Chronic Pancreatitis Cancer Research Articles

Pancreatic Cancer in Chronic Pancreatitis: Pathogenesis and Diagnostic Approach.

Chronic pancreatitis is one of the main risk factors for pancreatic cancer, but it is a rare event. Inflammation and oncogenes work hand in hand as key promoters of this disease. Tobacco is another co-factor. During alcoholic chronic pancreatitis, the cumulative risk of cancer is estimated at 4% after 15 to 20 years. This cumulative risk is higher in hereditary pancreatitis: 19 and 12% in the case of PRSS1 and SPINK1 mutations, respectively, at an age of 60 years. The diagnosis is difficult due to: (i) clinical symptoms of cancer shared with those of chronic pancreatitis; (ii) the parenchymal and ductal remodeling of chronic pancreatitis rendering imaging analysis difficult; and (iii) differential diagnoses, such as pseudo-tumorous chronic pancreatitis and paraduodenal pancreatitis. Nevertheless, the occurrence of cancer during chronic pancreatitis must be suspected in the case of back pain, weight loss, unbalanced diabetes, and jaundice, despite alcohol withdrawal. Imaging must be systematically reviewed. Endoscopic ultrasound-guided fine-needle biopsy can contribute by targeting suspicious tissue areas with the help of molecular biology (search for KRAS, TP53, CDKN2A, DPC4 mutations). Short-term follow-up of patients is necessary at the clinical and paraclinical levels to try to diagnose cancer at a surgically curable stage. Pancreatic surgery is sometimes necessary if there is any doubt.

Pancreatic cancer in chronic pancreatitis – the diagnostic and therapeutic dilemma; an overview of cases

Introduction: Any mass in chronic pancreatitis (CP) is a difficult diagnostic and therapeutic problem. The aim of the study is a) to use our own group to determine the actual incidence of non-malignant masses in CP where any mass is highly suspected of being malignant; and b) to determine the actual incidence of malignant tumors in CP. Methods: We present a retrospective analysis of our group of patients operated in 2015–2019 for CP, a mass in CP and suspected malignancy in the mass in CP. Additionally, we present difficult cases in terms of preoperative diagnosis. Results: Thirty-three of 340 (9.7%) pancreatic resection were done due to any form of chronic pancreatitis in 2015–2019. A mass in the pancreatic head was present in 16 (48%) patients; of these, pancreatic ductal adenocarcinoma (PDAC) was suspected in 10 (62%) patients based on EUS, CT or PETCT, and also based on positive tissue diagnosis using EUS-FNA in 6 cases. Bypass or Frey procedure were done in 59 patients (HJA, PJA, Frey). Preoperative tissue sampling was done in 8 (13%) patients and malignancy was suspected in 25%. Intraoperatively, malignancy was confirmed only in one patient assessed as non-malignant in the preoperative period. The clinical course in 3 other patients undergoing HJA, although tumor-free at the time of the surgery, indicated PDAC in CP. Conclusion: The ability to detect malignant cells in a mass in CP remains poor even using all of the available sophisticated methods and the success depends on many variable factors. The rate of “unnecessary” right-sided resections of a mass in CP reached 48% in our patient group, while the rate of resections which should have been performed instead of bypass procedures was 7%. A certain percentage of the so-called excessive pancreatic resections, as well as the failure to perform a resection due to an undetected/unrecognized pancreatic tumor in CP should continue to be expected.

Surveillance for Pancreatic Cancer in Chronic Pancreatitis

Pancreatic cancer can arise in the background of chronic pancreatitis (CP). The relative risks for pancreatic cancer in CP vary considerably according to other contributing factors such as disease duration, excess alcohol consumption, tobacco consumption, eating habits, physical activity, and late-onset diabetes. The incidence of pancreatic cancer is estimated to be about 10 per 105 per year, and the incidence and prevalence of CP are estimated to be 5-12 per 105 and 50 per 105 per year, respectively. The pooled relative risk estimates for pancreatic cancer in CP patients range from 2.7 to 13.3. Subsets of CP subjects with a family history of pancreatic cancer or those with newly developed diabetes over the age of 50 have a higher risk for pancreatic cancer. However, the prevalence of pancreatic cancer is not high enough to justify general screening of the adult CP population. Thus, it is necessary to select subsets of CP cohorts with a significantly high risk of pancreatic cancer. We need a better overall disease model that can define the interaction of multiple risk factors and their cumulative or potential effects on pancreatic cancer.

