Esophageal Ulcer as a Cause of Death: A Population-Based Study. Mortality of Esophageal Ulcer Disease.

BACKGROUND: This study aimed at defining the mortality and the nature of fatal complications that arise out of esophageal ulcer for one clearly defined geographical area. METHODS: In this national, population-based study, the occurrence of fatal esophageal ulcer or ulcer requiring hospital treatment between January 1987 and December 2000 was assessed by the use of Finland's administrative databases. Medical records provided etiology of fatal ulcer and agonal symptoms. RESULTS: Due to an esophageal ulcer, 2,242 patients received treatment in Finnish hospitals, at an annual frequency of 3.2/100,000. Ulcer with hemorrhage (53.5%), perforation (38.4%), or aspiration pneumonia (2.3%) was the cause of death in 86 patients for an annual mortality of 0.12/100,000. Based on the number of ulcers treated, 3.8% cases ended fatally. Gastroesophageal reflux disease (GERD) seemed to be the etiologic factor for ulcer in 68 (79.0%) patients. The most common agonal symptoms were hematemesis (41.8%), abdominal pain (25.6%), melaena (22.1%), and dyspnea (17.4%). Twenty (23.3%) patients were found dead at home. CONCLUSION: The rarity of the disease, related disorders, and the diversity of symptoms make the complicated esophageal ulcer a diagnostic challenge. Effective monitored treatment for severe GERD may be an important step to prevent fatal outcome.

Medico-legal autopsy in postoperative hemodynamic collapse following coronary artery bypass surgery.

Sudden unexpected postoperative hemodynamic collapse with a high mortality develops in 1-3% of patients undergoing coronary artery bypass surgery (CABG). The contribution of surgical graft complications to this serious condition is poorly known and their demonstration at autopsy is a challenging task. Isolated CABG was performed in 8,807 patients during 1988-1999. Of the patients, 76 (0.9%) developed sudden postoperative hemodynamic collapse resulting in subsequent emergency reopening of the median sternotomy and open cardiac massage. Further emergency reoperation could be performed in 62 (82%) whereas 14 patients died prior to reoperation and a further 21 did not survive the reoperation or died a few days later. All 35 (46%) patients who did not survive were subjected to medico-legal autopsy combined with postmortem cast angiography. By combining clinical data with autopsy and angiography data, various types of graft complications were observed in 27 (36%, 1.3 per patient) of the 76 patients with hemodynamic collapse. There were no significant differences in the frequency (33 vs. 40%) or number of complicated grafts per patient (1.2 vs. 1.4) between those who survived reoperation and who did not. Autopsy detected 25 major and minor findings not diagnosed clinically. Postmortem cast angiography visualized 2 graft twists not possible to detect by autopsy dissection only. Surgical graft complications were the most frequent single cause for sudden postoperative hemodynamic collapse in CABG patients leading to a fatal outcome in almost half of the cases. Postmortem angiography improved the accuracy of autopsy diagnostics of graft complications.

Complications in antireflux surgery: national-based analysis of laparoscopic and open fundoplications.

HYPOTHESIS: Longer experience of surgeons has reduced the rate of complications in antireflux surgery. DESIGN: Comparison of the rate of serious complications between open and laparoscopic fundoplication in Finland at the national level. SETTING: University teaching hospital. PATIENTS: From January 1, 1992, to December 31, 2001, 10 846 fundoplications were performed in Finland. Of these, 3987 (37%) were open and 6859 (63%) were laparoscopic. MAIN OUTCOME MEASURES: Administrative databases provided the number of fundoplications, the rate of severe complications, and the mortality. Medical records allowed for evaluation of the nature and cause of severe complications of laparoscopic and open fundoplications. RESULTS: From January 1, 1992, to December 31, 2001, hospital mortality was significantly lower after laparoscopy (P = .01). In comparable groups, surgical mortality or the overall rate of serious complications did not differ. The rate of serious complications decreased after both open surgery (P = .01) and laparoscopic surgery (P = .03). After laparoscopy, patients made claims for injuries more often (P = .003) and had a higher rate of dysphagia (P < .001). In all of the patients with severe dysphagia or fundic perforations after laparoscopy, the short gastric vessels were not divided. Furthermore, 1 open fundoplication and 22 laparoscopic fundoplications had to have reoperations performed owing to dysphagia, mostly involving technical failure. CONCLUSIONS: At the national level, the first 10-year experience of laparoscopic fundoplication reduced the rate of serious complications. The complications largely were technical failures related to the lack of a standardized surgical technique.

