Barrett's Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett's esophagus: report of the RIBBON network.

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

A new clinical scoring system to define pneumonia following esophagectomy for cancer.

BACKGROUND: Pneumonia is a frequently observed complication following esophagectomy. The lack of a uniform definition of pneumonia leads to large variations of pneumonia rates in literature. This study was designed to develop a scoring system for diagnosing pneumonia following esophagectomy at the hospital ward. METHODS: In a prospective cohort study of esophagectomy patients, known risk factors for pneumonia, temperature, leukocyte count, pulmonary radiography and sputum culture added were evaluated. Primary outcome was defined as the decision to treat suspected pneumonia. Multivariate Cox regression analysis with backward selection was used to identify predictors of pneumonia treatment. RESULTS: The majority of postoperative pneumonia treatments (88.2%) occurred at the hospital ward, where treatment was observed in 67 (36.2%) of 185 patients. Independent diagnostic determinants for pneumonia treatment were temperature (hazard ratio (HR) = 1.283, p = 0.073), leukocyte count (HR = 1.040, p = 0.078) and pulmonary radiography (HR >11.0, p = 0.000). Sputum culture did not influence the decision to treat pneumonia. These findings were used to develop a scoring system which includes temperature, leukocyte count and pulmonary radiography. CONCLUSION: The decision to treat pneumonia is based on temperature, leukocyte count and pulmonary radiography findings. The proposed clinical scoring system for pneumonia following esophagectomy at the hospital ward has the potential to aid clinical practice and improve comparability of future research in esophageal cancer surgery.

Risk of thromboembolic events after perioperative chemotherapy versus surgery alone for esophageal adenocarcinoma.

BACKGROUND: Major oncologic surgery is associated with a high incidence of thromboembolic events (TEE). Addition of perioperative chemotherapy in esophageal cancer surgery may increase the risk of TEE. METHODS: The thromboembolic toxicity profile was analyzed in patients with esophageal adenocarcinoma (EAC). Two groups were identified: patients who underwent esophagectomy and received perioperative chemotherapy with epirubicin, cisplatin, and capecitabine (ECC; n = 52), and patients who were treated with surgery alone (n = 35). RESULTS: A total of 22 TEEs was observed in 17 patients (32.7%) in the chemotherapy group and 3 patients (7.5%) in the surgery-alone group (P < .01). The relative risk of developing a TEE for patients receiving perioperative chemotherapy during the whole treatment period was 3.8 (95% confidence interval 1.2-12.0). A preoperatively occurring TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay (P = .325). Median postoperative hospital stay was 23 days (range 14-78) for patients with a postoperative TEE and 15 days (range 10-105) for patients without TEE (P = .126). Perioperative chemotherapy with the epirubicin, cisplatin, and capecitabine regimen was independently associated with the development of TEE in the combined preoperative and postoperative period (P = .034). CONCLUSIONS: Perioperative chemotherapy improves survival for operable esophageal cancer but comes at the price of toxicity. Perioperative chemotherapy for EAC increases the risk of TEE. However, chemotherapy-related preoperative TEE did not increase the risk of postoperative TEE, nor did it increase postoperative hospital stay, justifying its use in clinical practice.

End-to-end cervical esophagogastric anastomoses are associated with a higher number of strictures compared with end-to-side anastomoses.

BACKGROUND: Leakage and benign strictures occur frequently after esophagectomy. The objective of this study was to analyze the outcome of hand-sewn end-to-end versus end-to-side cervical esophagogastric anastomoses. METHODS: A series of 390 consecutive patients who underwent esophagectomy with gastric conduit reconstruction was analyzed. RESULTS: The end-to-end technique was performed in 112 (29 %) patients and the end-to-side in 278 (71 %) patients. Anastomotic leakage occurred in 20 (18 %) patients with an end-to-end anastomosis versus 58 (21 %) patients with an end-to-side anastomosis (p = 0.50). A higher incidence in anastomotic strictures was seen in end-to-end anastomoses (48 (43 %)) compared with end-to-side anastomoses (89 (32 %); p = 0.04). Moreover, a median of 11 (7-17) dilations was necessary in patients with a benign anastomotic stricture in the end-to-end group compared with four (2-8) dilations in patients with a benign anastomotic stricture in the end-to-end group (p < 0.036). After multivariate analysis, the difference in anastomotic leakage rates remained nonsignificant (p = 0.74), whereas anastomotic stricture rate and number of dilations were higher in the end-to-end group (p = 0.03 and p = 0.01, respectively). CONCLUSION: The technique of anastomosis is not significantly related to anastomotic leakage rate. However, patients with end-to-end anastomoses develop postoperative strictures more frequently, requiring a higher number of dilations compared to end-to-side anastomoses.

Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study.

