Distal pancreatectomy using a no-touch isolation technique.

BACKGROUND AND AIMS: Distal pancreatectomy is the only effective treatment for cancers of the pancreatic body and tail. The recurrence rate after DP has remained high. In an effort to over-come this problem, we developed a no-touch surgical technique for DP. This is a pilot study to see if distal pancreatectomy can be technically done using a no-touch surgical technique with-out deteriorating the post-operative prognosis. PATIENTS AND METHODS: From November 2000 through May 2011, 16 pancreatic ductal adeno-carcinoma patients have been operated on using a no-touch technique by a single operator. We described the surgical technique, and we reported our preliminary experience. During the procedure, the pancreatic body and tail is neither grasped nor squeezed by the surgeon. And all drainage vessels from the pancreatic body and tail are ligated and divided during the early phase of the operation. Furthermore, for improved dissection of the retroperitoneal tissue (rightward and posterior margins), we use a hanging and clamping maneuver and dissection behind Gerota's fascia. RESULTS: In the current series, the posterior and rightward resection margins were free in all patients, although seven were positive for anterior serosal invasion. The post-operative prognosis was not deteriorated with this technique. CONCLUSION: No-touch distal pancreatectomy technique may have some theoretical advantages, which merit future investigation in randomized controlled trials.

Helicobacter pylori in alcohol induced acute pancreatitis.

BACKGROUND AND AIMS: The objective of this study was to measure the association of Helicobacter pylori infection with alcoholic acute pancreatitis. MATERIAL AND METHODS: This study comprised of 50 patients with their first alcoholic pancreatitis and 50 alcoholic controls with no history of pancreatitis but similar alcohol use recruited from an alcohol rehabilitation center. Helicobacter infection was measured using Enzygnost EIA IgG-test. Complications and length of hospital stay were also recorded in patients with alcoholic pancreatitis. RESULTS: The seroprevalence of Helicobacter pylori was 10/50 (20%) in the pancreatitis group and 15/50 (30%) in the control group (p = NS). The median length of hospital stay of pancreatitis patients was 7 days, 11 days for those tested positive (range 6-25) and 6 days for those tested negative (range 3-47) for Helicobacter pylori, p = 0.013. As determined with the Atlanta criteria, seropositive patients tended to have more often severe pancreatitis, 4/10 (40%) vs. 6/40 (15%), OR 3.78 (95% CI 0.815-17.52), p = 0.097. CONCLUSIONS: This study suggests that Helicobacter pylori infection is not associated clinically significantly with the development of alcoholic pancreatitis. However, Helicobacter pylori infection may be associated with longer hospital stay due to more severe disease, which needs to be studied in a larger series of patients.

Late postoperative quality of life following pancreatic head resections.

BACKGROUND/AIMS: To evaluate health-related quality of life (HRQoL) in patients that have undergone pancreatic resection and compare the results with representative population samples in early and late stage evaluations. Also, this study aims to observe possible associations with postoperative complications. METHODOLOGY: Twenty-seven single-institute patients operated on during a 3-year period due to a benign or malignant process of the periampullary region. HRQoL was measured by the 15D instrument. Data were compared with those obtained from representative Finnish general population samples. RESULTS: Twenty-five patients were interviewed in the early stage (24 months postoperatively). Fifteen had a benign and 12 a malignant disease. No differences were found in the postoperative HRQoL when the nature of the disease or the postoperative complications were considered. When compared with the general population in the early stage, HRQoL was lower in the study group in whole, and also when sleep, elimination (bladder or bowel function) and sexual activity were considered separately. In the late stage evaluation (110 months postoperatively) the study group consisted of 15 surviving patients. There were no differences in comparison to the general population. Also when comparing the same patients in 2 evaluation points (24 and 110 months), we did not find any difference in any of the 15D parameters. CONCLUSIONS: Postoperative HRQoL deteriorated in comparison to general population in the early stage but there were no differences in the late stage. This study encourages us to continue the use of the 15D at least as a part of HRQoL evaluation, because it allows comparisons between different diseases and the general population.

Alcohol consumption in patients with acute or chronic pancreatitis.

