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Individuals with acute recurrent and chronic pancreatitis may have an inherited predisposition to the development of the disease. Pancreatitis in the setting of a significant family history of the disease can be classified as hereditary or familial pancreatitis. In this article, the authors closely examine the specific genes implicated in pancreatitis, investigate the role of genetic testing for diagnosis, and describe the impact of genetic testing results on clinical management.

Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

Authors report on 3 cases of children treated by therapeutic endoscopic retrograde cholangiopancreatography for pancreatitis (ERCP). The first child presented with familial pancreatitis: he was treated by sphincterotomy and lithiasis extraction. The second child presented with pancreatitis secondary to pancreas divisum: she was treated by sphincterotomy and stunt of small caroncula. The third child presented with severe pancreatitis with pseudocyst: after drainage she was treated by sphincterotomy, Wirsung dilatation and lithiasis extraction. ERCP is a beneficial treatment and may be alternative to surgery in complicated pancreatitis.

Hereditary pancreatitis is presently receiving much attention and deservedly so, not only because of the identification of three genes in separate families, but also because of the unraveling of at least one pathogenetic mechanism. At this point, it is useful to review some historical high points in understanding of this condition. Although familial pancreatitis is a generic term encompassing many family members affected with pancreatitis, with or without a genetic defect (examples include alcoholic pancreatitis or hyperlipidemia), hereditary pancreatitis relates to a specific genetic defect identified in all the members of a family affected with pancreatitis. Three genetic abnormalities are reviewed in greater detail.

PRSS1 and SPINK1 are 2 important genes in the defense mechanism guarding against the development of pancreatitis. This study aimed to evaluate the prevalence of PRSS1 and SPINK1 mutations and to explore the presence of any ethnic specificity in Korean patients.A total of 47 patients from 40 families including 37 patients with idiopathic pancreatitis and 10 patients with familial pancreatitis were prospectively enrolled. Fifty healthy controls were included for analysis of SPINK1 IVS3+2T site.PRSS1 mutations were observed in 6 patients from 2 families and SPINK1 mutations in 13 patients from 11 families, respectively. In case of SPINK1 mutations, N34S and IVS3+2TC were identified in 3 and 11 patients, respectively, including one with compound N34S/IVS3+2TC heterozygote. The prevalence of SPINK1 IVS3+2TC mutations was 26.8% among 41 patients without PRSS1 mutations, whereas the prevalence among 50 healthy controls was 0%. Only PRSS1 R122H was identified. Late onset of symptoms at the age of 36 years and absence of symptoms at the age of 47 years were observed in 2 patients with PRSS1 mutations.PRSS1 and SPINK1 mutations were not rare in Korean patients with idiopathic and familial pancreatitis. SPINK1 IVS3+2TC was a prevalent mutation in this population.

Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation.Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases.In generation II, 12 siblings exhibit 6 cases of pancreatitis, 3 pancreatic cancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis of enrolled members is 32.5 years; average age at pancreatic cancer diagnosis is 59 years. There is no association with known cancer syndromes. Those affected generally present with mild epigastric pain, and CT scans demonstrate characteristic fatty infiltration of the pancreatic body and tail with sparing of the head and neck. Full sequence analysis of genes associated with hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms.Based upon pedigree evaluation and preliminary DNA analysis, we believe that the family members with P/PC carry a novel genetic mutation resulting in hereditary pancreatitis. This mutation is autosomal dominant, expressed with high penetrance, and is part of a unique hereditary syndrome that significantly increases pancreatic cancer risk.

