PRE-PDAC: Evaluation of Polygenic Risk scorE for Pancreatic Ductal AdenoCarcinoma Risk Prediction: a Case-control Study
Phase: NA
Conditions: Pancreatic Ductal Adenocarcinoma (mPDAC)
Sponsor: Catholic University of the Sacred Heart

 
 
 
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PROTOCOL 
Version 4.0 - Data 18/12/2025 
 
“PRE-PDAC: Evaluation of Polygenic Risk scorE for Pancreatic Ductal AdenoCarcinoma risk prediction: 
a case-control study” 
 
Principal Investigator (PI): Prof.ssa Stefania Boccia 
Sub-Investigators:  
o Prof. Claudio Sette (Co-Proponente) 
o Prof. Gabriele Capurso (Co-Proponente) 
o Dott.ssa Roberta Pastorino (Co-Proponente) 
   
 
 
ACRONYM: PRE-PDAC (Polygenic Risk scorE for Pancreatic Ductal AdenoCarcinoma) 
 
Promoter: Università Cattolica del Sacro Cuore (UCSC), Largo Francesco Vito 1, 00168, Rome (Italy) 
 
 
Funding: No Profit co-funded:  
o Complementary National Plan PNC-I.1 "Research initiatives for innovative technologies and 
pathways in the health and welfare sector” D.D. 931 of 06/06/2022, DARE - DigitAl lifelong 
pRevEntion initiative, code PNC0000002.  
 
 
 

 
 
 
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UNITA’ COINVOLTE 
o Università Cattolica del Sacro Cuore (Roma) 
o Dipartimento Scienze della Vita e Sanità Pubblica - Sezione di Igiene Generale e Applicata 1 
(IG1): 
o Prof.ssa Stefania Boccia (PI) 
o Dott.ssa Roberta Pastorino (Co-Proponente) 
o Dott.ssa Alessandra Maio 
o Dott. Luigi Russo 
o Dott.ssa Eleonora Pascucci 
o Dott.ssa Alessandra Verduchi 
o Dott.ssa Doriana Lacalaprice 
o Dipartimento di Neuroscienze – Sezione di Anatomia Umana 
o Prof. Claudio Sette (Co-Proponente) 
o Dipartimento Scienze dell’Invecchiamento, Ortopediche e Reumatologiche - UOC 
Reumatologia ed Immunologia Clinica 
§ 
Prof.ssa Maria Antonietta D’Agostino 
§ 
Dott.ssa Giulia Wlderk 
§ 
Dott.ssa Silvia Laura Bosello 
§ 
Dott.ssa Marina Murdolo 
o Istituto Scientifico San Raffaele IRCCS (Milano) 
o UOC Endoscopia Bilio-pancreatica e Ecoendoscopia, Centro Pancreas 
o Prof. Gabriele Capurso (Co-Proponente) 
o Dr.ssa Laura Apadula (Study Coordinator) 
o Prof. Paolo Giorgio Arcidiacono 
o Dr.ssa Livia Archibugi 
o Dr. Ruggero Ponz de Leon 
 
 
 
 
 

 
 
