Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis.

Only 3-5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode (n = 60) and recurrent AAP (n = 43) and from heavy alcohol users without a history of AAP (n = 98) as well as from a control population (n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32-5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15-74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.

Plasma suPAR may help to distinguish between chronic pancreatitis and pancreatic cancer.

OBJECTIVES: SuPAR (soluble urokinase-type plasminogen activator receptor) is a biomarker reflecting the inflammatory state of the human body. Earlier studies suggest that urinary suPAR/creatinine ratio levels are elevated in chronic pancreatitis (CP), and that plasma suPAR (P-suPAR) level is elevated in pancreatic cancer (PC). Our aim was to study the levels of P-suPAR in CP in a long-term prospective follow-up setting to explore the possibility of distinguishing between PC and CP. MATERIALS AND METHODS: Two patient groups were compared. The first group included 83 patients who were prospectively followed up after their first acute alcohol-induced pancreatitis (AAP) for median 7.0 (range 0.3-9.8) years. Twelve patients in this group developed CP during follow-up, and two patients were further excluded from the CP cohort. The second group consisted of 25 patients operated on for suspicion of pancreatic malignancy and final pathological diagnosis of PC. P-suPAR levels were measured and compared within and between these groups. RESULTS: P-suPAR levels remained low during follow-up despite the development of CP. P-suPAR was significantly higher in PC patients [median 3.7 (IQR 3.1-4.4) ng/mL] than in CP patients [2.6 (1.8-3.6) ng/mL]; p = .014. A cutoff value of 2.8 ng/mL resulted from a ROC curve with area under curve (AUC) of 0.79 (95% CI 0.61-0.97), p = .009 in differentiation between PC and CP with a sensitivity and a specificity of 88% and 70% respectively. CONCLUSION: P-suPAR is higher in patients with PC than in patients with CP, and it could thus be used in differentiating between PC and CP.

Quality of life in patients with pancreatic ductal adenocarcinoma undergoing pancreaticoduodenectomy.

INTRODUCTION: Survival for pancreatic ductal adenocarcinoma (PDAC) is relatively short even after complete resection. Pancreaticoduodenectomy (PD) carries a high risk for postoperative morbidity, and the effect on quality of life (QoL) is unclear. We aimed to study QoL in PDAC patients undergoing PD. PATIENTS AND METHODS: Sixty patients with suspected PDAC and planned PD were asked to complete EORTC QoL questionnaires QLQ-C30 and QLQ-PAN26 preoperatively and at 3-6-12-18-24 months postoperatively. RESULTS: 47 PDAC patients who underwent PD (66 (21-84) years, 53% men) were included. Follow-up was completed by 81% (6 months) and 45% (24 months) post-PD. Compared to preoperative level, QoL tended to improve or remained the same in 63% during the follow-up. At three months after PD patients had less hepatic symptoms (decreased by 100%; p < 0.001), pancreatic pain and sexuality symptoms tended to decrease by 33% and global and functional QoL tended to slightly improve. These parameters remained at the achieved level during the longer follow-up. A temporary rising tendency was seen in digestive symptoms at three months but this later reverted to the preoperative level. More altered bowel movements and sexuality symptoms tended to arise during the longer follow-up. A negative correlation was found between reported financial difficulties and length of survival. CONCLUSIONS: PD does not worsen the QoL in most of the patients with PDAC. The potentially beneficial effect on QoL is apparent already at three months after surgery. This information may be helpful for the clinician and patient, when deciding on the treatment for PDAC.

The Long-term Prospective Follow-up of Pancreatic Function After the First Episode of Acute Alcoholic Pancreatitis: Recurrence Predisposes One to Pancreatic Dysfunction and Pancreatogenic Diabetes.