Hereditary pancreatitis (HP) is the strongest known risk factor for pancreatic cancer. The aim of the present study is to establish diagnostic criteria for HP to predict and identify high-risk groups for pancreatic cancer.We collected clinical data for 210 patients with recurrent acute or chronic pancreatitis, and examined mutations of the cationic trypsinogen (CT) gene in 57 patients with a family history of pancreatitis or with early-onset idiopathic recurrent acute or chronic pancreatitis (40 years of age or younger). DNA was extracted from peripheral blood leukocytes, and exons 2 and 3 of the CT gene were individually amplified by polymerase chain reaction (PCR) and sequenced.Of these 57 patients in whom mutations of the CT gene were examined, the R122H (20 patients) and N29I (5 patients) mutations in the CT gene were observed in 25 patients (43.9%). From the analysis of clinical records and the CT gene of these patients, we proposed the following adaptations to the diagnostic criteria for HP: (1) at least one of the affected members in a family has no known etiological factors, (2) we deleted the definition of "different generation", but included the upper limit of the age of onset of pancreatitis in the case of siblings (at least 1 of the patients in a family40 years of age). According to these criteria, all patients with the CT gene mutations in the present study could be classified as having HP, with the exception of 2 sporadic cases with the R122H and N29I mutations, respectively. Based on these findings, we revised the criteria for the diagnosis of HP; (1) recurrent acute or chronic pancreatitis with R122H or N29I mutation of the CT gene, or (2) recurrent acute or chronic pancreatitis with a family history of 2 or more affected patients, irrespective of generation, with at least 1 of the patients having no known etiological factors, and in case of siblings only, the onset of the disease in at least 1 of the patients is under age 40 years.The revised criteria in the present study are appropriate and of clinical usefulness to diagnose patients with HP even in cases without the genetic testing. However, if and when more genes are detected, it will be important to reexamine the mutation-negative patients now classified as HP based on our proposed criteria.

The elucidation of the precise molecular genetic defect in a large kindred with familial pancreatitis was one of the seminal events in pancreatology. 16 Expectations were high. Some anticipated that clinical trials designed to exploit this new understanding of the pathophysiology would start within 1 or 2 years. More than 2 years after the description of the gene defect, clinicians are beginning to understand that knowledge is power, but it may not be immediate power. Clinicians have known the exact molecular defect of several disorders, such as sickle cell anemia for more than 30 years, and in most of them have made only marginal progress in disease treatment. There have been no cures.

The Frey procedure is an established procedure for treatment of pain in chronic pancreatitis. A laparoscopic technique for this procedure has not been described previously. In this video we describe a laparoscopic-assisted redo Frey procedure with a peustow-type pancreaticojejunostomy performed with the Da Vinci robot in a 46y old female with familial pancreatitis who previously underwent a peustow procedure to the body and tail of the pancreas. The patient remains asymptomatic 2y after surgery. Laparoscopic Frey procedure may provide a new treatment option for intractable pain from chronic pancreatitis.

A young man and his father, both with pancreatitis, were recently seen at the Mayo Clinic. The histories, physical findings, and laboratory values were those of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography was valuable in confirming the gross pathological changes and in orienting the surgeon preoperatively.

The authors observed 329 consecutive cases of chronic calcifying pancreatitis (CCP) from January 1963 to January 1986. Alcoholism was the etiological agent in 282 cases (86%). In 34 patients (10%) no cause was detectable (idiopathic). Malnutrition was responsible for 10 cases (3%) and chronic familial pancreatitis was diagnosed in 3 cases (0.9%). The mean age at the apparent onset of symptoms was 36.5 +/- 10.5 for the alcoholics, 22.6 +/- 15.4 in the idiopathic cases and 7.3 +/- 3.0 for the nutritional etiology patients. Mean age differences are statistically significant for the 3 groups. Pancreatic calcifications were found in 224 alcohol-induced cases (79%), in 32 idiopathic cases (94%), in 8 patients with malnutrition (80%) and in one patient with familial pancreatitis (33%). All cases of nutritional etiology presented severe protein-caloric deficiencies with edema, and none complained of pain, but 9 had pancreatic insufficiency. Mean daily ethanol intake for the alcohol-addicted patients was 396.6 +/- 286 g (range 80-1664 g) with the onset of alcoholism at 19.1 +/- 6.8 yr old and 20.8 +/- 8.3 (4-44) yr of alcohol indulgence. Pancreatic carcinoma developed in 7 cases. Six cases of chronic pancreatitis were seen among relatives in the group with CCP of alcoholic etiology.