Understanding of the relation between the alcoholic consumption and the development of pancreatitis should help in defining the alcoholic etiology of pancreatitis. Although the association between alcohol consumption and pancreatitis has been recognized for over 100 years, it remains still unclear why some alcoholics develop pancreatitis and some do not. Surprisingly little data are available about alcohol amounts, drinking patterns, type of alcohol consumed and other habits such as dietary habits or smoking in respect to pancreatitis preceding the attack of acute pancreatitis or the time of the diagnosis of chronic pancreatitis. This review summarizes the current knowledge. Epidemiological studies clearly show connection between the alcohol consumption in population and the development of acute and chronic pancreatitis. In the individual level the risk to develop either acute or chronic pancreatitis increases along with the alcohol consumption. Moreover, the risk for recurrent acute pancreatitis after the first acute pancreatitis episode seems also to be highly dependent on the level of alcohol consumption. Abstaining from alcohol may prohibit recurrent acute pancreatitis and reduce pain in chronic pancreatitis. Therefore, all the attempts to decrease alcohol consumption after acute pancreatitis and even after the diagnosis of chronic pancreatitis should be encouraged. Smoking seems to be a remarkable co-factor together with alcohol in the development of chronic pancreatitis, whereas no hard data are available for this association in acute pancreatitis. Setting the limits for accepting the alcohol as the etiology cannot currently be based on published data, but rather on the 'political' agreement.

Detection of postoperative pancreatitis after pancreatic surgery by urine trypsinogen strip test.

BACKGROUND: The urine trypsinogen strip test has been used successfully in the diagnosis of pancreatitis of various aetiologies, but has not been studied in postoperative pancreatitis. The aim of this study was to evaluate this test for the diagnosis of postoperative pancreatitis after pancreatic resection. METHODS: Fifty patients undergoing pancreatic resection were included. The urine trypsinogen strip test was done daily during the first postoperative week, blood was analysed before and 4, 6 and 10 days after surgery, and amylase activity in the drainage fluid was measured on days 4 and 6. Patients underwent computed tomography (CT) before operation and on days 2 and 6 afterwards. RESULTS: Thirteen patients (26 per cent) developed CT-detected pancreatitis after operation. In 12 of these patients pancreatitis was detected on the second postoperative day. The urine trypsinogen test was positive in all 13 patients with postoperative pancreatitis, and was already positive on the first day after surgery in 12. The sensitivity, specificity, and positive and negative predictive values of the trypsinogen strip test in detection of postoperative pancreatitis were 100, 92, 81 and 100 per cent respectively. In receiver-operator characteristic analysis the area under the curve (AUC) was higher for the urine trypsinogen strip test (AUC 0.959) than for a serum amylase level more than two (AUC 0.731) or three times (AUC 0.654) above the upper normal range in the diagnosis of postoperative pancreatitis. Patients whose recovery was complicated by pancreatic fistula, detected by drain output measurements on day 6, more often had a positive urine trypsinogen test than patients without a fistula (11 of 12 versus five of 38; P < 0.001). CONCLUSION: This study suggests that the urine trypsinogen strip test might be a valuable method for diagnosis of pancreatitis after pancreatic surgery.

Duodenal diazepam-binding protein expression and plasma cholecystokinin after alcoholic pancreatitis.

OBJECTIVE: After the first acute alcohol-induced pancreatitis (AAIP) episode 46 % of patients will have a recurrent attack, but the pathophysiology is unclear. The hyperstimulation of the pancreas with cholecystokinin (CCK) induces acute pancreatitis. Alcohol induces temporary stimulation of the pancreas and CCK could be a mediator. CCK is regulated by releasing peptides - diazepam-binding protein (DBI) being a possible candidate. The aim of this study was to investigate the possible association between CCK plasma levels and DBI expression in patients with AAIP or its recurrence. MATERIAL AND METHODS: The study comprised 44 subjects (mean age 42 years): A) Patients with a first episode of AAIP (n = 9); B) patients with three or more episodes of AAIP (n = 11); C) patients with a heavy alcohol consumption, with no detected AAIP (n = 11) and D) healthy controls (n = 13). CCK levels were measured by radioimmunoassay (RIA). Duodenal biopsies were analyzed for DBI mRNA and histology. RESULTS: There was no significant difference in CCK plasma levels, DBI expression or CCK/DBI ratio between the groups. CONCLUSIONS: There were no changes in fasting CCK plasma levels or DBI expression. This may suggest that they do not play a major role as risk factors for alcohol-induced pancreatitis.

The differentiation between pancreatic neoplastic cysts and pancreatic pseudocyst.

