Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors.

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis.

BACKGROUND: The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. METHODS: In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. RESULTS: The linear model from the differentially expressed blood small EV miR-95-3p divided by miR-26b-5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19-9 (CA19-9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR-95-3p was associated with a "consequence" of "cancer" and miR-26b-5p as a "cause" of "pancreatitis." A subgroup analysis revealed that blood small EV miR-335-5p/miR-340-5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). CONCLUSIONS: This study indicated that blood small EV miR-95-3p/miR-26b-5p and its combination with serum levels of CA19-9 could separate PDAC from CP, and miR-335-5p/miR-340-5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.

Prevalence and Impact of Sarcopenia in Chronic Pancreatitis: A Review of the Literature.

INTRODUCTION: Malnutrition is a common sequela of chronic pancreatitis (CP). Alterations in body composition and the assessment of sarcopenia have gained the interest of clinicians in recent years. There is a scarcity of data currently available concerning sarcopenia in patients with CP. This review aims to investigate the prevalence and impact of sarcopenia in CP. METHODS: Embase and Medline databases were used to identify all studies that evaluated sarcopenia and outcomes in patients with chronic pancreatitis. Due to paucity of data, conference abstracts were included. PRISMA guidelines for systematic reviews were followed. RESULTS: Six studies, with a total of 450 individuals were reviewed. Three full-text studies and three conference abstracts met the predetermined eligibility criteria. The prevalence of sarcopenia in CP from all studies ranged from 17-62%. Pancreatic exocrine insufficiency was associated as an independent and significant risk factor for sarcopenia. Sarcopenia was found to be associated with a reduced quality of life, increased hospitalisation, and reduced survival. It was associated with significantly lower islet yield following total pancreatectomy with islet auto transplantation in CP. CONCLUSION: The review of these existing studies amalgamates the limited data on sarcopenia and its impact on CP. It has shown that sarcopenia is exceedingly prevalent and an important risk factor in CP patients. The data presented emphasises that sarcopenia has a significant prognostic value and should be included in future prospective analyses in the outcomes of CP.

Characterization of patients with advanced chronic pancreatitis using natural language processing of radiology reports.

STUDY AIM: To develop and apply a natural language processing algorithm for characterization of patients diagnosed with chronic pancreatitis in a diverse integrated U.S. healthcare system. METHODS: Retrospective cohort study including patients initially diagnosed with chronic pancreatitis (CP) within a regional integrated healthcare system between January 1, 2006 and December 31, 2015. Imaging reports from these patients were extracted from the electronic medical record system and split into training, validation and implementation datasets. A natural language processing (NLP) algorithm was first developed through the training dataset to identify specific features (atrophy, calcification, pseudocyst, cyst and main duct dilatation) from free-text radiology reports. The validation dataset was applied to validate the performance by comparing against the manual chart review. The developed algorithm was then applied to the implementation dataset. We classified patients with calcification(s) or ≥2 radiographic features as advanced CP. We compared etiology, comorbid conditions, treatment parameters as well as survival between advanced CP and others diagnosed during the study period. RESULTS: 6,346 patients were diagnosed with CP during the study period with 58,085 radiology studies performed. For individual features, NLP yielded sensitivity from 88.7% to 95.3%, specificity from 98.2% to 100.0%. A total of 3,672 patients met cohort inclusion criteria: 1,330 (36.2%) had evidence of advanced CP. Patients with advanced CP had increased frequency of smoking (57.8% vs. 43.0%), diabetes (47.6% vs. 35.9%) and underweight body mass index (6.6% vs. 3.6%), all p<0.001. Mortality from pancreatic cancer was higher in advanced CP (15.3/1,000 person-year vs. 2.8/1,000, p<0.001). Underweight BMI (HR 1.6, 95% CL 1.2, 2.1), smoking (HR 1.4, 95% CL 1.1, 1.7) and diabetes (HR 1.4, 95% CL 1.2, 1.6) were independent risk factors for mortality. CONCLUSION: Patients with advanced CP experienced increased disease-related complications and pancreatic cancer-related mortality. Excess all-cause mortality was driven primarily by potentially modifiable risk factors including malnutrition, smoking and diabetes.

