Adenocarcinoma Of Distal Esophagus Research Articles

The Impact of Multimodality Therapy of Distal Esophageal and Gastroesophageal Junction Adenocarcinomas on Treatment-Related Toxicity and Complications

The benefit of multimodality therapy is clearly established for adenocarcinomas of the distal esophagus and gastroesophageal junction, but its impact on toxicity is not well defined. We reviewed data from prospective randomized trials to better define the risks of multimodality therapy. The rates of surgical mortality and complications range from 0% to 10% and 23% to 49%, respectively. Multimodality therapy increases acute toxicity. The rate of severe acute hematologic toxicity varies considerably between trials (3%-78%) and appears to be primarily attributable to chemotherapy. Common severe acute nonhematologic toxicities include esophagitis (16%-63%), infection (2%-30%), pain (3%-24%), and gastrointestinal (6%-60%) and cardiac (3%-19%) events. The individual contribution of each modality to nonhematologic toxicities is unclear, but toxicity is increased when adding radiosensitizing chemotherapy to radiotherapy. There is an acute decrease in quality of life with multimodality therapy; however, quality of life usually returns to, or exceeds, baseline by 12 months after therapy. Late toxicities are less well defined, but commonly include esophageal, pulmonary, and cardiac toxicities.

Gastropericardial Fistula: A Life Threatening Complication after Esophagectomy

Purpose: A 59-year-old male presented with acute onset of abdominal pain, hematemesis, melena, chest pain and dyspnea. His past medical history was significant for T3 N1 distal esophageal adenocarcinoma for which he had an esophagectomy with gastric pedicle pull-up 15 months ago and received neoadjuvant chemoradiation. Restaging studies 3 months ago showed 2 gastric body ulcers on EGD with benign histopathology while on proton pump inhibitors. He initially presented to his primary care physician with bilateral shoulder pain medicated with NSAIDs and prednisone therapy. On presentation hemoglobin was 7 and ECG revealed new onset atrial fibrillation. Upper endoscopy revealed a large ulcer extending from below the esophago-gastric anastomosis to the duodenum at the lesser curvature of the stomach, covered by clot without evidence of active bleeding or visible vessel. A CT scan of thorax, abdomen and pelvis showed new pericardial thickening and pneumopericardium, with suggestive images of connection between distal stomach and pericardium, along with extensive pulmonary ground glass opacities. There was no extravasation of contrast into pleura or pericardium. Patient underwent exploratory laparotomy that revealed extensive gastric ulceration and full thickness erosion of the conduit wall with communication to pericardium, invasion of right lower lobe and erosion of pulmonary veins. An excision of conduit, jejunostomy, thoracotomy and cervical esophagostomy were performed. There were no malignant cells on histopathology. The patient's course was complicated by empyema and pulmonary embolism on 4 months follow-up. Esophageal cancer patients have prolonged survival after esophagectomy. Late complications of this include anastomotic stricture, conduit ulceration and functional conduit disorders. Perforated ulcers of gastric tubes can penetrate neighbor structures in the posterior mediastinum such as the pericardium, leading to gastropericardial fistula. This is a very rare and highly lethal condition, with a mortality of more than 50%. The clinical presentation includes chest pain with shoulder radiation, epigastric pain, dyspnea and arrhythmias. ECG may show changes consistent with atrial fibrillation or pericarditis. CT scan and endoscopy are helpful to establish the diagnosis. However, excessive air insufflation by the endoscope may trigger a cardiac tamponade. Sudden death can occur due to cardiac tamponade. Prognosis with surgical drainage is better that in conservative therapy or percutaneous drainage. GPF of a gastric ulcer should be part of the differential diagnosis in patients with an esophagectomy that present with chest pain.

Distal esophageal carcinomas in Chinese patients vary widely in histopathology, but adenocarcinomas remain rare

In Western countries, distal esophageal adenocarcinoma has outnumbered squamous cell carcinoma because of a dramatic increase in the prevalence of columnar-lined esophagus. Because the relative prevalence of these diseases remains unknown in China, we investigated the histopathology of distal esophageal neoplasm in resection specimens from a high-volume medical center in China. A computerized search of esophageal cancer was conducted in the pathology database between 2004 and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal junction were retained for analysis. Pathology reports were reviewed along with medical, radiologic, and endoscopic records. All histology slides of selected cases were reevaluated (median, 13 per case). Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma were categorized according to the World Health Organization classification of esophageal cancers. The presence of columnar-lined esophagus and other pathologic changes were assessed in cases with residual esophageal mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1% of the cases, respectively. Synchronous carcinomas were found in 12% and consisted of primarily squamous cell carcinoma (50%) and proximal gastric adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases, among which intestinal metaplasia was present in 30% and low-grade dysplasia in 7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide histopathologic spectrum with predominant squamous cell carcinoma and rare esophageal adenocarcinoma. Although common, columnar-lined esophagus appears pathogenetically insignificant for most distal esophageal carcinomas.