The number of small and often asymptomatic cystic lesions detected in pancreas has increased during the last decade. Historically the vast majority of the pancreatic cystic lesions were considered pseudocysts, but in recent series the incidence of various neoplastic cysts, such as intraductal papillary mucinous neoplasm, serous cystadenomas and cystic endocrine tumours, has increased. The possible malignant potential in these cystic neoplasms warrants careful diagnostic workup to choose the optimal treatment for each patient. Patient's age, symptoms and a possible history of acute or chronic pancreatitis with known aetiology together with high quality imaging studies are important in the differential diagnosis between pseudocysts and neoplastic cysts. Endoscopic ultrasound, cyst fluid analysis and positron emission tomography may be used in selected patients, but the accuracy of these methods needs further investigation.

The profile of leg symptoms, clinical disability and reflux in legs with previously operated varicose disease.

PURPOSE: It is difficult to assess the severity and location of venous insufficiency in legs with recurrent varicose disease. This present purpose was to evaluate the distribution of reflux and the diagnostic role of current classifications in a consecutive series of legs with previously operated varicose disease. METHODS: A total of 90 legs in a cohort of 66 patients were included. The examination comprised CEAP clinical class, clinical disability score (CDS) and leg symptoms. Colour-flow duplex imaging (CFDI) was used to observe reflux in deep and superficial veins. Details of prior surgery were assessed. RESULTS: The site of superficial reflux was at the groin in 58% (recurrent or residive vein trunk or unoperated great saphenous vein), and the rate in the popliteal fossa was 11% (unoperated short saphenous vein). In 58% of the legs presenting superficial reflux at groin level, previous surgery at the saphenofemoral junction was noted. A sensation of pain was observed in 74% of the legs, sensation of oedema in 64%, itching in 26 %, and night cramps in 8%, respectively. Only itching was significantly infrequent in uncomplicated (CEAP C 2-3) legs, and in legs with local reflux was restricted to vein tributaries. Higher CDS (classes 2-3) were significantly more frequent among complicated legs (CEAP clinical class C2-3: 22% versus CEAP clinical class C4-6: 77%; p < 0.005). A similar situation was noted when legs with only local reflux were compared to those with more severe reflux (local reflux: 7% versus severe reflux: 48%; p < 0.005). CONCLUSIONS: Superficial reflux is frequently detected at groin level despite prior surgery. Unstructured evaluation of leg symptoms is not beneficial. Clinical disability scores associate well with the severity of the venous disease.

Chest computed tomography in the staging of pancreatic and periampullary carcinoma.

BACKGROUND: Staging of the tumours in the pancreas and periampullary region usually consists of abdominal computed tomography (CT). Laparoscopy is also advocated. Little attention has been paid to extra-abdominal staging. In addition to peritoneal, lymphatic and hepatic metastases, lung metastases are frequently found. The chest CT scan has been demonstrated as better than the plain chest roentgenogram or conventional tomography in demonstrating lung tumours. This study was done to evaluate whether the chest CT scan gives information additional to the plain chest roentgenogram in the staging of pancreatic and periampullary tumours. METHODS: Fifty-three patients with a pancreatic or periampullary tumour underwent helical CT scan of the chest in addition to the abdominal CT scan. The CT scans and the chest roentgenograms were read separately without the result of the other being known; the results were compared with each other and with the clinical and operative findings. RESULTS: In the chest CT scan, 7 out of 53 (13%) patients had nodules in the lungs. The chest pathologies were not seen in the chest roentgenogram except for pneumonia in one patient and lung tumours in another (sensitivity of the chest roentgenogram 2/7 = 29%). Liver metastasis, local invasion of the tumour or poor general condition of the patient made lung biopsy or bronchoscopy unnecessary or impossible. CONCLUSION: Lung metastases seldom appear in patients with pancreatic or periampullary carcinoma without other contraindications for resection, which is why the chest CT scan cannot be recommended in the staging of these tumours for operation.

Alcoholic, but not biliary, pancreatitis varies seasonally in occurrence.