 
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Background 
Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type of pancreatic cancer, 
accounting for 85%-95% of all solid pancreatic tumors [1]. Originating from the epithelium of the pancreatic 
ductal tree, PDAC is characterized by its remarkable biological aggressiveness and its high resistance to current 
therapeutic options, including chemotherapy and radiotherapy [2]. Despite advancements in clinical 
management, PDAC remains one of the deadliest malignancies, with a 5-year survival rate of less than 10% 
[3]. These data highlight the urgent need for more effective approaches to combat this disease. 
A major challenge in managing PDAC is late diagnosis, largely due to the asymptomatic nature of the disease 
in its early stages [4]. Consequently, approximately 50%-55% of patients are diagnosed at a metastatic stage 
and 30%-35% at a locally advanced stage, significantly reducing the availability of curative treatment options 
[5,6].  Surgical resection, for instance, is feasible in only about 20% of cases, further exacerbating the prognosis 
[7,8]. This scenario underscores the critical need for novel strategies aimed at improving both early diagnosis 
and prevention. 
From an epidemiological perspective, the incidence of PDAC in the general population is relatively low, 
rendering mass screening an ineffective and economically unsustainable solution [9,10]. Moreover, the 
absence of non-invasive, reliable, and scalable screening tests, combined with the risk of false positives, limits 
the feasibility and efficacy of such approaches [11]. As a result, primary prevention plays a pivotal role in 
reducing PDAC incidence. 
Primary prevention efforts primarily target modifiable risk factors known to contribute to PDAC development. 
These include smoking, obesity, diabetes, excessive alcohol consumption, and genetic predisposition [12,13]. 
Promoting healthy lifestyle choices and addressing high-risk behaviors are essential components of preventive 
strategies against PDAC. 
In recent years, scientific evidence has suggested that combining traditional risk factors, blood biomarkers, 
and genetic information could enhance the identification of high-risk populations [14]. A promising approach 
in this context is the polygenic risk score (PRS). The PRS offers a quantitative estimate of an individual’s 

 
 
 
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genetic predisposition to a specific disease by combining the effects of multiple genetic variants, known as 
single-nucleotide variants (SNVs), identified through genome-wide association studies (GWAS). While the 
contribution of each individual variant is relatively small, their combined effect enables a moderate yet 
cumulative estimate of genetic risk [15,16]. The PRS is calculated by weighting each SNV according to its 
association with the disease of interest, resulting in a single score that represents the cumulative genetic burden 
[17]. 
In the context of PDAC, recent studies have highlighted the potential of the PRS as a predictive tool. Research 
has shown that the PRS is significantly associated with an increased risk of PDAC, and the incorporation of 
genetically predicted ABO blood groups into the PRS further strengthens its association with PDAC risk, 
thereby enhancing the predictive accuracy of the model [18]. The integration of the PRS with clinical risk 
factors, such as smoking and diabetes, has further enhanced the predictive accuracy of models, making them 
more effective in identifying high-risk populations [19]. 
These findings suggest that the PRS is a promising tool for risk stratification within the general population, 
allowing for the identification of high-risk subgroups who may benefit from targeted preventive interventions 
[20]. However, the scientific literature in this field is still evolving, and further studies are necessary to validate 
the effectiveness of the PRS in clinical practice. 
The aim of our study is to evaluate the effectiveness of the PRS in predicting PDAC risk, contributing to the 
development of more accurate predictive models that could improve clinical management and the prevention 
of PDAC. 
 
 

 
 
 
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Objectives 
Primary objective 
Evaluation of the association between the PRS, derived from the combination of known risk-associated SNPs, 
including ABO alleles, and the risk of developing PDAC in a case-control study. 
 
Secondary objectives 
i. 
In the case-control study, we will calculate a multifactorial risk score by integrating the weighted 
PRS PDAC with two well-established risk factors (smoking and diabetes); 
ii. 
In the PDAC patient cohort, we will evaluate the association of the PRS PDAC with the following 
variables: 
1. Clinical and pathological characteristics; 
2. Serological levels of exploratory biomarkers (CA19-9 and IL-6); 
3. Cancer management (including surgery and medical treatments). 
 
ENDPOINTS 
Primary endpoints 
- 
Odds of developing PDAC by different PRS percentiles. 
 
Secondary endpoints 
i. 
Odds of developing PDAC by different multifactorial risk score percentiles; 
ii. 
According to PRS percentiles: 
1. Frequency distribution of age, sex, stage, and primary localization (head versus body-tail); 
2. Frequency distribution of Ca19-9 levels and Il-6 levels; 
3. Frequency of surgery, chemotherapy, radiotherapy, EUS-guided ablative therapy. 
 