Practice patterns in the treatment of locally advanced resectable esophageal carcinoma: A national survey of Canadian thoracic surgeons.

e14695 Background: Many institutions have adopted a multimodality strategy for treating locally advanced resectable esophageal cancer including surgery, chemotherapy and radiation. While many neoadjuvant protocols have been studied, there is no well defined standard treatment. In order to determine current practices and clinician opinions regarding treatment of esophageal cancer, a survey study of practicing Canadian thoracic surgeons was performed. Methods: Members of the Canadian Association of Thoracic Surgeons were contacted by email; those who currently treat esophageal cancer were asked to complete an online survey. Three separate emails were sent to maximize participation. Results: The response rate was 54% (56 /104). Of the respondents, 85% exclusively practiced general thoracic surgery, 87% worked at a University-affiliated hospital. We presented a hypothetical patient with bulky, resectable distal esophageal adenocarcinoma with enlarged paraesophageal lymph nodes (T3N1M0). 54% stated that neoadjuvant chemoradiation followed by surgery was their institution’s treatment of choice, while 33% used neoadjuvant chemotherapy plus surgery. When asked to choose the best treatment for this patient based on available evidence, 33% chose neoadjuvant chemoradiation, 33% favored neoadjuvant chemotherapy, 31% were undecided. Regarding neoadjuvant chemotherapy vs. chemoradiation, 63% strongly agreed or agreed there was insufficient evidence to decide whether or not one treatment was superior to the other. 73% strongly agreed or agreed to support a future randomized trial of preoperative chemotherapy vs. preoperative chemoradiation for esophageal cancer patients. Conclusions: Most Canadian thoracic surgeons use either neoadjuvant chemotherapy or chemoradiation followed by surgery for locally advanced resectable esophageal cancer. There is wide variation in practice patterns with no clear standard approach. 63% feel there is insufficient evidence to decide whether or not one treatment is superior to the other, and the majority support a future trial of neoadjuvant chemotherapy vs. chemoradiation. A pilot study is being planned to determine feasibility.

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64±0.14 and 4.50±0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88±0.04 and 0.81±0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions.

TomoTherapy stereotactic body radiation therapy (SBRT) for the salvage treatment of locally recurrent esophageal adenocarcinoma following trimodality therapy: A case report

Esophageal cancer patients with local recurrence after chemoradiation and surgery (trimodality therapy) have limited palliative treatment options. We present a case of local recurrence successfully palliated using TomoTherapy stereotactic body radiation therapy (SBRT). The patient was a 58-year-old man with distal esophageal adenocarcinoma initially treated with trimodality therapy. Symptomatic local recurrence developed 4 years later. Using TomoTherapy SBRT successful palliation was achieved with 3500 cGy in 7 fractions given every other weekday. He remained free of local recurrence without requiring further local therapies, eventually succumbing to metastatic disease 11 months after radiation. Presently there are no reported cases of malignant esophageal obstruction treated with SBRT. Radiosurgery is increasingly used in extracranial sites such as the liver, lung and spine. Reirradiation was convenient and well tolerated by our patient and the response durable. Palliation of local recurrence in esophageal cancer initially treated with trimodality therapy can be achieved using SBRT and is a reasonable option in appropriately selected patients. Further studies are needed to clarify its role in this and other body sites.

Distal Esophageal Adenocarcinoma Remains Rare Among Chinese Population: A Clinicopathologic Study of 211 Resection Cases

Distal Esophageal Adenocarcinoma Remains Rare Among Chinese Population: A Clinicopathologic Study of 211 Resection Cases

Abstract 4673: Host genetic polymorphisms at TIMP3 are associated with survival of patients with adenocarcinoma of esophagus and gastoeophageal junction

