Prevalence Of Intraductal Papillary Mucinous Neoplasms Research Articles

Patients with deleterious germline mutations: A heterogeneous population for pancreatic cancer screening?

Modest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high-risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high-risk deleterious germline mutations have a higher prevalence of IPMN. All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed. Of 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow-up 2.7 years). IPMN was found in 127 patients (35.5%). The prevalence of IPMN in mutation carriers (18%) was higher than in the general population (p < 0.01). Germline mutation was an independent predictor of IPMN (odds ratio [OR] = 3.2; p < 0.01), while family history was not (p = 0.22). IPMN prevalence was distributed unevenly between mutation types (67%-Peutz-Jeghers; 43%-HNPCC, 24%-BRCA2; 17%-ATM; 9%-BRCA1; 0%-CDKN2A and PALB2). In this series, 18% of mutation carriers harbored IPMN, higher than the general population. Germline mutation, but not a family history of PC, was independently associated with IPMN. This prevalence varied across mutation subtypes, suggesting not all mutation carriers develop precancerous lesions. Genetic testing for patients with a positive family history may improve screening modalities for this high-risk population.

Patients with deleterious germline mutations: a heterogeneous population for pancreatic cancer screening?

Presenter: Alexandra M. Roch MD, MS | Indiana University Background: Many germline mutations are associated with an increased risk of pancreatic adenocarcinoma (PDAC). Screening at our institution is currently offered for mutation carriers or patients with at least one first-degree relative or two family members with PDAC. High-risk screening protocol includes complete history and physical examination, tumor markers (CA19-9 and CEA), and cross-sectional imaging (CT or MRI/MRCP with Gadolinium and Secretin enhancement), followed by semi-annual to annual clinic visits. Little data exists on the benefits of screening and surveillance for high-risk individuals with inherited genetic syndromes. Intraductal papillary mucinous neoplasm (IPMN) are well-established cystic precursors of PDAC. We hypothesized that patients with deleterious germline mutations in a pancreatic cancer susceptibility gene have a higher prevalence of IPMN. Methods: All consecutive patients undergoing going surveillance at our Pancreatic Cyst and Cancer Early Detection Center from 2013 to 2019 were included in the present study. We analyzed the prevalence and risk factors for IPMN in this high-risk population. Prevalence was compared to historical data from extensive literature review. Results: Of the 1166 patients in the surveillance program, 358 (31%) had a germline mutation and/or a strong family history of PDAC without a known mutation. Gender ratio was 3.5 in favor of women with a median age of 58 years, and a median follow-up of 2.7 years [range 1month-6years]. 201 patients (56%) were known to harbor a deleterious germline mutation, the most common being BRCA2 in 89 patients (25%). A total of 250 patients (70%) had a family history of pancreatic cancer. 132 patients had an IPMN (37%) and 8 had a PDAC (2%). The prevalence of IPMN was higher in the mutation carriers than in the general population (18% vs. 1%, p<0.0001). In multivariate analysis, germline mutation (RR=3.2; 95% CI 1.6-6.4, p=0.001), age, and symptoms were independent predictors of presence of IPMN, with no influence of family history of pancreatic cancer (p=0.22). Interestingly, the prevalence of IPMN was not distributed equally between all mutation types, ranging from 67% in patients with Peutz-Jeghers to 43% in HNPCC patients, 24% in BRCA2 patients, 14% in patients with ATM mutation, and 0% in CDKN2A, PALB2 or FAMM/p16 mutation patients. Conclusion: In this series, 18% of mutation carriers harbored IPMN. A strong family history of PDAC was not an independent risk factor for developing IPMN. The prevalence of IPMN was highly variable depending on the mutation subtype. This series suggests that not all mutation carriers may develop precancerous lesions, and relying on cross-sectional imaging alone for screening and follow-up may be suboptimal. Genetic testing for patients with positive family history may help better tailor surveillance modalities for this high-risk population.

Prevalence of Asymptomatic Intraductal Papillary Mucinous Neoplasms in Healthy and Ill Populations Detected by Ultrasonography: A Single-Center Study of 6353 Outpatients.

The aim of this study was to establish the prevalence of intraductal papillary mucinous neoplasms (IPMNs) without and with high-risk stigmata (HRS)/worrisome features (WF) and the epidemiologic association between IPMNs and other diseases. Ultrasound examinations of outpatients were evaluated. The IPMN was confirmed by magnetic resonance imaging. The prevalence of IPMNs and HRS/WF IPMNs was calculated. The association between IPMNs and other diseases was studied. The prevalence rate of IPMNs was 3.4%. A total of 1,531,264 IPMNs were expected in Italian population (2.5%), whereas 2257 per 100,000 citizens (2.3%) were expected in the European standard population (ESP2013). The prevalence rates of HRS/WF IPMNs were 0.5%, 0.7%, and 0.6%, in our, the Italian, and the ESP2013 populations, respectively. A total of 432,881 and 620 HRS/WF IPMNs per 100,000 residents were expected in the Italian and the ESP2013 populations, respectively. The IPMN prevalence increased over 50 years of age (odds ratio [OR], 3.2; P < 0.001) and over 70 years of age (OR, 1.9; P < 0.001). Female sex was related to the presence of IPMNs (OR, 1.9; P < 0.001). Intraductal papillary mucinous neoplasms had a high prevalence in asymptomatic nonhospitalized populations. Age older than 50 years identified a possible risk category.

