Acute Alcohol-induced Pancreatitis Research Articles

Treatment for acute alcoholic-alimentary pancreatitis with peritoneal syndrome

A large number of publications on surgical treatment of acute alcohol-induced pancreatitis (AAP) with peritonitis indicates the importance of the problem and the need for a differentiated approach to treatment. The aim of this study is to determine the optimal treatment policy for acute alcohol-associated pancreatitis with peritonitis. The study included 114 male patients diagnosed with acute alcoholic pancreatitis and peritoneal sepsis, with an average age of 48.6 ± 6.4 years. They were admitted to the surgical departments of clinical hospitals between 2013 and 2023. The diagnosis of AAP was confi med based on clinical, laboratory, and instrumental findings. The classification of acute pancreatitis recommended by the National Clinical Guidelines of the Ministry of Health of the Russian Federation (2015 and 2020) has been applied. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scale has been used to assess the severity and prognosis of the disease, while the Sequential Organ Failure Assessment (SOFA) scale has been used to evaluate organ failure. Based on the results, an algorithm for the treatment of acute alcoholic and alimentary pancreatitis with peritoneal syndrome has been proposed, taking into account the type of pancreatic necrosis, the extent of pancreatic damage, and the nature of fl uid accumulation. For patients with edematous pancreatitis, small-focal sterile pancreatic necrosis, and enzymatic peritonitis, percutaneous ultrasound-guided abdominal and omental drainage is recommended. In severe and moderate acute alcoholic-alimentary pancreatitis, with enzymatic peritonitis (more than 8 points on the APACHE II scale), which is manifested during diagnostic and sanitation laparoscopy by the presence of a hemorrhagic effusion and a large number of plaques of steatonecrosis on the parietal peritoneum and the large omentum, we should use an endovisual method of draining the abdominal cavity and the omentum to minimize anesthesiological and surgical aggression and to form and maintain general cavities, as well as to create good access to the pancreatic area. For patients with large-focal, infected subtotal or total pancreatic necrosis and purulent peritonitis, it is advisable to perform laparotomy, abdominalization of the pancreas, necrectomy, omentobursostomy, and drainage of purulent foci in the abdominal cavity and retroperitoneal tissue.

Plasma soluble urokinase-type plasminogen activator receptor (P-suPAR) in the diagnostics between malignant and non-malignant pancreatic lesions

BackgroundSoluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker elevated in several inflammatory conditions and cancers. It has recently been shown to be elevated in pancreatic ductal adenocarcinoma (PDAC). Plasma suPAR (P-suPAR) predicts the severity of the disease in first acute alcohol-induced pancreatitis (AAP) and ten-year mortality after recovery from first AAP. According to our previous results, P-suPAR is not elevated in chronic pancreatitis (CP) and could possibly be used in distinguishing pancreatic cancer (PC) from CP. When imaging creates a suspicion of a pancreatic lesion, the distinction between malignant and non-malignant disease is crucial. Additional tools are needed, and we still lack a sufficiently sensitive and specific biomarker. Our aim was to further investigate whether preoperatively measured P-suPAR is beneficial in distinguishing between malignant and non-malignant pancreatic lesions. MethodsOne hundred and seventy-six patients evaluated in Tampere University Hospital for pancreatic surgery for suspected malignant pancreatic lesion were recruited for the study. The final study group consisted of 113 patients. P-suPAR and other covariates were measured before the planned operation. ResultsP-suPAR was significantly higher in patients with pancreatic cancer (PC) [median 4.1 (IQR 3.3–5.1) ng/mL] than in patients with non-malignant [3.3 (2.9–4.4) ng/mL; p = 0.012] histology. ROC curve analysis resulted in an AUC of 0.65 (95% CI 0.55–0.76); p = 0.007 and a cutoff value of 3.2 ng/mL. Crosstabulation yielded sensitivity of 82% and specificity of 43%. A combination of positive P-suPAR and elevated plasma carbohydrate antigen 19–9 (P-CA19-9) tests did not improve sensitivity but elevated specificity up to 86–88%. ConclusionsPreoperative P-suPAR is elevated in patients with PC compared to patients with a non-malignant pancreatic lesion. Combining P-suPAR with P-CA19–9 may improve diagnostic accuracy.