Abstract BACKGROUND: During the past two decades, several countries have experienced a dramatic increase in adenocarcinoma incidence for both the esophagus and gastroesophageal junction (GEJ). Because of this increase and generally poor survival, distal esophageal and GEJ adenocarcinomas are important in cancer research. Similarities and shared prognostic factors suggest these cancers can be considered a single neoplastic entity in many contexts. The American Joint Committee on Cancer (AJCC) Cancer Staging Manual uses “single-stage grouping” across the entire lower esophagus and GEJ area. The current study was conducted to examine the effect of polymorphism at TIMP and MMP genes as a host-related prognosis factor. METHODS: This study used a prospective cohort of patients with adenocarcinoma of the esophagus and GEJ in British Columbia (BC) admitted to the BC Cancer Agency (BCCA). Germline DNA was extracted from patients’ blood or saliva. Selected SNPs were genotyped using Sequenom multiplex iPLEX Gold assays. Patient characteristics and clinical information were obtained from BCCA medical charts and preadmission questionnaires. Cox proportional hazards regression was used to estimate the effect of SNPs adjusted for patient age, tumour location, disease stage and treatment received. P-values less than 0.05 were considered statistically significant. The false discovery rate (FDR) method was applied to address multiple comparisons. RESULTS: 4 genetic polymorphism at TIMP3 gene were associated with survival of patients. These associations were also observed after adjustment for patient age, tumour location, disease stage and treatment received. A SNP in the promoter region of TIMP3 (rs1962223) was associated with about a 3-fold increase in the HR for patients who carried the CG genotype. A tagSNP (rs130274) showed a more than 3-fold increased HR for the dominant and codominant models and 2-fold increased HR for the additive model. A tagSNP (rs715572) was associated with about a 3-fold increased HR for the dominant and codominant models and a 2-fold reduction in the HR for the additive model. Finally, a tagSNP (rs5754312) was associated with a 4-fold reduction in the HR in the recessive and codominant model, and a 2-fold reduction in the HR for the additive model, In haplotype analysis, a block including rs5754312 and rs715572 showed significant association with the patients’ survival (p=0.002). CONCLUSION: Adenocarcinoma of the esophagus and GEJ are deadly diseases that are often diagnosed at a stage when the treatment options are limited and have limited effectiveness. Modeling survival based on host factors including genetic polymorphisms is an emerging field in cancer research. Compared to tumour, the patient's constitutional genetic material is relatively easy to obtain, and can be assessed before treatment is started. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4673. doi:10.1158/1538-7445.AM2011-4673

Association of Adenocarcinomas of the Distal Esophagus, “Gastroesophageal Junction,” and “Gastric Cardia” With Gastric Pathology

Controversy exists as to whether adenocarcinomas occurring in the gastroesophageal junctional region and gastric cardia originate in the esophagus or the stomach. Esophageal adenocarcinoma is known to be strongly associated with gastroesophageal reflux disease; gastric adenocarcinoma with Helicobacter pylori gastritis, and gastric intestinal metaplasia. This study evaluates the association of these tumors with pathologic findings in the biopsies of the gastric body and the antrum. It is hypothesized that if these malignancies are esophageal, they should have little or no significant association with gastric pathology; if they are gastric, these patients should have a high prevalence of gastric pathology. Between 2004 and 2008, 234 patients were diagnosed with high-grade dysplasia (HGD) and/or adenocarcinoma; 107 were distal esophageal, 79 straddled the distal end of the tubular esophagus, and 48 were in the "gastric cardia." Simultaneous biopsies of the distal body and antrum were present in 185 patients; 49 had biopsy of either antrum or body. Gastric biopsies were assessed for inflammation, H. pylori infection, and intestinal metaplasia. During this period, 2146 patients had nonmalignant columnar epithelia in the esophagus with similar assessment of the stomach; these acted as a control group. The gastric biopsy was normal in 201/234 (85.9%) patients and showed significant inflammation, H. pylori infection, and/or gastric intestinal metaplasia in 33/234 (14.1%) patients. There was no gastritis, H. pylori infection, or intestinal metaplasia in 88/107 (82.2%) of the patients with distal esophageal HGD and/or adenocarcinoma, 70/79 (88.6%) with junctional HGD and/or adenocarcinoma, and 43/48 (85.9%) with "gastric cardiac" HGD and/or adenocarcinoma. The incidence of gastritis was significantly higher in the patients with HGD and/or adenocarcinoma (33/234 or 14.1%) than in the control population (146/2146 or 9.0%; P=0.01). This difference was largely the result of a higher incidence of gastritis in patients with HGD and/or adenocarcinoma in the distal third of the esophagus (19/107 or 17.8%) versus the control population (146/2146 or 9.0%; P=0.01). The incidence of H. pylori positivity was also significantly higher in the patients with HGD and/or adenocarcinoma in the distal third of the esophagus (13/107 or 12.2%) than in the control population (117/2146 or 5.5%; P=0.01). There was no significant difference between the control group and the patients with junctional and gastric cardiac HGD and/or adenocarcinoma for gastritis, H. pylori infection, or the gastric intestinal metaplasia. The absence of gastritis, H. pylori, and the gastric intestinal metaplasia in 85.9% of the patients with HGD and/or adenocarcinoma of the gastroesophageal junctional region strongly suggest that most of these originate in the esophagus. In the small minority of patients whose HGD and/or adenocarcinoma were associated with gastric pathology, the incidence of gastritis and H. pylori infection was significantly higher in patients with HGD and/or adenocarcinoma in the distal third of the esophagus and not in the junctional and "gastric cardiac" tumors. This suggests that the reflux of the gastric juice whose composition has been altered by gastritis and H. pylori infection may be associated with an increased tendency to HGD and/or adenocarcinoma in the distal third of the esophagus.