Five-year mortality trends associated with chronic pancreatitis in South Korea: A population based cohort study.

BACKGROUND: Chronic pancreatitis (CP) is associated with all-cause and cancer-related mortality; however, the risk of mortality associated with alcoholic and non-alcoholic CP remains controversial. This study investigated whether CP increased the risk of 5-year all-cause and cancer-specific mortality compared to a control population. METHODS: This population-based study used data from a sample cohort of the National Health Insurance Service (NHIS) database in South Korea. CP was defined as disease code K86.0 (alcohol-induced CP) and K86.1 (other CP and non-alcoholic CP) from the tenth edition of the International Classification of Diseases. RESULTS: The prevalence of chronic alcoholic pancreatitis increased from 0.01% in 2002 to 0.07% in 2015, and the prevalence of chronic non-alcoholic pancreatitis increased from 0.08% in 2002 to 0.50% in 2015. In the 2010 NHIS cohort (n = 826,909), CP was associated with an increased risk of 5-year all-cause mortality (hazard ratio [HR] = 1.25, 95% confidence interval [CI]: 1.25 to 1.66, P < 0.001). Additionally, non-alcoholic CP was associated with an increased risk of 5-year all-cause mortality (HR = 1.47, 95% CI: 1.27 to 1.71, P < 0.001); in contrast, alcohol-induced CP was not significantly associated with mortality risk (P = 0.569). Similar tendencies were observed for the 5-year cancer-related mortality risk. CONCLUSIONS: In South Korea, the prevalence of alcoholic and non-alcoholic CP increased during 2002-2015. CP may be an independent risk factor for 5-year all-cause and cancer-related mortality. In this study, this association was more evident in patients with non-alcoholic CP.

Conservative Treatment of Chronic Pancreatitis: A Practical Approach.

BACKGROUND: Chronic pancreatitis is a long-standing, inflammatory condition of the pancreas that leads to the progressive damage and loss of function of pancreatic parenchyma and to the development of possible locoregional and systemic medical complications. MATERIALS AND METHODS: In this review, we tried to summarize the current evidence on non-surgical treatment trying to suggest a practical approach to the management of chronic pancreatitis. RESULTS: Besides the unclear pathophysiological mechanism and a poorly unknown epidemiology, chronic pancreatitis is a complex syndrome that displays different possible challenges for physicians. Despite being traditionally considered as a benign disease, chronic pancreatitis encompasses 10-year mortality rates which are superior to the ones reported for some of the most common cancers. CONCLUSIONS: Chronic pancreatitis encompasses the management of multiple and complex medical co-morbidities that needs to be understood and addressed in a multidisciplinary specialist context.

Natural course of chronic pancreatitis and predictors of its progression.

BACKGROUND: The natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP. METHODS: This study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model. RESULTS: A total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5-7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4-2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34-0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66-1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03-1.7); p = 0.028] and diabetes[HR:2.7(2.2-3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7-31.2); p < 0.001], smoking-history[HR:6.5(2.2-19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05-0.4); p < 0.001]. CONCLUSION: ACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.

Pancreatic Surgery in Chronic Pancreatitis Complicated by Extrahepatic Portal Hypertension or Cavernous Transformation of the Portal Vein: A Systematic Review.

OBJECTIVES: Chronic pancreatitis produces disabling pain and loss of pancreatic endocrine/exocrine function. Almost half of the patients will need surgery during the course of the disease. Certain conditions, such as extrahepatic portal hypertension or cavernous transformation of the portal vein, can increase the risk of morbidity and mortality. These complications must be borne in mind in the design of the surgical treatment of chronic pancreatitis. This study is a systematic review on the coexistence of chronic pancreatitis and extrahepatic portal hypertension/cavernous transformation in patients undergoing pancreatic surgery. METHODS: We conducted an unlimited search updated on 10 December 2017, which yielded 535 results. We selected 11 articles. RESULTS: Main indication for surgery was intractable pain. Presence of extrahepatic portal hypertension and/or cavernous transformation increased intraoperative bleeding and general postoperative morbidity, though the increase in general morbidity was less when the different postoperative complications were analyzed individually. Case series showed a higher mortality in patients with extrahepatic portal hypertension. CONCLUSION: Little is known about the presence of extrahepatic portal hypertension in patients undergoing pancreatic surgery for chronic pancreatitis. More studies are needed in order to standardize criteria for vascular involvement in patients with chronic pancreatitis, in order to select the surgical technique and, if necessary, to establish contraindications, in this subgroup of patients.