BACKGROUND: Data on the prevalence of pancreatic dysfunction after an episode of acute pancreatitis are conflicting. Our aim was to evaluate the natural course of endocrine and exocrine pancreatic function in the long-term follow-up after the first episode of acute alcoholic pancreatitis (AAP). METHODS: A total of 77 patients who survived their first episode of AAP between January 2001 and February 2005 were prospectively followed up for a maximum of 13 years. During the follow-up, patients were repeatedly interviewed and monitored for recurrences, new diabetes, and chronic pancreatitis. The pancreatic function was evaluated repeatedly during the follow-up. RESULTS: Of the patients, 35% had ≥1 recurrent acute pancreatitis (RAP) episodes during the follow-up. New pancreatogenic diabetes developed in 19% of the previously nondiabetic patients, but only in patients with RAP (13/26 vs. 0/42; OR=39; 95% CI, 4.6-327.1). In addition, 55% of the patients developed new prediabetes or diabetes, and even this was more frequent in patients with RAP (86% vs. 42%; OR=8.2; 95% CI, 1.2-54.3). Exocrine dysfunction developed in 24% of the patients and was associated with abnormal findings in the endocrine function (P=0.003). Patients with RAP had a higher overall mortality compared with patients without RAP episodes during the follow-up (36% vs. 13%; HR=4.0; 95% CI, 1.4-11.0). CONCLUSIONS: The risk for pancreatic endocrine dysfunction, pancreatogenic diabetes and mortality increases significantly if the patient has recurrent episodes of AAP. The risk of developing pancreatic dysfunction after AAP should be recognized and pancreatic function should be screened routinely during the years after the first episode of AAP.

Impaired gallbladder function in patients after total gastrectomy.

BACKGROUND AND AIMS: The incidence of gallstones and gallbladder sludge is higher in patients after total gastrectomy than in general population. Formation of gallstones after gastrectomy is multifactorial. Here, we investigate the changes in gallbladder and biliary tract functions by cholescintygraphy and monitored changes in cholecystokinin (CCK) release in long-term survivors after total gastrectomy for gastric carcinoma. MATERIAL AND METHODS: Patients had undergone total gastrectomy for gastric carcinoma at least five years ago. The final study population consisted of 25 patients. RESULTS: Eight patients had undergone cholecystectomy before or at the time of gastrectomy. Gallstone formation was observed in seven of the remaining 17 patients during follow-up (41%). Maximum uptake of radioactivity and gallbladder maximum uptake was significantly delayed in the gastrectomy group than in the control group. There was no significant difference in CCK levels after the overnight fasting and at 60 minutes after stimulation among patients with or without stones in situ compared with healthy volunteers, but 30 minutes after the energy-rich drink patients had higher CCK levels than the control group. CONCLUSIONS: In gastrectomy patients, technetium isotope visualisation of the gallbladder and time for maximum activity was significantly delayed. This may indicate impaired gallbladder function. On the contrary, CCK release was not impaired.

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone. BACKGROUND: Soft pancreas is a well-known risk factor for PPDC. Previously, we have shown that patients with >40% acini in the pancreatic transection line are most prone to PPDC. Recent studies have demonstrated that surgical trauma leads to inflammation of the pancreatic remnant, which precedes PPDC. METHODS: On the basis of power analysis, randomized controlled trial (RCT) (Clinicaltrials.gov NCT01460615), 155 patients (February 2011-May 2015) scheduled for pancreaticoduodenectomy were randomized to intravenous (i.v.) treatment with hydrocortisone 100 mg or placebo. All patients received the first dose at the induction of anesthesia. During the operation, the percentage of acini was calculated from pancreatic transection line frozen samples by a pathologist. As planned, only the high-risk patients with >40% acini (n = 62) continued in the study to receive in total 8 doses of randomization-based hydrocortisone/placebo every 8 hours. Primary endpoints were urine trypsinogen positive days and overall complications (Clavien-Dindo III-IV). Postoperative pancreatic fistulas (POPFs), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE) were also graded. RESULTS: Hydrocortisone treatment did not alter trypsinogen release (2 or more positive days 46% vs 50%), but it significantly reduced overall complications compared with placebo in the high-risk patients (18% vs 41%; P < 0.05; Clavien-Dindo III-IV). Also, clinically significant POPF (11% vs 27%), PPH (14% vs 24%), and DGE (29% vs 44%) tended to be lower in the hydrocortisone group. Ninety-day mortality was zero. CONCLUSIONS: This RCT shows that in high-risk patients, overall PPDC can be significantly reduced with hydrocortisone treatment. Inflammation may be an important mediator of PPDC.