An uncommon mediastinitis from infected pancreatic pseudocyst

A 48-year-old man with a history of alcoholism and recurrent abdominal pain developed acute alcohol-induced pancreatitis

The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis

Heavy alcohol consumption is a common cause of acute pancreatitis; however, alcohol abuse does not always result in clinical pancreatitis. As a consequence, the factors responsible for alcohol-induced pancreatitis are not well understood. In experimental animals, it has been difficult to produce pancreatitis with alcohol. Clinically, alcohol use predisposes to hypophosphatemia, and hypophosphatemia has been observed in some patients with acute pancreatitis. Because of abundant protein synthesis, the pancreas has high metabolic demands, and reduced mitochondrial function leads to organelle dysfunction and pancreatitis. We proposed, therefore, that phosphate deficiency might limit adenosine triphosphate synthesis and thereby contribute to alcohol-induced pancreatitis. Mice were fed a low-phosphate diet (LPD) before orogastric administration of ethanol. Direct effects of phosphate and ethanol were evaluated invitro in isolated mouse pancreatic acini. LPD reduced serum phosphate levels. Intragastric administration of ethanol to animals maintained on an LPD caused severe pancreatitis that was ameliorated by phosphate repletion. In pancreatic acinar cells, low-phosphate conditions increased susceptibility to ethanol-induced cellular dysfunction through decreased bioenergetic stores, specifically affecting total cellular adenosine triphosphate and mitochondrial function. Phosphate supplementation prevented ethanol-associated cellular injury. Phosphate status plays a critical role in predisposition to and protection from alcohol-induced acinar cell dysfunction and the development of acute alcohol-induced pancreatitis. This finding may explain why pancreatitis develops in only some individuals with heavy alcohol use and suggests a potential novel therapeutic approach to pancreatitis. Finally, an LPD plus ethanol provides a new model for studying alcohol-associated pancreatic injury.

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.

S0042 Acute Biliary Pancreatitis Has Better In-Hospital Outcomes Compared to Acute Alcohol-Induced Pancreatitis: Results of a Nationwide Analysis

INTRODUCTION: Acute pancreatitis (AP) is an acute inflammatory process involving the pancreas with considerable morbidity and mortality. The most common cause of AP is biliary disease followed by alcohol, accounting for estimated 70–80 percent of all cases of AP. Determination of the etiology may reliably guide immediate management of patient. METHODS: We queried the National Inpatient Sample (NIS) databases 2016 and 2017 using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system to identify the following: (A) Patients with primary diagnosis of Acute Pancreatitis (AP) (B) Patients with a primary diagnosis of Acute Alcohol-induced Pancreatitis (AAP) and Acute Biliary Pancreatitis (ABP). Analysis was performed with STATA software. RESULTS: 553,480 adult patients who were diagnosed with AP during hospitalization in 2016 and 2017 were identified. Mean age was 51.8 years, and majority of patients were male (53.22%). 25.3% patients had AAP and 17.44% patients had ABP. Patients with ABP were more likely to be females compared to patients with AAP (59.4% vs 30.73%, P < 0.01), and were older (57.03 years vs 45.31 years, P < 0.01).The total mortality in patients with AAP was 0.42% and in patients with ABP was 0.82% with no significant difference on multivariate analysis (aOR: 0.95, 95% CI: 0.69–1.31, P = 0.79). Patients with ABP had a significantly longer Length of Stay (LOS) when compared with patients with APP (+0.48 days, P < 0.01). In addition, the ABP group had a significantly higher mean adjusted hospitalization charges and costs with a difference of $ +19,958 (P < 0.01) in charges and $+4,848 (P < 0.01) in cost. Patients with ABP had significantly lower likelihood of shock when compared to patients with AAP (aOR: 0.75, 95% CI: 0.59–0.95, P < 0.05). They were significantly less likely to develop AKI (aOR 0.76, 95% CI: 0.71-0.82, P < 0.01) or to be admitted to ICU (aOR 0.74, 95% CI: 0.62–0.88, P < 0.01). They were more likely to be discharged home (aOR 1.26, 95% CI: 1.18–1.34, P < 0.01). CONCLUSION: Our study showed no difference in mortality between patients with AAP and ABP. We found that patients with ABP had increased resource utilization. Patients with ABP are more likely to undergo invasive procedures like ERCP/cholecystectomy and this is likely the reason for increased resource use. Patients with ABP had significantly lower odds of AKI, shock and ICU stay. Further studies are needed to assess the reason for this difference and guide clinical practice.Figure 3.: Pooled rates of technical success, clinical success, and AE of POP, EHL and LL.

