Eero Kivilaakso

Early antibiotic treatment in acute necrotising pancreatitis

Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.

Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis

BACKGROUND Laparoscopic cholecystectomy (LC) has become the treatment of choice for elective cholecystectomy, but controversy persists over use of this approach in the treatment of acute cholecystitis. We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy (OC) in patients with acute cholecystitis. METHODS 63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The primary endpoints were hospital mortality and morbidity, length of hospital stay, and length of sick leave from work. Analysis was by intention to treat. Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography (LC group) or intraoperative cholangiography (OC group). FINDINGS The two randomised groups were similar in demographic, physical, and clinical characteristics. 48% of the patients in the OC group and 59% in the LC group were older than 60 years. 13 patients in each group had gangrene or empyema, and one in each group had perforation of the gallbladder causing diffuse peritonitis. Five (16%) patients in the LC group required conversion to OC, in most because severe inflammation distorted the anatomy of Calots triangle. There were no deaths or bile-duct lesions in either group, but the postoperative complication rate was significantly (p=0.0048) higher in the OC than in the LC group: seven (23%) patients had major and six (19%) minor complications after OC, whereas only one (3%) minor complication occurred after LC. The postoperative hospital stay was significantly shorter in the LC than the OC group (median 4 [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7). INTERPRETATION Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality rate, and the morbidity rate seems to be even lower than that in OC. However, a moderately high conversion rate must be accepted.

Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis

BACKGROUND Acute pancreatitis can be difficult to diagnose. We developed a rapid dipstick screening test for pancreatitis, based on the immunochromatographic measurement of urinary trypsinogen-2. METHODS We prospectively compared the urinary trypsinogen-2 dipstick test with a quantitative urinary trypsinogen-2 assay, a urinary dipstick test for amylase, and serum and urinary amylase assays in 500 consecutive patients with acute abdominal pain at two emergency departments. Acute pancreatitis was diagnosed according to standardized criteria. RESULTS The urinary trypsinogen-2 dipstick test was positive in 50 of the 53 patients with acute pancreatitis (sensitivity, 94 percent), including all 7 with severe pancreatitis. Two patients with urinary trypsinogen-2 concentrations below the sensitivity threshold of the test (50 ng per milliliter) and one with a very high concentration had false negative results. The test was also positive in 21 of the 447 patients without pancreatitis (specificity, 95 percent), including 7 with abdominal cancers, 3 with cholangitis, and 2 with chronic pancreatitis. The sensitivity and specificity of the dipstick test were similar to those of the quantitative urinary trypsinogen-2 assay and higher than those of the urinary amylase dipstick test. The serum amylase assay had a sensitivity of 85 percent (with a cutoff value of 300 U per liter for the upper reference limit) and a specificity of 91 percent. The sensitivity and specificity of the urinary amylase assay (cutoff value, 2000 U per liter) were 83 and 88 percent, respectively. CONCLUSIONS In patients with acute abdominal pain seen in the emergency department, a negative dipstick test for urinary trypsinogen-2 rules out acute pancreatitis with a high degree of probability. A positive test usually identifies patients in need of further evaluation.

Adenocarcinoma arising in Barrett's esophagus

The main goal of this study was to evaluate the development of adenocarcinoma in patients with Barretts esophagus. During the period from January 1975 to December 1985, a total of 134 patients had endoscopically severe esophagitis and/or Barretts esophagus. In these patients, 32 (24%) met the macroscopic and histologic criteria for the diagnosis of Barretts esophagus. A check-up study of these patients was performed in 1987. Adenocarcinoma developed in three patients during the follow-up period of 166.1 patient-years. Dysplasia in the columnar epithelium was found in two of these patients six and 15 months before the diagnosis of adenocarcinoma. The third patient with adenocarcinoma was detected in endoscopic follow-up in 1987. In addition, the endoscopic examination showed unchanged Barretts epithelium in all but three patients despite the operative and/or medical treatment 3–12 years (mean 6.7 years) earlier. We conclude that Barretts esophagus is a potential premalignant condition and careful endoscopic surveillance for dysplasia in the columnar epithelium of the distal esophagus is mandatory in patients with Barretts esophagus.