Outcome and long-term quality of life after total pancreatectomy (PANORAMA): a nationwide cohort study.

BACKGROUND: The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients' quality of life. Contemporary data on postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking. METHODS: We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006-2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes. RESULTS: Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P < .05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P = .03) and daily health status (0.83 vs 0.87, P < .01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (<3, 3-5, or >5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes. CONCLUSION: This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes.

Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE.

OBJECTIVE: The aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors. STUDY DESIGN: Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable. RESULTS: Of 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%). CONCLUSIONS: Children with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

How Durable Is Total Pancreatectomy and Intraportal Islet Cell Transplantation for Treatment of Chronic Pancreatitis?

BACKGROUND: A total pancreatectomy and intraportal islet cell autotransplant (TPIAT) is increasingly being offered to patients with chronic pancreatitis (CP). The benefits include removal of the root cause of pain and amelioration of diabetes. However, the long-term durability of this operation remains unclear. STUDY DESIGN: Of the 742 patients who have undergone a TPIAT at our center, 215 who did so between 1998 and 2008 now have at least 10 years of follow-up time and were eligible for this single-center observational study. Our outcomes measures included abdominal pain relief, narcotic use, islet graft function (subdivided into 3 groups: insulin independence; partial graft function, defined by C-peptide level > 0.6 mg/dL; and no function, defined by C-peptide level < 0.6 mg/dL), and health-related quality of life. RESULTS: The 10-year actuarial survival rate was 72%. A BMI > 30 kg/m2 (p = 0.04) predicted 10-year mortality. The rates of pain relief were 82% at 10 years and 90% at 15 years. Narcotic use declined with time: the rates were 50% at 5 years and 37% at 10 years. At 10 years, the rate of insulin independence was 20%; the rate of partial graft function, 32%. Transplantation of islet equivalents/kg > 4,000 was the strongest predictor of islet graft function at 10 years. Pediatric patients were more likely to have islet function than adults (p = 0.01). Health-related quality of life continued to improve at 10 years, even in patients on narcotics. CONCLUSIONS: This represents the first and largest series to examine long-term outcomes (10 years or more) in TPIAT patients. In our series, this dual procedure produced durable pain relief and sustained islet graft function, even past 10 years postoperatively.

Duodenum-preserving pancreatic head resection: A retrospective analysis of the Hamburg Modification.

BACKGROUND: Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. METHODS: We retrospectively evaluated-for long-term outcomes concerning pain control, quality of life, and symptom control-500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. RESULTS: After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0-100), and the global quality of life revealed a median of 92 (0-100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. CONCLUSION: Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.

PANCREATICODUODENECTOMY: IMPACT OF THE TECHNIQUE ON OPERATIVE OUTCOMES AND SURGICAL MORTALITY.