Mediastinal Dislocation of the Esophageal Stents

Purpose: Abstract: We report a case of mediastinal abscess associated with dislocation of esophageal stents and disruption of esophagogastric anastomosis. Introduction: Esophageal stents are mostly used as a non-surgical alternative for palliation of esophageal cancers. Though the complication rate is low, serious complications like rupture of esophageal wall and respiratory arrest may occur. Case Report: Our case is a 62 year- old white man diagnosed with stage III, T2N1M0 adenocarcinoma of distal esophagus in April of 2009. He had neoadjuvent chemoradiation followed by esophagectomy with gastric pull-through in September of 2009. One week after the surgery he developed esophagogastric anastomotic leak leading to sepsis. He had multiple stents placed to stop the leak and had indwelling chest tube for drainage. In December of 2009, he presented with intractable cough associated with swallowing and vomiting for three days. He was found to be in severe respiratory distress and in septic shock. CT scan of the chest showed dislocation of the stents (Image 1), air fluid level with possibility of abscess in right chest and mediastinum and diffuse patchy pulmonary infiltrates. He had surgical exploration of chest that revealed two migrated esophageal stents with abscess in the mediastinum. Discussion:Esophageal stents are self-expanding metal or plastic stents. Their use is mostly limited to palliation of symptoms for patients with esophageal cancer. Esophageal stents have also been used in patients with benign conditions such as refractory strictures, perforation, and postoperative leaks. Complications include chest pain, foreign body sensation, obstruction, aspiration, malposition, bleeding, migration. Severe complications like perforation and respiratory arrest are rare. Conclusion: There is always a possibility of esophageal stents getting dislodged if the supporting tissue around the ends of the stent is friable. Our case had radiation therapy to the esophagus preoperatively which induced radiation esophagitis rendering already diseased esophageal wall further weak. Patients with persistent anastomotic leaks are at high risk for stent dislocation and migration.Figure: [463] Dislocated stent in the mediastinum.

The Traction that Broke the Anti-reflux Stentʼs Back - A Rare but Important Complication

Purpose: The Cook Dua Esophageal Stent with Anti-Reflux Valve was developed to reduce reflux of stomach contents in patients with cancers of the esophagus. We report a case of a spontaneously torn anti-reflux flap previously noted to be in working order. Methods: The patient was a 55-year-old male with metastatic distal esophageal adenocarcinoma with progressive dysphagia. Previous placement of a partially covered esophageal Wallflex stent had allowed oral intake, but resulted in significant reflux symptoms secondary to the stent traversing the gastroesophageal junction. Decision to attempt placement of a Dua Anti Reflux Stent within the previously placed stent in order to curb the reflux of gastric contents. A gastroscope was advanced to the stomach traversing the previously placed Wallstent, retroflexion revealed the stent to be well situated beneath the lower esopohageal sphincter. A 12 cm Cook esophageal Z-stent with Dua anti-reflux valve was then passed over a Savory guide-wire with the distal most radio-opaue marker positioned over the distal margin of the previous stent. The stent was deployed into excellent position under fluroscopic guidance. The gastroscope was then advanced with no resistance and verification of positioning of both stents was confirmed. Post placement x-ray showed no evidence of perforation or migration and the patient was discharged with symptomatic improvement in reflux related discomfort. Results: Two weeks post placement, the patient returned with unbearable chest pain secondary to progressive reflux symptoms. The patient had severe dysphagia to both liquids and solids and had no chest wall tenderness and crepitis. Repeat Esophagogastroduodenoscopy (EGD) with fluroscopy revealed the two stents to be in good position. The scope was passed through the center of the stents into the stomach. The anti-reflux flaps of the Dua stent appeared to be partially torn along the distal edge of the stent with prolapse into the esophagus. A rat tooth forceps was used to grasp the proximal edge of the Z- stent and under fluroscopic guidance the stent was removed. The endoscope was passed again through the previous Wallflex stent which remained in good position without migration and tissue in-growth. The patient was medically managed for reflux and will be considered for repeat stent placement. Conclusion: Previous reports have noted overstrain or defective materials as the reason for the rupture. We believe the etiology of the tear of the anti-reflux valve in this instance to be from direct contact injury from the distal edge of the previously placed Wallflex esophageal stent. We recommend that post-placement tear with consequent dysphagia and recurrent reflux symptoms be cited as a potential complication.

