Predictive Factors for Pancreatic Cancer and Its Early Detection Using Special Pancreatic Ultrasonography in High-Risk Individuals

Because pancreatic cancer has a dismal prognosis, a strategy for early diagnosis is required. This study aimed to identify predictive factors of neoplastic progression in patients at high risk for pancreatic cancer and examined the efficiency of surveillance using transabdominal special ultrasonography focusing on the pancreas (special pancreatic US). Patients with slight main pancreatic duct (MPD) dilatation (≥2.5 mm) and/or pancreatic cysts (≥5 mm) were enrolled in a prospective surveillance study with special pancreatic US in a Japanese cancer referral center. A total of 498 patients undergoing surveillance for ≥3 years were included. During the median follow-up of 5.9 years, neoplastic progression developed in 11 patients (2.2%), including 9 patients who underwent pancreatectomy. Eight patients (72.7%) were diagnosed with stage 0/I disease, with an overall survival duration of 8.8 years. Findings of both MPD dilatation and pancreatic cysts at initial surveillance, MPD growth (≥0.2 mm/year) and cyst growth (≥2 mm/year) during surveillance were identified as independent risk factors for neoplastic progression. In summary, surveillance with special pancreatic US for high-risk individuals contributed to earlier detection of neoplastic progression, leading to a favorable prognosis. During surveillance, attention should be paid to MPD growth as well as to cyst growth.

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Long-term follow-up of neoplastic pancreatic cysts without high-risk stigmata: how often do we change treatment strategy because of malignant transformation?

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.2016.1179338 ◽

2016 ◽

Vol 51 (9) ◽

pp. 1138-1143 ◽

Cited By ~ 3

Author(s):

Selma J. Lekkerkerker ◽

Marc G. Besselink ◽

Olivier R. Busch ◽

Frederike Dijk ◽

Marc R. Engelbrecht ◽

...

Keyword(s):

High Risk ◽

Malignant Transformation ◽

Treatment Strategy ◽

Pancreatic Cysts ◽

Long Term Follow Up

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Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.142042 ◽

2011 ◽

Vol 70 (6) ◽

pp. 1083-1086 ◽

Cited By ~ 104

Author(s):

Amelia Ruffatti ◽

Teresa Del Ross ◽

Manuela Ciprian ◽

Maria T Bertero ◽

Sciascia Salvatore ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Univariate Analysis ◽

Thrombotic Event ◽

Multivariate Logistic Regression Analysis ◽

Antiphospholipid Antibody ◽

History Of ◽

Ischaemic Attack ◽

Independent Risk Factors

ObjectivesTo assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments.MethodsInclusion criteria were age 18–65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred.Results258 subjects were prospectively observed between October 2004 and October 2008. The mean±SD follow-up was 35.0±11.9 months (range 1–48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively).ConclusionsHypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.

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Characteristics and Clinical Outcomes of Individuals at High Risk for Pancreatic Cancer: A Descriptive Analysis from a Comprehensive Cancer Center

Gastrointestinal Disorders ◽

10.3390/gidisord1010008 ◽

2018 ◽

Vol 1 (1) ◽

pp. 106-119

Author(s):

Griffin McNamara ◽

Karla Ali ◽

Shraddha Vyas ◽

Tri Huynh ◽

Monica Nyland ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Clinical Outcomes ◽

Genetic Risk ◽

Incidental Findings ◽

The United States ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Pancreatic Cysts ◽

Sporadic Cases

Pancreatic cancer (PC), a leading cause of cancer-related deaths in the United States, is typically diagnosed at an advanced stage. To improve survival, there is an unmet need to detect pre-malignant lesions and early invasive disease. Prime populations to study for early detection efforts include cohorts of high risk individuals (HRI): those with increased risk to develop pre-malignant pancreatic cysts and PC because of a familial or hereditary predisposition to the disease and those in the general population of sporadic cases who are incidentally found to harbor a pre-malignant pancreatic cyst. The objective of this study was to describe the characteristics and clinical outcomes of cohorts of HRI identified at Moffitt Cancer Center. We set out to determine the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected. Of a total of 329 HRI, roughly one-third were found to have pancreatic lesions, most of which constituted pre-malignant cysts known as intraductal papillary mucinous neoplasms. Individuals with the highest genetic risk for PC were found to have smaller cysts at a much earlier age than sporadic cases with incidental findings; however, many individuals at high genetic risk did not have abdominal imaging reports on file. We also identified a subset of HRI at moderate genetic risk for PC that were found to have cystic and solid pancreatic lesions as part of a diagnostic work-up rather than a screening protocol. These findings suggest the pancreatic research community should consider expanding criteria for who should be offered screening. We also emphasize the importance of continuity of care between cancer genetics and gastrointestinal oncology clinics so that HRI are made aware of the opportunities related to genetic counseling, genetic testing, and screening.

