the Integrated Patient Outcome Scale (IPOS) were used to assess QOL, symptoms and problems. Differences between patients with a curative and a palliative treatment strategy were analysed using t-test and Mann-Whitney U test. The QLQ-C30 and QLQ-OG25 scores were compared to published reference data on the general Swedish population. RESULTS: Among all, the QOL was markedly lower, compared with general Swedish population (mean ± SD, 55.9 ± 24.7 vs 76.4 ± 22.8, p < 0.001). Compared to general population, the patients had significant impairment in all QOL aspects, particularly for role and emotional functioning and for symptoms such as eating-related problems, fatigue, insomnia and dyspnea. Majority of patients also reported severe anxiety among family and friends. Among patients with oesophageal cancer those with a palliative treatment strategy, compared with curative strategy, reported significantly lower QOL (mean ± SD, 50.8 ± 28.6 vs 62.0 ± 22.9 p = 0.030), physical (65.5 ± 22.6 vs 83.9 ± 16.5, p < 0.001) and role functioning (55.7 ± 36.6 vs 73.9 ± 33.3, p = 0.012), and a higher burden of several symptoms and problems. No significant differences between treatment groups were shown among patients with gastric cancer. CONCLUSIONS: Patients newly diagnosed with oesophageal and gastric cancer, and especially those with incurable oesophageal cancer, have a severely affected QOL and several burdensome symptoms and problems. To better address patients' needs, it seems important to integrate a palliative approach into oesophageal and gastric cancer care.

Early endoscopic assessment after esophagectomy can predict anastomotic complications: a novel scoring system.

BACKGROUND: Anastomotic leakage after esophagectomy is a serious and demanding complication. Early detection and treatment can probably prevent clinical deterioration of the patient. We have used early endoscopic assessment and a novel endoscopy score to predict anastomotic complications. METHODS: 57 patients planned for Ivor Lewis esophagectomy were included. Endoscopy videos were recorded and biopsies were taken from the gastric conduit on day 7 or 8 after esophagectomy. A scoring system based on the endoscopic appearance, the combined endoscopy score (0-6), was developed. Scoring of the videos was done blinded. Patient outcome with regards to anastomotic complications was registered on postoperative day 30 in accordance with the ECCG definitions and compared to histopathology assessment and the combined endoscopy score retrospectively. RESULTS: The rate of anastomotic defect (necrosis and leakage, ECCG definitions) was 19%. 7 out of 8 patients with a combined endoscopy score of ≥ 4 developed anastomotic defects. The combined endoscopy score was the only predictor for anastomotic complications. CONCLUSION: Prediction of anastomotic complications enables early detection and treatment which often limits the clinical extent of the complication. Early postoperative endoscopy is safe and a relatively simple procedure. The combined endoscopy score is an accurate tool to predict anastomotic complications.

Health care utilization among patients with oesophageal and gastric cancer: the impact of initial treatment strategy and assignment of a contact nurse.

BACKGROUND: Patients diagnosed with oesophageal and gastric cancer face a poor prognosis and numerous challenges of symptom management, lifestyle adjustments and complex treatment regimens. The multifaceted care needs and rapid disease progression reinforce the need for proactive and coherent health care. According to the national cancer strategy, providing coherent health care and palliative support is an area of priority. More knowledge is needed about health care utilization and the characteristics of the health care service in order to understand the readiness, accessibility and quality of current health care. The aim of this study was to describe individuals' health care use from the time of treatment decision until death, and investigate the impact of the initial treatment strategy and assignment of a contact nurse (CN) on health care use among patients with oesophageal and gastric cancer. METHODS: This population-based cohort study included patients who died from oesophageal and gastric cancer in Sweden during 2014-2016. Through linking data from the National Register for Oesophageal and Gastric Cancer, the National Cause of Death Register, and the National Patient Register, 2614 individuals were identified. Associations between the initial treatment strategy and CN assignment, and health care use were investigated. Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated using Poisson regression. RESULTS: Patients receiving palliative treatment and those receiving no tumour-directed treatment had a higher IRR for unplanned hospital stays and unplanned outpatient care visits compared with patients who received curative treatment. Patients receiving no tumour-directed treatment also had a lower IRR for planned hospital stays and planned outpatient care visits compared with patients given curative treatment. Compared with this latter group, patients with palliative treatment had a higher IRR for planned outpatient care visits. Patients assigned a CN had a higher IRR for unplanned hospital stays, unplanned outpatient care visits and planned outpatient care visits, compared with patients not assigned a CN. CONCLUSIONS: A palliative treatment strategy and no tumour-directed treatment were associated with higher rates of unplanned health care compared with a curative treatment strategy, suggesting that a proactive approach is imperative to ensure quality palliative care.

Third time recurrent Boerhaave's syndrome: a case report.