BACKGROUND: Protein kinase mammalian target of rapamycin (mTOR) is an important downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In several tumour types, phosphorylated mTOR (p-mTOR) over-expression is an independent prognostic marker for poor survival. However, p-mTOR expression has not been assessed in oesophageal adenocarcinoma (OAC). MATERIALS AND METHODS: Tumour cores of 154 patients with OAC were included in a tissue microarray (TMA). Scoring criteria were based on p-mTOR staining intensity. RESULTS: 147 (95.5%) patients were available for immunohistochemical evaluation. Over-expression of p-mTOR was detected in 29 (19.7%) tumours, whereas 118 (80.3%) patients showed negative expression. Over-expression was significantly associated with poor overall survival in univariate analysis (HR 1.648; 95% CI 1.019 to 2.664; p=0.042). Median survival was 21.2 months in patients with p-mTOR over-expression and 29.0 in the negative p-mTOR group (p=0.040). In addition, a trend towards p-mTOR over-expression and vasoinvasive growth was seen (p=0.057). In multivariate analysis, including clinical and pathological variables (p<0.10), only T-stage (HR 2.795; 95% CI 1.343 to 5.813; p=0.006) and differentiation grade (HR 2.198; 95% CI 1.353 to 3.570; p=0.001) were independent prognostic markers of poor survival. CONCLUSION: p-mTOR over-expression was detected in 19.7% of patients with OAC and was associated with poor overall survival.

Gastric conduit resection and jejunal interposition for recurrent esophageal cancer.

We describe the case of a 58-year-old man with recurrent adenocarcinoma at the site of an esophagogastrostomy that we treated by radical surgical resection and jejunal interposition. Oral intake was started on the 6th postoperative day and the patient was discharged on the 11th postoperative day. Seven months after the surgical procedure no signs of tumor recurrence were detected. Resection of localized (recurrent) esophageal cancer may well be a valuable treatment option and is therefore an interesting therapeutic option in patients with recurrent disease. However this needs to be investigated in a randomized controlled trial.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial).

BACKGROUND: For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. METHODS/DESIGN: This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥ 18 and ≤ 80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. DISCUSSION: This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. TRIAL REGISTRATION: Dutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790.

How to define a positive circumferential resection margin in T3 adenocarcinoma of the esophagus.

A positive circumferential resection margin (CRM) is associated with poor survival after esophagectomy for cancer. The Royal College of Pathologists (RCP) defines a CRM when tumor is found <1 mm of the lateral margin whereas the College of American Pathologists (CAP) defines CRM when tumor cells are located at the lateral margin. This study evaluates the clinical prognostic significance of CRM on overall survival (OS) and disease-free survival (DFS) in patients who underwent esophagectomy for T3 esophageal adenocarcinoma. Analysis included 132 patients. CRM was found in 26 cases (19.7%) corresponding to CAP criteria versus 89 cases (67.4%) corresponding to RCP criteria. Median OS using RCP criteria was 16.4 (95%CI, 8.5-24.2) months for CRM patients versus 21.0 (95%CI 16.3-25.6) months in CRM patients (P=0.144). With CAP criteria, median OS in CRM and CRM patients was 9.4 (95%CI, 7.6-11.2) months versus 21.6 (95%CI, 18.9-24.3) months, respectively (P=0.000). Median DFS using RCP criteria was 18.0 (95%CI, 11.5-24.6) months for CRM patients versus 11.0 (95%CI, 8.1-14.0) months for CRM patients (P=0.257). Applying the CAP criteria, median DFS in CRM and CRM patients was 16.3 (95%CI, 10.6-22.0) months versus 7.0 (95%CI, 6.3-7.8) months, respectively (P=0.000). Effects of a CRM according to CAP criteria remained significant after multivariate testing [OS: hazard ratio (HR), 2.43; 95%CI, 1.52-3.90; DFS: HR, 2.09; 95%CI, 1.32-3.30]. Only with the CAP criteria, CRM is an independent prognostic factor for survival and recurrence in patients with T3 adenocarcinoma of the esophagus. The circumferential margin should only be considered positive (ie, R1) if the tumor is found at the inked lateral margin of resection in accordance with the CAP criteria.

Barrett's esophagus: treatments of adenocarcinomas I.

The following on the treatments of adenocarcinomas in Barrett's esophagus contains commentaries on endo mucosal resection; choice between other ablative therapies; the remaining genetic abnormalities following stepwise endoscopic mucosal resection and possible recurrences; the Fotelo-Fotesi PDT; the CT TNM classification of early stages of Barrett's carcinoma; the indications of lymphadenectomy in intramucosal cancer; the differences in lymph node yield in transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and the importance of the length of proximal esophageal resectipon; and indications of sentinel node dissection.

Barrett's esophagus: treatments of adenocarcinomas II.

The following topics are explored in this collection of commentaries on treatments of adenocarcinomas related to Barrett's esophagus: the importance of intraoperative frozen sections of the margins for the detection of high dysplasia; the preferable way for sentinel node dissection; the current role of robotic surgery and of video-endoscopic approach; the value of the Siewert's classification of adenocarcinomas; the indications of two-step esophagectomy; the evaluation of pathological complete response; the role of PET scan in staging and response assessment; the role of p53 in the selection of adenocarcinomas patients; chemotherapy regimens for adenocarcinomas; the use of monoclonal antibodies in the control of cell proliferation; he attempt to define a stage-specific strategy, and the possible indications of selective therapy; and changes in mortality rates from esophageal cancer.