International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

BackgroundPatients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. MethodsThe international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach’s alpha reliability coefficient. ResultsIn the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. ConclusionsPatients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation.

RESULTS OF SURGICAL TREATMENT OF PATIENTS WITH CHRONIC PANCREATITIS AND THE RISK OF CANCER AFTER SURGICAL TREATMENT

The aim: To analyze results of surgical treatment of patients with chronic pancreatitis (CP) and to assess the causes of pancreatic cancer after surgical treatment. Materials and methods: 137 patients had duodenum-preserving resections of the pancreas. Results: In the histological examination of the pancreas it was established that the growth of fibrous tissue was registered in patients with CP., which in 19 (13.8%) almost completely replaced the acinar tissue. In the long term after the operation from 6 months to 2 years in 8 patients (5.8%) pancreatic cancer was detected. Possible causes of tumor origin were analyzed, the value of preservation of ductal hypertension, which affects the state of the duct’s epithelium, was established. The most commonly used for treatment of chronic pancreatitis the Frey surgery removed pancreatic hypertension but in two patients during the operation an insufficient volume of the pancreatic head was reconstructed. In the case of the abandonment of a large array of fibrous tissue, local hypertension was retained in the region of the ductal structures of the head, which led to the transformation of the duct epithelium. An essential factor in the problem of the preservation of pancreatic hypertension were the stenosis of pancreatic intestinal anastomoses, they arose in the long term in 4 operated patients. With stenosis of anastomosis after duodenum-preserving resection both the hypertension factor and the regeneration factor could be realized, which under certain circumstances might be significant. Conclusion: After resection of the pancreas for CP cancer was diagnosed in 5.8% of patients. The main method of preventing the risk of cancer was performing the Frey surgery for CP eliminating pancreatic hypertension in the head region of the pancreas. Diagnosis of stenosis in the late period after resection of the pancreas was an important element in the prevention of recurrence of cancer since a timely reconstructive operation could improve the drainage of duct structures.

Incidence of and risk factors for pancreatic cancer in chronic pancreatitis: A cohort of 1656 patients

BackgroundRisk of pancreatic cancer may increase in chronic pancreatitis patients. AimsThis study aimed to identify the incidence of and risk factors for pancreatic cancer in chronic pancreatitis patients. MethodsChronic pancreatitis patients admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic cancer and survival rates were calculated. The standardized incidence ratio was calculated based on the pancreatic cancer incidence in general population of China. Risk factors for pancreatic cancer were identified. ResultsIn a total of 1656 patients, the median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21 patients (1.3%). The expected number of cases of pancreatic cancer was 1.039, yielding a standardized incidence ratio of 20.22. The standardized incidence ratios for patients with a >60 pack-year smoking history were much higher (145.82). Two risk factors for pancreatic cancer were identified: age at the onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking history (hazard ratio, 11.83). ConclusionThe risk of pancreatic cancer is markedly increased in chronic pancreatitis patients compared with the general population, especially in patients with an older age at onset and a >60 pack-year smoking history. The high-risk populations were suggested to be followed up closely.

The phosphoinositide-3-kinase PI3Kalpha inhibition protects from exocrine pancreatic cell susceptibility to cancer in chronic pancreatitis

The association between mindfulness and selflessness is firmly grounded in classical Indo-Sino-Tibetan contemplative traditions, but has received limited empirical attention from Western researchers. In Buddhism, the relationship between mindfulness and the self is of central concern to the cultivation of well-being. Mindfulness is believed to encourage insight into the truly insubstantial nature of the self, an understanding that is thought to encourage well-being. The present study explores these relationships, attending to dispositional mindfulness, the self as it exists on a continuum from self-centered to selfless, and psychological well-being. Results indicate a positive relationship between selflessness, dispositional mindfulness, and psychological well-being. It appears that construing the self as interdependent and interconnected with a broader social, natural, and cosmic context is linked with greater psychological well-being and dispositional mindfulness. Path analyses revealed that selflessness mediated the relationship between dispositional mindfulness and psychological well-being.

Chronic Pancreatitis: Landmark Papers, Management Decisions, and Future.

