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

BACKGROUND: Soluble 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. METHODS: One 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. RESULTS: P-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%. CONCLUSIONS: Preoperative 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.

Thirty-Day Readmission Among Patients with Alcoholic Acute Pancreatitis.

BACKGROUND/OBJECTIVES: Alcoholic acute pancreatitis (AAP) comprises the second most common cause of acute pancreatitis in the USA, and there is lack of data regarding 30-day specific readmission causes and predictors. We aim to identify 30-day readmission rate, causes, and predictors of readmission. METHODS: Retrospective analysis of the 2016 National Readmission Database of adult patients readmitted within 30 days after an index admission for AAP. RESULTS: Totally, 76,609 AAP patients were discharged from the hospital in 2016. The 30-day readmission rate was 12%. The main cause of readmission was another episode of AAP. Readmission was not associated with higher mortality (1.3% vs. 1.2%; P = 0.21) or prolonged length of stay (5.2 vs. 5.0 days; P = 0.06). The total health care economic burden was $354 million in charges and $90 million in costs. Independent predictors of readmission were having Medicaid insurance, a Charlson comorbidity index score ≥ 3, use of total parenteral nutrition, opioid abuse disorder, prior pancreatic cyst, chronic alcoholic pancreatitis, and other chronic pancreatitis. Obesity was associated with lower odds of readmission. CONCLUSION: Readmission rate for AAP is high and its primary cause are recurrent episodes of AAP. Alcohol and substance abuse pose a high burden on our health care system. Public health strategies should be targeted to provide alcohol abuse disorder rehabilitation and cessation resources to alleviate the burden on readmission, the health care system and to improve patient outcomes.

Risk factors for the concomitant occurrence of alcoholic chronic pancreatitis and alcoholic liver cirrhosis: a 10-years cohort study at a tertiary hospital in China.

OBJECTIVE: Concomitant occurrence of alcoholic chronic pancreatitis (ACP) and alcoholic liver cirrhosis (ALC) is rare with few reported cases. The present study aimed to identify the potential risk factors of chronic pancreatitis (CP) and liver cirrhosis (LC) in ALC patients and ACP patients, respectively. METHODS: A retrospective analysis was performed on 536 patients with CP and 647 ALC patients without CP (Group A). Among the 536 CP patients, 213 ACP cases were divided into two groups: ACP with LC (Group B, n = 52) and ACP without LC (Group C, n = 161). A comparison between Group A and B was carried out to identify the potential risk factors of CP in ALC patients, while Group B and C were compared to determine the independent risk factors of LC in ACP patients. RESULTS: Concomitant occurrence of ACP and ALC accounted for 24.4% (52/213) in this cohort. Significant risk factors for CP in ALC patients included smoking [odds ratio (OR), 2.557; 95% confidence interval (CI): 1.531-5.489; P = 0.003] and multiple bouts of acute pancreatitis (OR, 4.813; 95% CI: 3.625-12.971; P < 0.001). Hepatitis B virus (HBV) infection (OR, 4.237; 95% CI: 1.742-7.629; P = 0.012) was the only independent risk factor associated with LC in ACP patients. CONCLUSION: HBV infection exacerbated liver damage in ACP patients. Alcoholic patients who smoked and suffered from ongoing bouts of acute pancreatitis are prone to develop CP.

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

BACKGROUND: Soluble 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. METHODS: Eighty-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. RESULTS: P-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. CONCLUSIONS: P-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.

Alcohol-related chronic exocrine pancreatic insufficiency: diagnosis and therapeutic management. A proposal for treatment by the Italian Association for the Study of the Pancreas (AISP) and the Italian Society of Alcohology (SIA).

Current estimates of the prevalence of chronic pancreatitis, one of the most common causes of exocrine pancreatic insufficiency, are in the range of 3-10 per 100,000 people in many parts of the world. Alcohol consumption is a very important risk factor for exocrine pancreatic insufficiency and is involved in nearly half of all cases. The main hypothesis regarding the role of chronic alcohol consumption in pancreatitis is that there must be additional environmental or genetic risk factors involved for ongoing damage to occur. Treatment of patients with alcohol-related exocrine pancreatic insufficiency is complex, as the patient has two concomitant pathologies, alcohol-use disorder (AUD) and exocrine pancreatic insufficiency/chronic pancreatitis. Alcohol abstinence is the starting point for treatment, although even this along with the most advanced therapies allow only a slowdown in progression rather than restoration of function. This position paper of the Italian Association for the Study of the Pancreas and the Italian Society of Alcohology provides an overview of the pathogenesis of alcohol-related pancreatitis and discuss diagnostic issues. Treatment options for both exocrine pancreatic insufficiency/chronic pancreatitis (with a focus on pancreatic enzyme replacement therapy) and AUD (acamprosate, disulfiram, oral naltrexone, long-acting injectable naltrexone, sodium oxybate, nalmefene, baclofen, and psychosocial interventions) are also reviewed.