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Genetic counselling and personalised risk assessment in the Australian pancreatic cancer screening program

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-019-0129-1 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Tanya Dwarte ◽

Skye McKay ◽

Amber Johns ◽

Katherine Tucker ◽

Allan D. Spigelman ◽

...

Keyword(s):

Risk Assessment ◽

Pancreatic Cancer ◽

Genetic Testing ◽

High Risk ◽

Genetic Counselling ◽

Screening Program ◽

Pathogenic Variant ◽

Recruitment Strategy ◽

Close Relative

Abstract Background Pancreatic cancer (PC) is an aggressive disease with a dismal 5-year survival rate. Surveillance of high-risk individuals is hoped to improve survival outcomes by detection of precursor lesions or early-stage malignancy. Methods Since 2011, a national high-risk cohort recruited through St Vincent’s Hospital, Sydney, has undergone prospective PC screening incorporating annual endoscopic ultrasound, formal genetic counselling and mutation analysis as appropriate. PancPRO, a Bayesian PC risk assessment model, was used to estimate 5-year and lifetime PC risks for familial pancreatic cancer (FPC) participants and this was compared to their perceived chance of pancreatic and other cancers. Genetic counselling guidelines were developed to improve consistency. Follow-up questionnaires were used to assess the role of genetic counselling and testing. Results We describe the Australian PC screening program design and recruitment strategy and the results of the first 102 individuals who have completed at least one-year of follow-up. Seventy-nine participants met the FPC criteria (≥ two first-degree relatives affected), 22 individuals had both a BRCA2 pathogenic variant and a close relative with PC and one had a clinical diagnosis of Peutz-Jeghers syndrome. Participants reported a high perceived chance of developing PC regardless of their genetic testing status. PancPRO reported FPC participants’ mean 5-year and lifetime PC risks as 1.81% (range 0.2–3.2%) and 10.17% (range 2.4–14.4%), respectively. Participants’ perceived PC chance did not correlate with their PancPRO 5-year (r = − 0.17, p = 0.128) and lifetime PC risks (r = 0.19, p = 0.091). Two-thirds felt that current genetic testing would help them, and 91% of tested participants were glad to have undergone genetic testing. Overall, 79% of participants found genetic counselling to be helpful, and 88% reported they would recommend counselling to their relatives. Conclusions Participants reported multiple benefits of genetic counselling and testing but continue to seek greater clarification about their individual PC risk. Extension of PancPRO is required to enable personalised PC risk assessment for all high-risk sub-groups. More detailed discussion of PC risk for BRCA2 pathogenic variant carriers, providing a written summary in all cases and a plan for genetics review were identified as areas for improvement.

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Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

BioMed Research International ◽

10.1155/2014/925845 ◽

2014 ◽

Vol 2014 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Zhiwen Xiao ◽

Guopei Luo ◽

Chen Liu ◽

Chuntao Wu ◽

Liang Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Event ◽

High Risk ◽

Prognostic Factor ◽

Lymphatic Metastasis ◽

Clinical Course ◽

Cellular Mechanisms ◽

Poor Prognostic Factor ◽

Dismal Prognosis ◽

Low Rate

As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs) and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

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Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy

International Journal of Endocrinology ◽

10.1155/2015/318916 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7

Author(s):

Kyung-Hee Kim ◽

Min-Hee Kim ◽

Ye-Jee Lim ◽

Ihn Suk Lee ◽

Ja-Seong Bae ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Total Thyroidectomy ◽

Radioactive Iodine ◽

Significant Risk ◽

Disease Status ◽

Radioactive Iodine Therapy ◽

Papillary Thyroid ◽

Independent Risk Factors

Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients.Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis.Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%.Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.

