Attila Dubecz

Temporal Trends in Long-Term Survival and Cure Rates in Esophageal Cancer: A SEER Database Analysis

Purpose: To assess long-term temporal trends in population-based survival and cure rates in patients with esophageal cancer and compare them over the last 3 decades in the United States. Methods: We identified 62,523 patients with cancer of the esophagus and the gastric cardia diagnosed between 1973 and 2007 from the Surveillance, Epidemiology, and End Results database. Long-term cancer-related survival and cure rates were calculated. Stage-by-stage disease-related survival curves of patients diagnosed in different decades were compared. Influence of available variables on survival and cure was analyzed with logistic regression. Results: Ten-year survival was 14% in all patients. Disease-related survival of esophageal cancer improved significantly since 1973. Median survival in Surveillance, Epidemiology, and End Results stages in local, regional, and metastatic cancers improved from 11, 10, and 4 months in the 1970s to 35, 15, and 6 months after 2000. Early stage, age 45 to 65 years at diagnosis and undergoing surgical therapy were independent predictors of 10-year survival. Cure rate improved in all stages during the study period and were 73%, 37%, 12%, and 2% in stages 0, 1, 2, and 4, respectively, after the year 2000. Percentage of patients undergoing surgery improved from 55% in the 1970s to 64% between 2000 and 2007. Proportion of patients diagnosed with in situ and local cancer remains below 30%. Conclusion: Long-term survival with esophageal cancer is poor but survival of local esophageal cancer improved dramatically over the decades. Complete cure of nonmetastatic esophageal cancer seems possible in a growing number of patients. Early diagnosis and treatment are crucial.

A New Era in Esophageal Diagnostics: The Image-Based Paradigm of High-Resolution Manometry

BACKGROUND The development of high-resolution (HRM) catheters and software displays of manometric recordings in color-coded pressure plots has changed the diagnostic assessment of esophageal disease. HRM may offer advantages over conventional methods, including improved identification of motility disorders, hiatal hernia, and outflow obstruction, and ease interpretation. STUDY DESIGN HRM studies were obtained in 50 healthy volunteers and 106 patients. HRM was performed using a 36-channel catheter, with sensors spaced at 1-cm intervals. Manometric findings were classified into abnormalities of the gastroesophageal barrier and those of the esophageal body and validated by comparison with endoscopic and radiographic diagnostic methods. RESULTS The mean time for HRM was significantly lower than that for a conventional method (8.1versus 24.4 minutes; p < 0.0001). A structurally defective lower esophageal sphincter (LES) was present in 53 (57.3%) patients, a hypertensive LES in 6 (7.8%), and impaired LES relaxation in 17 patients (16.7%). Validating the LES findings, 86.3% (44 of 51) of patients with a defective sphincter by HRM had radiographic or endoscopic evidence of a hiatal hernia, and 80% (41 of 51) had a positive pH study, endoscopic erosive esophagitis, or Barretts esophagus. Evidence of a hiatal hernia by HRM was seen in 33 (56%) patients; a hiatal hernia was seen in 91% (30 of 33) of these on endoscopy and 81% (17 of 21) on barium swallow. Fifty-eight patients (54.7%) had an abnormal body motility. CONCLUSIONS HRM studies are shorter than those using conventional methods. Interpretation is image based, and correlation with objective endoscopic and physiologic findings confirms the accuracy of interpretation. The introduction of HRM is a significant advance in the outpatient evaluation of esophageal function.

Oesophageal cancer—an overview

Oesophageal carcinoma is one of the most virulent malignant diseases and a major cause of cancer-related deaths worldwide. Diagnosis and accuracy of pretreatment staging have substantially improved throughout the past three decades. Therapy is challenging and the optimal approach is still debated. Oesophagectomy is considered to be the procedure of choice in patients with operable oesophageal cancer. Endoscopic measures and limited surgical procedures provide an alternative in patients with early carcinomas confined to the oesophageal mucosa. Chemotherapy and radiotherapy or concurrent chemoradiotherapy are also frequently applied, either as definitive treatment or as neoadjuvant therapy within multimodal approaches. The question of whether multimodal treatment offers improved results has been the focus of many studies since the 1990s. Although results are discordant and even some meta-analyses remain inconclusive, it is now widely accepted that multimodal therapy leads to a modest survival benefit. The role of minimally invasive oesophagectomy is not yet defined. Endoscopic stent insertion, radiotherapy and other palliative measures provide relief of tumour-related symptoms in advanced, unresectable tumour stages.