Cross-sectional prevalence of pancreatic cystic lesions in patients with acromegaly, a single-center experience.

Acromegaly is a disease associated with an increased risk for several kinds of neoplasms including colon and thyroid cancer. Although the association between acromegaly and pancreatic neoplasms has not been elucidated, it has recently been reported that GNAS gene mutations were found in 58% of intraductal papillary mucinous neoplasms (IPMNs), which are representative pancreatic cystic lesions, suggesting a link between IPMNs and acromegaly. To assess the prevalence of pancreatic cystic lesions in patients with acromegaly, we performed a retrospective cross-sectional single institute study. Thirty consecutive acromegalic patients (20 females and 10 males; mean age, 60.9 ± 11.9years) who underwent abdominal contrast-enhanced computed tomography or magnetic resonance imaging between 2007 and 2015 at Kobe University Hospital were recruited. We also analyzed the relationship between presence of pancreatic cystic lesions and somatic GNAS mutations in pituitary tumors. Seventeen of 30 (56.7%) patients studied had pancreatic cystic lesions. Nine of 17 patients (52.9%) were diagnosed with IPMNs based on imaging findings. These results suggest that the prevalence of IPMNs may be higher in acromegalic patients in acromegalic patients than historically observed in control patients (up to 13.5%). In patients with pancreatic cystic lesions, the mean patient age was higher and the duration of disease was longer than in those without pancreatic cystic lesions (67.0 ± 2.3 vs. 53.0 ± 2.7years, p < 0.001, 15.5 ± 2.4 vs. 7.3 ± 2.8years, p = 0.04). There were no differences in serum growth hormone levels or insulin-like growth factor standard deviation scores between these two groups (21.3 ± 6.4 vs. 23.0 ± 7.4ng/ml, p = 0.86, 6.6 ± 0.5 vs. 8.0 ± 0.6, p = 0.70). Neither the presence of somatic GNAS mutation in a pituitary tumor nor low signal intensity of the tumor in T2 weighted magnetic resonance imaging was associated with the presence of pancreatic cystic lesions. These data demonstrate that old or long-suffering patients with acromegaly have a higher prevalence of pancreatic cystic lesions. Moreover, the prevalence of pancreatic cystic lesions may be increased in acromegalic patients.

Frequency of Intraductal Papillary Mucinous Neoplasm in Patients with and without Pancreas Cancer

Purpose: To determine the frequency of intraductal papillary mucinous neoplasm (IPMN) in patients with and without invasive ductal adenocarcinoma (IDAC). Methods: 82 patients underwent pancreatectomy for pancreas adenocarcinoma. 68/82 subjects underwent at least one preoperative imaging study including CT (n = 43), MRI (n = 25), or both (n = 12). Imaging studies were retrospectively evaluated to determine if IPMN was present in the gland at a location distant from IDAC. In 183 different adult patients undergoing MRI for renal mass, images were evaluated to determine the frequency of IPMN. Fisher's exact test was used to test whether the prevalence of IPMN was greater among patients with pancreas cancer than those without. Results: Five of 68 (7.3%) patients who underwent pancreatic resection for IDAC had IPMN at a site distant from the cancer. Two of 182 (1.1%) patients undergoing MRI for renal cancer had imaging evidence of IPMN. There was a significant difference (p = 0.017) in the prevalence of IPMN between patients with and without IDAC. The odds ratio for IPMN as a predictor of pancreas cancer was estimated as 7.18. Conclusion: IPMN occurs with increased frequency in patients with pancreas cancer as opposed to those without pancreas cancer.

Prevalence of Pancreatic Cystic Lesions Including Intraductal Papillary Mucinous Neoplasms in Patients With End-Stage Renal Disease on Hemodialysis

Pancreatic cystic (PC) lesions are not necessarily rare, and it is important to diagnose whether PC lesions are neoplastic such as intraductal papillary mucinous neoplasm (IPMN) because of its malignant potential. Reports on PC lesions in hemodialysis (HD) patients are remarkably limited. The aim of this study was to clarify the prevalence and characteristics of PC lesions in HD patients. We reviewed 1012 consecutive HD patients and 11,100 patients (controls) without renal disease who underwent transabdominal ultrasonography between January 2003 and December 2005. Patients' sex ratio (female-to-male) was less, and the age was older in HD patients. Clinical findings of these patients were examined. The prevalence both of PC lesions and IPMNs was significantly higher in HD patients than in controls (9.3% vs 1.3% and 2.8% vs 0.2%, P < 0.0001). The incidence of IPMNs in HD patients with PC lesions was higher than that in controls with PC lesions (29.8% vs 17.0%, P = 0.021). Multivariate logistic regression analysis revealed that the odds ratios of PC lesions and IPMNs were 6.38 (95% confidence interval, 4.82-8.45) and 9.39 (95% confidence interval, 5.36-16.49) in HD patients compared with controls. The prevalence of PC lesions in HD patients is higher, and HD patients with PC lesions have high prevalence of IPMNs.