BACKGROUND: Alcohol is the most common cause of acute pancreatitis in Finland (70%). The amount of alcohol consumed has been shown to be associated with the prevalence of pancreatitis in the country, and also to be an important determinant of the severity of the first episode of acute alcoholic pancreatitis. We have a clinical suspicion that the use of alcohol and the incidence of pancreatitis are increased during holiday periods in summer, although no seasonal variations have been reported in a German population. METHODS: Between 1972 and 1992 a total of 1556 episodes with acute alcoholic pancreatitis were treated at Tampere University Hospital; 552 were first episodes and 1004 were recurrent. For comparison, we investigated 297 episodes of acute biliary pancreatitis treated in that same time period. We investigated the monthly prevalence of acute alcoholic (first and recurrent) pancreatitis and compared this with the monthly absolute alcohol consumption. RESULTS: Taking all alcoholic pancreatitis episodes into account, significant differences can be seen between prevalence and month of onset of the disease (P < 0.0001), whereas among biliary pancreatitis episodes there were no differences (P = 0.3). Prevalence of acute alcoholic pancreatitis was significantly higher than the expected prevalence in July and August, and the amount of alcohol consumption (100% alcohol, litres) was highest during these same months. Also during March, October and December the prevalence was higher than expected. CONCLUSION: Months with holiday seasons, Christmas, Easter, summer and autumn, are associated with the highest alcohol consumption and the highest prevalence of acute alcoholic pancreatitis.

Mechanism of the prorelaxing effect of thyroxine on the sphincter of Oddi.

BACKGROUND: Disturbances in the function of sphincter of Oddi (SO) may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. Previously, we have shown increased prevalence of hypothyroidism in CBDS patients. METHODS: In animal (pig) experiments, thyroxine (T4) and triiodothyronine have a specific inhibitory effect on SO contractility, which raises the possibility that the lack of this prorelaxing effect in hypothyroidism could, at least in part, explain the increased prevalence of CBDS. The aims of the present study were to investigate, whether human SO reacts similarly to T4, and to study the mechanisms of the T4 prorelaxing effect. RESULTS: We found that T4 had similar inhibitory effects on both human and pig SO contractions. The T4 effect was dose-dependent, and maximum was observed in 30 min. The maximal prorelaxing effect was achieved with 0.1 nM T4 concentration, the effect of the physiological T4 concentration (0.01 nM) being about half of the maximal effect. Addition of alpha-adrenoceptor antagonist phentolamine, beta-adrenoceptor antagonist propranolol, nitric oxide (NO)-synthesis inhibitor L-NAME, nerve conductance blocker tetrodotoxin, or cyclooxygenase inhibitor diclofenac did not affect the T4-induced inhibition of contraction. Addition of transcription inhibitor actinomycin D or translation inhibitor cyclophosphamide partially reversed the T4-induced inhibition of contraction. Addition of K+ channel blocker glibenclamide totally reversed the T4-induced inhibition of contraction. In Western blotting, the thyroid hormone receptor (TR) antibody recognized 53 kDa and 58 kDa proteins, corresponding to beta1 and beta2 isoforms of TR, in the human SO tissue. CONCLUSIONS: We conclude that T4 has a direct prorelaxing effect on human SO that expresses TR beta1 and beta2. This effect is mediated through a transcriptional mechanism that requires new mRNA and protein synthesis and subsequently leads to the activation of K+ channels.

Bile flow to the duodenum is reduced in hypothyreosis and enhanced in hyperthyreosis.

Disturbances in sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, which may be explained by thyroxine-induced inhibition of SO contractility, in addition to previously suggested changes in bile composition and hepatocytic excretion. The aim of this study was to investigate biliary dynamics in relation to altered thyroid gland function in rat, a rodent without a gallbladder. Euthyroid, hypothyroid or hyperthyroid Spraque-Dawley rats were anaesthetized with i.p. urethane, and exsanguinated at 15, 45, or 60 min after intravenous 99mTc HIDA injection. At these timepoints, the bile flow to intestine was determined by measuring the relative intestine vs. liver radioactivity. At 45 min this was 44% lower in hypothyroid rats and at 60 min 73% higher in hyperthyroid rats compared to euthyroid rats, while hepatic radioactivity at 15 min and blood pressure at injection were similar in the groups. We conclude that the bile flow to duodenum is reduced in hypothyreosis and enhanced in hyperthyreosis.

Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis--a single-center randomized study.