Endoscopic stent insertion for anastomotic leakage following oesophagectomy

Introduction Intrathoracic anastomotic leakage following oesophagectomy is a crushing condition. Until recently, surgical re-exploration was the preferred way of dealing with this life threatening complication. However, mortality remained significant. We therefore adopted endoscopic stent implantation as the primary treatment option. The aim of this study was to investigate the feasibility and results of endoscopic stent implantation as well as potential hazards and pitfalls. Methods Between January 2004 and December 2011, 292 consecutive patients who underwent an oesophagectomy at a single high volume centre dedicated to oesophageal surgery were included in this retrospective study. Overall, 38 cases with anastomotic leakage were identified and analysed. Results A total of 22 patients received endoscopic stent implantation as primary treatment whereas a rethoracotomy was mandatory in 15 cases. There were no significant differences in age, frequency of neoadjuvant therapy or ASA grade between cases with and without a leak. However, patients with a leak were five times more likely to have a fatal outcome (odds ratio: 5.10, 95% confidence interval: 2.06–12.33, p<0.001). Stent migration occurred but endoscopic reintervention was feasible. In 17 patients (77%) definite closure and healing of the leak was achieved, and the stent was removed subsequently. Two patients died owing to severe sepsis despite sufficient stent placement. Moreover, stent related aortic erosion with consecutive fatal haemorrhage occurred in three cases. Conclusions Stent implantation for intrathoracic oesophageal anastomotic leaks is feasible and compares favourably with surgical re-exploration. It is an easily available, minimally invasive procedure that may reduce leak related mortality. However, it puts the already well-known risk of stent-related vascular erosion on the spot. Awareness of this life threatening complication is therefore mandatory.

Predictors of Lymph Node Metastasis in Surgically Resected T1 Esophageal Cancer

BACKGROUND The application of endoscopic therapies for early cancers of the esophagus is limited by the possible presence of regional lymph node metastases. Our objective was to determine the prevalence and predictors of lymph node metastases in patients with pT1 carcinoma of the esophagus and the gastric cardia. METHODS The National Cancer Institutes Surveillance Epidemiology and End Results Database (2004 to 2010) was used to identify all patients with pT1 carcinomas who underwent primary surgical resection for squamous cell carcinoma (SCC) or adenocarcinoma (EAC) of the esophagus and of the esophagogastric junction (AEG). Prevalence of lymph node metastases was assessed, and survival in all types of cancer was calculated. Multivariate logistic regression was used to identify factors predicting positive lymph node status. RESULTS There were 1,225 patients (84% male), with a mean age of 64 ± 10 years, and 90% were white. Intramucosal disease was present in 44% of patients, and submucosal invasion (T1b) was present in 692 (56%). Prevalence of lymph node metastases in EAC, SCC, and AEG was 6.4%, 6.9%, and 9.5% for pT1a tumors and 19.6%, 20%, and 22.9% for pT1b tumors, respectively. In patients with more than 23 lymph nodes removed during resection, prevalence of lymph node metastases in EAC, SCC, and AEG was 8.1%, 25%, and 7.4% for pT1a tumors and 27.8%, 33.3%, and 22% for pT1b tumors, respectively. Positive lymph node status was associated with worse overall 5-year survival in EAC (N0 vs N+: 78% vs 52%) and AEG (N0 vs N+: 83% vs 44%) but did not have a significant effect on the long-term survival of patients with SCC. Infiltration of the submucosa, tumor size exceeding 10 mm, and poor tumor differentiation were independently associated with the risk of nodal disease. Prevalence of lymph node metastasis negative for these three risk factors was only 4.8%. CONCLUSIONS Prevalence of lymph node metastasis in early esophageal cancer is high in patients with T1 cancer. Inadequate lymphadenectomy underestimates lymph node status. Endoscopic treatment can be considered only in a select group of patients with early esophageal cancer.