On May 16, 2015 at the invitation of the American Gastroenterological Association Institute Council E.P.D. presented a state-of-the-art lecture at Digestive Disease Week 2015. The aims were to discuss a selection of landmark papers in chronic pancreatitis (CP) that influence modern management and to conclude by suggesting some future directions. This is based on that presentation. We will specifically review the following: duct anatomy and pancreas divisum, description of chronic relapsing pancreatitis and its differentiation from recurrent acute pancreatitis and established CP (ECP), natural histories and gene discoveries of alcoholic, idiopathic and hereditary pancreatitis, development of pancreatic cancer in CP, exocrine pancreatic insufficiency and calculation of dose and delivery of enzymes, endoscopic ultrasonography, and autoimmune pancreatitis. With some exceptions, we exclude basic science and surgery.

IL-17 and Reg3β are emerging players in the microenvironment by promoting pancreatic cancer in chronic pancreatitis

IL-17 and Reg3β are emerging players in the microenvironment by promoting pancreatic cancer in chronic pancreatitis

Pancreatic cancer in chronic pancreatitis.

Data exists to indicate a definite association between chronic pancreatitis and pancreatic cancer. The strength of this association varies between various causes of pancreatitis, with hereditary and tropical pancreatitis more likely to result in malignancy. Pathogenesis may involve genetic factors, diabetes, smoking and alcohol consumption. Clinically a significant overlap exists between the two conditions, with histology difficult to obtain and interpret in this setting. Biomarkers like CA19-9 and others may be useful, as is a variety of newer imaging modalities. Treatment needs to be individualised as surgery offers the only chance of cure, albeit in but a few.

Clinical features and risk factors of pancreatic cancer in chronic pancreatitis

Clinical features and risk factors of pancreatic cancer in chronic pancreatitis

Sa1532 Diagnosing Cancer in Chronic Pancreatitis: The Struggle Persists

Sa1532 Diagnosing Cancer in Chronic Pancreatitis: The Struggle Persists

Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

Alcohol and cigarettes: Partners in crime in chronic pancreatitis

Alcohol and cigarettes: Partners in crime in chronic pancreatitis

Der betagte Patientmit chronischer Pankreatitis/Pankreaskarzinom

Chronic pancreatitis is mostly caused by heavy alcohol consumption and is characterized by the onset of symptoms in the fourth and fifth decade. Beginning in patients older than 65 years of age is rare. Leading symptom is recurrent or persisting abdominal pain which is missed only in approximately 5% of the cases. Chronic pancreatitis is classified as idiopathic if there is no anamnesis of alcohol abuse or some rare specific causes. The Idiopathic Chronic Senile Pancreatitis (ICSP) is a subset of the non-alcoholic pancreatitis and is characterized by advanced age at the time of first manifestation. Although life expectancy especially in chronic alcoholic pancreatitis is reduced, there are many patients who reach older age. The natural history in all forms of chronic pancreatitis shows a decrease in pain and the manifestation of exocrine and endocrine insufficiency as late complications. Especially in the elderly loss of weight may occur with steatorrhea and pancreatic diabetes mellitus as the dominating clinical problem of chronic pancreatitis. If pain persists treatment is symptomatically with analgesics. The possibility of causal surgery or the indication for endoscopic treatment of painful chronic pancreatitis should be proven in every single case. Standard pancreatin treatment consisting of large amounts of enzymes will abolish maldigestion. Pancreatic diabetes requires often insulin, there is a tendency to hypoglycaemia. In contrast to chronic pancreatitis cancer of the pancreas is a typical and frequent disease of the elderly. The prognosis is bad and one year life expectancy is just about 11%. One of the reasons is, that the diagnosis is found lately because early symptoms are missing. Specific symptoms like pain, weight loss or jaundice occur lately. In suspicion of pancreatic cancer a lot of methods of morphological diagnostic are available such as CT, MRCP, ultrasound, ERCP and PET, in addition the specific tumor markers CA 19-9 and CEA. After diagnostic is completed, curative resection is possible in only a low percentage of all cases. Old age is no contraindication for surgery, prognosis and the risk of surgery don't differ to other age groups. In most cases palliative therapy is the only possible option because of an advanced tumor stage. Sufficient pain therapy, endoscopic stenting in case of obstructive jaundice or gastroenterostomy in case of duodenal are useful interventions.