Helicobacter pylori Infection may be Implicated in the Topography and Geographic Variation of Upper Gastrointestinal Cancers in the Taihang Mountain High‐Risk Region in Northern China

Helicobacter pylori infection is prevalent in China. Chronic infection of the bacterial not only causes distal stomach cancer, but also confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is inversely associated with esophageal adenocarcinoma, globally the infection rate is significantly correlated with the ratio of squamous carcinoma to adenocarcinoma of the esophagus. These agree with the topography of upper gastrointestinal cancer observed in the Taihang Mountain high-risk region where both gastric cardia and non-cardia adenocarcinoma coincide with esophageal squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover, as altitude increases from plain to mountains, we observed progressively increasing incidence rates of gastric adenocarcinomas in recent years in the region. Because H. pylori infection is a definite carcinogen to gastric adenocarcinoma and is more prevalent in the mountain than in plain areas due to undeveloped living conditions, the observation gives the impression as though H. pylori infection is implicated. This article aims to note the role of H. pylori infection in upper gastrointestinal cancer in the Taihang Mountain high-risk region in northern China. First the unique topography and geographic variation of upper gastrointestinal cancer in the region is described to indicate a possible role of H. pylori infection, then we review studies on prevalence of H. pylori infection in the high-risk region and describe difference in socioeconomic development and water hygiene between the plains and the mountains as related to the prevalence of H. pylori infection. Coincidence of gastric cancer in the region and a progressively increasing rate of the cancer from the plain towards the mountains indicate H. pylori infection may be implicated in upper gastrointestinal cancer. International collaboration is needed to study H. pylori and upper gastrointestinal cancer in the region when rapid industrialization is just beginning.

Initial Institutional Experience with Thoracoscopic Assisted Esophagectomy

We report our initial experience with thoracoscopic assisted esophagectomy (TAE) in patients with esophageal carcinoma. Clinical outcome measures are reported for 14 consecutive patients who underwent thoracoscopically assisted esophagectomy at our institution between January 2007 and June 2009. These outcomes were compared with 18 patients who underwent open esophagectomy (OE) during this time. All 14 patients were male, with a median age of 63. All had distal esophageal adenocarcinoma: stage I (7), II A (2), II B (3), and III (2). Surgical approaches included laparotomy combined with thoracoscopy and cervical (n=12), or intrathoracic anastomosis (n=2). Compared with an open approach, the thoracoscopic assisted esophagectomies were longer (median time 460 vs. 386 minutes), and they were associated with less blood loss (250 mL vs. 500 mL) and less respiratory complications (14.3% vs. 27.8%). In our TAE group more lymph nodes were removed (median number 12 in TAE vs. 10 in OE). The overall morbidity was similar in both groups (42.8% in TAE vs. 50% in OE group), but the in-hospital mortality was reduced with TAE (7.1% with TAE vs. 16.7% with OE). TAE is feasible with a low conversion rate, acceptable morbidity, and low mortality.

A safe and reproducible anastomotic technique for minimally invasive Ivor Lewis oesophagectomy: the circular-stapled anastomosis with the trans-oral anvil