S0078 Gender Differences in Outcomes of Acute Pancreatitis in Hospitalized Patients: Results From Nationwide Analysis

INTRODUCTION: Acute pancreatitis (AP) has multiple etiologies, the most common causes being alcohol and gallstone disease. Acute alcohol-induced pancreatitis is more common in men while acute biliary pancreatitis is more common in women. Gender based differences in disease incidence, time of disease onset, disease course, diagnosis, severity, and outcome are well recognized and are documented in literature for numerous illnesses. Gender is found to be independent risk factor for multiple GI diseases. In our study, we looked into gender effect on acute pancreatitis outcome using nationwide analysis. METHODS: We queried the National Inpatient Sample (NIS) databases 2016 and 2017 using International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system to identify all patients with primary diagnosis of Acute Pancreatitis (AP). Statistical analyses were performed using STATA software. RESULTS: A total of 553,480 adult patients with AP were included in the study. Mean age was 51.8 years, and majority of patients were male (53.22%). Female patients were older (52.81 years vs 50.97 years, P < 0.01), had Medicare as the primary insurance (34.89%) and majority were white (64.15%). Female patients had higher prevalence of CHF (5.79% vs 25.4%, P < 0.01), ESRD (2.32% vs 2.00%) and obesity (19.85% vs 14.46%). Male patients had higher prevalence of liver cirrhosis (3.91% vs 3.03%, P < 0.01), Type 1 Diabetes (1.25% vs 1.03%, P < 0.01), Type 2 Diabetes (26.69% vs 23.66%, P < 0.01) and smoking (66.17% vs 30.75%).The total mortality in male patients was 0.67% and in female patients was 0.51%. On multivariate analysis, female patients had significantly lower likelihood of in-hospital mortality compared to male patients (aOR: 0.69, 95% CI: 0.59–0.82, P < 0.01).There was no significant difference in mean LOS, mean hospitalization charges and costs between males and females with AP. Female patients had significantly lower likelihood of shock compared to male patients (aOR: 0.64, 95% CI: 0.56–0.73, P < 0.01), sepsis (aOR: 0.70, 95% CI: 0.65–0.75, P < 0.01), AKI (aOR 0.66, 95% CI: 0.63–0.69, P < 0.01), ICU admission (aOR 0.53, 95% CI: 0.47–0.59, P < 0.01) and pancreatic drainage (aOR 0.61, 95% CI: 0.51–0.72, P < 0.01). CONCLUSION: In our study, we demonstrated that female patients with AP had significantly lower in hospital mortality rates, and in hospital clinical outcomes compared to male patients. Further studies are needed to accurately understand these differences to guide clinical practice.Figure 1.: Outcomes in patients with acute pancreatitis: Male vs Female.

Acute biliary pancreatitis has better outcomes but increased resource utilization compared to acute alcohol-induced pancreatitis: insights from a nationwide study.

