H. Gislason

Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population‐based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990–2003 were evaluated with an immunohistochemical panel including staining for c‐kit. The age‐adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty‐seven of the mesenechymal gastrointestinal tumors were positive for c‐kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high‐risk category while half of the nongastric tumors (11 of 22) fall into this high‐risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high‐risk category is 46%. The negative predictive value of low‐ and very‐low‐risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population‐based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs.

Acute pancreatitis in Bergen, Norway. A study on incidence, etiology and severity.

Background: Studies on the incidence and etiology of acute pancreatitis show large regional differences. This study was performed to establish incidence, etiology and severity of acute pancreatitis in the population of Bergen, Norway. Methods: A study of all patients with acute pancreatitis admitted to Haukeland University Hospital over a 10-year period was performed. Information was obtained about the number of patients with acute pancreatitis admitted to the Deaconess Hospital in Bergen. Results: A total of 978 admissions of acute pancreatitis were recorded in these two hospitals giving an incidence of 30.6 per 100 000. Haukeland University Hospital had 757 admissions of acute pancreatitis in 487 patients. Pancreatitis was severe in 20 % (96/ 487) of patients, more often in males (25 %) than in females (14 %). Mortality due to acute pancreatitis was 3 % (16/487). Gallstones were found to be an etiological factor in 48.5 % and alcohol consumption in 19 % of patients. The risk of recurrent pancreatitis was 47 % in alcohol induced and 17 % in gallstone induced pancreatitis. The last five years of the study period, endoscopic sphincterotomy of patients with gallstone pancreatitis, resulted in drop in relapse rate from 33 % to 1.6 %. Conclusion: The incidence of acute pancreatitis was found to be 30.6 per 100 000 with 48.5 % associated with gallstones and 17 % alcohol induced. Incidence of first attack was 20/100 000. Pancreatitis was classified as severe in 20 % of cases with a mortality of 3 %.

Pain management in chronic pancreatitis.

Introduction Chronic pancreatitis is a disease characterized by a painful progressive destruction of the pancreatic gland [1]. Even though other symptoms may occur pain is the predominant symptom both from the point of view of the patient and of his or her doctor. For an important part of the patient population the pain is so severe that all a patient’s waking hours are devoted to pain control, and the quality of life is low in every respect. Although much has been done to improve our understanding of the pathophysiology of chronic pancreatitis, there is still no therapy that counteracts the inflammatory process of the disease. As patients with chronic pancreatitis can, at best, be only symptom free, but never cured, the treatment continues to be directed against symptoms and complications, of which pain is the most dominant. The management of symptoms should therefore be of prime concern in most patients with chronic pancreatitis.

Role of blood flow in adaptive protection of the cat gastric mucosa

This study was designed to test the hypothesis that adaptive cytoprotection is related to increased blood flow caused by mild irritants. The stomach of cats was perfused with saline at pH 1.0. Mucosal blood flow was determined by radioactive microspheres, and celiac artery blood flow was measured by Doppler ultrasound. Gastric blood flow was left undisturbed or reduced by tightening a vessel loop around the celiac artery. Mucosal exposure to absolute ethanol for 2 minutes caused extensive damage to the surface epithelium, the pits, and the upper half of the glands. Pretreatment of the mucosa with 2 mol/L NaCl for 10 minutes prevented the development of mucosal lesions after subsequent application of absolute ethanol. The mucosal blood flow increased markedly after treatment with 2 mol/L NaCl. When this hyperemic response was inhibited by reducing celiac artery blood flow, ethanol caused lesions of similar degree as in animals not pretreated with 2 mol/L NaCl. A highly significant correlation was obtained between mucosal blood flow, as determined just before the application of ethanol, and the degree of ethanol-induced damage. At a chosen level of blood flow, ethanol caused the same degree of damage with or without pretreatment with 2 mol/L NaCl. In conclusion, high mucosal blood flow caused by a mild irritant is an important factor in adaptive gastric protection. With the present experimental setup, the protection could be fully explained as a result of the hyperemic response caused by 2 mol/L NaCl.