Biodegradable biliary stents have a different effect than covered metal stents on the expression of proteins associated with tissue healing in benign biliary strictures.

BACKGROUND: Benign biliary strictures (BBS) are primarily treated endoscopically with covered self-expandable metal stents (CSEMS). Biodegradable biliary stents (BDBS) may be the future of endoscopic therapy of BBS. The aim was to assess the expression of proteins related to tissue healing in BBS compared with the intact bile duct (BD), and to study the protein expression after therapy with CSEMS or BDBS. METHODS: Pigs with ischemic BBS were endoscopically treated either with BDBS or CSEMS. Samples were harvested from pigs with intact BD (n = 5), untreated BBS (n = 5), and after six months of therapy with BDBS (n = 4) or CSEMS (n = 5) with subsequent histologic analysis. Two-dimensional electrophoresis with protein identification was performed to evaluate protein expression patterns. RESULTS: In BBS, the expression of galectin-2 and annexin-A4 decreased, compared to intact BD. Treatment with biodegradable stents normalized galectin-2 level; with CSEMS therapy it remained low. Transgelin expression of intact BD and BBS remained low after BDBS treatment but increased after CSEMS therapy. Histologic analysis did not show unwanted foreign body reaction or hyperplasia in the BD in either group. CONCLUSIONS: The expression of proteins related to tissue healing in BBS is different after treatment with biodegradable stents and CSEMS. Treatment with biodegradable stents may bring protein expression towards what is seen in intact BD. BDBS seem to have a good biocompatibility.

Can Laparoscopic Cholecystectomy Prevent Recurrent Idiopathic Acute Pancreatitis?: A Prospective Randomized Multicenter Trial.

OBJECTIVE: The aim of the present trial was to ascertain whether laparoscopic cholecystectomy (LCC) can prevent recurrent attacks of idiopathic acute pancreatitis (IAP). SUMMARY: Up to 50% to 75% of IAP may be due to microlithiasis, which is undetectable by conventional imaging methods. METHODS: This randomized, prospective trial included 85 patients (39 in the LCC and 46 in the control group) in 8 hospitals in Finland. We included adult patients (over 18 years) with their first attack of IAP. The diagnosis of IAP was based on the exclusion of common etiological reasons for acute pancreatitis (AP), whereafter the patients were randomized into conservative watchful waiting (controls) or LCC group. The primary end point was the number of patients with recurrent AP during the follow-up. All recurrent attacks of AP after an initial IAP episode were registered. RESULTS: During a median follow-up of 36 (5-58) months, the recurrence of IAP was significantly higher in the control group than in LCC group (14/46 vs. 4/39, P = 0.016), as was also the number of recurrences (23/46 vs. 8/39, P = 0.003). In the subgroup of patients with at least 24 months' follow-up, the recurrence was still higher among controls (14/37 vs. 4/35, P = 0.008). In patients with normal liver function, recurrence was also significantly higher in the control than in the LCC group (13/46 vs. 4/39, P = 0.026). During surgery, 23/39 (59%) of the gallbladders were found to contain biliary stones or sludge. CONCLUSIONS: LCC can effectively prevent the recurrence of IAP when all other possible etiologies of pancreatitis are carefully excluded. A total of 5 patients needed to be treated (NNT-value) to prevent 1 IAP.

Cyst fluid SPINK1 may help to differentiate benign and potentially malignant cystic pancreatic lesions.

OBJECTIVE: Differential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions. DESIGN: Sixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at -70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type). RESULTS: The acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13-3602) vs. 18 (0.1-278) µg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2-116] µg/L) than in main duct IPMN or MCA (638 [66-3602] µg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 µg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 µg/L). CONCLUSIONS: Cyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions.

Validation of intraluminal and intraperitoneal microdialysis in ischemic small intestine.