 

 
 
 
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METODHS 
Study design 
We will conduct a case-control multicenter study. 
Study population 
The population of the case-control study is composed as follow:  
- 
Cases: consecutive patients with histologically confirmed PDAC, enrolled at the Ospedale San 
Raffaele in Milan, with samples stored at the hospital’s biobank; 
- 
Controls: consecutive people with no personal history of PDAC, enrolled at the Fondazione Policlinico 
Universitario A. Gemelli IRCCS, with samples stored at the Hygiene Section of the Università 
Cattolica del Sacro Cuore. In addition, we will also recruit patients at the Complex Operational Unit 
of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, from whom a blood 
sample will be collected. 
The population of the cohort study (cases) is composed as follow:  
- 
Consecutive patients with histologically confirmed PDAC, enrolled at the Ospedale San Raffaele. 
Inclusion criteria 
For cases: 
- 
Histologically confirmed PDAC; 
- 
First diagnosis; 
- 
Age ≥ 18 years; 
- 
Written informed consent; 
- 
Available of a blood sample. 
For controls: 
- 
Individuals without a diagnosis of PDAC in the previous 10 years; 
- 
Age ≥ 18 years; 
- 
Written informed consent; 

 
 
 
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- 
Available blood sample. 
 
A formal matching between cases and controls will not be applied in order to ensure cases have a comparable 
age distribution to the controls. However, the selection of controls from the archives of the Hygiene Section 
of the Università Cattolica del Sacro Cuore (Protocol N. 2580, in which participants were enrolled during a 
routine visit, upon informed consent, between February 2019 and February 2021) will be based on the age 
distribution observed in the context of a biobank/exposome observational registry study, approved by the 
Institutional Review Board (BIO-PANCREAS protocol 96/INT/2021, previously named BIOGASTRO/2011) 
performed within the Pancreas Translational and Clinical Research Centre of Ospedale San Raffaele. In more 
detail, PDAC cases were enrolled at the time of diagnosis, upon informed consent, between April 2016 and 
September 2024. The observed age distribution is as follows: 
- 
<40 yrs: 1% of cases; 
- 
[40-50) yrs: 7% of cases; 
- 
[50-60) yrs: 19% of cases; 
- 
[60-70) yrs: 32% of cases; 
- 
[70-80) yrs: 35% of cases; 
- 
>=80 yrs: 6% of cases. 
Exclusion Criteria 
For cases at least one of the following: 
- 
Previous diagnosis of PDAC; 
- 
DNA sample not available or insufficient quality for analysis. 
For controls at least one of the following: 
- 
Personal history of PDAC or other pancreatic diseases; 
- 
Presence of concomitant malignancies; 
- 
DNA sample not available or insufficient quality for analysis. 

 
 
 
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PROCEDURE 
Informed consent and participant contact 
Both cases and controls will be contacted to obtain written informed consent for the molecular analyses and 
the use of data collected through questionnaires. Specifically, participants will be informed about the purpose 
of the study, the type of analyses to be performed, and their right to withdraw at any time.  
For prospectively enrolled controls, written informed consent will be obtained at recruitment, and a blood 
sample will be collected. 
Type of data collected 
For eligible participants the following data were collected: 
- 
Sex; 
- 
Age at enrollement; 
- 
Smoking; 
- 
Alcohol consumption; 
- 
BMI (Body Mass Index); 
- 
Personal and family history of cancer (particularly pancreas and breast cancer); 
- 
Personal history of pancreatic diseases, diabetes, hypertension, periodontitis, ulcers (gastric or 
duodenal), Helicobacter pylori infection; 
- 
Previous surgical interventions (such as gastrectomy and cholecystectomy); 
- 
Pharmacological history (use of aspirin, NSAIDs, statins, PPIs, ACE inhibitors, ARBs): 
- 
PRS. 
For cases the following additional information were required for: 
- 
Diagnosis: age at diagnosis, primary localization (head versus body-tail); 
- 
Surgery: type of surgery; 

 
 