Surgical and medical therapy for pancreatic carcinoma

Progress on the treatment of pancreatic ductal adenocarcinoma has involved advances in medical and surgical care with important contributions from disciplines such as radiology and intensive care. In the last decade large randomized controlled trials have been undertaken that demonstrate the improved patient outcomes. There is an increased risk of pancreatic cancer in chronic pancreatitis, hereditary pancreatitis and a variety of familial cancer syndromes. The optimum outcome from pancreatic cancer needs management by multidisciplinary teams in regional specialist units. Endoscopic stenting, good pain relief and pancreatic enzyme supplementation are the basis of care in advanced pancreatic cancer. Chemotherapy prolongs survival in advanced pancreatic cancer with little to be gained using drugs other than 5FU. Resection, if possible, prolongs life and provides the best quality of life. Adjuvant chemoradiotherapy is of no benefit but chemotherapy may improve survival. Alongside the evolution in clinical management has been the elucidation of the molecular events that underlie pancreatic cancer and this knowledge has guided the introduction of targeted treatments for pancreatic cancer.

4566 Tumor versus pseudotumor?: a prospective study of factors associated with missed cancers and nondiagnostic eus/fna in patients with pancreaticobilary lesions.

EUS/FNA is an accurate method of diagnosing pancreatico-biliary cancer (CA) but missed lesions have been reported. AIMS: 1) To evaluate the factors associated with non-diagnostic EUS/FNA and missed CA. 2) To determine the accuracy of EUS/FNA in diagnosing CA in chronic pancreatitis (CP) and the yield of adding FNA to EUS. METHODS: The history, CT scan, cytology, and pathology results were prospectively evaluated in patients (pts) with a suspicion of a pancreatico-biliary CA. The EUS diagnoses and technical aspects of FNA were recorded. EUS/FNA was performed with a 22-gauge needle and on-site cytologist. Final diagnoses were determined by surgery, repeat EUS/FNA (21 pts), or clinical follow-up. RESULTS: 232 pts underwent EUS, 129 had EUS/FNA, and 79 had surgery. 81 tumors were diagnosed (71 adenoCA, 1 acinar cell CA, 6 islet cell, 1 lymphoma). 1 CA with no mass by CT or EUS was found by random EUS/FNA passes. The EUS false negative rate for tumor was 3.7% (96% sensitivity). There were 2 missed adenoCA without a mass and 1 islet cell tumor misdiagnosed as pancreas divisum and CP. All were not evident by prior radiologic tests. 1 adenoCA was missed by surgical exploration and diagnosed only by random biopsies at a second operation. The EUS false positive rate was 9% (96% specificity) due to focal CP (n=5), primary sclerosing cholangitis (n=1), and pancreatic hamartoma (n=1). FNA gave a correct histologic diagnosis in all but 9 adenoCA (84% sensitivity). 3 of these had prior nondiagnostic CT-guided FNA. 7 were unresectable. 6 had firm or hard masses and all but 1 had inadequate specimens despite 6-12 passes. 1 mass was not seen well during EUS/FNA. 1 neuroendocrine tumor was misdiagnosed by EUS/FNA as an adenoCA (98% specificity). Nondiagnostic EUS/FNA for CA was not significantly associated with acute or chronic pancreatitis, pancreas divisum, mass location, tumor differentiation, or difficulty penetrating the lesion. 48 pts had CP;38% had a mass at EUS (12 with CA). 27% of EUS/FNA specimens from tumors in CP were inadequate. CP lowered the sensitivity of EUS/FNA for CA(87% to 80%). Although specificity was high (97%), FNA did not improve EUS accuracy for CA in CP (92%) or in its absence. CONCLUSION: EUS alone is highly accurate for the diagnosis of CA. FNA provides a specific histologic diagnosis but does not increase EUS accuracy in CP. Cancers missed by EUS are infiltrating lesions without a distinct mass and FNA should be performed if suspicion is high.

Influence of alcohol and tobacco on the development of calcification, diabetes and pancreas cancer in chronic pancreatitis

Influence of alcohol and tobacco on the development of calcification, diabetes and pancreas cancer in chronic pancreatitis

Increased incidence of cancer in chronic pancreatitis.

Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.