Gastroesophageal reflux patients' defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4-year follow-up.

BACKGROUND: Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD). AIM: To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery. METHODS: In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by superoxide dismutase activity (SOD), and glutathione content (GSH) was measured from proximal esophageal samples. RESULTS: In proximal esophagus of GERD patients compared to controls', antioxidative capacity appearing as GSH level was significantly decreased (P < 0.001) at all time points and as SOD levels preoperatively (P < 0.001) and 4 years postoperatively (P = 0.01). MPO activity of patients was significantly lower than controls' preoperatively, and 6 months and 4 years postoperatively (P < 0.05). MPO activity remained lower than that of the distal esophagus at 6 months and 4 years (P < 0.01 for both). CONCLUSIONS: In GERD patients, proximal esophageal mucosal antioxidative defense is defective before and after antireflux surgery. Antireflux surgery seems not to change the level of oxidative stress in proximal esophagus, suggesting that defective mucosal antioxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD.

Gastroesophageal reflux disease as a cause of death is increasing: analysis of fatal cases after medical and surgical treatment.

OBJECTIVES: The population impact of modern treatment on complicated gastroesophageal reflux disease (GERD) is not well understood. Our aim was to determine the current mortality from GERD in Finland and compare this with the use of health resources. METHODS: In this population-based retrospective study, Finland's administrative databases provided figures on the nationwide use of antireflux medication, rate of antireflux surgery, and mortality from GERD. Any deceased person included had classic symptoms as well as objective findings of GERD. RESULTS: After analysis of the medical records of 306 patients, 213 were included. Annual mortality from GERD increased (P < 0.001) from 0.18/100,000 in 1987 to 0.46/100,000 in 2000. During that time, use of H2-blockers and proton pump inhibitors and the annual rate of antireflux surgery increased significantly (P < 0.001). Mortality from antireflux surgery, including fundoplication and gastric and esophageal resection, remained around 1.9/1,000 operations. Of the 213 patients whose cause of death was considered to be GERD, 180 (85%) had received medical treatment, including 4 patients whose death was related to either diagnostic or therapeutic endoscopy. Early complications of antireflux surgery caused 24 (11%) deaths; 9 (4%) were late failures of antireflux surgery. Causes of death in the medical group were hemorrhagic esophagitis (82, 47%), aspiration pneumonia (41, 23%), ulcer perforation (25, 14%), rupture with esophagitis (15, 9%), and stricture (13, 7%). CONCLUSIONS: Regardless of the increased use of health resources, mortality from GERD, especially with medical treatment, rose. Surgery for GERD was also associated with early mortality and usually could not prevent the fatal outcome.

Predictive factors of hemodynamic collapse after coronary artery bypass grafting: a case-control study.

OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG) surgery is a complication with high morbidity and mortality. The aim of this study was to explore factors possibly predictive of this major complication. DESIGN: Retrospective case-control study. SETTING: University hospital, department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of 8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively matched patients (by age, sex, New York Heart Association classification, number of diseased vessels, left ventricular ejection fraction, and diabetes) served as a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular collapse underwent emergency reopening of the sternotomy and open cardiac massage (OCM group). Several pre-, intra-, and postoperative variables were compared, and significant parameters in match-pair analysis were further tested with regression techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76) versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group, cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH, p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients more frequently required postoperative inotropic (epinephrine, p = 0.0002) and mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis revealed a correlation between cardiopulmonary resuscitation risk and low cardiac index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue perfusion, postoperative myocardial ischemia, and increased need for inotropic and mechanical support preceded hemodynamic collapse. Interventions to improve tissue perfusion and to prevent and treat myocardial ischemia may result in a more favorable outcome.