BACKGROUND: We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GI-tract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia with higher sensitivity and specificity. METHODS: IL and IP microdialysate lactate, pyruvate, glucose and glycerol were analysed from small intestine of pancreaticoduodenectomy patients before and after occluding the mesenteric vasculature and routine resection of a segment of small intestine. Ex vivo time sequences of microdialysate metabolites were described and ROC analyses after 0-30, 31-60, 61-90 and 91-120 minutes after the onset ischemia were calculated. RESULTS: IL lactate to pyruvate ratio (L/P ratio) indicated ischemia after 31-60 minutes with 0.954 ROC AUC (threshold: 109) in contrast to IP L/P (ROC AUC of 0.938 after 61-90 minutes, threshold: 18). At 31-60 minutes IL glycerol concentration indicated ischemia with 0.903 ROC AUCs (thresholds: 69 µmol/l). IP glycerol was only moderately indicative for ischemia after 91-120 minutes with 0,791 ROC AUCs (threshold 122 µmol/l). After 31-60 minutes IL and IP lactate to glucose ratios (L/G ratio) indicated ischemia with 0.956 and 0,942 ROC AUCs (thresholds: 48,9 and 0.95), respectively. CONCLUSIONS: The results support the hypothesis that intraluminal application of microdialysis and metabolic parameters from the small intestinal lumen indicate onset of ischemia earlier than intraperioneal microdialysis with higher sensitivity and specificity.

Serum lipid levels are associated with the severity of acute pancreatitis.

BACKGROUND/AIMS: Serum lipid concentrations react during acute disease. We sought to measure changes in the serum lipid profile during acute pancreatitis and ascertain whether these changes were associated with the severity of the disease. METHODS: A total of 233 patients (71% male, median age 48 years) hospitalized for acute pancreatitis were included in the study. The most common etiology for acute pancreatitis was alcohol (n = 131, 56%), followed by biliary (n = 48, 21%) and idiopathic pancreatitis (n = 36, 16%). Serum lipid levels were measured enzymatically. We analyzed samples obtained during the first days of hospitalization and later follow-up samples to measure changes during the course of the disease. RESULTS: We report profound changes in the serum lipid concentrations during acute pancreatitis. Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol concentrations measured within 2 days of admission (n = 203) were significantly lower in patients who developed severe pancreatitis (3.20 vs. 3.80 mmol/l, p = 0.001; 0.72 vs. 1.05 mmol/l, p < 0.000, and 1.60 vs. 2.14 mmol/l, p < 0.000, respectively). Low serum total cholesterol, HDL cholesterol and LDL cholesterol concentrations were moreover associated with in-hospital mortalities and longer hospitalization (p < 0.05). In the subgroup analysis, the findings remained statistically significant in patients with alcohol-induced acute pancreatitis. CONCLUSION: Levels of serum total cholesterol, HDL cholesterol and LDL cholesterol are significantly lower in patients with severe acute pancreatitis and are associated with longer hospitalization.

Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction.

AIMS: To determine the recurrence of pancreatitis and subsequent pancreatic function in patients who stop drinking after the first episode of alcohol-associated pancreatitis. METHODS: Of a total of 118 patients suffering from their first alcohol-associated pancreatitis, 18 (all men, age median 47 (27-71) years) met the inclusion criterion for abstinence during follow-up. The criterion for abstinence was alcohol consumption <24 g per 2 months (self-estimated), which is in line with questionnaires eliciting alcohol consumption and dependency (Alcohol Use Disorders Identification Test < 8 and Short Alcohol Dependence Data < 9). Recurrent attacks of acute pancreatitis were studied. Smoking, body mass index and laboratory tests detecting heavy consumption of alcohol were recorded. Blood and faecal tests were studied to assess endocrine and exocrine pancreatic function. RESULTS: During a mean follow-up time of 5.15 (1.83-9.13) years and a total of 92.7 patient-years, there were no recurrent attacks of acute pancreatitis among the 18 abstainers. Two patients had diabetes prior to and one was diagnosed immediately after the first episode of acute pancreatitis. One patient had impaired glucose metabolism at 2 years. Two patients had low insulin secretion in glucagon-C-peptide test, one at 4 years and the other at 5 years. Only one patient (6%) maintained low elastase-1 activity during the abstinence follow-up. Of the 100 non-abstainers, 34% had at least one recurrence during the follow-up. CONCLUSION: Regardless of the mediator mechanisms of acute alcoholic pancreatitis, abstinence after the first episode protects against recurrent attacks. Pancreatic dysfunction is also rare among abstinent patients.