Clinical study on gastrointestinal stromal tumors (GIST) in Iceland, 1990-2003

This is a whole population-based study on clinical symptoms, surgical treatment, and outcome of GIST. All mesenchymal tumors in the digestive tract diagnosed from 1990 to 2003 were identified. All reports were reviewed, all tumors were stained with antibodies to c-kit, and the diagnosis of GIST was confirmed. Clinical, pathological, treatment, and outcome data were analyzed. The study included 53 patients with GIST. The mean age at diagnosis was 65.8±13.6 years (SD). Tumor distribution included 62% in the upper, 32% in the middle, and 6% in the lower digestive tract. Mean tumor size was 4.9±4.4 cm (SD). Gastrointestinal (GI) bleeding was the main symptom in 53% (20/38) of symptomatic cases; most presented with acute gastrointestinal bleeding. Complete surgical resection was performed in 87% (46/53) of patients. Eight of the 53 tumors (15.1%) metastasized, 7 of which were nongastric. The disease-specific death rate at 5 years was 85%, and 5-year survival after complete resection was 64.1%. We conclude that GISTs are often found incidentally but GI bleeding is the most common presentation. Five-year survival is better than previously reported and gastric GIST seems to be more benign than nongastric. GIST seems to metastasize mainly intra-abdominally.

Mass Closure Technique: An Experimental Study on Separation of Wound Edge

OBJECTIVE To study separation of wound edges in midline laparotomy incisions closed with either a mass stitch or a stitch incorporating only aponeurosis. DESIGN Experimental study in pig. SETTING University hospital, Norway. ANIMALS 8 domestic pigs. METHODS Steel sutures were used and metallic clips were placed in the aponeurosis. After increasing the intra-abdominal pressure the distance between the lateral edge of stitches and between pairs of clips was measured on sequential radiographs. RESULTS After three hours with raised intra-abdominal pressure the lateral edge of stitches became separated by a mean (SD) of 5.6 (1.3) mm with a mass stitch and by 0.5 (0.6) mm with stitches placed only in the aponeurosis (p < 0.001). Corresponding figures for separation of clips was 3.6 (1.5) mm and 0.1 (0.3) mm (p < 0.001). The suture cut through the muscle by more than 3mm in 25 out of 36 mass stitches. Muscle and peritoneum included in the mass stitch was compressed, darkly discoloured, and there were signs of haemorrhage. CONCLUSIONS Wound edges become separated with a mass stitch but not with stitches placed only in the aponeurosis when the intra-abdominal pressure is raised after closure of midline laparotomy incisions. This results from sutures compressing or cutting through subcuticular fat, muscle, and peritoneum enclosed in a mass stitch.

Role of Adenosine and Nitric Oxide in the Hyperemic Response to Superficial and Deep Gastric Mucosal Injury and H+ Back-Diffusion in Cats

BACKGROUND This study was undertaken to examine the role of adenosine and nitric oxide (NO) in the hyperemic response to H+ back-diffusion into superficially or deeply injured gastric mucosa, and the role of adenosine in mucosa when blood flow was reduced with indomethacin. METHODS Cat stomachs were exposed to 2 M NaCl for 10 min followed by luminal perfusion at pH 1. Gastric mucosal blood flow was determined by radioactive microspheres, portal vein blood flow by transit-time flowmetry, and H+ back-diffusion/secretion by pH-stat titration, and concentrations of histamine in aortic and portal vein blood were measured. RESULTS In the antrum pretreatment with the adenosine blocker 8-phenyltheophylline (8-PT) or with NG-methyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, had no effect on the hyperemic response or mucosal injury. However, pretreatment with 8-PT in addition to indomethacin produced extensive deep lesions in the antrum. In the corpus/fundus 8-PT had no effect on the hyperemic response and did not increase indomethacin-induced lesions. L-NMMA significantly reduced the hyperemic response in corpus/fundus. In areas with deep lesions very high blood flow was observed in the vital part of the mucosa below the necrotic tissue. This hyperemia was reduced by L-NMMA but not by 8-PT. Indomethacin increased the release of histamine during base-line conditions, whereas 8-PT reduced histamine release after damage. CONCLUSIONS This study indicates that usually adenosine is not involved in the hyperemic response to mucosal damage, but it appears to have important protective functions in the antral mucosa under marginal circulatory conditions. NO is one of the mediators of the hyperemic response to mucosal injury in the corpus/fundus.