BackgroundThe differences in outcomes between acute biliary pancreatitis (ABP) and acute alcohol-induced pancreatitis (AAP) have not been well studied. We sought to examine the differences between ABP and AAP as regards to in-hospital outcomes and resource utilization, using a large nationwide database.MethodsWe queried the National Inpatient Sample databases 2016 and 2017 using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system to identify the patients with a primary diagnosis of AAP and ABP. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were hospital length of stay (LOS), hospitalization charge/cost, shock, acute kidney injury (AKI), intensive care unit (ICU) admission, and home discharge. Analysis was performed with STATA software.ResultsThere was no significant difference in mortality between patients with AAP and ABP (0.42% vs. 0.82%, adjusted odds ratio [aOR] 0.95, 95% confidence interval [CI] 0.69-1.31; P=0.79). Patients with ABP had a significantly longer LOS (+0.48 days, P<0.001). Patients with ABP had significantly higher adjusted mean hospitalization charges ($+19,958, P<0.001) and costs ($+4,848, P<0.001). Patients with ABP had a significantly lower likelihood of shock (aOR 0.75, 95%CI 0.59-0.95; P=0.02), AKI (aOR 0.76, 95%CI 0.71-0.82; P<0.001) or ICU admission (aOR 0.74, 95%CI 0.62-0.88; P=0.001). They were more likely to be discharged home (aOR 1.26, 95%CI 1.18-1.34; P<0.001).ConclusionAlthough there was no difference in all-cause mortality, patients with ABP had better hospitalization outcomes but greater resource utilization.

Pseudo-Wellens syndrome, acute pancreatitis, and an anomalous coronary artery: a case report

BackgroundChest pain associated with transient electrocardiogram changes mimicking an acute myocardial infarction have been described in acute pancreatitis. These ischemic electrocardiogram changes can present a diagnostic dilemma, especially when patients present with concurrent angina pectoris and epigastric pain warranting noninvasive or invasive imaging studies.Case presentationA 45-year-old African-American man with a history of alcohol use disorder presented to the emergency department of our institution with 36 hours of concurrent epigastric pain and left-sided chest pain radiating to his left arm and associated with nausea and dyspnea. On physical examination, he was afebrile; his blood pressure was elevated; and he had epigastric tenderness. His laboratory test results were significant for hypokalemia, normal troponin, and elevated serum lipase and amylase levels. Serial electrocardiograms for persistent chest pain showed ST-segment elevations with dynamic T-wave changes in the right precordial electrocardiogram leads, consistent with Wellens syndrome. He was immediately taken to the cardiac catheterization laboratory, where selective coronary angiography showed normal coronary arteries with an anomalous origin of the right coronary artery from the opposite sinus. Given his elevated lipase and amylase levels, the patient was treated for acute alcohol-induced pancreatitis with intravenous fluids and pain control. His chest pain and ischemic electrocardiogram changes resolved within 24 hours of admission, and coronary computed tomography angiography showed an interarterial course of the right coronary artery without high-risk features.ConclusionsClinicians may consider deferring immediate cardiac catheterization and attribute electrocardiogram changes to acute pancreatitis in patients presenting with angina pectoris and acute pancreatitis if confirmed by normal cardiac enzymes and elevated levels of lipase and amylase. However, when clinical signs and electrocardiogram findings are highly suggestive of myocardial ischemia/injury, immediate noninvasive coronary computed tomography angiography may be the best approach to make an early diagnosis.

1264 Mediastinal Pancreatic Pseudocyst With Expansion Into Bilateral Pleural Spaces

INTRODUCTION: Pseudocysts are a common complication of both acute and particularly chronic pancreatitis. Uncommonly, pseudocysts may communicate with thoracic cavities, including the mediastinum. We describe a case of acute pancreatitis complicated by a mediastinal pseudocyst with bilateral pleural space involvement. CASE DESCRIPTION/METHODS: A 51-year-old male with a history of alcohol abuse presented shortly after discharge from a prolonged hospitalization for his first lifetime episode of acute alcohol-induced pancreatitis. A CT of the chest ordered on admission for new onset respiratory distress demonstrated bilateral pleural effusions. Fluid analysis showed a right sided empyema and left sided aseptic exudative effusion. The right empyema resolved after chest tube placement but there was rapid recrudescence of a right pleural effusion after chest tube removal. Repeat fluid analysis was significant for a pancreatic specific amylase level of 2620. Repeat CT imaging demonstrated a posterior mediastinal fluid collection that arose from the pancreas, extended through the esophageal hiatus and was contiguous with new fluid collections in both pleural spaces and this was confirmed with MRCP. The mediastinal pseudocyst was deemed not amenable to endoscopic drainage so ERCP was performed with stent placement to the ventral pancreatic duct along with chest tube placement for the larger right sided fluid collection and subcutaneous octreotide administration, with eventual reduction of pseudocyst size. DISCUSSION: Mediastinal pseudocysts are a rare complication of acute pancreatitis more commonly seen in chronic pancreatitis, though exceedingly rare in general. It is theorized that mediastinal pseudocysts occur based on ease of pancreatic fluid movement. The pararenal and pelvic extraperitoneal spaces are typically the easiest spaces for this fluid to penetrate but conditions that create inflammatory fibrosis of these areas may make ascending flow into the mediastinum the path of least resistance. On CT scan and on MRCP, our patient had a mediastinal pseudocyst that communicated directly and inseparably with both the right and left pleural space. To our knowledge, this has not been previously seen in the limited case reports of mediastinal pseudocysts. Despite not being amenable to endoscopic drainage based on location, the use of octreotide coupled with pancreatic duct stenting proved effective in reducing the caliber of this mediastinal pseudocyst on interval imaging.