Pancreatic infection is the main indication for surgery and the principal determinant of prognosis in acute necrotizing pancreatitis. Previous studies on the effects of antibiotics have not, however, uniformly demonstrated any reduction in the need for surgery or any decrease in mortality among these patients, although the incidence of pancreatic infections was significantly reduced. This single-center randomized study was designed to compare early vs. delayed imipenem treatment for acute necrotizing pancreatitis. Ninety patients with acute necrotizing pancreatitis (C-reactive protein > 150 mg/L, necrosis on CT) were randomized within 48 hours either to a group receiving imipenem (1.0 g plus cilastatin intravenously 3 times a day) or a control group. Not included were those who had been started on antibiotics at the referring clinic, those who were taken directly to the intensive care unit for multiorgan failure, and those who refused antibiotics or might have had adverse reactions. Thirty-two patients were excluded because they were over 70 years of age (not potentionally operable) or for any study violation. There were 25 patients in the imipenem group and 33 patients in the control group. The main end point was the indication for necrosectomy due to infection (i.e., after the initial increase and decrease, there was a second continuous increase in temperature, white blood cell count [> 30%] and C-reactive protein [> 30%], with other infections ruled out, or bacteria were found on Gram stain of the pancreatic fine-needle aspirate). In the control group, imipenem was started when the operative indication was fulfilled. Conservative treatment was continued for at least 5 days before necrosectomy. The study groups did not differ from each other with regard to sex distribution, patient age, etiology, C-reactive protein concentration, and extent of pancreatic necrosis on CT. Two (8%) of 25 patients in the imipenem group compared to 14 (42%) of 33 in the control group fulfilled the operative indications (P = 0.003). Nine patients in the control group responded to delayed antibiotics but five had to undergo surgery. Of those receiving antibiotics, 2 (8%) of 25 in the early antibiotic (imipenem) group needed surgery compared to 5 (36%) of 14 in the delayed antibiotic (control) group (P = 0.04). Two (8%) of 25 patients in the imipenem group and 5 (15%) of 13 patients in the control group died (P = NS [no significant difference]). Seven (28%) of 25 in the imipenem group and 25 (76%) of 33 in the control group had major organ complications (P = 0.0003). Based on the preceding criteria, early imipenem-cilastatin therapy appears to significantly reduce the need for surgery and the overall number of major organ complications in acute necrotizing pancreatitis, and reduces by half the mortality rate; this is not, however, statistically significant in a series of this size.

Direct effect of thyroxine on pig sphincter of Oddi contractility.

Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function disturbances (stenosis or dyskinesia) may prevent normal bile flow and thus enhance the probability of common bile duct (CBD) stone formation. Previously we have shown that there is an increased prevalence of diagnosed hypothyroidism in CBD stone patients, compared with gallbladder stone patients or age-, sex-, and hospital-admission-adjusted controls. The present study was done to test the hypothesis that thyroxine directly effects the SO. The specificity of the effects of thyroxine were studied by comparing with triiodothyronine (T3), progesterone, cortisone, estrogen, and testosterone. For ex vivo studies three or four successive 1 to 1.5-mm SO rings were prepared from each pig and placed between two hooks in oxygenated physiologic salt solution at 37 degrees C. SO contraction was measured with isometric force displacement transducers and registered on a polygraph. Each SO ring was stimulated with KCl (125 mM), acetylcholine (ACh; 10 or 100 microM) and histamine (Hist; 10 or 100 microM) with and without thyroxine (10(-10) or 10(-8) M), T3 (10(-9) or 10(-7) M), progesterone (1 microM), cortisone (1 microM), estrogen (1 microM), or testosterone (1 nM) in the medium. KCI, ACh, and Hist induced strong contractions in the SO rings. The addition of thyroxine did not influence significantly the KCl-induced contractions, but the ACh- and Hist-induced contractions decreased by a mean of 37-44% (P < 0.001) and 54-56% (P < 0.001), respectively, as compared to the contractions without thyroxine. Triiodothyronine had a similar inhibitory effect to thyroxine, whereas cortisone, estrogen, and testosterone had no effect. Progesterone decreased the KCl-, ACh-, and Hist-induced SO contractions. In conclusion, physiological concentrations of thyroxine have an inhibitory effect on receptor-mediated ACh and Hist, but not on the nonspecific KCl-induced SO contraction ex vivo. The inhibitory effect is similar in thyroxine and triiodothyronine. Of the steroid hormones, only progesterone nonspecifically ameliorates SO contractions ex vivo. Because the effect of thyroxine on the SO is prorelaxing, the lack of thyroxine may result in an increased tension of the SO.