Role of bicarbonate in blood flow-mediated protection and repair of damaged gastric mucosa in the cat

BACKGROUND/AIMS The hyperemic response after superficial gastric mucosal damage is essential for repair of the mucosa. Only indirect evidence suggests that this is caused by supply of bicarbonate. Therefore, this study tested the effect of maintaining the availability of bicarbonate after prevention of the hyperemic response after damage by 2 mol/L NaCl. METHODS Celiac artery flow was reduced, as monitored by Doppler ultrasonography, by gradual constriction of the vessel after mucosal damage. Saline (pH 1.0) was perfused through the stomach lumen and thereafter through a closed chamber with pH and PCO2 electrodes. RESULTS Exposure to 2 mol/L NaCl produced a marked increase of mucosal blood flow as measured by microspheres (P < 0.025) and a high degree of mucosal restitution 90 minutes after damage as judged by microscopy, whereas prevention of the hyperemic response caused extensive erosions and much less restitution (P < 0.001). The latter effect was completely counteracted by intravenous bicarbonate. High blood concentration of bicarbonate increased luminal release of bicarbonate, whereas high mucosal blood flow did not. CONCLUSIONS These data show that bicarbonate is an important factor in blood flow-mediated protection and repair of damaged gastric mucosa and suggest that concentration gradients are the major determinants for transport of bicarbonate across the damaged and restituted mucosa.

Gastric mucosal injury and associated changes in mucosal blood flow and gastric fluid secretion caused by dimethyl sulfoxide (DMSO) in rats

Dimethyl sulfoxide applied intragastrically for 10 min in rats caused extensive mucosal damage. In concentrations of 5%, 10%, or 100%, dimethyl sulfoxide caused superficial damage to 33%, 36%, and 97%, respectively, of the corpus mucosa, and 28%, 44%, and 96%, respectively, of the antral mucosa. Concentrated dimethyl sulfoxide also caused damage to the pits and glands in some areas of the mucosa. The amount of fluid in the stomach increased by 0.24 ml, 0.48 ml, and 2.07 ml during application of 5%, 10%, and 100% dimethyl sulfoxide. The 10% dimethyl sulfoxide increased mucosal blood flow by 0.57 ml/min/g in the antrum, and 100% dimethyl sulfoxide increased mucosal blood flow by 2.21 ml/min/g in the antrum and by 1.17 ml/min/g in the corpus. We conclude that dimethyl sulfoxide is a gastric irritant, which should be considered when it is used as an oxygen radical scavenger, as a drug or carcinogen vehicle, or as oral medication in patients. The protective effect of intragastric dimethyl sulfoxide against stress and various drug-induced gastric injury may be due to “adaptive cytoprotection” rather than an oxyradical scavenger effect.

Role of prostaglandins and histamine in hyperemic response to superficial and deep gastric mucosal injury and H+ back-diffusion in cats.

This study was undertaken to examine the role of prostaglandins and histamine in the hyperemic response to gastric mucosal damage followed by H+ back-diffusion. Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the surface epithelium, increased gastric mucosal blood flow, and increased release of histamine, PGE2, and 6-keto PGF1α (prostacyclin) into portal venous blood. The effect of indomethacin and histamine blockers (H1+H2) on the hyperemic response to acid back-diffusion was related to the depth of the mucosal injury and the region of the stomach. In the corpus, indomethacin enhanced mucosal injury. In areas with superficial damage, the hyperemia was inhibited by indomethacin and antihistamines and eliminated by the combination of both. In corpus areas with indomethacin-induced deep lesions, the blood flow was very high, and this hyperemia was partly inhibited by antihistamines. In the antrum the hyperemic response was reduced by antihistamines. Indomethacin increased the release of histamine into the portal venous blood (baseline recordings) and reduced basal gastric mucosal blood flow.