In expert hands, the intrathoracic oesophago-gastric anastamosis usually provides a low rate of strictures and leaks. However, anastomoses can be technically challenging and time consuming when minimally invasive techniques are used. We present our preliminary results of a standardised 25 mm/4.8mm circular-stapled anastomosis using a trans-orally placed anvil. We evaluated a prospective cohort of 37 consecutive patients offered minimally invasive Ivor Lewis oesophagectomy at a tertiary referral centre. The oesophago-gastric anastomosis was created using a 25-mm anvil (Orvil, Autosuture, Norwalk, CT, USA) passed trans-orally, in a tilted position, and connected to a 90-cm long polyvinyl chloride delivery tube through an opening in the oesophageal stump. The anastomosis was completed by joining the anvil to a circular stapler (end-to-end anastomosis stapler (EEA XL) 25 mm with 4.8-mm staples, Autosuture, Norwalk, CT, USA) inserted into the gastric conduit. Primary outcomes were leak and stricture rates. Thirty-seven patients (mean age 65 years) with distal oesophageal adenocarcinoma (n=29), squamous cell cancer (n=5) or high-grade dysplasia in Barrett's oesophagus (n=3) underwent an Ivor Lewis oesophagectomy between October 2007 and August 2009. The abdominal portion was operated laparoscopically in 30 patients (81.1%). The thoracic portion was done using a muscle-sparing mini-thoracotomy in 23 patients (62.2%) and thoracoscopic techniques in 14 patients (37.8%). There were no intra-operative technical failures of the anastomosis or deaths. Five patients had strictures (13.5%) and all were successfully treated with endoscopic dilations. One patient had an anastomotic leak (2.7%) that was successfully treated by re-operation and endoscopic stenting of the anastomosis. The circular-stapled anastomosis with the trans-oral anvil allows for an efficient, safe and reproducible anastomosis. This straightforward technique is particularly suited to the completely minimally invasive Ivor Lewis oesophagectomy.

Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus

The Siewert classification system differentiates between adenocarcinoma of the gastroesophageal junction and that of the distal esophagus. The purpose of this study was to evaluate whether there were differences in the location and prevalence of lymph node metastases, type of recurrence, and survival with these tumors that warrant distinguishing between them in clinical practice. Records of all patients who underwent resection for adenocarcinoma of the distal esophagus or gastroesophageal junction from 1987 to 2007 were retrospectively reviewed. Based on the endoscopic location of the epicenter of the tumor in relation to the gastroesophageal junction, tumors were categorized in 301 patients as being of the distal esophagus and in 208 as being of the gastroesophageal junction. There were no significant differences in age, sex, or body mass index between patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Patients with adenocarcinoma of the distal esophagus were more likely to have reflux symptoms (75% vs 53%, P < .0001) and peritumoral intestinal metaplasia (73% vs 51%, P < .0001) and be in a surveillance program (54% vs 9%, P = .0005) compared with patients with adenocarcinoma of the gastroesophageal junction. However, the prevalence and location of nodal metastases was similar, and in node-positive patients mediastinal node involvement was present in more than 40% of the patients in each group (distal esophageal adenocarcinoma, 47%; gastroesophageal junction adenocarcinoma, 41%). Survival was similar (5 years: distal esophageal adenocarcinoma, 45%; gastroesophageal junction adenocarcinoma, 38%; P = .14), as was the prevalence and type of recurrence. The prevalence and distribution of lymph node metastases in patients with adenocarcinoma of the distal esophagus and gastroesophageal junction were similar, and after esophagectomy, there was no difference in overall survival or recurrence. Efforts to differentiate between these tumors are unnecessary, and both are effectively treated with esophagectomy.

Survival of patients with distal esophageal and gastric cardia tumors: A population-based analysis of gastroesophageal junction carcinomas

Distal esophageal tumors and gastric cardia tumors, although only physically separated by centimeters, have different staging systems and are usually treated differently. We hypothesized that gastroesophageal junction adenocarcinomas (eg, gastric cardia and distal esophageal tumors) were not distinct entities and had similar survival. Using the Surveillance, Epidemiology, and End Results database (1988-2005), we identified patients with adenocarcinomas of the distal esophagus (n = 1474) and gastric cardia (n = 192). We performed an unadjusted survival analysis using the Kaplan-Meier method, and we used a Cox proportional hazards regression model to adjust for potential confounding covariates. A 2-sided significance level was used for all statistical testing. Even after adjusting for potential confounding covariates (location, stage, race, cancer-directed surgery, and radiation therapy), we found no significant difference between distal esophageal and gastric cardia tumors with regard to overall (hazard ratio, 1.18; 95% confidence interval, 0.99-1.41) and cancer-specific (hazard ratio, 1.09; 95% confidence interval, 0.90-1.31) survival. Both cancer-directed surgery (hazard ratio, 0.45; 95% confidence interval, 0.37-0.54) and radiation therapy (hazard ratio, 0.63; 95% confidence interval, 0.55-0.71) had a beneficial influence on survival. Through a large, population-based analysis of gastric cardia and distal esophageal adenocarcinomas, we found that patients with gastroesophageal junction adenocarcinomas have similar survival rates. Cancer-directed surgery was beneficial. Adenocarcinomas of the gastroesophageal junction are not distinct entities delineated by anatomic boundaries and as such should be managed by one skilled in both esophageal and gastric resections.