Plasma level of soluble urokinase plasminogen activator receptor (suPAR) predicts long-term mortality after first acute alcohol-induced pancreatitis

BackgroundSoluble urokinase plasminogen activator receptor (suPAR) is a biomarker associated with inflammatory and certain malignancies. Earlier we have shown that plasma suPAR (P-suPAR) predicts severity of acute alcohol-induced pancreatitis (AAP) on admission. Our aim was to investigate whether P-suPAR levels predict AAP recurrences or mortality during long-term follow-up after first AAP. MethodsEighty-three patients (median age 47.5, range 25–71 years) suffering their first AAP during 2001–2005 were recruited and followed prospectively for 9 years with a median follow-up time of 7.0 (range 0.3–9.8) years. P-suPAR was measured by enzyme-linked immunosorbent assay (ELISA) from the samples taken at follow-up visits. Survival was registered in November 2014. ResultsP-suPAR level on admission or after recovery of the first AAP did not predict the recurrence of AAP. However, higher P-suPAR measured after recovery of first AAP (3.6 vs. 2.9 ng/mL) predicted mortality during follow-up period (hazard ratio 1.48, p = .008). Cut-off value for P-suPAR indicating a higher risk for 10-year mortality resulted a value of ≥3.4 ng/mL. When adjusted for other covariates, P-suPAR above cut-off level retained its statistical significance as an independent factor. ConclusionsP-suPAR level on admission or after recovery of the first AAP does not predict the recurrence of AAP during long-term follow-up. However, P-suPAR ≥3.4 mg/mL measured after recovery from first AAP is associated with an increased risk of 10-year mortality as an independent factor. This can be used to detect patients with highest risk after AAP, in order to focus the preventive healthcare actions.

High level of plasma soluble urokinase plasminogen activator receptor (P-suPAR) on recovery predicts the long-term mortality after first acute alcohol-induced pancreatitis (AAP)

High level of plasma soluble urokinase plasminogen activator receptor (P-suPAR) on recovery predicts the long-term mortality after first acute alcohol-induced pancreatitis (AAP)

The Impact of Social Work Intervention in Alcohol-Induced Pancreatitis in Ireland: a Single-Center Experience.

To evaluate the effect on recurrent admission for alcohol-induced pancreatitis (that can be up to 48%) of a brief social work intervention for alcohol dependence in a single center in Ireland Retrospective cohort study of patients admitted with acute alcohol-induced pancreatitis to a tertiary hospital in Ireland from January 2009 to December 2012. The relapse rate in the cohort of 160 patients with alcohol-induced pancreatitis was 28.1%. There was no difference in the relapse rate of those patients who received a social work intervention compared with those who did not (ANOVA, P = 0.229). The employment status was a significant risk factor for relapse (ANOVA, P = 0.027), but did not differ between those who did, and did not, receive the intervention. Although the cohort size did not allow great statistical power, it appears that our hospital's current social work intervention for alcohol-induced pancreatitis is ineffective in preventing relapse. Long-term prospective studies are required to formulate and better implement more efficacious interventions for such patients.