The different course of alcoholic and idiopathic chronic pancreatitis: A long-term study of 2,037 patients.

BACKGROUND: Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP). METHODS: CP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated. RESULTS: A total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients. CONCLUSION: The long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.

Acute Pancreatitis: Etiology, Pathology, Diagnosis, and Treatment.

Acute pancreatitis is a fascinating disease. In the United States, the two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. C-reactive protein, pro-calcitonin, and the Bedside Index for Severity of Acute Pancreatitis appeared to be the best tools for the early and accurate diagnosis of severe pancreatitis. Early laparoscopic cholecystectomy is indicated for patients with mild gallstone pancreatitis. For patients who are going to have a prolonged hospitalization, enteral nutrition is preferred. Total parenteral nutrition should be reserved for patients who cannot tolerate enteral nutrition. Prophylactic antibiotics are not indicated for patients with pancreatic necrosis. Surgical intervention for infected pancreatic necrosis should be delayed as long as possible to improve patient outcomes.

Endovascular Treatment of Visceral Artery Pseudoaneurysms in Patients with Chronic Pancreatitis: Our Single-Center Experience.

BACKGROUND: To analyze our experience in endovascular treatment as first-line approach for severe and acute hemorrhage in patients with chronic pancreatitis. METHODS: From 2010 to 2016 at our institution, 12 males (mean age 66 years) with bleeding pseudoaneurysms (PSAs) underwent urgent visceral angiography and endovascular treatment. All patients had chronic pancreatitis. True visceral artery aneurysms and PSAs arising after surgery were excluded from the study. RESULTS: Pancreatitis was caused by alcohol abuse in 9 (9/12, 75%) patients and biliary lithiasis in 3 (3/12, 25%). Involved arteries were gastroduodenal (5/12, 50%), splenic (2/12, 16%), common hepatic (2/12, 16%), middle colic (1/12, 9%), and celiac trunk (1/12, 9%). All patients underwent computed tomography angiography (CTA) scan and visceral angiography followed by endovascular treatment using different devices. Technical success rate was 100%. Bleeding was stopped in all patients, and no one required reembolization. No major complications occurred. There were 2 complications associated with the endovascular procedure: in one case, a coil migration and in another case, in-stent restenosis at 6 months. Follow-up included CTA performed during hospitalization and at 6 months after the procedure. CONCLUSIONS: Our experience confirms the role of CTA and visceral angiography as diagnostic and therapeutic tool, respectively.

Pancreatoduodenectomy for groove pancreatitis Report of two cases.

Groove pancreatitis is a rare condition with patients having clinical characteristics similar to those of chronic pancreatitis. Differentiating on clinical and radiological basis between groove pancreatitis and paraduodenal head cancer can be extremely challenging. Due to diagnostic uncertainty and to poor response to medical treatment surgery may offer these patients the best chance of cure. As the main localization of the inflammatory process is at the groove between the duodenum and the head of the pancreas, pancreato-duodenectomy is proposed as the most reliable surgical procedure. We report about two patients presenting with clinical and radiological features suggesting a groove pancreatitis in which control of symptoms was achieved by pancreatoduodenectomy. KEY WORDS: Groove pancreatitis, Paraduodenal pancreatic cancer.

Serum Carbohydrate-Deficient Transferrin in Pancreatic Diseases of Different Etiologies.