A novel radiopaque biodegradable stent for pancreatobiliary applications--the first human phase I trial in the pancreas.

BACKGROUND/AIMS: During the recent years we have developed and experimentally tested a biodegradable stent for pancreatobiliary applications. Such stents may be used in benign strictures or when securing the flow of bile, pancreatic juice or a fluid collection after endoscopic or surgical procedures. The lack of suitable devices has so far prohibited clinical endoscopic or percutaneous tests whereas surgical application has become possible. Recently we described a modified binding (purse string) pancreaticojejunostomy, where a biodegradable stent is introduced to secure the lumen opening when tightening the bowel over the pancreas with a purse string. Although routine use of any stent in pancreaticojejunostomy has been under debate, we used this setting to run for the first phase I human clinical trial with a biodegradable stent in a pancreatobiliary application. METHODS: After 29 pancreaticoduodenectomies, a braided gamma sterilized radiopaque 96L/4D polylactide stent was introduced into the duct of pancreas remnant, which was then sunk into the Roux-Y jejunal limb. Complications, stent disappearance and late anastomotic patency (MRI) were monitored. RESULTS: Hospital mortality was zero. One patient developed Grade C fistula (overall fistula rate 3%). She also developed Grade C hemorrhage and Grade C delayed gastric emptying (DGE). One other patient developed Grade B hemorrhage (overall hemorrhage rate 7%) and B DGE. Three other patients developed clinically significant Grade B-C DGE (5/29=17%). In addition, 10 other patients were not on solid food only on post-operative day 8, and were classified as Grade A DGE (34%). Most of these patients were eating normally and could be discharged from hospital by day 10. Nine out of 26 patients (35%) with negative preoperative trypsinogen test, developed post-operative trypsinogen release suggesting pancreatitis. Within 12 months four patients died and one quitted the study. The stents disappeared in median 3 months. MRI interpretation of the anastomosis failed in one patient having ascites. Of the 23 patients, 13 (57%) had the anastomosis well open, three (13%) had some narrowing, while seven (30%) had the anastomosis obstructed. CONCLUSION: Compared with our previous experiences obtained in pancreaticoduodenectomy, a biodegradable stent is well tolerated in the human pancreatic duct, encouraging further development for future applications and tests in randomized trials.

Serum lipid and fatty acid profiles are highly changed in patients with alcohol induced acute pancreatitis.

BACKGROUND/AIMS: Hyperlipidemia is one known etiology of acute pancreatitis. Alcohol use is known to induce changes in lipid metabolism and might alter the serum lipid and fatty acid profile. We hypothesized that these changes may explain individual susceptibility of developing acute pancreatitis. We compared lipid and fatty acid profiles of patients with acute alcoholic pancreatitis and alcoholic controls. METHODS: 19 patients with their first alcoholic pancreatitis and 20 controls were included. Late follow-up samples were obtained from 16 patients. Serum lipids were analyzed enzymatically and the fatty acid profile using gas chromatography. RESULTS: The concentrations of serum total cholesterol, LDL-cholesterol and HDL-cholesterol were markedly lower in patients than in controls during the acute disease but normalized after follow-up. Patients had statistically significantly lower fatty acid proportions of saturated C14:0, polyunsaturated C18:2, C18:3 and C20:3 of the n-6-series and C18:3 of the n-3-series than controls. In contrast, patients had higher percentages of saturated C16:0 and monounsaturated C18:1n9 fatty acids than controls. Mead acid, C20:3n9, marker of essential fatty acid deficiency, was lower in patients than in controls. C14:0, C20:3n6, C18:3n3 and C20:3n9 remained altered after follow-up. CONCLUSION: Serum lipid and fatty acid levels were significantly altered during the acute disease and returned toward normal after 18-24 months, suggesting that the changes are secondary to acute pancreatitis. They are unlikely to be the much sought 'trigger factor' of pancreatic necro-inflammation. However, further studies are warranted to fully establish this point.