Polymorphisms of the TNF, CD14, and HSPA1B Genes in Patients With Acute Alcohol-Induced Pancreatitis

Genotype assessment has been suggested to be a tool for predicting disease severity in acute pancreatitis (AP). To study this hypothesis, we performed genotype analysis of tumor necrosis factor (TNF) -308 A/G, CD14 -159C/T, and HSPA1B +1267 A/G polymorphisms. This is a case-control association study of 397 patients with AP (214 of whom had an alcohol-induced AP) and 300 controls. The control group comprised 218 subjects with detailed data of alcohol consumption, 70 of whom were heavy drinkers (daily alcohol intake >40 g), and 92 blood donors. The severity of AP was determined according to the Atlanta classification. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-assisted genotyping method. Major allele frequency in TNF gene was 0.87 for patients with AP and 0.86 for controls. For CD14, the gene major allele frequency was 0.60 for patients and 0.63 for controls. For HSPA1B, the major allele frequencies were 0.52 for patients and 0.49 for controls, respectively. The allele frequencies did not differ significantly between AP patients with organ failure and those with mild disease, patients with alcohol-induced AP, or those with biliary AP. The patients with septic infectious complications (n = 47) had genotype distribution no different from those with mild, uncomplicated disease (n = 245). The TNF, CD14, and HSPA1B polymorphisms studied seem not to play a role in determining the severity of AP or the risk of alcohol-induced AP and thus do not serve as a tool for predicting disease severity.

Risk factors for recurrent acute alcohol-associated pancreatitis: A prospective analysis

Objective. In an earlier retrospective study we showed that 46% of patients with acute alcoholic pancreatitis had recurrent attacks within 10–20 years, about 30% having a recurrence during the first 3 years. The aim of this prospective follow-up study was to determine the risk factors associated with recurrences. Material and methods. Sixty-eight patients, (59 M, 9 F, mean age 46 years, range 25–71 years) who survived their first acute alcohol-induced pancreatitis from January 2001 to January 2004 volunteered to participate in the study. The diagnostic criteria for acute pancreatitis were epigastric pain, serum amylase >3 times the upper normal range, elevated serum C-reactive protein (CRP), and signs of acute pancreatitis in imaging. Other etiologies were excluded. Alcohol consumption and dependency were detected by the Alcohol Use Disorders Identification Test (AUDIT) and the Short Alcohol Dependence Data (SADD), respectively, and by attempting to evaluate recent use in grams of pure alcohol. Social and demographic data of the patients, smoking, body mass index, and the severity of the pancreatitis were recorded. Serum and fecal markers of the endocrine and exocrine function and secretin-stimulated MRCP were studied. The patients were followed for a median 38 (25–61) months for recurrences, and at the 2-year time-point had a follow-up visit to investigate any changes in alcohol consumption. Results. Seventeen (25%) patients had recurrences of acute alcoholic pancreatitis during the follow-up. Pre-illness alcohol consumption, the severity of the pancreatitis, patient's social or demographic data, pancreatic function tests or morphologic changes in MRCP, or smoking did not correlate with recurrence. None of the 13 patients with consistent total abstinence from alcohol at 2 years developed recurrent pancreatitis compared with 17 out of 51 (33%) patients with at least some alcohol consumption (p=0.02). Use of other sedatives than alcohol before the first attack of pancreatitis was an independent risk factor associated with recurrence (HR = 6.95, 95% CI 2.45–19.72, p<0.001). A lower reduction in dependency on alcohol (less decreased SADD points) during 2 years was associated with a higher recurrence rate (HR = 0.921/each reduced point, 95% CI 0.872–0.974, p=0.004). Conclusions. Contrary to chronic pancreatitis, smoking was not found to be a risk factor for recurrent episodes after the first attack of acute alcoholic pancreatitis. Abstinence from alcohol protects against recurrent pancreatitis. Patients who developed recurrent acute pancreatitis had increased dependency on alcohol, demonstrated by the use of other sedatives in addition to alcohol and supported by the less decreased dependency during the follow-up.

Intestinal Ileus as a Possible Cause of Hypobicarbonatemia

The possible occurrence of metabolic acidosis in patients with intestinal ileus is not well recognized. We describe a patient with acute alcohol-induced pancreatitis and a large transverse colon ileus in which plasma bicarbonate dropped rapidly in the absence of an increase in the plasma anion gap. The urinary anion gap and ammonium excretion were consistent with an appropriate renal response to metabolic acidosis and against the possibility of respiratory alkalosis. The cause of the falling plasma bicarbonate was ascribed to intestinal bicarbonate sequestration owing to the enhancement of chloride-bicarbonate exchange in a dilated paralyzed colon.