BACKGROUND: The aim of this study was to find out whether pancreatic diseases invalidate the use of CDT for the detection of high alcohol intake and if CDT can distinguish between alcoholic and non-alcoholic pancreatitis. METHODS: The study was carried out on 110 patients with pancreatic diseases. Serum CDT was determined using the N Latex CDT test. RESULTS: The mean relative (%) and absolute (mg/L) CDT levels in acute and chronic pancreatitis were significantly higher than in controls and patients with primary pancreatic cancer. No significant difference was found in CDT concentrations between acute and chronic pancreatitis. The relative and absolute CDT concentrations in alcohol-induced pancreatitis were significantly higher compared to the controls and biliary-induced pancreatitis. CONCLUSIONS: Acute and chronic alcoholic pancreatitis, but not biliary pancreatitis, may affect CDT levels. Pancreatitis does not invalidate the use of CDT as a marker of alcohol abuse. CDT can be a useful test for distinguishing alcoholic from non-alcoholic pancreatitis. Changes in CDT level indicate disturbances in transferrin glycosylation in the course of alcoholic pancreatic diseases.

[Scrotal Mass as a Rare Initial Manifestation of Necrotising Pancreatitis]. / Skrotale Raumforderung als seltene Erstmanifestation einer nekrotisierenden Pankreatitis.

A scrotal mass as initial manifestation of necrotising pancreatitis is very rare. In addition, the diagnosis is very difficult because diseases that occur more frequently produce similar symptoms. Therefore, it is very important to think about rare entities in the differential diagnosis for testicular pain.

Alcohol Abuse and Pancreatic Diseases: An Overview.

BACKGROUND: Alcohol is one of the etiological factors of chronic pancreatitis and there is evidence that acute pancreatitis is the first episode of preexisting chronic pancreatitis and is sometimes not evident from a clinical point of view. The diagnosis of acute pancreatitis is based on the presence of abdominal pain, serum increase of pancreatic enzymes or their presence in urine and/or the presence of alterations of the pancreas imaging. AIMS: To revise actual knowledge on the relationship between alcohol use and pancreatic diseases benign as well as malignant. RESULTS: In occasional drinkers, levels of serum amylase were found to be abnormally high in approximately 13% of subjects, while pancreatic isoamylase and lipase were found to be abnormally high in serum in only 2%. The reason might be related to the fact that alcohol can affect the salivary glands. In chronic alcoholics without abdominal pain, amylase and lipase in serum are elevated in 14% of subjects and, in patients with alcoholic acute pancreatitis, pancreatic amylase and isoamylase are elevated in 94% of cases and lipase is generally more sensitive (100% of cases). CONCLUSIONS: Chronic abuse of alcohol, but not occasional alcoholic intoxication, causes pancreatic damage. Regarding pancreatic neoplasms, the role of alcohol is under debate in ductal pancreatic adenocarcinoma as well as in pancreatic neuroendocrine tumors. Few relevant patents are also described in this review.

Heavy Smoking Is Associated With Lower Age at First Episode of Acute Pancreatitis and a Higher Risk of Recurrence.

OBJECTIVE: There is limited data on cigarette smoking and the risk of acute pancreatitis (AP). We evaluated the influence of cigarette smoking on AP risk and clinical presentation in a large cohort of Veteran's Administration (VA) patients. METHODS: Retrospective study of VA patients from 1998 to 2007. Exclusion criteria included (1) history of chronic pancreatitis (n = 3222) or gallstones (n = 14,574) and (2) age younger than 15 years (n = 270). A 2-year washout period was used to exclude patients with pre-existing recurrent AP. RESULTS: The study included 484,624 patients. From 2001 to 2007, a total of 6799 (1.4%) patients had AP. Alcohol (risk ratio, 4.20) and smoking (risk ratio, 1.78) were independent significant risk factors of AP on multiple regression analysis. Smoking increased the risk of AP in both nonalcoholics (0.57% vs 1.1%) and alcoholics (2.6% vs 4.1%). Smoking was associated with younger mean age at first episode of AP and higher likelihood of recurrent AP (≥4 episodes) in both nonalcoholics and alcoholics. The interval between recurrent episodes was not altered by alcohol or smoking. CONCLUSIONS: In a large cohort of VA patients, smoking is an independent risk factor for AP and augmented the effect of alcohol on the risk, age of onset, and recurrence of AP.

Alcohol Consumption and the Risk for Developing Pancreatitis: A Case-Control Study in Japan.