Luminal lactate in acute pancreatitis--validation and relation to disease severity.

BACKGROUND: Increased rectal luminal lactate concentration may be associated with the severity of the septic shock and high dose of vasopressors. It suggests hypoperfusion of the gut mucosa. This is potentially associated with bacterial translocation from the gut leading to local and systemic inflammation. In acute pancreatitis (AP) bacterial translocation is considered as the key event leading to infection of necrotic pancreatic tissue and high severity of illness. METHODS: We used rectal luminal equilibration dialysis for the measurement of gut luminal lactate in 30 consecutive patients admitted to hospital due to acute pancreatitis to test the hypothesis that a single measurement of rectal luminal lactate predicts the severity of acute pancreatitis, the length of hospital stay, the need of intensive care and ultimately, mortality. We also tested the physiological validity of luminal lactate concentration by comparing it to luminal partial tension of oxygen. Additionally, a comparison between two different L-lactate analyzers was performed. RESULTS: High rectal luminal lactate was associated with low mucosal partial tension of oxygen (R = 0.57, p = 0.005) thereby indicating the physiological validity of the method. Rectal luminal lactate at the hospital admission was not associated with the first day or the highest SOFA score, CRP level, hospital length of stay, length of stay in intensive care or mortality. In this cohort of unselected consecutive patients with acute pancreatitis we observed a tendency of increased rectal lactate in the severe cases. Low precision and high bias was observed between two lactate analyzers. CONCLUSIONS: The association between rectal luminal lactate and oxygen tension indicates that luminal lactate is a marker mucosal anaerobiosis. Comparison between two different analyzers showed poor, non-constant precision over the range of lactate concentrations. Rectal luminal lactate concentration at the time of hospital admission did not predict the severity of pancreatitis.

Polyamine catabolism in relation to trypsin activation and apoptosis in experimental acute pancreatitis.

BACKGROUND: Overinduced polyamine catabolism (PC) in a transgenic rat model has been suggested to be a mediator of trypsin activation which is important in acinar cell necrosis. PC has also been observed in experimental taurodeoxycholate pancreatitis. We hypothesized that PC may be a mediator of trypsin activation in taurodeoxycholate pancreatitis. METHODS: Pancreatitis was induced in wild-type rats by 2 or 6% taurodeoxycholate infusion or in transgenic rats by overexpressing spermidine/spermine N(1)-acetyltransferase (SSAT). The time courses of necrosis, caspase-3 immunostaining, SSAT, polyamine levels, and trypsinogen activation peptide (TAP) were monitored. The effect of the polyamine analogue bismethylspermine (Me(2)Spm) was investigated. RESULTS: In a transgenic pancreatitis model, TAP and acinar necrosis increased simultaneously after the activation of SSAT, depletion of spermidine, and development of apoptosis. In taurodeoxycholate pancreatitis, necrosis developed along with the accumulation of TAP. SSAT was activated simultaneously or after TAP accumulation and less than in the transgenic model, with less depletion of spermidine than in the transgenic model. Supplementation with Me(2)Spm ameliorated the extent of acinar necrosis at 24 h, but contrary to previous findings in the transgenic model, in the taurodeoxycholate model it did not affect trypsin activation. Compared with the transgenic model, no extensive apoptosis was found in taurodeoxycholate pancreatitis. CONCLUSIONS: Contrary to transgenic SSAT-overinduced pancreatitis, PC may not be a mediator of trypsin activation in taurodeoxycholate pancreatitis. The beneficial effect of polyamine supplementation on necrosis in taurodeoxycholate pancreatitis may rather be mediated by other mechanisms than amelioration of trypsin activation. and IAP.

[Pain caused by chronic pancreatitis]. / Kroonisen haimatulehduksen aiheuttama kipu.

