Hereditary Pancreatitis in North America: The Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study

Applebaum-Shapiro, S; Finch, Robert A.; Pfützer, Roland H.; Hepp, L.A.; Gates, Lawrence K.; Amann, Stephen T.; Martin, Stephen P.; Ulrich, Charles D.; Whitcomb, David C.

doi:10.1159/000055844

Cited by 73 publications

(25 citation statements)

References 12 publications

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“…12 The prevalence of hereditary pancreatitis is variable and dependent on the geographic region, with the highest among the mid and southeastern regions of the United States and parts of France, England, and Germany. 12,13 The greater ease of mobility in the past decades has resulted in migration of patients throughout the world. In addition, the incomplete penetrance, difficulty in getting accurate family history, and small family sizes have proved challenging in establishing a definitive diagnosis of hereditary pancreatitis on the basis of clinical criteria alone.…”

Section: Discussionmentioning

confidence: 99%

The Histopathology of PRSS1 Hereditary Pancreatitis

Singhi

Pai

Kant

et al. 2014

American Journal of Surgical Pathology

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Hereditary pancreatitis is an autosomal dominant disorder with 80% penetrance and variable expressivity. The vast majority of cases have been linked to mutations within the cationic trypsinogen gene, also referred to as serine protease 1 (PRSS1). Other than inheritance, PRSS1 pancreatitis has been considered clinically and pathologically indistinguishable from other etiologies of chronic pancreatitis. However, to date, the histologic findings of PRSS1 pancreatitis have not been well described. We, therefore, collected pancreatic specimens from 10 PRSS1 patients of various ages and examined their clinicopathologic features. Patients at the time of resection ranged in age from 9 to 66 years (median, 29 y), with a slight female predominance (60%). All patients reported a history of intermittent abdominal pain, with an age of onset ranging from infancy to 21 years of age. Examination of the gross and microscopic findings suggested a sequential pattern of changes with increasing patient age. In pediatric patients (n=4), although in most cases the pancreas was grossly normal, there was microscopic variation in lobular size and shape. Although the central portions of the pancreas displayed parenchymal loss accompanied by loose perilobular and interlobular fibrosis, the periphery was remarkable for replacement by mature adipose tissue. These changes were more developed in younger adults (n=2), in whom fatty replacement seemed to extend from the periphery to the central portions of the pancreas. With older patients (n=4), the pancreas showed marked atrophy and extensive replacement by mature adipose tissue with scattered islets of Langerhans and rare acinar epithelium concentrated near the main pancreatic duct. In summary, PRSS1 hereditary pancreatitis is characterized by progressive lipomatous atrophy of the pancreas.

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Section: Discussionmentioning

confidence: 99%

The Histopathology of PRSS1 Hereditary Pancreatitis

Singhi

Pai

Kant

et al. 2014

American Journal of Surgical Pathology

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“…All patients were Caucasian, reflecting the ethnicity of hereditary pancreatitis. 22 In the present study, hereditary pancreatitis was defined as otherwise unexplained pancreatitis in an individual from a family in which the pancreatitis phenotype appears to be inherited in an autosomaldominant pattern, or from a family with an incidence of pancreatitis that is greater than would be expected by chance alone. For MGST1 and GSTM3, we studied 30 patients with hereditary pancreatitis from 26 kindreds that were tested negative for PRSS1 mutations, and 55 controls.…”

Section: Patientsmentioning

confidence: 99%

Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis

et al. 2004

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“…In 1996, Whitcomb et al [7] identified the first mutation associated with hereditary pancreatitis, namely the R122H mutation in the cationic trypsinogen gene (PRSS1). Several other mutations (A16V, K23R, N29I, N29T, R122C) and triplication as well as duplication of the PRSS1 locus have been subsequently described [4,12,13,14,15,16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

Clinical and Morphological Characteristics of Sporadic Genetically Determined Pancreatitis as Compared to Idiopathic Pancreatitis: Higher Risk of Pancreatic Cancer in CFTR Variants

Hamoir¹,

Pepermans

Piessevaux³

et al. 2013

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Background/Aims: Idiopathic pancreatitis is considered to be a multigenic and multifactorial disease. Genetically determined pancreatitis is associated with mutations in the PRSS1,SPINK1 and CFTR genes. This study aimed at examining the clinical and morphological characteristics of patients diagnosed with genetically determined sporadic pancreatitis. Methods: Inclusion criteria were the presence of PRSS1,CFTR or SPINK1 gene mutations in patients with idiopathic recurrent or chronic pancreatitis. Patients with hereditary pancreatitis were excluded. Age- and sex-matched patients with idiopathic pancreatitis and negative genetic testing served as controls (n = 68). Results: Genetic testing was performed in 351 probands referred to our centre since 1999. Sixty-one patients (17.4%) carried at least 1 detected mutation in 1 of the 3 tested genes (34 CFTR, 10 PRSS1 and 13 SPINK1 mutations), and 4 patients showed a combination of mutations. Follow-up has been currently extended to a median of 5 years (range 1-40). Similar clinical features were noted in the case and matched groups except for an earlier age of onset of pancreatic symptoms and a higher incidence of pancreatic cancer in the case group and in patients with CFTR mutations compared to the control group (p < 0.05). The standardized incidence ratio, the ratio of observed to expected pancreatic cancers, averaged 26.5 (95% confidence interval 8.6-61.9). All pancreatic cancer patients were smokers. Conclusion: Clinical parameters of patients with sporadic idiopathic pancreatitis and gene mutations are similar to those of age- and sex-matched patients without gene mutations, except for the age of pancreatic disease onset. A significantly higher occurrence of pancreas cancer was observed in the case group, particularly in those patients carrying CFTR mutations. We therefore suggest to include patients with CFTR variants presenting with risk factors in a screening and surveillance programme and to strongly advise them to stop smoking.

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Hereditary Pancreatitis in North America: The Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study

Cited by 73 publications

References 12 publications

The Histopathology of PRSS1 Hereditary Pancreatitis

The Histopathology of PRSS1 Hereditary Pancreatitis

Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis

Clinical and Morphological Characteristics of Sporadic Genetically Determined Pancreatitis as Compared to Idiopathic Pancreatitis: Higher Risk of Pancreatic Cancer in CFTR Variants

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