 
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- 
Histology: stage (defined according to NCCN as resectable, borderline resectable, locally advanced, 
or metastatic [21]) 
- 
Treatment: chemotherapy, radiotherapy, EUS-guided ablative therapy. 
Medical form 
At the time of diagnosis of cases, the physician completed the questionnaire provided in Appendix A, which 
includes both the medical history (physiological, familial, pathological, and pharmacological) and the 
diagnostic-therapeutic pathway, with the latter being updated progressively. 
For controls, during a routine visit, the physician completed the questionnaire provided in Appendix B, which 
focuses exclusively on questions related to the medical history (physiological, familial, pathological, and 
pharmacological) relevant to PDAC. 
For prospectively enrolled controls, during a routine visit, the physician will complete the questionnaire 
provided in Appendix B, which focuses exclusively on questions related to the medical history (physiological, 
familial, pathological, and pharmacological) relevant to PDAC. 
The questionnaires included in Appendix A and B are the same as those used in previous studies (Protocol No. 
2580 and the BIO-PANCREAS protocol 96/INT/2021) and were developed based on clinical expertise and 
relevant scientific literature. 
Molecular analysis 
The PRS analysis will be conducted using blood samples collected at the time of diagnosis for cases and at the 
time of enrollment during a routine visit for controls. A minimum of 3 mL of blood will be required to extract 
sufficient DNA quantity (100–200 ng). 
The selection of genotyped SNPs for inclusion in the PRS will be guided by the findings of a study that 
developed a 30-SNP PRS, integrating SNPs associated with PDAC risk and those necessary for inferring ABO 
blood groups from genotypes to incorporate blood group data into the score calculation [18]. 
DNA extraction and PRS testing will be performed in the Section of Hygiene at UCSC (blood samples from 
cases will be shipped from San Raffaele to UCSC to this end). PRS testing will be performed using the Gene 
Titan Thermo Fisher system and the Axiom PMDA (Precision Medicine Diversity Array) kit. The Axiom™ 

 
 
 
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analysis workflow includes the use of Axiom™ Analysis Suite, Applied Biosystems™ Analysis Power Tools, 
and the SNPolisher™ package to perform quality control (QC) for samples and plates, SNP filtering prior to 
downstream analyses, and advanced genotyping methods [22].  
Blood samples from PDAC patients will also be analyzed using the INFINITE 200PRO® CON i-
CONTROLTM, in order to measure the concentration of CA19-9, a glycoprotein currently used as biomarker 
of gastrointestinal cancers, including PDAC, and interleukin-6 (IL-6), a proinflammatory cytokine implicated 
in the biological processes of tumor progression [23]. Although these biomarkers are primarily validated for 
diagnostic and prognostic purposes in clinical settings [24], in this study they will be explored for their 
potential association with genetic risk profiles within the PDAC patient cohort. 
Sample size calculation 
For the case-control study, the sample size was calculated based on the findings reported by Galeotti et al. [18] 
which reported an association between the PRS and an increased risk of PDAC with an odds ratio (OR) of 2.70 
(95% CI 1.99-3.68) for the highest quintile compared to the lowest quintile of the weighted PRS. A sample 
size of 570 subjects in the control group and 570 subjects in the case group provides more than 80% power to 
detect a difference between the PRS distributions in controls and cases, assuming a significance level (alpha) 
of 0.05. 
Statistical analysis 
All analyses will perform using Stata software (STATA/BE 17.0 for Windows, StataCorp LP, College Station, 
TX 77845, USA), with a statistical significance level set at p<0.05. Patients’ characteristics will be described 
as absolute frequencies and percentages for categorical variables and as medians with ranges or means with 
standard deviations for continuous variables, as appropriate.  Differences between groups (cases and controls) 
will be assessed using the chi-square test or Fisher’s exact test for categorical variables, while numerical 
variables will be tested for normality using the Shapiro-Francia test, followed by Student’s t-test or the Mann-
Whitney U test, based on the normality assessment. 