The changing epidemiology of upper gastrointestinal cancers in Israel: clinical and screening implications

Western countries and now developing countries have noted a decreasing incidence of upper gastrointestinal (UGI) (esophageal and gastric) cancers, but increasing distal esophageal adenocarcinoma and a shift to fundal-sited gastric cancer. We examined these trends in Israeli Jewish and non-Jewish populations, drawing conclusions on the need to promote prevention and/or screening. Israel Cancer Registry UGI cancer data were computed by ethnicity, immigration after 1990, sex, sites and histology, examining age-standardized rates (ASR)/10 for 2000-2005 and incidence trends during 1980-2005. In Jews, male esophageal cancer incidence has increased (P<0.01) and is highest in European-American-born males (ASR/10, 1.98), but decreasing in the upper two-thirds of esophagus so that in men 89% now occur in the lower one-third. In both sexes this was associated with decreasing squamous cell carcinoma (P<0.01) but increased adenocarcinoma to cause 72.6% of esophageal cancers in men. Gastric cancer incidence is highest in European-American-born males (ASR/10, 11.75); there is a decreasing incidence in both sexes (P<0.01) and gastric site trends are stable. In non-Jews, esophageal cancer incidence is three times higher in men (ASR/10, 0.82); they are only squamous cell cancers and incidence trends are stable. Gastric cancer incidence is twice as high in men (ASR/10, 8.45) and gastric site trends are stable. UGI cancer incidence in Jews and non-Jews, men and women, is low as compared with most developing countries. The important findings are the low but prominent incidence of distal esophageal and gastric adenocarcinoma in male immigrants. This requires attention to possible preventive measures in at-risk groups.

Multimodality treatment for distal esophageal (DE) and gastroesophageal junction (GEJ) adenocarcinoma (ACA) with celiac lymph node (CLN) involvement

4574 Background: CLN involvement is a predictor of poor outcome in patients (pts) with DE or GEJ ACA. Pre-treatment identification of such patients depends on clinical staging including endoscopic ultrasound (EUS), computerized tomography (CT), and positron emission tomography (PET). This review of our CLN positive pts was undertaken to define the impact of clinical staging on prognosis after concurrent chemoradiotherapy (CCRT) and surgery. Methods: We retrospectively identified all pts with DE or GEJ ACA, CLN involvement by EUS, CT or PET, and no evidence of distant hematogenous metastases, who were treated with the same CCRT and surgery protocol at the Cleveland Clinic. Pts not staged with all three modalities were excluded. Induction CCRT consisted of radiation (30 Gy at 1.5 Gy bid), and chemotherapy with cisplatin (20 mg/m2/d) and fluorouracil (1000 mg/m2/d) both given as continuous intravenous infusions during the first 4 days of radiation. Surgery was performed in 4–6 weeks and identical CCRT was planned 6–10 weeks post-operatively. Outcomes examined included locoregional control (LRC), distant metastatic control (DMC), freedom from recurrence (FFR) and overall survival (OS). Results: Between 2/00 and 12/07, 54 pts with clinically staged CLN involvement were treated with this protocol. CLN involvement was found by EUS in 70%, CT in 69% and PET in 54% of pts. No single or combination of clinical staging tests proved predictive of outcome except for LRC which was worse in pts with all 3 tests positive (p = 0.008). With a median follow-up of 27 (range 8–71) months, the 2-year Kaplan-Meier projected LRC is 87%, DMC 18%, FFR 18%, and OS 28%. DE (vs. GEJ) primary site predicted for better DMC (p &lt; 0.001), FFR (p = 0.002), and OS (p = 0.025). Negative surgical margins predicted for better DMC and FFR (p=0.005 both outcomes). Only tumor location remained significant in multivariable analysis. Conclusions: CLN involvement portends a poor but not hopeless prognosis after multimodality therapy. Despite excellent LRC, distant failure predominates. DMC, FFR, and OS were worse in pts with GEJ primaries, but were independent of how the CLN involvement was clinically identified. No significant financial relationships to disclose.