Pain is a predominant symptom in chronic pancreatitis. When diagnosing chronic pancreatitis it is important to exclude other causes of abdominal pain. Diagnostic evaluation can be started with upper abdominal ultrasound examination and fecal elastase-1 assay. Treatment of pancreatic pain should be actively carried out in order to prevent the pain to become chronic. If the pain cannot be managed with anti-inflammatory drugs and modifications of lifestyle, endoscopic, radiologic and surgical treatments have to be contemplated.

The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial.

BACKGROUND & AIMS: In the long term, half of patients with their first alcohol-associated acute pancreatitis (AP) develop acute recurrence, alcohol consumption being the main risk factor. None of the recent national or international guidelines for treatment include recommendations aimed to decrease recurrences, possibly because of a lack of studies. This study investigated whether AP recurrences can be reduced. METHODS: One hundred and twenty patients admitted to a university hospital for their first alcohol-associated AP were randomized either to repeated intervention (n = 59) or initial intervention only (n = 61). The patients in the 2 groups did not differ. A registered nurse performed an intervention in both groups before discharge, after which it was repeated in the study group at 6-month intervals at the gastrointestinal outpatient clinic. Acute recurrences during the next 2 years were monitored. RESULTS: There were 9 recurrent AP episodes in 5 patients in the repeated-intervention group compared with 20 episodes (P = .02) in 13 patients (P = .04) in the control group. The recurrence rates were similar during the first 6 months (4 vs 5 episodes), after which the repeated-intervention group had fewer recurrences than the control group (5 vs 15 episodes; P = .02). CONCLUSIONS: The repeated visits at 6-month intervals at the gastrointestinal outpatient clinic, consisting of an intervention against alcohol consumption, appear to be better than the single standardized intervention alone during hospitalization in reducing the development of recurrent AP during a 2-year period.

Bile duct stone procedures are more frequent in patients with hypothyroidism. A large, registry-based, cohort study in Finland.

OBJECTIVE: Delayed bile flow may induce the formation/accumulation of common bile duct stones (CBDS). Bile flow is delayed in hypothyroidism, partly due to insufficient sphincter of Oddi relaxation. Patients with CBDS have higher incidences of clinical and subclinical hypothyroidism compared to healthy controls and gallbladder stone patients. The aim of this large registry-based study was to investigate the prevalence of CBDS in patients with diagnosed hypothyroidism compared to age-, sex- and living area-adjusted glaucoma (control) patients. MATERIAL AND METHODS: Between 1987 and 2001, all patients with approved Special Medical Coverage (SMC) for hypothyroidism or glaucoma, and without other SMC approvals, were included. The glaucoma (control) cohort was adjusted for age, sex and area of residence. For each patient, onset of SMC, all prescription drugs and treatments for CBDS were noted. RESULTS: A total of 14,334 patients in each group met the inclusion criteria. Thirty-three patients (0.23%) in the hypothyroidism cohort and 23 (0.16%) in the glaucoma cohort had been treated for CBDS (p = 0.018). The groups did not differ in the number of CBDS treatments before the diagnosis of hypothyroidism or glaucoma. However, after the diagnosis of hypothyroidism or glaucoma there were significantly more CBD stone patients in the hypothyroid cohort (n = 25) than in the glaucoma cohort (n = 14) (p < 0.05). CONCLUSIONS: Diagnosed hypothyroidism is a significant risk factor for CBDS. We hypothesize that CBD stone formation begins during the untreated period and develops/matures even after the medication has been initiated, raising the question of the efficiency of treatment in this respect. When treating CBDS patients, one should be aware of the possible hypothyroid background.

[Hypothyroidism is common in bile duct stone patients]. / Sappitiekivipotilailla on usein hypotyreoosi.

For decades, one well-known risk factor for the development of gallbladder stones has been hypothyroidism. Recent studies have reported that the risk for common bile duct stones particularly increases both in clinical and subclinical hypothyroidism. There are multiple factors that may contribute to the formation and/or accumulation of common bile duct stones in hypothyroid patients, including decreased liver cholesterol metabolism, diminished bile secretion, and reduced sphincter of Oddi relaxation. When treating patients with common bile duct stones or microlithiasis, the clinicians should be aware of the possible hypothyroid background, and consider the need for thyroid function assessment in these patients.