Post-ERCP pancreatitis: reduction by routine antibiotics.

Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 IU/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRP reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP. These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis

Effects on endogenous acetaldehyde production by disulfiram and ethanol feeding on rat pancreas.

Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the pancreas in some isolated pancreas models, whereas in vivo such treatment has failed to induce pancreatitis. In vivo exogenous acetaldehyde may not be effective because it is rapidly metabolized. The aim of this study was to investigate whether endogenous acetaldehyde accumulates in the pancreas after ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, and whether this treatment can induce pancreatitis-like injury in the rat. The liver was studied for comparison. In part I of the experiment, adult male Wistar rats were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol plus disulfiram for 1 week (n = 24) or 3 weeks (n = 24) and for 3 weeks with (n = 6) and without (n = 6) hypovolemia. In part II of the experiment, rats were given water (n = 6), ethanol (n = 6), and high-dose disulfiram (n = 6) and ethanol plus high-dose disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood, liver, and pancreas were measured. Animal behavior was monitored, and weight changes, plasma amylase activity, water content, and histomorphology of the pancreas and liver were studied without knowing the group. No increases in plasma amylase activity and no histomorphologic changes in the pancreas were observed under light or electron microscopy in part I of the experiment. In part II, treatment with ethanol induced acetaldehyde accumulation in the liver (33.6 +/- 2.6 micromol/L), but to a lesser degree in the blood (9.6 +/- micromol/L) and pancreas (5.0 +/-.2 micromol/L). Ethanol plus disulfiram induced marked accumulation of acetaldehyde in the liver (83.2 +/- 15.9 micromol/L), blood (280.0 +/- 47.4 micromol/L), and pancreas (43.6 +/- 4.7 micromol/L). When tissue acetaldehyde levels reached 30 to 40 micromol/L, we found a decrease in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acinar cells and accumulation of lipid droplets in the hepatocytes, whereas physiologic signs of pancreatitis (hyperamylasemia, edema) or increases in liver enzymes did not develop. High levels of acetaldehyde accumulate in the liver and pancreas with the treatment described. Although this was accompanied by lipid degeneration of the hepatocytes and some subcellular changes in the acinar cells, physiologic signs of pancreatitis did not develop. Thus acetaldehyde accumulation alone, or in combination with hypovolemia, is not responsible for the induction of acute pancreatitis.

Histamine in the control of porcine and human sphincter of Oddi activity.

Histamine decreases sphincter of Oddi (SO) contractility in vivo in opossum, but increases contractility in vitro in guinea-pig. In resistor-like SO, such as in pig and man, the histamine effect is poorly known. We investigated the effect of histamine on pig SO in vivo and in vitro and on human SO in vitro. Perfusion manometry catheter and two silver electrodes for simultaneous pressure and electromyography registration were inserted into the SO transduodenally by laparotomy in six anaesthetized pigs weighing for 25-28 kg. Histamine (5-10 microgram kg-1) was infused intra-arterially (i.a.) into the pancreaticoduodenal artery with and without diphenhydramine (75 microgram kg-1) i.a. premedication. Acetylcholine (4 microgram kg-1) i.a., a potent SO stimulator, was used as positive control. After these experiments, the SO was removed and, together with seven human SO from Whipple specimens, were cut into 1.0-1.5 mm thick transverse sections (rings). The rings were placed between two hooks in oxygenated organ bath solution at 37 degrees C. The SO contraction force was measured with isometric force-displacement transducers and registered on a polygraph. SO rings were incubated with histamine (10-100 micromol L-1) and acetylcholine (100 micromol L-1) with or without diphenhydramine (10 micromol L-1), cimetidine (10 micromol L-1), or atropine (1 micromol L-1). Acetylcholine induced huge electrical bursts, and basal SO pressure increased by 20 +/- 10 mmHg. Histamine (10 microgram kg-1) induced strong SO contraction and the SO remained oedematous for over 10 min. Histamine (5 microgram kg-1) resulted in electromyographic burst activity with phasic SO contractions and increase in basal SO pressure by 34 +/- 19 mmHg for over 15 min. Diphenhydramine did not alter acetylcholine-induced SO motility, but significantly decreased histamine-induced contractions and almost abolished electrical activity. In vitro, acetylcholine induced SO contractions in pig (335 +/- 111 mg) and in man (323 +/- 54 mg). Histamine did not change SO tone in man, but in pig it induced dose-dependent contractions in the same way as acetylcholine. These contractions could be inhibited by diphenhydramine, but not by cimetidine or atropine. We conclude that histamine has a stimulatory effect, mediated by H1-receptor, on the pig SO motility. The SO response to histamine is different in adult humans from that observed in young pigs.