Surgical Resection for Locoregional Esophageal Cancer Is Underutilized in the United States

BACKGROUND Although esophagectomy provides the highest probability of cure in patients with esophageal cancer, many candidates are never referred for surgery. We hypothesized that esophagectomy for esophageal cancer is underused, and we assessed the prevalence of resection in national, state, and local cancer data registries. STUDY DESIGN Clinical stage, surgical and nonsurgical treatments, age, and race of patients with cancer of the esophagus were identified from the Surveillance, Epidemiology and End Results (SEER) registry (1988 to 2004), the Healthcare Association of NY State registry (HANYS 2007), and a single referral center (2000 to 2007). SEER identified a total of 25,306 patients with esophageal cancer (average age 65.0 years, male-to-female ratio 3:1). HANYS identified 1,012 cases of esophageal cancer (average age 67 years, M:F ratio 3:1); stage was not available from NY State registry data. A single referral center identified 385 patients (48 per year; average age 67 years, M:F 3:1). For SEER data, logistic regression was used to examine determinants of esophageal resection; variables tested included age, race, and gender. RESULTS Surgical exploration was performed in 29% of the total and only 44.2% of potentially resectable patients. Esophageal resection was performed in 44% of estimated cancer patients in NY State. By comparison, 64% of patients at a specialized referral center underwent surgical exploration, 96% of whom had resection. SEER resection rates for esophageal cancer did not change between 1988 and 2004. Males were more likely to receive operative treatment. Nonwhites were less likely to undergo surgery than whites (odds ratio 0.45, p < 0.001). CONCLUSIONS Surgical therapy for locoregional esophageal cancer is likely underused. Racial variations in esophagectomy are significant. Referral to specialized centers may result in an increase in patients considered for surgical therapy.

Risk of Stent-Related Aortic Erosion After Endoscopic Stent Insertion for Intrathoracic Anastomotic Leaks After Esophagectomy

BACKGROUND Intrathoracic anastomotic leakage after esophagectomy is associated with high morbidity and mortality. Because of disappointing results after surgical reexploration endoscopic stent implantation was introduced as primary treatment option with improved outcome. Aortoesophageal fistula is a very rare complication and has thus far only anecdotally been reported after esophagectomy. The aim of this retrospective study was to investigate if endoscopic stent implantation increases the incidence of postoperative aortoesophageal fistula by reason of stent-related erosion of the thoracic aorta. METHODS Between January 2004 and October 2010, 213 patients underwent esophageal resection mainly for esophageal cancer. An intrathoracic esophageal anastomotic leak was endoscopically verified in 25 patients. Seventeen patients received endoscopic implantation of a self-expanding stent as primary treatment. In 8 patients a rethoracotomy was mandatory. RESULTS After successfully accomplished endoscopic stent placement, complete closure of the anastomotic leak was radiologically proven in all 17 patients. In 13 cases, definitive closure and healing of the leak was achieved and the stent could subsequently be removed. In 1 patient, because of early recurrence of very malignant small cell cancer, the stent remained in situ. Three patients developed an erosion of the thoracic aorta with subsequent massive hemorrhage. The mean time between stent insertion and occurrence of aortoesophageal fistula was 26 days. All 3 patients died of exsanguination with severe hypovolemic shock. Postmortem examination confirmed an aortoesophageal fistula in each case. CONCLUSIONS While endoscopic stent implantation seems to be effective in the control of intrathoracic anastomotic leakage, nevertheless the incidence of aortoesophageal fistula caused by stent-related aortic erosion exceeds the thus far reported numbers. Awareness of this life-threatening complication after stent insertion is therefore mandatory.

Management of anastomotic leakage-induced tracheobronchial fistula following oesophagectomy: the role of endoscopic stent insertion