 
 
 
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Logistic regression will be employed to assess the association between individual SNPs and the outcome 
(PDAC: yes/no). The relationship between ABO blood groups derived from genotypes and PDAC risk will 
also be evaluated using logistic regression, with blood group O serving as the reference category.  
Two types of PRS will be calculated: an unweighted PRS and a weighted PRS. Both will be assessed as 
continuous and categorical variables. The unweighted PRS will be computed by summing the total number of 
risk alleles for each individual (assigning a value of 1 to each risk allele) and incorporating ABO blood group 
values, with 0 assigned for group OO, 1 for OA/OB, and 2 for group AB. The weighted PRS will be calculated 
as the sum of an individual’s risk alleles, weighted by the odds ratios (ORs) derived from GWAS data on 
PDAC, with similar weighting applied for ABO blood groups. 
The PRS will be categorized into the following percentiles based on its distribution in the control group: 
[0,5%), [5%,10%), [10%,20%), [20%,40%), [40%,60%), [60%,80%), [80%,90%), [90%,95%), and 
[95%,100%]. The lowest 5% ([0,5%]) will represent the lowest PRS group, while the highest 5% 
([95%,100%]) will represent the highest PRS group. The middle percentile range ([40%,60%]) will be used as 
the reference category. 
Multifactorial risk scores will also be calculated by integrating the weighted PRS with tobacco smoking and 
diabetes variables. The calculated scores will be analyzed for their association with PDAC risk using logistic 
regression.  
All analyses will adjust for the following variables: age, sex, primary tumor localization, stage, and family 
history of cancer. 
In addition, given the different recruitment periods between cases and controls, potential biases may arise due 
to temporal changes in clinical practice, lifestyle factors, or exposure prevalence. To address this, we will 
include adjustment for the recruitment period in the regression models where applicable, and perform 
sensitivity analyses to evaluate whether the association between PRS and PDAC risk is affected by recruitment 
timing. 
Finally, the frequency of the following variables will be calculated based on PRS percentiles: age, sex, stage, 
Ca19-9 and IL-6 levels, primary localization, surgery, chemotherapy, radiotherapy, and EUS-guided ablative 
therapy. Statistical tests will then be performed to explore any potential associations. 

 
 
 
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Data collection and management 
A customized eCRF will be developed to collect clinical data for participants included in the study. Pseudo-
anonymized data will be collected and managed using REDCap electronic data capture tools hosted at 
https://redcap-irccs.policlinicogemelli.it/. REDCap (Research Electronic Data Capture) [25] is a secure, web-
based software platform designed to support data capture for research studies. It is fully compliant with 21 
CFR Part 11 and GDPR, offering:  
1. An intuitive interface for accurate data acquisition; 
2. Audit trail to track data management and export activities.;  
3. Automated export functions for compatibility with common statistical software; 
4. Procedures to integrate and synchronize data with external sources [26].  
All recorded information is confidential, and the database is privacy-protected, ensuring that no data can be 
traced back to individual patients in research reports. Access to the database is restricted, and only authorized 
individuals, officially registered as investigators or data managers, will receive user credentials. Access will 
be granted via multifactor authentication through the REDCap web platform, enabling secure data entry and 
management. 
 
 
Data quality and standards 
The eCRF will be developed in alignment with the study protocol, incorporating dataset configuration, 
validation, and programmed edit checks. The dataset will only be activated to accept data once it has been 
thoroughly reviewed and tested. 
Investigators participating in the study are responsible for ensuring that the CRFs are accurately and 
comprehensively completed. Clinical data sources include the physician’s patient records, hospital 
documentation, original laboratory reports, pharmacy records, imaging results, and other relevant materials. 
Data entry into the CRF must be truthful, precise, and completed in a timely manner. Each Investigator is 

 
 
 
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accountable for maintaining high data quality. Personal medical information may be reviewed to confirm 
patient safety and will always remain confidential. 
During the data collection phase, remote monitoring and automated data quality checks will be implemented 
to address discrepancies and inconsistencies, triggering the generation of queries where necessary. The “Data 
Resolution Workflow” module will facilitate the documentation and resolution of data issues, including the 
creation, response, and closure of queries. User privileges will be assigned as needed, allowing appropriate 
control over who can view, initiate, respond to, or close data queries. 
  