BACKGROUND: Pancreaticoduodenectomy (PD) is a procedure associated with significant morbidity and mortality. Initially described as gastropancreaticoduodenectomy (GPD), the possibility of preservation of the gastric antrum and pylorus was described in the 1970s. AIM: To evaluate the mortality and operative variables of PD with or without pyloric preservation and to correlate them with the adopted technique and surgical indication. METHOD: Retrospective cohort on data analysis of medical records of individuals who underwent PD from 2012 through 2017. Demographic, anthropometric and operative variables were analyzed and correlated with the adopted technique (GPD vs. PD) and the surgical indication. RESULTS: Of the 87 individuals evaluated, 38 (43.7%) underwent GPD and 49 (53.3%) were submitted to PD. The frequency of GPD (62.5%) was significantly higher among patients with pancreatic neoplasia (p=0.04). The hospital stay was significantly shorter among the individuals submitted to resection due to neoplasias of less aggressive behavior (p=0.04). Surgical mortality was 10.3%, with no difference between GPD and PD. Mortality was significantly higher among individuals undergoing resection for chronic pancreatitis (p=0.001). CONCLUSION: There were no differences in mortality, surgical time, bleeding or hospitalization time between GPD and PD. Pancreas head neoplasm was associated with a higher indication of GPD. Resection of less aggressive neoplasms was associated with lower morbidity and mortality.

Chronic pancreatitis and resectable synchronous pancreatic carcinoma: A survival analysis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a risk factor for pancreatic cancer (PDAC). CP and PDAC are characterized by an abundance of desmoplastic tissue. The effect of this pancreatic desmoplastic tissue on PDAC is poorly understood. In literature, negative and positive effects on the natural course of PDAC have been discussed. The present analysis aims to assess the impact of CP on patients with resectable synchronous PDAC regarding short- and long-term survival. METHODS: All patients who underwent pancreatic resection at our institution from January 2005 to January 2014 were retrospectively evaluated. Definition of CP was based on clinical and radiological aspects and histological confirmation as used previously. We identified patients with CP, CP and PDAC, and PDAC without CP and compared perioperative course and survival. Statistical analysis was performed by chi-square, Kruskal-Wallis/Mann-Whitney-U and Breslow survival analysis. P-values <0.05 were defined as statistically significant. RESULTS: 159 patients met our inclusion criteria for CP. 49 of them (30.8%) had synchronous PDAC. 145 patients had PDAC without a history of CP. There was a more advanced nodal involvement in PDAC patients with CP. Perioperative outcome and long-term survival of PDAC patients with and without CP did not differ significantly. CONCLUSION: In a large clinical series CP had no impact on survival of patients with PDAC after resection with curative intent.

Long-term outcomes of 6-mm diameter fully covered self-expandable metal stents in benign refractory pancreatic ductal stricture.

BACKGROUND AND AIM: Fully covered self-expandable metal stent (FCSEMS) placement has been tried for pancreatic ductal strictures in chronic pancreatitis. However, the long-term outcome of this procedure remains unknown. The present study aimed to investigate the procedural and long-term outcomes of FCSEMS placement in patients with benign refractory pancreatic ductal strictures. METHODS: Between August 2011 and September 2015, 18 patients underwent endoscopic treatment with FCSEMS for benign refractory pancreatic ductal stricture. Technical success, clinical success, radiological success, and adverse events were assessed. RESULTS: Stent placement was successful in all patients (technical success rate, 100%). Reduction in pain score of >50% was achieved in 15 of the 18 patients (clinical success rate, 83.3%). In all patients, stents could easily be removed at a median of 7.5 months (interquartile range [IQR], 6-13.6) after their insertion. FCSEMS migration did not develop in any patient. Ductal stricture was improved in 15 patients (radiological success rate, 83.3%). After definite stent removal, 13 of the 15 (86.7%) patients who had responded to pancreatic stenting maintained the response during follow up (median of 47.3 months; IQR, 7.4-57.1). CONCLUSIONS: FCSEMS placement appears to be safe and effective for the treatment of benign refractory pancreatic ductal strictures as it can provide persistent improvement in the stricture in long-term follow up.

The relationship between the use of statins and mortality, severity, and pancreatic cancer in Danish patients with chronic pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is associated with a shortened life expectancy. Statins have anti-inflammatory properties and we aimed to evaluate the association between the use of statins and the risk of death, progression of CP, and pancreatic cancer in patients with CP. PATIENTS AND METHODS: We carried out a nested case-cohort study and included patients with CP. We used claims of proton pump inhibitors as an active comparator. Patients with cirrhosis or cancer were excluded. We evaluated the exposure on the basis of pharmacy claims of statins. We used propensity score matching with a statins : nonstatins ratio of 1 : 1. RESULTS: A total of 4807 patients were eligible for propensity score matching; 33% were women and the mean (SD) age at cohort entry was 56 (10) years. During follow-up, a total of 2073 (43%) patients had died and the risk of death was significantly lower among patients using statins versus no statins among 678 matched patients [hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.49-0.83]. Use of statins versus no statins was associated with decreased progression of CP, with an HR of 0.21 (95% CI: 0.17-0.26). Pancreatic cancer occurred in 117 (2.4%) patients and we found a lower risk of pancreatic cancer in statin-treated patients compared with no statins, with a HR of 0.21 (95% CI: 0.06-0.70). CONCLUSION: In this nationwide study, we found lower risks of mortality, disease progression, and pancreatic cancer in patients with CP using statins. The study is limited by its retrospective design, but supports the hypothesis that statins may affect the course of CP.

Patient Selection for Total Pancreatectomy with Islet Autotransplantation in the Surgical Management of Chronic Pancreatitis.

BACKGROUND: Best practice to select patients with chronic pancreatitis for surgical management with total pancreatectomy with islet autotransplantation (TPIAT) is in evolution as new discoveries are made in the pathogenesis of chronic pancreatitis. STUDY DESIGN: A prospectively maintained database of patients undergoing TPIAT was reviewed. Islet function was inferred from daily insulin requirement. Pain relief was evaluated by healthcare use and narcotic use. Quality of life (QOL) was measured with the RAND 12-Item Short Form Survey. RESULTS: One hundred and ninety-five patients (141 women, aged 40.3 years, BMI 26.5 kg/m2) underwent TPIAT. Mean duration of disease before operation was 8.1 years. Fifty-six (29%) patients had pancreatic operations before TPIAT, 37 (19%) patients were diabetic preoperatively, and 52 (27%) patients were smokers. A mean of 3,253 islet equivalents transplanted/kg were harvested. Insulin independence was achieved in 29%, 28%, and 23% of patients at 1, 2, and 5 years postoperative. Nonsmokers with a shorter duration of chronic pancreatitis and no earlier pancreas operation were more likely to be insulin free. Median number of preoperative emergency department visits and hospitalizations were 6.6 and 4.3 annually, respectively, compared with 0 at 1, 2, and 5 years postoperative. Median oral morphine equivalents were 214 mg/kg preoperation and 60, 64, 69, at 1, 2, 5 years postoperative. Preoperative, 1, 2, 5 years postoperative QOL scores were 29, 36, 34, and 33 (physical; p < 0.01) and 39, 44, 42, and 42 (mental health; p < 0.02). Genetic pancreatitis patients were more often narcotic free and had better QOL than patients with pancreatitis of other causes. At 5 years, overall survival was 92.3%. CONCLUSIONS: Total pancreatectomy with islet autotransplantation is a durable operation, with islet function, pain relief, and QOL improvements persisting to 5 years postoperative. Patients with genetic pancreatitis, short duration of disease, and nonsmokers have superior outcomes.

Increased Risk of Mortality Associated With Pancreatic Exocrine Insufficiency in Patients With Chronic Pancreatitis.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is a common serious complication in chronic pancreatitis (CP); however, little is known about its effect on mortality in these patients. In this study, we assessed the mortality risk of PEI in patients with CP. STUDY: A prospective, longitudinal cohort study conducted in patients with CP under long-term follow-up. CP and PEI were diagnosed using pancreatic imaging and the C-labeled mixed triglyceride breath test, respectively. Multivariate analysis was performed to evaluate the impact of PEI and other clinical features on mortality risk. RESULTS: Patients (N=430) were analyzed (79.1% male; mean age, 47.8 y) during a mean follow-up of 8.6±4.6 years. PEI prevalence was 29.3% and mortality was 10.9%. Most frequent causes of death were cancer (40.4%), infection (21.3%), and acute cardiovascular event (14.9%). Multivariate analyses showed associations between increased mortality and presence of PEI [hazard ratio (HR), 2.59; 95% confidence interval (CI), 1.42-4.71; P<0.003], liver cirrhosis (HR, 3.87; 95% CI, 1.95-7.69; P<0.001), age at diagnosis (HR, 1.05; 95% CI, 1.03-1.09; P<0.001), toxic etiology of CP (HR, 3.11; 95% CI, 1.11-8.70; P<0.05) and respiratory comorbidity (HR, 2.19; 95% CI, 1.12-4.31; P<0.03). Nutritional markers were significantly lower in patients with PEI versus those without PEI (P<0.001) and in those who died versus survivors (P<0.001). CONCLUSIONS: PEI was a significant independent risk factor for mortality in patients with CP. These results support further research into the optimal treatment of PEI to reduce mortality in this population.

Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis.

Cancer stem cells (CSC) play an important role in pancreatic carcinogenesis and prognosis. The study aimed at examining the expression of CD24, CD44, and CD133 in human PDAC and CP in order to evaluate its clinicopathological correlations and the clinical significance. Surgical specimens from 23 patients with PDAC and 15 patients with chronic pancreatitis after pancreatic resection were stained with CD24, CD44, and CD133 antibodies. The intensity of staining was scored from 0 (negative) to 3 (strongly positive). Results. Mean CD24 staining score in PDAC was 1.38 ± 0.76 and was significantly higher than that in CP: 0.70 ± 0.53 (p < 0.01); CD44 score in PDAC was 2.23 ± 0.42 and was significantly higher than that in CP: 1.87 ± 0.55 (p < 0.05); CD133 score 0.93 ± 0.58 was not different from CP: 0.71 ± 0.43 (p > 0.05). CD44 immunoreactivity was significantly higher (p < 0.05) in pT1 and pT2 patients together as regards pT3: 2.45 ± 0.37 versus 2.06 ± 0.38 as well as in N0 patients compared to N1 patients: 2.5 ± 0.38 versus 2.04 ± 0.34. Conclusions. CD24 and CD44 are upregulated in human pancreatic cancer compared to chronic pancreatitis. CD44 immunoreactivity decreases with the tumor advancement and may represent the negative PDAC prognostic factor. Each CSC marker was differently related to PDAC advancement. CD133 may lack clinical significance in PDAC.

Pancreatic head excavation for tissue diagnosis may reduce unnecessary pancreaticoduodenectomies in the setting of chronic pancreatitis.

BACKGROUND: The necessity to obtain a tissue diagnosis of cancer prior to pancreatic surgery still remains an open debate. In fact, a non-negligible percentage of patients undergoing pancreaticoduodenectomy (PD) for suspected cancer has a benign lesion at final histology. We describe an approach for patients with diagnostic uncertainty between cancer and chronic pancreatitis, with the aim of minimizing the incidence of PD for suspicious malignancy finally diagnosed as benign disease. METHODS: Eighty-eight patients (85.4%) with a clinicoradiological picture highly suggestive for malignancy received formal PD (group 1). Fifteen patients (14.6%) in whom preoperative diagnosis was uncertain between pancreatic cancer and chronic pancreatitis underwent pancreatic head excavation (PHEX) for intraoperative tissue diagnosis (group 2): those diagnosed as having cancer received PD, whereas those with chronic pancreatitis received pancreaticojejunostomy (PJ). RESULTS: No patient received PD for benign disease. All patients in group 1 had adenocarcinoma on final histology. Eight patients of group 2 (53.3%) received PD after intraoperative diagnosis of cancer, whereas 7 (46.7%) received PJ because no malignancy was found at introperative frozen sections. No signs of cancer were encountered in patients receiving PHEX and PJ after a median follow-up of 42 months. Overall survival did not differ between patients receiving PD for cancer in the group 1 and those receiving PD for cancer after PHEX in the group 2 (P=0.509). CONCLUSION: Although the described technique has been used in a very selected group of patients, our results suggest that PHEX for tissue diagnosis may reduce rates of unnecessary PD, when the preoperative diagnosis is uncertain between cancer and chronic pancreatitis.