OBJECTIVES Tracheobronchial fistulas are rare but life-threatening complications after oesophagectomy. Leakage of the oesophagointestinal anastomosis with inflammatory involvement of the tracheobronchial tree is the predominant reason for postoperative fistulization between the airways and the oesophagus or the gastric tube. Successful management is challenging and still controversially discussed. After promising results in the treatment of intrathoracic anastomotic leaks, we adopted endoscopic stent implantation as the primary treatment option in patients with anastomotic leak-induced tracheobronchial fistula. The aim of this study was to investigate the feasibility, the limits and the results of this procedure. METHODS Between January 2004 and December 2010, 222 consecutive patients underwent oesophageal resection mainly for oesophageal cancer. An anastomotic leak-induced tracheobronchial fistula was bronchoscopically verified in seven patients. Four patients received endoscopic implantation of either a self-expanding tracheal or oesophageal stent or both as primary treatment. Surgical re-exploration was mandatory in 2 patients because of necrosis of the pulled-up gastric tube or gangrene of the airways. One patient was conservatively managed. RESULTS Endoscopic stent placement was successfully accomplished in all 4 patients. Two patients received an oesophageal stent, one patient a tracheal stent and one patient both an oesophageal and a tracheal stent. Closure of the fistula was achieved in all cases and 3 patients finally recovered while one died by reason of respiratory failure. In both surgical re-explored patients resection of the gastric tube was performed, and in one patient, because of subtotal gangrene of the right bronchial tree, emergency pneumectomy was also mandatory. Both patients died due to severe sepsis and respiratory failure. The one conservatively treated patient died from severe pneumonia. CONCLUSIONS Treatment of anastomotic leak-induced tracheobronchial fistulas by means of oesophageal and tracheal stent implantation is feasible. If stent insertion is limited by gastric tube necrosis or bronchial gangrene, the prognosis is likely to be fatal.

Treatment of intrathoracic esophageal anastomotic leaks by means of endoscopic stent implantation

Intrathoracic anastomotic leakage in patients with esophagectomy is associated with high morbidity and mortality. Until recently surgical reexploration was the preferred way of dealing with this life-threatening complication. But mortality remained significant. After the first successful reports we adopted endoscopic stent implantation as a primary treatment option. The aim of this study was to investigate the feasibility and the results of endoscopic stent implantation. Between January 2004 and December 2009, 167 patients underwent an esophageal resection. Surgery was mainly the result of esophageal cancer. An intrathoracic esophageal anastomotic leak was endoscopically verified in 17 patients. Twelve patients received an implantation of a self-expanding stent as a primary treatment. An endoscopic stent placement was accomplished in all 12 patients. In nine patients a definitive closure of the leak was achieved and the stent could subsequently be removed. Two patients died due to severe sepsis in spite of sufficient stent placement. Because of early recurrence of very malign small cell cancer the stent remained in situ in one patient. In conclusion, stent implantation for intrathoracic esophageal anastomotic leaks is feasible and compares favorable with the results of surgical reexploration. It is an easily available minimally-invasive procedure which may reduce leak-related mortality and morbidity.

Association of Kyphosis and Spinal Skeletal Abnormalities with Intrathoracic Stomach: A Link Toward Understanding its Pathogenesis

BACKGROUND Modern-day concepts about the pathogenesis of an intrathoracic stomach include crural diaphragm muscular deterioration, loss of phrenoesophageal ligament integrity, and presence of abdominothoracic pressure gradients. The role of spinal abnormalities has received little attention. Based on clinical observation, we hypothesized that kyphosis and other spinal diseases are components of the pathophysiology of an intrathoracic stomach. STUDY DESIGN The study population consisted of 98 patients (men, n = 22; women, n = 76; mean age 69.4 years) undergoing operations for type III or IV hiatal hernia with an intrathoracic stomach. Twenty-four age- and gender-matched control patients without hiatal hernia undergoing pulmonary or pleural procedures were used for comparison. Chest radiographs were assessed for spinal abnormalities, including degree of kyphosis, measured from superior T4 to inferior T12 (modified Cobb method), spinal fractures, osteoporosis, and scoliosis. Statistical analyses included two-sample t-test and Fishers exact test. RESULTS Patients with intrathoracic stomach had a greater degree of kyphosis than control patients (Cobb angle, 50.2 degrees versus 39.7 degrees; p < 0.001). This difference was most pronounced in women (Cobb angle, 51.7 degrees versus 40.4 degrees; p < 0.001), although the difference in men was not significant (Cobb angle, 45.0 degrees versus 38.1 degrees; p = 0.25). Patients with an intrathoracic stomach had significantly more vertebral fractures (37 of 98 [38%] versus 3 of 24 [13%]; p < 0.05). There was no difference in prevalence of degenerative changes (51 of 98 [52%], versus 13 of 24 [54%]), osteopenia (30 of 98 [31%] versus 6 of 24 [25%]), and scoliosis (27 of 98 [28%] versus 6 of 24 [25%]). CONCLUSION Patients with an intrathoracic stomach have a higher degree of kyphosis and more vertebral fractures than age- and gender-matched controls. These data suggest that change in spinal curvature can be important in the pathogenesis of the intrathoracic stomach, a growing problem of our aging population.