The impact of antireflux surgery on oxidative stress of esophageal mucosa caused by gastroesophageal reflux disease: 4-yr follow-up study.

BACKGROUND AND AIM: Oxidative stress to esophageal mucosa plays a key role in the pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus, and adenocarcinoma. We investigated whether successful antireflux surgery eliminates oxidative stress. METHODS: Oxidative stress of esophageal mucosa was measured in 20 GERD patients, before antireflux surgery and 6 and 48 months after it, and compared with normal controls' mucosa (N = 9). Preoperatively, 12 of the 20 had erosive esophagitis or Barrett's metaplasia. Postoperatively, healing of GERD was verified with endoscopy and 24-h pH monitoring. We measured oxidative stress by myeloperoxidase activity (MPA), superoxide dismutase activity, and glutathione content (GSH) in distal esophagus samples from endoscopy. RESULTS: No patient had reflux symptoms after surgery, and pH measurements had normalized. MPA in the distal esophagus decreased (p < 0.05) after successful antireflux surgery, but remained higher than that of controls both 6 months and 4 yr postoperatively (p < 0.05). At all time-points, MPA was higher in patients with preoperatively detected erosive reflux disease (ERD) as compared to non-erosive reflux disease (NERD) (p < 0.01, p < 0.05, and p < 0.05, respectively). GSH values decreased with time only in NERD. At all time-points, GSH levels in distal esophagus were lower than control levels. CONCLUSIONS: Antireflux surgery can heal macroscopic esophagitis but cannot fully reverse the oxidative stress (as reflected by MPA and GSH) upon the distal esophageal mucosa.

Gastropericardial fistula, purulent pericarditis, and cardiac tamponade after laparoscopic Nissen fundoplication.

Gastropericardial fistula, purulent pericarditis, and cardiac tamponade developed 7 years after laparoscopic Nissen fundoplication. The patient was successfully managed through a thoracotomy by open drainage of the pericardium, excision and closure of the fistula, and an omentum flap.

Adenocarcinoma of the esophagus and the esophagogastric junction: positron emission tomography improves staging and prediction of survival in distant but not in locoregional disease.

In adenocarcinoma of the esophagus and esophagogastric junction for prognostication and treatment allocation, one prerequisite is accurate pretreatment staging. This staging, we hypothesized, would be improved by the use of positron emission tomography (PET). After 55 patients suitable for radical esophageal resection were staged with PET, spiral computed tomography (CT), and endoscopic ultrasonography (EUS), results were compared with histopathology and with survival. Accuracy in detecting locoregional lymph node metastasis did not differ significantly between EUS (72%), PET (60%), and CT (58%). Adding PET to standard staging failed to improve the accuracy of N staging (P=0.250). In M staging, accuracy between CT (75%) and PET (76%) did not differ. The accuracy of combined studies of CT and PET and of EUS, CT, and PET were 87% (P=0.016 versus CT) and 91% (P=0.031 versus EUS and CT), respectively. Of the 55 patients, 19 (35%) had metastatic lesions. By combined use of CT and EUS and by combined use of CT, EUS, and PET, 8 and 14 (P=0.031), respectively, could be detected. In nodal disease without distant metastases, PET did not improve the prediction of survival. However, positive PET for distant metastasis by either positive EUS or CT predicts well the poor survival of these patients. The staging value of PET by itself in adenocarcinoma of the esophagus is limited because of low accuracy for nodal and the lack of specificity for distant disease prognosis. Adding PET to standard staging does, however, improve detection of stage IV disease and its associated poor survival.