THE RECURRENCE OF ALCOHOL INDUCED PANCREATITIS MAY BE REDUCED BY 6-MONTH INTERVENTION THERAPY

Backround: Previously we have shown that continuing alcohol abuse is the most important risk factor for recurrent acute pancreatitis (RP) after the first acute alcohol induced pancreatitis (AAIP). In this prospective random study we investigated whether a repeated intervention at 6-month intervals results in reduced rate of RP. Patients and Methods: Between 2001 and 2005 overall 120 patients (60/group) were included into the study. This number was needed to show the reduction of the expected recurrence rate into half to be significant at p < 0.05 and 80 % power. AAIP was diagnosed with epigastric pain, serum amylase > 3 × UNR, increased CRP, acute pancreatitis in abdominal imaging and heavy alcohol consumption detected with WHO recommended AUDIT-questionnaire and interview. All patients had the intervention against alcohol abuse before discharge. The patients were randomised to study group (repeated outpatient intervention every 6 months for 2 years) or to control group (control visit at 2 years). After the 2-year study period, patients in both groups had a follow-up visit annually to monitor RP. By June 2006 there were 100 patients who had finished at least the 2-year follow-up (82 male, 13 female, mean age 45 y.). Four patients had died for reasons unrelated to pancreatitis. Results: At 2-year follow-up the number of totally abstinent patients was similar (6 vs. 5), but in the study group the reported alcohol consumption had decreased into half from the control group. During the 2-year study period after the AAIP, 6/48 (13%) in the study group compared with 14/48 (29%) in the control group (p < 0.05) had suffered from RP. After the 2-year study period, with the similar follow up at 12-month intervals, RP in study group patients increased the difference after median follow-up of 3,75 years (2-5,5 years) being no more significantly different. Conclusion: This interim analysis of the on-going prospective random trial suggests that repeated intervention against alcohol consumption at 6-month intervals reduces the recurrence rate after the first AAIP when compared to 24-month interval intervention. This effect seems not to maintain after the 2-year study period with return to 12-month follow-up.

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.

Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol.

The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis.

An investigation of whether polymorphisms of cytochrome P4502E1 are genetic markers of susceptibility to alcoholic end-stage organ damage in a chinese population

The human cytochrome P4502E1 gene (P4502E1), coding for an ethanol-inducible nitrosamine-metabolizing P-450, is involved in the metabolism of ethanol and many known carcinogens. Recently, restriction fragment length polymorphisms (RFLPs) within the P4502E1 have been suggested as genetic markers of susceptibility to alcohol-induced liver disease but the previous studies disagree whether alcoholics with c1 or c2 allele are more susceptible to alcohol-induced liver diseases. Using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the RsaI and PstI polymorphism of P4502E1 in 77 Chinese alcoholic patients (54 with alcohol-induced cirrhosis and 23 with acute alcohol-induced pancreatitis) and 164 non-alcoholics and compared them with previously published data. The PCR-RFLPs showed three P4502E1 genotypes: type A, homozygote c1/c1; type B, heterozygote c1/c2; and type C, homozygote c2/c2. The RsaI and PstI polymorphism of P4502E1 were completely linked in both Chinese alcoholics and nonalcoholic controls. The rare allele (c2) occurs at similar frequency of 0.232 and 0.234 (P > .05) in nonalcoholic controls and alcoholics, respectively. The genotype distributions of P4502E1 between Chinese alcoholics and nonalcoholics are not significantly different. The genotype and allele frequencies of P4502E1 for Chinese are significantly different from those of Swedes, European-Americans, and African-Americans, respectively (P < .00001), but very similar to Japanese (P > .05). In conclusion, ethnic variations exist between Asians and Caucasians and between Asians and African-Americans. No allelic variants at loci associated with RsaI/PstI RFLPs result in phenotypes displaying greater susceptibility to alcohol-induced cirrhosis or alcoholism in Chinese populations, which contradicts previous reports from Japanese groups.