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Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance

Gastroenterology ◽

10.1053/j.gastro.2018.05.035 ◽

2018 ◽

Vol 155 (3) ◽

pp. 740-751.e2 ◽

Cited By ~ 80

Author(s):

Marcia Irene Canto ◽

Jose Alejandro Almario ◽

Richard D. Schulick ◽

Charles J. Yeo ◽

Alison Klein ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Neoplastic Progression

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Preoperative gemcitabine based chemoradiotherapy in locally advanced nonmetastatic pancreatic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15677 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15677-e15677

Author(s):

D. Maximous ◽

M. E. Abdel-Wanis ◽

M. A. Aboziada ◽

M. I. El-Sayed ◽

A. A. Abd-Elsayed

Keyword(s):

Pancreatic Cancer ◽

Surgical Resection ◽

Locally Advanced ◽

Tumour Response ◽

Metastatic Pancreatic Cancer ◽

Surgical Reconstruction ◽

Biliary Leakage ◽

Dismal Prognosis ◽

Radical Surgical Resection

e15677 Background: Almost 30% of patients with pancreatic cancer present with locally advanced tumours in absence of distant metastasis. Because surgical resection is often contraindicated by vascular invasion, this disease has a dismal prognosis. The combination of gemcitabine with concurrent radiation therapy is a promising approach that is being investigated in patients’ unresectable pancreatic cancer. Aim of the work: The efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients locally advanced, non metastatic pancreatic cancer was assessed. Methods: 25 patients were treated by preoperative gemcitabine based chemo-radiotherapy. Approximately 6 weeks after completion of chemo radiation, evaluation was performed regarding tumour response and resectability. Pancreatico-duodenectomy was done for operable patients with surgical reconstruction. Results: Patients who achieved complete remission (CR) were 2 out of 25 patients while those achieved partial remission (PR) were 11 out of 25, 6 of them were considered operable. Thus Pancreatico- duodenectomy was done for 8 patients with surgical reconstruction. The postoperative 30 day mortality occurred only in one patient. The postoperative morbidity occurred in the form of minor biliary leakage occurred only in 1 patient & leakage from gastrointestinal anaestomosis in 1 patient. Out of 8 patients who underwent radical surgical resection, only one patient developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival was 12 months. Conclusions: preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity. No significant financial relationships to disclose.

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The clinical utility of the 2017 Fukuoka Guidelines and 2015 American Gastroenterological Association Guidelines for the management of intraductal papillary mucinous neoplasms.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.640 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 640-640

Author(s):

Gandhi Lanke ◽

Donald Campbell ◽

Emmanuel Coronel ◽

Manoop S. Bhutani ◽

Brian Weston ◽

...

Keyword(s):

High Risk ◽

Predictive Value ◽

Clinical Utility ◽

Operating Characteristic ◽

Pancreatic Head ◽

Pancreatic Cysts ◽

American Gastroenterological Association ◽

Mucinous Neoplasms ◽

Worrisome Feature

640 Background: Mucinous cystadenocarcinoma are malignant and mucinous pancreatic cysts (PC) have malignant potential. The management of PC remains controversial despite consensus guidelines. This study aims to evaluate the clinical utility of the 2017 Fukuoka Guidelines (FG) and 2015 American Gastroenterological Association Guidelines (AGA-G) for the management of PC. Methods: 212 patients who underwent EUS for PC between 2010 and 2017 were identified. The FG and AGA-G were used to define worrisome and high-risk cyst features. Receiver Operating Characteristic (ROC) curve was used to define sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV). Results: 141 of 212 patients had IPMNs.EUS-FNA was performed in 76.5% with no reported complications. Median follow-up was 4.2 years. The majority of the IPMNs were in the pancreatic head (44.7%) or body (39.7%) while only 15.6 % were in the tail. Using the FG, 46.1% had at least one worrisome feature (FG-W) and 7.1% had at least one high risk feature (FG-HR). Using the AGA-G, 28.4% had at least one HR feature (AGA-HR1) and 1.4% patients had two or more risk factors (AGA-HR2). A change in cyst character (increase of > 5 mm in 2 years, development of a solid component, or new pancreatic duct dilation) was noted in 43.2% patients. The median time to cyst change was 21 months. For prediction of cyst changes, the FG-W had a SN of 45.8%, SP of 55.4%, PPV 45%, and NPV 56%. FG-HR had a SN of 14.3%, SP of 53.2%, PPV 1.7%, and NPV 91.8%. AGA-HR1 had a SN of 35.3%, SP of 51.5%, PPV 20%, and NPV 69.9%. AGA-HR2 had a SN of 0%, SP of 54.2%, PPV 0%, and NPV 97.3%. No difference was seen in cyst change or development of high risk or worrisome features with CEA > 192 vs. < 192 (p = 0.99). During follow up, 14 patients died, but only one patient died of pancreatic cancer. Conclusions: FG and AGA-G are difficult to validate because malignant cyst transformation is rare. There was no correlation between any cyst characteristics on EUS and cyst changes. FG-W had the best performance in predicting changes. Surgical candidates should be carefully selected, as these guidelines have a limited clinical utility.

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