Oesophageal histology in gastro-oesophageal reflux disease is of minor pre- and postoperative diagnostic value.

BACKGROUND AND AIM: The clinical value of oesophageal histology in non-complicated gastro-oesophageal reflux disease (GORD) is controversial. Our aim was to explore the role of histology in preoperative diagnosis and postoperative follow-up in GORD. METHODS: From 40 patients 2 histopathologists graded and scored 191 oesophageal biopsies in a blinded manner to evaluate inter- and intraobserver variation pre- and postoperatively. Correlation between preoperative histology and objective clinical findings (endoscopy, esophageal 24-hour pH monitoring, and manometry) was calculated as well. RESULTS: Pathologist I interpreted 16 (50%) preoperative biopsies as normal, 5 (16%) with mild, 4 (12.5%) moderate, and 7 (21.9%) severe reflux changes. Pathologist II interpreted 11 (35.5%) preoperative biopsies as normal, 11 (35.5%) with mild, 6 (19.4%) moderate, and 3 (9.7%) severe reflux changes. In preoperative biopsies, interobserver variation was 33.8% and intraobserver variation 9.7%. A positive correlation was detectable between preoperative endoscopic and morphologic findings; no correlation existed between either acid reflux or LES pressure and oesophageal morphology. Normal pH monitoring and fundic wrap were noted postoperatively in all cases. In postoperative histology no significant differences according to pathologist I existed when compared with preoperative changes: 22 normal (69%), 7 mild (22%), 1 moderate (3.1%), and 2 severe (6.3%). Compared to preoperative analysis, pathologist II interpreted 24 (77%, p = 0.001) of the postoperative findings as normal, 1 (3%, p = 0.003) as mild, 4 (12.9%, n.s.) as moderate, and 2 (6.5% n.s.) as severe reflux changes. In postoperative biopsies interobserver variation was 21.1% and intraobserver variation 5.6%. CONCLUSION: The role of oesophageal histology in preoperative diagnosis and postoperative follow-up of GORD may be considered limited.

Fate of patients with adenocarcinoma of the esophagus and the esophagogastric junction: a population-based analysis.

OBJECTIVE: At the population level, a detailed picture of the nature of adenocarcinoma at the distal esophagus and esophagogastric junction under modern treatment is lacking. We evaluated the fate of these patients and the results of various types of therapeutic procedures using unselected population-based data. METHODS: Primary data on patients with these adenocarcinomas in two health care districts in Finland were retrieved from the Finnish Cancer Registry. The fate of all 402 patients treated between 1990 and 1998 in 23 units was analyzed. RESULTS: The 5-yr survival rate of these patients was 12.5%. Median survival was 36.5 days (0 days- 68.1 months) with best supportive care (18.9%), 116.5 days (0 days-59.5 months) with palliative (33.8%), mainly either endoscopic or oncological treatment, 211 days (113 days-26.6 months) with exploratory surgery (4.7%), and 17.6 months (0-101.1) after esophageal resection (42.5%). The 5-yr and 8-yr survival rates in this unselected material after esophageal resection including 8.8% operative mortality were 29.0% and 26.0%. The best chance for cure and long-term survival came from esophagectomy with 2-field lymphadenectomy compared to less extensive operations (50.0%vs 23.2% survival at 5 yrs, p= 0.005). Between these groups no statistically significant difference (p= 0.4) existed in pathological TNM stages or in the distribution of node-negative tumors (47.6%vs 41.8%). CONCLUSIONS: Although overall prognosis for adenocarcinoma near the esophagogastric junction is poor, a substantial percentage of patients eligible for major surgery achieve long-term survival.

Simultaneous progression of oxidative stress and angiogenesis in malignant transformation of Barrett esophagus.