BACKGROUND: Effort rupture of the esophagus or Boerhaave's syndrome is a rare entity, and prognosis is largely dependent on early diagnosis and treatment. Recurrent effort ruptures are very rare, only reported in a few case reports in English literature. We present a case with a third time effort rupture, and to the best of our knowledge there are no such previous publications. Furthermore, the presented case is also distinct because each episode was treated by different methods, reflecting the pathophysiology of recurrent disease as well as the last decade's advancements in the management of esophageal perforations in our clinic and globally. CASE PRESENTATION: The patient is a 60-year-old White male, suffering from alcohol abuse, mild reflux esophagitis, and a history of effort esophageal ruptures on two previous occasions. He was now admitted to our ward once again because of a third bout of Boerhaave's syndrome. The first time, 10 years ago, he was managed by thoracotomy and laparotomy with primary repair, and the second time, 5 years ago, by transhiatal mediastinal drainage through a laparotomy and endoscopic stent placement. Now he was successfully managed by endovascular vacuum-assisted closure therapy alone. CONCLUSIONS: Recurrent cases of Boerhaave's syndrome are very rare, and treatment must be tailored individually. The basic rationale is, however, no different from primary disease: (1) early diagnosis, (2) adequate drainage of extraesophageal contamination, and (3) restoration of esophageal integrity. Recurrent disease is usually contained and exceptionally suitable for primary endoscopic treatment. To cover the full panorama and difficult nature of complex esophageal disease, endoscopic modalities such as stent placement and endovascular vacuum-assisted closure, as well as the capacity for prompt extensive surgical interventions such as esophagectomy, should be readily accessible within every modern esophageal center.

The impact of initial treatment strategy and survival time on quality of end-of-life care among patients with oesophageal and gastric cancer: A population-based cohort study.

BACKGROUND: Oesophageal and gastric cancer are highly lethal malignancies with a 5-year survival rate of 15-29%. More knowledge is needed about the quality of end-of-life care in order to understand the burden of the illness and the ability of the current health care system to deliver timely and appropriate end-of-life care. The aim of this study was to describe the impact of initial treatment strategy and survival time on the quality of end-of-life care among patients with oesophageal and gastric cancer. METHODS: This register-based cohort study included patients who died from oesophageal and gastric cancer in Sweden during 2014-2016. Through linking data from the National Register for Esophageal and Gastric Cancer, the National Cause of Death Register, and the Swedish Register of Palliative Care, 2156 individuals were included. Associations between initial treatment strategy and survival time and end-of-life care quality indicators were investigated. Adjusted risk ratios (RRs) with 95% confidence intervals were calculated using modified Poisson regression. RESULTS: Patients with a survival of ≤3 months and 4-7 months had higher RRs for hospital death compared to patients with a survival ≥17 months. Patients with a survival of ≤3 months also had a lower RR for end-of-life information and bereavement support compared to patients with a survival ≥17 months, while the risks of pain assessment and oral assessment were not associated with survival time. Compared to patients with curative treatment, patients with no tumour-directed treatment had a lower RR for pain assessment. No significant differences were shown between the treatment groups regarding hospital death, end-of-life information, oral health assessment, and bereavement support. CONCLUSIONS: Short survival time is associated with several indicators of low quality end-of-life care among patients with oesophageal and gastric cancer, suggesting that a proactive palliative care approach is imperative to ensure quality end-of-life care.

Surface Microdialysis Detects Ischemia After Esophageal Resection-An Experimental Animal Study.

BACKGROUND: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (µD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compartment aiming at early detection of ischemia. This animal study evaluates ischemia of the gastric tube reconstruction using a novel method-µD on organ surfaces. This promising method may have the potential to detect an anastomotic leakage before clinical symptoms develop. METHODS: Anesthetized normoventilated pigs were used. Surface microdialysis (S-µD) catheters and an intraparenchymal oxygen tension catheter were placed on the stomach. A gastric tube was made and the gastroepiploic artery was divided halfway along the greater curvature to produce severe ischemia at the top of the gastric tube. µD data from four locations (gastric tube, ileum and peritoneal cavity) were recorded every 20 min during the experiment. Tissue samples from all catheter sites underwent histopathological analysis. Intraparenchymal oxygen partial pressure, systemic blood tests, and hemodynamic parameters were recorded. RESULTS: S-µD data showed values indicating severe ischemia at the top of the gastric tube and intermediate ischemia at the level of transection of the gastroepiploic artery. Ischemia was verified by histopathological analysis of tissue samples and intraparenchymal oxygen tension data. CONCLUSIONS: S-µD can detect and grade severity of local ischemia in real time, in an animal model.

Thoracoabdominal gastrectomy and distal 2/3 esophageal resection with wide lymph node dissection for type II and III adenocarcinoma at the gastro-esophageal junction.