Helicobacter pylori Infection and Barrett's Esophagus: A Systematic Review and Meta-Analysis

The majority of distal esophageal adenocarcinomas are believed to arise in patients with Barrett's esophagus (BE). Helicobacter pylori (H. pylori) infection plays an etiological role in gastric carcinogenesis, but any possible role in BE is uncertain. We aimed to explore the possible relationship between H. pylori infection and BE by meta-analysis. Observational studies comparing the prevalence of H. pylori infection in patients with BE and healthy controls conducted in adult populations and published in all languages were identified through MEDLINE, EMBASE, and Cochrane database searches up to week 5, 2008. H. pylori infection had to be confirmed by histology and/or serology and/or RUT and/or culture. Studies were excluded if no raw data for outcomes of interest were available or controls were patients with disease or duplicate publications. Summary effect size was calculated as odds ratio (OR) and 95% confidence intervals (CIs) by the random-effects model using Review Manager 4.2.8. Of 519 citations identified, a total of 12 case-control studies compared the prevalence of H. pylori infection in BE (n=550) and controls (9 studies included controls with normal endoscopy and 3 studies used healthy blood donors as control, n=2,979). There was no significant difference in the overall prevalence of H. pylori infection between BE and controls (42.9% vs. 43.9%, OR=0.74, 95% CI 0.40-1.37, P=0.34), but with significant heterogeneity. Subgroup analysis showed that the prevalence of H. pylori infection was significantly lower in BE than in endoscopically normal healthy controls (23.1% vs. 42.7%, OR=0.50, 95% CI 0.27-0.93, P=0.03) with significant heterogeneity observed between studies. The heterogeneity was eliminated by excluding a single Asian outlier study. In contrast, H. pylori infection was significantly increased in BE patients in the three studies using healthy blood donors as "normal controls" (71.2% vs. 48.1%, OR=2.21, 95% CI 1.07-4.55). In BE patients, the prevalence of H. pylori infection was significantly lower in the esophagus than in the stomach (3.3% vs. 24.7%, OR=0.14, 0.03-0.67) in three studies. H. pylori infection and BE are inversely related when compared with endoscopically normal controls but not blood donor controls. Limited evidence suggests that there is no clear association between H. pylori infection and BE. To determine more accurately the effect size of H. pylori infection in BE, high quality prospective case-control studies with age-matched, endoscopically normal healthy controls are needed.

Clinicopathological characteristics of Barrett's carcinoma, cardia carcinoma type II and distal gastric carcinoma: Influence of observed parameters on the five-year postoperative survival of patients

INTRODUCTION In the past two decades, the increased frequency of distal esophageal adenocarcinoma, esophagogastric junction and proximal gastric adenocarcinoma has been observed. The vast majority of these tumours are diagnosed in advanced stages, when the prognosis is poorer than in other gastric cancers. The aim of our study was to analyze the demographic and clinicopathological characteristics of patients operated on for Barrett's, cardia and distal gastric adenocarcinomas, as well as to study the influence of manifestations of each cancerogenetic indication on the studied clinicopathological parameters and to analyze the 5-year survival rate of patients surgically treated for cardia adenocarcinoma in relation to the patients operated on for distal gastric adenocarcinoma. We analyzed gender and age, tumour type, depth of tumour invasion, involvement of blood and lymph vessels in 66 patients surgically treated at the Centre for Oesophageal Surgery of the Institute for Digestive Diseases of the Belgrade Clinical Centre. Except for significant differences in the depth of tumour invasion during surgery, there were no other statistically significant differences between the studied groups of patients. In the patients operated on for Barrett's and cardia cancers, the tumours invaded more deeply the wall layers, i.e. they were significantly more invasive than the distal gastric tumour. The lymph node involvement was present in 87.5% of patients with Barrett's cancer, in 80% with cardia cancer and in 87% with distal gastric cancer. The 3-year survival rate of patients operated on for cardia cancer was 47.4% and the 5-year survival rate was 31.6%, while the 3-year survival rate of patients operated on for distal gastric cancer was 46.2% and the 5-year survival rate was 34.6%. These differences were not statistically significant (Wilcoxon 0.036; p = 0.85). Singly, the patients' gender, cancer type and the degree of tumour differentiation had no influence on the length of patients' postsurgical survival rate. At the time of diagnosis cardia cancer and cancers developed at the location of the Barrett's oesophagus, developed significant deeper per continuitatem than gastric cancer. There were no other differences in regard to the analyzed clinicopathological parameters among the tumours of these three locations, and there was no difference between the 3-year and 5-year survival rate between the patients operated on for gastric cancer and cardia cancer. Each studied clinicopathological parameter had no influence on the illness course.