17q12‐21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: A comparative genomic hybridization study

We studied DNA copy number changes in gastric cancer (GC) using comparative genomic hybridization (CGH) analysis on 35 resected gastric carcinomas (22 of the intestinal type and 13 of the diffuse type). Eighty‐three percent of the cases showed DNA copy number changes. Gains were more common than losses (median of 3 and 1 in primary tumors of the intestinal and diffuse type, respectively). The most common gains were detected on 20q [46%; 12 intestinal type (55%) and four diffuse type (31%)], 8q [37%; 10 intestinal type (45%) and three diffuse type (23%)], and 17q12‐21 [29%; all but one intestinal type (41%)]. The most frequent losses were detected on 18q [26%; all intestinal type (41%)] and on 4q [23%; all intestinal type (32%)]. High‐level amplifications were observed in the intestinal type of tumors at 17q12‐21 (three tumors), 20q (three tumors), 2p (one tumor), and 18q (one tumor). In the diffuse type, high‐level amplification was detected once at 13q. Genes Chromosom. Cancer 20:38–43, 1997.

Early Detection of Acute Fulminant Pancreatitis by Contrast-Enhanced Computed Tomography

Twenty-eight consecutive patients with a first attack of acute alcohol-induced pancreatitis were examined by computed tomography (CT). After a survey scan of the abdomen a rapid contrast bolus (400 mg I/kg) was given intravenously, and the contrast enhancement of the pancreatic parenchyma was measured from a consecutive series of pancreatic scans. Nine patients with a fulminant course of the disease were operated on, and haemorrhagic necrotizing pancreatitis was found in eight. In all of these the contrast enhancement was decreased or absent. Patients recovering by conservative treatment showed normal or increased enhancement. The contrast enhancement seems to constitute a useful criterion for the early differentiation of acute fulminant pancreatitis from less severe forms of the disease.

Serum complex of trypsin 2 and alpha 1 antitrypsin as diagnostic and prognostic marker of acute pancreatitis: clinical study in consecutive patients.

Abstract Objective: To estimate the usefulness of serum concentrations of the complex of trypsin 2 and (alpha)1 antitrypsin in diagnosing and assessing the severity of acute pancreatitis in comparison with serum C reactive protein, amylase, and trypsinogen 2 concentrations (reference markers). Design: Markers were measured in consecutive patients admitted with acute abdominal pain that was either due to pancreatitis or to other disease unrelated to the pancreas (controls). Setting: Department of surgery of a teaching hospital in Helsinki. Subjects: 110 patients with acute pancreatitis and 66 with acute abdominal diseases of extrapancreatic origin. On the basis of the clinical course, acute pancreatitis was classified as mild (82 patients) or severe (28 patients). Main outcome measures: Clinical diagnosis of acute pancreatitis and severity of the disease. Results: At admission all patients with acute pancreatitis had clearly raised concentrations of trypsin 2-(alpha)1 antitrypsin complex (32 μg/l), whereas only three of the controls had such values. Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex had the largest area under the receiver operating curve, both in differentiating acute pancreatitis from extrapancreatic disease and in differentiating mild from severe disease. Conclusions: Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex was the most accurate in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for acute pancreatitis. Key messages This complex can be accurately measured in a sensitive immunoassay In this study the diagnostic and prognostic accuracy of serum concentrations of trypsin 2-(alpha)1 antitrypsin complex was determined in acute pancreatitis The complex was more accurate than trypsinogen 2, C reactive protein, and amylase in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for the disease If the immunoassay could be automated determination of concentrations of trypsin 2-(alpha)1 antitrypsin complex could greatly improve the diagnosis of this common and potentially lethal disease

A new method for the diagnosis of acute hemorrhagic-necrotizing pancreatitis using contrast-enhanced CT

Twenty-eight consecutive patients with a first attack of alcohol-induced pancreatitis were studied using contrast-enhanced CT. The findings on CT were then related to the course of the disease. The patients with acute hemorrhagic-necrotizing pancreatitis showed significantly lower enhancement values of the pancreatic parenchyma than those with milder forms of the disease.The next 20 patients with severe pancreatitis were scanned using a slightly modified procedure. The enhancement values were calculated and plotted on the graphs for the 2 former groups.Two categories of pancreatic enhancement were found: “low enhancement” and “high enhancement.” In all 10 patients with “low-enhancement” values surgery revealed hemorrhagic-necrotizing pancreatitis. In the 10 patients with “highenhancement” values conservative treatment was continued, and the clinical course was nonfulminant in all of them.

