Tuomo K. Rantanen

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 Barretts 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, Barretts 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 Barretts epithelium without dysplasia. Only in Barretts 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 Barretts epithelium without dysplasia and progressively lower in Barretts 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 Barretts oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.

Fatal complications of adult paraesophageal hernia: A population-based study

OBJECTIVES Data on mortality from paraesophageal hernia are scarce. This study focused on mortality associated with its natural history or conservative treatment. METHODS For this population-based retrospective study, Finlands administrative databases provided preliminary data. Among 333 patients who died from benign esophageal diseases or hiatal hernias, analysis of medical records led us to include 32. RESULTS From 1987 through 2001 in Finnish hospitals, 563 patients underwent surgical intervention and 67 underwent conservative treatment for paraesophageal hernia. This hernia caused death (mortality, 0.6/1,000,000 of the adult population; 95% confidence interval, 0-1.8/1,000,000) in 32 patients, 29 (91%) with concomitant diseases. The overall mortality rate for the 563 having surgical treatment was 2.7% (15 patients). Three died after elective repair. Of 67 patients hospitalized for symptomatic paraesophageal hernia and treated conservatively, 11 (16.4%) died in the hospital within a mean of 42 months (range, 2-96 months) from onset of symptoms. Four (13%) deaths might have been prevented by elective surgical intervention. Of the 32 deceased patients, 4 (12.5%) had type II, 16 (50%) had type III, and 9 (28.1%) had type IV hiatal hernias. In 3 (9.4%) patients type remained unknown. Death resulted from incarceration in 24 (75%), complications of surgical intervention in 6 (18.8%), and bleeding ulcer in 2 (6.2%). CONCLUSIONS Overall, most deaths were related to type III or IV hernias in aged patients with concomitant diseases, with those with severe symptoms requiring hospitalization at significant risk. Except for those at high surgical risk, we recommend repair of the paraesophageal hernia, at least in symptomatic patients.

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 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, Finlands 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.

Comparison of the effects of esomeprazole and fundoplication on airway responsiveness in patients with gastro‐oesophageal reflux disease

Gastro‐oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non‐acidic reflux.

Esophageal adenocarcinoma arising after antireflux surgery: a population-based analysis.

OBJECTIVE Fundoplication is widely used to treat gastroesophageal reflux disease (GERD). Whether it diminishes the development of esophageal adenocarcinoma (EAC) is, however, controversial. Our aim was to define, at the national level in Finland, frequency and predisposing factors for post-fundoplication EAC. METHODS For this population-based study from 1980 to 2006, Finlands administrative databases provided preliminary data. Analyses of EAC patient records (N = 1035) led us to include those with preceding antireflux surgery. Conservatively treated patients were not analyzed. The EAC incidence in patients with antireflux surgery was compared with that in the general population (1987-2006) by means of standardized incidence ratio (SIR). RESULTS A total of 53 (5.1%) EAC patients had undergone antireflux surgery. Of these patients with male predominance (74%), preoperatively 41 (77%) had developed endoscopic esophagitis, 40 (75%) hiatal hernia, 24 (45%) Barretts esophagus (BE), nine (17%) ulcer in the esophagus or gastroesophageal junction, and three (6%) stricture. Postoperatively, histologically confirmed BE was present in 42 (79%). Antireflux surgery had preceded EAC at a mean interval of 10.1 years (range 0.5-25.6 years). This interval was significantly (p=0.02) shorter in patients with long-term functioning fundoplication (n = 15; 30%) at EAC diagnosis (6.4 years, range 0.5-15.2 years) than in those (n = 22, 44%) with failure (11.2 years, range 4.0-24.3 years). Overall, the SIR for EAC after antireflux surgery (1987-2006) was 9.21. CONCLUSIONS Intention-to-treat GERD with antireflux surgery does not prevent EAC. It often develops more than 5 years postoperatively, also in the patients with a good antireflux barrier. Only one-third of the patients had, however, a functioning fundoplication. Preoperative BE and endoscopic esophagitis may be risk factors. Prospective, long-term, randomized studies in experienced centers may reveal the definite effect of antireflux surgery on EAC development.

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.

The effect of fundoplication on proliferative and anti‐apoptotic activity of esophageal mucosa in gastroesophageal reflux disease: 4‐year follow‐up study

OBJECTIVE:  The capacity of fundoplication to prevent esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti‐apoptosis, for which little data exist as to their response to fundoplication. Therefore, we wanted to clarify the effect of fundoplication on the magnitude of Ki‐67 and B‐cell lymphoma 2 (Bcl‐2) during 48 months of follow up.

Cholecystectomy Patients with High Plasma Level of Catalase Have Significantly Lower Analgesia Requirement: A Prospective Study of Two Different Cholecystectomy Techniques with Special Reference to Patients with Cancer

Background/Aim: The plasma level of the oxidative stress biomarker catalase in patients with gallstone disease has not been previously compared with that of patients with cancer. Moreover, the number of analgesic doses required during the first 24 h postoperatively (NAD24) after laparoscopic cholecystectomy (LC) or mini-cholecystectomy (MC) in patients with gallstones is unreported. The aim of the present study was to determine the correlation between the plasma catalase level in patients with gallstones according to cholecystectomy technique versus patients with cancer. Patients and Methods: Initially, 114 patients with symptomatic gallstone disease were randomized into LC (n=54) or MC (n=60) groups. The plasma level of catalase was measured immediately before, immediately after and 6 hours after operation. Results: The median plasma catalase levels preoperatively and following surgery in the LC and MC patients versus those with cancer did not differ statistically significantly. The median plasma level of catalase increased immediately after operation, but the alteration was statistically insignificant (p=0.132). Interestingly, there was a statistically significant weak inverse correlation between the individual NAD24 and median plasma catalase values postoperatively in patients with gallstone disease (r=−0.283, p=0.042). Conclusion: The plasma catalase levels preoperatively and following surgery in the LC and MC patients versus those with cancer were quite similar. Cholecystectomy patients with high plasma levels of catalase appeared to require significantly fewer analgesic doses during the first 24 hours postoperatively (NAD24), suggesting that better oxidative balance following surgery could have a protective role against postoperative pain.

Contents Vol. 91, 2015

Founded as ‘Archiv für Verdauungskrankheiten’ 1895 by I. Boas Continued as ‘Gastroenterologia’ 1939–1967 Former Editors: P. Morawitz (1934–1936), R. Staehelin (1937–1943), A. Hurst (1940–1945), W. Löffler (1943–1961), T.C. Hunt (1947–1967), N. Henning (1953–1962), B. Ihre (1953–1967), H. Bartelheimer (1963–1967), M. Demole (1963–1971), H. Kapp (1968–1970), R. Lambert (1972–1978), W. Creutzfeldt (1979–1992), R. Arnold (1993–2003), C. Beglinger (2004–2011), B. Göke (2004–2014)