OBJECTIVE: This study aimed to estimate the association of alcohol consumption and pancreatitis in Japan. METHODS: We performed a nationwide case-control study, which included 982 patients (574 patients with acute pancreatitis and 408 patients with chronic pancreatitis) and 1015 controls who were individually matched for sex, age, hospital, and time of their first hospital visit. Conditional logistic regression was used to assess the association of alcohol consumption and smoking with pancreatitis. RESULTS: The patients had a mean (SD) age of 57.6 (17.0) years; 71.8% were male. Compared with nondrinkers, alcohol consumption of less than 20 g/d was not associated with the risk for total pancreatitis (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.7-1.4). In patients with acute pancreatitis, the ORs (95% CI) for alcohol consumption of 20 ≤ ∼ < 40 g/d, 40 ≤ ∼ < 60 g/d, 60 ≤ ∼ < 80 g/d, 80 ≤ ∼ < 100 g/d, and 100 g/d or greater were 1.7 (0.9-3.0), 3.1 (1.6-5.9), 4.2 (2.1-8.2), 5.3 (2.4-12.0), and 6.4 (3.4-12.4), respectively. In patients with chronic pancreatitis, the ORs (95% CI) for alcohol consumption of 20 ≤ ∼ < 40 g/d, 40 ≤ ∼ < 60 g/d, 60 ≤ ∼ < 80 g/d, 80 ≤ ∼ < 100 g/d, and 100 g/d or greater were 2.6 (1.2-5.5), 3.2 (1.5-7.1), 9.2 (4.1-20.3), 13.0 (5.3-31.6), and 19.6 (8.2-46.8), respectively. CONCLUSIONS: Our study precisely measured the quantitative effect of alcohol on the risk for developing pancreatitis.

Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the development of cystic fibrosis, is known as a pancreatitis susceptibility gene. Direct DNA sequencing of PCR-amplified CFTR gene segments is a first-line method to detect unknown mutations, but it is a tedious and labor-intensive endeavor given the large size of the gene (27 exons, 1,480 amino acids). Next-generation sequencing (NGS) is becoming standardized, reducing the cost of DNA sequencing, and enabling the generation of millions of reads per run. We here report a comprehensive analysis of CFTR variants in Japanese patients with chronic pancreatitis using NGS coupling with target capture. METHODS: Exon sequences of the CFTR gene from 193 patients with chronic pancreatitis (121 idiopathic, 46 alcoholic, 17 hereditary, and nine familial) were captured by HaloPlex target enrichment technology, followed by NGS. RESULTS: The sequencing data covered 91.6 % of the coding regions of the CFTR gene by ≥ 20 reads with a mean read depth of 449. We could identify 12 non-synonymous variants including three novel ones [c.A1231G (p.K411E), c.1753G>T (p.E585X) and c.2869delC (p.L957fs)] and seven synonymous variants including three novel ones in the exonic regions. The frequencies of the c.4056G>C (p.Q1352H) and the c.3468G>T (p.L1156F) variants were higher in patients with chronic pancreatitis than those in controls. CONCLUSIONS: Target sequence capture combined with NGS is an effective method for the analysis of pancreatitis susceptibility genes.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis.

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN). METHODS: Forty patients with mild AP, 40 patients with alcoholic CP, 33 patients with WOPN and 40 healthy subjects were examined. Serum concentrations of platelet derived growth factor BB (PDGF-BB), transforming growth factor ß-1 (TGFß-1), chemerin and high-mobility group box chromosomal protein 1 (HMBG1) were assayed by enzyme linked immunosorbent assay. RESULTS: Patients with mild AP and those with WOPN had significantly lower serum levels of PDGF-BB compared to healthy subjects (4.0 ± 0.61 ng/mL vs 6.2 ± 0.76 ng/mL, P = 0.027, and 1.60 ± 0.31 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001, respectively), while CP was associated with higher serum levels of PDGF-BB (12 ± 1.3 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001). Circulating TGFß-1 and chemerin levels were elevated in CP patients (57 ± 3.6 ng/mL vs 39 ± 3.6 ng/mL, P < 0.001 and 73 ± 7.2 ng/mL vs 48 ± 2.3 ng/mL, P < 0.001, respectively), but not in patients with AP and WOPN. No significant changes in serum HMBG1 levels were found either in patients with AP, WOPN or CP. CONCLUSION: The serum levels of some growth factors and cytokines differ significantly in AP, WOPN and CP. These data suggest that selected growth factors and cytokines may be considered as potential diagnostic biomarkers in patients with pancreatic diseases.