BACKGROUND: Oxidative stress and angiogenesis are important elements in the pathogenesis of inflammatory diseases and cancer. Our aim was to evaluate the role of both and of antioxidant capacity in the metaplasia-dysplasia-adenocarcinoma sequence in Barrett epithelium. METHODS: In mucosal specimens from 59 patients grouped as having symptomatic gastroesophageal reflux disease, Barrett epithelium, or adenocarcinoma in the esophagus, plus controls, we measured myeloperoxidase activity, superoxidase dismutase activity, glutathione content, and total aromatic DNA adducts. To evaluate blood vessel densities and angioarchitecture, we used immunohistochemistry and a modified whole-mount technique. Sections were stained with endothelium-specific markers and smooth muscle cell actin. RESULTS: The reflux disease-metaplasia-carcinoma sequence revealed progressively increased oxidative stress (increased myeloperoxidase activity), decreased antioxidant capacity (glutathione content), and simultaneous formation of DNA adducts. Pooled data show a negative correlation between glutathione content and DNA adducts (-0.28; P =.05). This sequence was also characterized by increased intensity in microvessels and an increasing percentage of immature blood vessels. In addition, the whole-mount technique offered 3-dimensional evidence that the rich new vascular bed is highly abnormal, with repeated twists, bends, or turns, even in nonmalignant Barrett esophagus. CONCLUSIONS: Increased oxidative stress, decreased antioxidant capacity, and a negative correlation between glutathione content and DNA adduct formation indicate a link between oxidative stress and malignant transformation of Barrett epithelium. Simultaneously, this transformation acquires angiogenic capacity, strong neovascularization, and abnormal angioarchitecture.

Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction.

BACKGROUND: Exact preoperative staging of esophageal cancer is essential for accurate prognosis and selection of appropriate treatment modalities. METHODS: Forty-two patients with adenocarcinoma of the esophagus or the esophagogastric junction suitable for radical esophageal resection were staged with positron emission tomography (PET), spiral computed tomography (CT), and endoscopic ultrasonography (EUS). RESULTS: Diagnostic sensitivity for the primary tumor was 83% for PET and 67% for CT; for local peritumoral lymph node metastasis, it was 37% for PET and 89% for EUS; and for distant metastasis, it was 47% for PET and 33% for CT. Diagnostic specificity for local lymph node metastasis was 100% with PET and 54% with EUS, and for distant metastasis, it was 89% for PET and 96% for CT. Accuracy for locoregional lymph node metastasis was 63% for PET, 66% for CT, and 75% for EUS, and for distant metastasis, it was 74% with PET and 74% with CT. Of the 10 patients who were considered inoperable during surgery, PET identified 7 and CT 4. The false-negative diagnoses of stage IV disease in PET were peritoneal carcinomatosis in two patients, abdominal para-aortic cancer growth in one, metastatic lymph nodes by the celiac artery in four, and metastases in the pancreas in one. PET showed false-positive lymph nodes at the jugulum in three patients. CONCLUSIONS: The diagnostic value of PET in the staging of adenocarcinoma of the esophagus and the esophagogastric junction is limited because of low accuracy in staging of paratumoral and distant lymph nodes. PET does, however, seem to detect organ metastases better than CT.

Oxidative stress has a role in malignant transformation in Barrett's oesophagus.

Mechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro-oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barrett's epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia. Only in Barrett's epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barrett's epithelium without dysplasia and progressively lower in Barrett's with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (-0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase-related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.

Incipient angiogenesis in Barrett's epithelium and lymphangiogenesis in Barrett's adenocarcinoma.

PURPOSE: Barrett's esophagus (BE), a precancerous condition for Barrett's adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barrett's adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barrett's adenocarcinoma cells to infiltrate regular lymph nodes. PATIENTS AND METHODS: Fifteen surgically resected Barrett's dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used. RESULTS: The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barrett's epithelium, giving its ominous salmon-red color. Barrett's epithelium-specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated. CONCLUSION: BE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barrett's adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis.