Association between chronic pancreatitis and pancreatic cancer at a central hospital in KwaZulu-Natal, South Africa.

BACKGROUND: The frequency of histological chronic pancreatitis (CP) evidence in the resident pancreas of resected periampullary cancers (PACs) has never been studied in Africa. This study aims to describe the spectrum of pathology and outcomes of pancreatic surgeries and address this deficit from a South African central hospital cohort. METHODS: A retrospective audit of patients undergoing pancreatic surgery at Inkosi Albert Luthuli Central Hospital (IALCH) between 2003 and 2023 was conducted. The patient demographics, human immunodeficiency virus (HIV) status, histological subtypes, type and extent of surgery, and 30-day and overall mortality were captured from medical records. The presence of CP in the resident pancreas of patients resected for pancreatic and PAC was obtained from the pathology reports. RESULTS: Of the cohort, 72% were Africans, presenting at an earlier average age than other races. Surgery was performed on 126 (107 for cancer, 19 for CP) patients. Of these, 77 were pancreaticoduodenectomy (PD), of which 34 were for pancreatic ductal adenocarcinoma (PDAC). The prevalence of CP in the resident pancreas was 29.9%, and 55.9% in PDAC. Age was the only factor significantly associated with 30-day mortality, as well as long-term survival amongst patients with pancreatic and PAC. The overall median survival for patients with PAC was seven months; 11 patients are alive. CONCLUSION: In a predominantly African cohort undergoing pancreatic surgery, PDAC presents at a younger age. The high perioperative mortality and low overall survival (OS) in the setting of high CP prevalence in the resident pancreas requires further investigation of its role in the aetiopathogenesis and prognosis in PDAC.

Serum trace elements during treatment in pancreatic cancer patients and their associations with cancer prognosis.

BACKGROUND & AIMS: In this study, we assessed serum trace element concentrations in patients with pancreatic cancer and compared the results to those of healthy controls and patients with chronic pancreatitis. We evaluated the association between trace element concentrations during cancer treatment and the risk of cancer progression and mortality in pancreatic cancer patients. METHODS: A retrospective cohort study was conducted at a tertiary center in Korea. Serum trace element concentrations of cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) were measured at diagnosis using an inductively coupled plasma-mass spectrometry in 124 patients with pancreatic cancer, 50 patients with chronic pancreatitis, and 120 healthy controls. Trace elements were measured after a median of 282.5 (95% confidence interval [CI], 224.0-326.5) days from treatment initiation to assess changes in trace element concentrations during treatment. RESULTS: Serum Co concentrations were significantly higher in patients with chronic pancreatitis and pancreatic cancer compared to healthy controls, while serum Se concentrations were significantly lower. During treatment, serum concentrations of Cu, Se, and Zn significantly decreased in patients with pancreatic cancer. During the follow-up (median 152.5; 95% CI, 142.8-160.0 months), 85.5% of patients experienced progression or relapse, and 84.7% of patients died. Patients with decreased Se and Zn concentrations during treatment had a higher mortality (hazard ratio [HR], 2.10; 95% CI, 1.31-3.38; P = 0.0020 for Se; HR, 1.72; 95% CI, 1.06-2.79; P = 0.0269 for Zn) compared to those with unchanged or increased trace element concentrations during treatment. Patients with a greater reduction in Zn concentrations during treatment had a higher mortality than those with a smaller reduction (HR, 1.59; 95% CI, 1.01-2.52; P = 0.0483). Patients whose Zn status changed from normal to deficient during treatment had an increased mortality (HR, 1.76; 95% CI, 1.16-2.67, P = 0.0084). Patients with multiple (≥2) trace element deficiencies after treatment had poorer outcomes than those with no or single trace element deficiency. CONCLUSIONS: This study revealed that decreases in Se and Zn concentrations during cancer treatment were associated with adverse outcomes in terms of cancer progression and mortality in patients with pancreatic cancer. Further prospective investigations are recommended.

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.

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.

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.

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.

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.

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.

Salvage Islet Auto Transplantation After Relaparatomy.

BACKGROUND: To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery. METHODS: From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy. RESULTS: The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT. CONCLUSIONS: Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

Laparoscopic Total Pancreatectomy With Islet Autotransplantation and Intraoperative Islet Separation as a Treatment for Patients With Chronic Pancreatitis.

Importance: Pain management of patients with chronic pancreatitis (CP) can be challenging. Laparoscopy has been associated with markedly reduced postoperative pain but has not been widely applied to total pancreatectomy with islet autotransplantation (TPIAT). Objective: To examine the feasibility of using laparoscopic TPIAT (L-TPIAT) in the treatment of CP. Design, Setting, and Participants: Thirty-two patients with CP presented for TPIAT at a tertiary hospital from January 1, 2013, through December 31, 2015. Of the 22 patients who underwent L-TPIAT, 2 patients converted to an open procedure because of difficult anatomy and prior surgery. Pain and glycemic outcomes were recorded at follow-up visits every 3 to 6 months postoperatively. Main Outcomes and Measures: Operative outcomes included operative time, islet isolation time, warm ischemia time, islet equivalent (IE) counts, estimated blood loss, fluid resuscitation, and blood transfusions. Postoperative outcomes included length of stay, all-cause 30-day readmission rate, postoperative complications, mortality rate, subjective pain measurements, opioid use, random C-peptide levels, insulin requirements, and glycated hemoglobin level. Results: Of the 32 patients who presented for TPIAT, 20 underwent L-TPIAT (8 men and 12 women; mean [SD] age, 39 [13] years; age range, 21-58 years). Indication for surgery was CP attributable to genetic mutation (n = 9), idiopathic pancreatitis (n = 6), idiopathic pancreatitis with pancreas divisum (n = 3), and alcohol abuse (n = 2). Mean (SD) operative time was 493 (78) minutes, islet isolation time was 185 (37) minutes, and warm ischemia time was 51 (62) minutes. The mean (SD) IE count was 1325 (1093) IE/kg. The mean (SD) length of stay was 11 (5) days, and the all-cause 30-day readmission rate was 35% (7 of 20 patients). None of the patients experienced postoperative surgical site infection, hernia, or small-bowel obstruction, and none died. Eighteen patients (90%) had a decrease or complete resolution of pain, and 12 patients (60%) no longer required opioid therapy at a median follow-up period of 6 months. Postoperative random insulin C-peptide levels were detectable in 19 patients (95%) at a median follow-up of 10.4 months. At a median follow-up of 12.5 months, 5 patients (25%) were insulin independent, whereas 9 patients (45%) required 1 to 10 U/d, 5 patients (25%) required 11 to 20 U/d, and 1 patient (5%) required greater than 20 U/d of basal insulin. The mean (SD) glycated hemoglobin level was 7.4% (0.5%). Conclusions and Relevance: This study represents the first series of L-TPIAT, demonstrating its safety and feasibility. Our approach enables patients to experience shorter operative times and the benefits of laparoscopy, including reduced length of stay and quicker opioid independence.