BACKGROUND: For locally advanced Siewert type II and III tumors we have performed total gastrectomy including resection of the distal 2/3 of the esophagus, through separate abdominal and right chest incisions (THX-ABD). The procedure involves wide lymphadenectomy in the abdomen/chest and a Roux-en-Y jejunostomy to the level of the azygos vein or above. The aim of the study was to investigate short- and long-term results for this rarely used procedure. METHODS: Retrospective study of 83 radio-chemotherapy naïve patients with adenocarcinoma at the gastro-esophageal junction (Siewert type II n = 65 and type III n = 18) operated upon 1986-2011. RESULTS: 2/83 (2.4%) patients died in hospital. 70/83 (84%) patients had R0-resections. 82/83 (99%) patients had free longitudinal resection margins. Overall 5-year survival was 22/83 (27%). CONCLUSION: THX-ABD can be performed with high rates of R0 resections and with low in-hospital mortality. Long-term survival rate was not better compared with less extensive surgical procedures.

The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC. DESIGN: A systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect to identify studies published between January 1990 and February 2015 of oesophageal cancer populations (with OAC diagnoses >50% of cases) that measured tumoural TP53 status and reported hazard ratios (HR), or adequate data for estimation of HR for survival for TP53-defined subgroups. Risk of bias for HR estimates was assessed using prespecified criteria for the appraisal of relevant domains as defined by the Cochrane Prognosis Methods Group including adherence to Grading of Recommendations, Assessment, Development and Evaluation and REporting recommendations for tumor MARKer prognostic studies guidelines, as well as assay method used (direct TP53 mutation assessment vs immunohistochemistry) and adjustment for standard prognostic factors. A pooled HR and 95% CI were calculated using a random-effects model. RESULTS: Sixteen eligible studies (11 with OAC only and 5 mixed histology cohorts) including 888 patients were identified. TP53 mutations were associated with reduced survival (HR 1.48, 95% CI 1.16 to 1.90, I2=33%). A greater prognostic effect was observed in a sensitivity analysis of those studies that reported survival for OAC-only cohorts and were assessed at low risk of bias (HR 2.11, 95% CI 1.35 to 3.31, I2=0%). CONCLUSIONS: Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.

Bariatric Surgery Provides a "Bridge to Transplant" for Morbidly Obese Patients with Advanced Heart Failure and May Obviate the Need for Transplantation.

BACKGROUND: In patients with advanced heart failure, morbid obesity is a relative contraindication to heart transplantation due to higher morbidity and mortality in these patients. METHODS: We performed a retrospective analysis of consecutive morbidly obese patients with advanced heart failure who underwent bariatric surgery for durable weight loss in order to meet eligibility criteria for cardiac transplantation. RESULTS: Seven patients (4 M/3 F, age range 31-56 years) with left ventricular ejection fraction (LVEF) ≤ 25 % underwent laparoscopic bariatric surgery. Median preoperative body mass index (BMI) was 42.8 kg/m(2) (range 37.5-50.8). There were no major perioperative complications in six of seven patients. Median length of hospital stay was 5 days. There was no mortality recorded during complete patient follow-up. At a median follow-up of 406 days, median BMI reduction was 12.9 kg/m(2) (p = 0.017). Postoperative LVEF improved to a median of 30 % (interquartile range (IQR) 25-53 %; p = 0.039). Two patients underwent successful cardiac transplantation. Two patients reported symptomatic improvement with little change in LV function and now successfully meet listing criteria. Three patients showed marked improvement of their LVEF and functional status, thus removing the requirement for transplantation. CONCLUSIONS: Bariatric surgery can achieve successful weight loss in morbidly obese patients with advanced cardiac failure, enabling successful heart transplantation. In some patients, cardiac transplantation can be avoided through surgical weight loss.

Robot-assisted oesophageal and gastric surgery for benign disease: antireflux operations and Heller's myotomy.

BACKGROUND: Robot-assisted general surgery operations are being performed more frequently. This review investigates whether robotic assistance results in significant advantages or disadvantages for the operative treatment of gastro-oesophageal reflux disease and achalasia. METHODS: The electronic databases (Medline, Embase, PubMed) were searched for original English language publications for antireflux surgery and Heller's myotomy between January 1990 and December 2013. RESULTS: Thirty-three publications included antireflux operations and 20 included Heller's myotomy. The publications indicate that the safety and effectiveness of robotic surgery is similar to that of conventional minimally invasive surgery for both operations. The six randomized trials of robot-assisted versus laparoscopic antireflux surgery showed no significant advantages but significantly higher costs for the robotic method. Gastric perforation during non-redo robotic fundoplication occurred in four trials. CONCLUSIONS: No consistent advantage for robot-assisted antireflux surgery has been demonstrated, and there is an increased cost with current robotic technology. A reported advantage for robotic in reducing the perforation rate during Heller's myotomy for achalasia remains unproven. Gastric perforation during robotic fundoplication may be due to the lack of haptic feedback combined with the superhuman strength of the robot.

High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma.

BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.

Robot-assisted gastrectomy and oesophagectomy for cancer.

BACKGROUND: Robot-assisted surgery is a technically feasible alternative to open and laparoscopic surgery, which is being more frequently used in general surgery. We undertook this review to investigate whether robotic assistance provides a significant benefit for oesophagogastric cancer surgery. METHODS: Electronic databases were searched for original English-language publications for robotic-assisted gastrectomy and oesophagectomy between January 1990 and October 2013. RESULTS: Sixty-one publications were included. Thirty-five included gastrectomy, 31 included oesophagectomy and five included both operations. Several publications suggest that robot-assisted subtotal gastrectomy can be as safe and effective as an open or laparoscopic procedure, with equal outcomes with regard to the number of lymph nodes resected, overall morbidity and perioperative mortality, and length of hospital stay. Robotic assistance is associated with longer operation times but also with less blood loss in some reports. A significant benefit for robotic assistance has not been shown for the more extensive operations of oesophagectomy or total gastrectomy with D2-lymphadenectomy. There are very few oncologic data regarding local recurrence or long-term survival for any of the robotic operations. CONCLUSIONS: No significant differences in morbidity, mortality or number of lymph node harvested have been shown between robot-assisted and laparoscopic gastrectomy or oesophagectomy. Robotic surgery, with its relatively short learning curve, may facilitate reproducible minimally invasive surgery in this field but operation times are reportedly longer and cost differences remain unclear. Randomized trials with oncologic outcomes and cost comparisons are needed.

Is the course of gastroesophageal reflux disease progressive? A 21-year follow-up.

OBJECTIVE. We re-evaluated a cohort of patients referred for reflux symptoms and objectively diagnosed with pathological reflux, with the purpose of clarifying the course of conservatively treated gastroesophageal reflux disease (GERD). MATERIAL AND METHODS. All consecutive patients with GERD diagnosed between 1984 and 1988 showing pathologic 24-h pH-metry in the interval 3.8-10% and without any previous surgery in the gastroesophageal tract were assessed for further follow-up. A total of 40 evaluable patients were followed in the years 2007-08 with endoscopy, manometry, 24-h pH-metry, Helicobacter pylori assessment and the self-administered questionnaires the GERD Impact Scale, the Reflux Disease Questionnaire, the Quality of Life in Reflux and Dyspepsia and the Medical Outcome Study Short Form-36 Health Survey. Baseline data from the 1980s were retrieved and compared with the evaluations conducted at follow-up. RESULTS. At follow-up 20.7 years (range 18.8-23.5 years) after referral, the study population showed more use of acid suppressants (p = 0.007) and increasing prevalences of esophagitis (p = 0.001) and Barrett's esophagus (p = 0.002). Esophagitis was seen in 16/40 patients (40%) at baseline and in 29/40 (72.5%) at follow-up. No significant deterioration was seen at follow-up in manometry data and in most pH data. Patients with esophagitis (ERD) were less likely to have a positive H. pylori test (hazard ratio 0.054; p = 0.002) than non-erosive (NERD) patients. Symptom evaluations showed significantly lower quality of life in the ERD group. CONCLUSIONS. After 20 years a considerable part of the cohort still experienced symptoms of reflux and showed endoscopic progression, although no significant deteriorations were seen in manometry data and in most pH-metry data. H. pylori infection was inversely associated with erosive esophagitis and this supports the hypothesis that H. pylori colonization is a protective factor against GERD.

Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. METHODS: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. RESULTS: Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. CONCLUSION: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.

Defective mismatch-repair as a minor tumorigenic pathway in Barrett esophagus-associated adenocarcinoma.

The malignant transformation that characterizes the development of Barrett esophagus-associated adenocarcinomas is a multi-step process in which genetic alterations in various tumor-associated genes accumulate. Defective mismatch repair (MMR) is the cause of microsatellite instability (MSI) pathway that characterizes a subset of gastrointestinal tumors and is specifically associated with tumor development within the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The few studies that have assessed MMR defects in Barrett-associated adenocarcinomas have reached different results. We therefore assessed the expression of the MMR proteins MLH1 and MSH2 in a series of 59 Barrett adenocarcinomas and found a loss of MMR protein immunostaining in 2/59 (3%) tumors; one tumor showed a loss of MSH2 expression, the other tumor showed a loss of MLH1, and both tumors displayed an MSI-high phenotype. Our findings suggest that only a small subset of Barrett adenocarcinomas develop because of defective MMR, but demonstrate that MLH1 and MSH2 are the primary targets for defective MMR also in this tumor type.