Association between common bile duct stones and treated hypothyroidism.

BACKGROUND/AIMS: The purpose of this study was to investigate the frequency of diagnosed hypothyroidism in patients with common bile duct stones. METHODOLOGY: The common bile duct stone group (Group I) consisted of all the patients who had verified gallstones in the common bile duct in endoscopic retrograde cholangiopancreatography during 1995. The control group (Group II) was matched for age, sex, and hospital admission. These patients did not have diagnosed gallbladder or common duct stones. In both groups there were 86 patients (56 women and 30 men). The median age in these groups was 73 (range: 22-92) years at the time of common bile duct stone diagnosis. Medical records of all patients were reviewed. RESULTS: In Group I the prevalence of previously diagnosed hypothyroidism was 7/86 (8%) compared with 1/86 (1%) in Group II (P = 0.01). Hypothyroidism was previously diagnosed only in the common bile duct stone patients (Group I) of over 60 years of age, where the prevalence was 7/66 (11%). In addition, we studied 36 consecutive gallbladder stone patients (Group III) of over 60 years, who had no evidence of common bile duct stones. Hypothyroidism had been diagnosed in them less frequently (2/36 = 6%) than in the age and hospital admission matched common bile duct stone patients (P = 0.01). Other diagnosed endocrine disorders did not differ between the study groups. CONCLUSIONS: There is a significant association between the common bile duct stones and previously diagnosed hypothyroidism. There stronger association between the common bile duct stones and hypothyroidism compared to gallbladder stones and hypothyroidism suggests a mechanism other than merely the cholesterol metabolism mediated mechanism. The 11% prevalence of previously diagnosed hypothyroidism in the common bile duct stone patients of over 60 years of age suggests all patients with common bile duct stones be screened for current thyroid dysfunction.

Long-term follow-up of patients with jejunal pouch reconstruction after total gastrectomy. A randomized prospective study.

BACKGROUND: Fifty-one patients were operated on during 1988-1992 and randomized after total gastrectomy to one of two reconstruction types. Twenty patients with jejunal pouch reconstruction and 14 patients with Roux-en-Y reconstruction (67% of all) survived at least 3 years after total gastrectomy. We studied symptoms, eating capacity, and nutrition in these patients during the clinical follow-up; 21 patients were assessed by mail questionnaire 8 years after total gastrectomy. METHODS: Postoperative symptoms, number of meals, and eating capacity were assessed by standard questionnaire during 3 years' follow-up. Weight loss and nutritional laboratory variables were measured, and upper intestinal endoscopy with biopsy was performed during the follow-up. Eight years after the operation symptoms, ability to eat, and number of meals consumed were studied by means of a mail questionnaire. RESULTS: Three years postoperatively dumping (64% compared with 10%, P < 0.05) and early satiety (86% compared with 5%, P < 0.05) were commoner in the Roux-en-Y group. In the pouch group eating capacity was better (96% of normal compared with 67%, P < 0.05), and the patients ate fewer meals per day (mean, 2.7 versus 5.3, P < 0.05) at 3 years. Mean weight loss at 3 years was 9.9 kg in the Roux-en-Y group compared with 1.5 kg in the pouch group (P < 0.05). 25 (OH) vitamin D concentration tended to be higher in the pouch group (47.3 nmol/l compared with 33.9 nmol/l). In the Roux-en-Y group serum alkaline phosphatase activity increased significantly during the 3 postoperative years (from mean 163 U/l to 248 U/l, P < 0.01) and tended to be higher (248 U/l compared with 216 U/l in the pouch group). None of the patients developed oesophagitis or pouchitis during the follow-up. One patient developed a bezoar in the pouch 5 years after gastrectomy. CONCLUSIONS: Pouch reconstruction after total gastrectomy is associated with diminished postoperative symptoms, better eating capacity, and decreased weight loss compared with Roux-en-Y reconstruction. Jejunal pouch reconstruction is thus the recommended surgical method after total gastrectomy.