Cysteamine and Propionitrile Inhibit the Rise of Duodenal Mucosal Alkaline Secretion in Response to Luminal Acid in Rats

Effects of subulcerogenic doses of cysteamine (100 mg/kg s.c.) and propionitrile (5 mg/kg) on alkaline secretion by duodenal surface epithelium and pH at the surface of this mucosa were assessed in duodenum of anesthetized rats. Alkaline secretion was titrated in situ, using segments of duodenum just distal to the Brunners glands area and devoid of pancreatic HCO3-. Surface pH was measured by advancing pH-sensitive microelectrodes from the luminal solution to the epithelial cell surface. Proximal duodenum from bullfrogs was used to study effects of cysteamine on alkaline secretion in vitro. Cysteamine caused an increase in alkaline secretion in the rat during the first hour after administration, but rates after 5 and 20 h were the same as in controls and cysteamine (1 mg/ml) had no effect on secretion in vitro. Neither in vitro nor in vivo did cysteamine affect the rise in alkaline secretion in response to exogenous prostaglandin E2 (and dibutyryl-cyclic adenosine monophosphate). Luminal acid is a potent stimulant of duodenal mucosal alkaline secretion. By delayed (5 h) actions, both cysteamine and propionitrile inhibited the rise in alkaline secretion in response to a 5-min exposure to luminal acid with pH 2.00 in the rat. Cysteamine also depressed the ability of this mucosa to maintain a high rate of alkaline secretion during sustained exposure at pH 2.00 but had no such effect at pH 5.00. The former resulted in acidification of the pH gradient at the mucosal surface. Cysteamine is thus probably without effect on the HCO3- secretory process itself but impairs the ability of the duodenal mucosa to respond to acid. Inhibition of mechanisms mediating this response may contribute to the duodenal ulcerogenic actions of cysteamine and propionitrile.

Anchoring complex components laminin-5 and type VII collagen in intestine: association with migrating and differentiating enterocytes.

Anchoring complex component laminin-5 and its subunits laminin (Ln)-alpha3 and Ln-beta3 chains, Type VII collagen, and integrin chains alpha3, alpha6, and beta4 were studied in developing and adult human intestine and compared with findings on Ln-alpha1 and Ln-alpha2 chains. In adult human duodenum, jejunum, and ileum, Ln-5 detected with a polyclonal antiserum and Ln-alpha3 and Ln-beta3 chains, detected with monoclonal antibodies (MAbs), were restricted to the epithelial basement membranes (BMs) of villi, whereas Ln-alpha2 chain was seen only focally in crypt bottoms. In double labeling experiments, the stretch of crypt BM corresponding to the proliferative cell compartment was found to be devoid of both Ln-alpha3 and Ln-alpha2 chains. Double labeling for Ln-5 and proliferating cell nuclear antigen also showed an abrupt onset of Ln-5 expression exactly at the upper edge of the proliferative cell compartment. Type VII collagen was negligible in duodenum and showed a rising duodenal-ileal gradient localizing to villar BMs. Double labeling for Ln-5 and Type VII collagen, however, indicated only partial co-distribution in the intestine. Electron microscopy of ileum revealed both anchoring filaments and anchoring fibrils but no hemidesmosomal plaques. Our results demonstrate the expression of Ln-5 in BMs outside of stratified epithelia and indicate that Ln-5 in the intestine is associated with the compartment of migrating and differentiating enterocytes. Absence of hemidesmosomes and the presence of other anchoring complex components, such as Ln-5, Type VII collagen, and integrin chains alpha3, alpha6, and beta4, suggests unique properties for epithelial cell attachment in the intestine.