Ethical consideration 
The study will adhere to the ethical principles outlined in the Declaration of Helsinki [27]. 
DNA samples of the patients will be stored in the Biobank of Fondazione Policlinico A. Gemelli-IRCCS, 
following signed informed consent. The processing of sensitive data will take place in compliance with 
Regulation (EU) No. 2016/679 (General Data Protection Regulation or GDPR) and Legislative Decree No. 
196/2003 (as amended by Legislative Decree no. 10 August 2018 n. 101) on provisions for the adaptation of 
national legislation to the provisions of Regulation (EU) 2016/679. The Biobank has obtained the UNI EN 
ISO 9001:2015 certification (Certificate No. IT317572). 
 
 
 

 
 
 
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Appendix A – Questionnaire for cases 
ENROLLMENT FORM 
Select the room: ☐ Room 5 ☐ Room 7 | Completed by: ______ | Date: ______ 
Tissue Biopsy for Research ☐ Yes ☐ No (If yes, tube number: ______) 
Date of Birth: ______  
PHYSIOLOGICAL HISTORY 
Weight 12 months before symptoms: ____ kg | Weight at diagnosis: ____ kg | Height: ____ cm 
☐ Smoker ☐ No ☐ Ex (since ____ years) | Cigarettes/day: ____ 
☐ Alcohol consumption ☐ No ☐ Ex (since ____ years) | Units/day: ____ 
☐ Coffee consumption: ____ cups/day for ____ years | Menarche age: ____ years 
Total pregnancies: ____ (age ____), Miscarriages: ____ | Children born: ____ 
☐ Breastfeeding ☐ No (Total months for all children: ____) 
☐ Contraceptive pill ☐ No (for ____ years) | Menopause age: ____ years 
☐ Post-menopausal hormone therapy ☐ No (for ____ years) | ☐ Irregular cycles ☐ No (for ____ years) 
Other gynecological disorders: ____ | ☐ Previous gynecological surgery ☐ No (Hysterectomy, 
unilateral/bilateral oophorectomy, year: ____) 
FAMILY HISTORY (Specify relation and age at onset) 
☐ Pancreatic cancer ☐ No | Relation: ____ | Age: ____ 
☐ Breast cancer ☐ No | Relation: ____ | Age: ____ 
☐ Other cancers ☐ No | Relation: ____ | Organ: ____ | Age: ____ 
MEDICAL HISTORY - COMORBIDITIES AT DIAGNOSIS 
☐ Diabetes ☐ No | Type (I/II): ____ | Since: ____ | Therapy: ☐ Insulin ☐ Metformin ☐ Other: ____ 
☐ Allergies ☐ No (Specify: drugs, animals, insect bites, other: ____) 
☐ Periodontitis ☐ No | Since: ____ | Dentist visit: ☐ No (since ____ years) 
☐ Tooth loss (How many: ____ ) | ☐ Oral surgery ☐ No (Year: ____) 
Have you been diagnosed with periodontitis or pyorrhea? Do your gums bleed easily or recede? Any 
abscesses near teeth? 
☐ Chronic pancreatitis ☐ No (Since: ____ Therapy: ____) | ☐ Hypertension ☐ No (Since: ____ Therapy: 
____) 
☐ Ulcer ☐ No | Gastric ☐ Duodenal ☐ | Diagnosis year: ____ | Therapy: ____ 
☐ H. Pylori infection ☐ No | Diagnosis year: ____ | ☐ Eradication therapy ☐ No (Year: ____) | Therapy: 
____ 
☐ Gastrectomy ☐ No | Year: ____ | Type: ____ | Indication: ____ 
☐ Cholecystectomy ☐ No | Year: ____ | Indication: ____ 
☐ Previous cancers/surgeries ☐ No (Specify: type, onset age, therapy: ____) 
☐ Other conditions/Previous surgeries ☐ No | Type: ____ | Year: ____ | Reason: ____ | Treatment: ___ 
PHARMACOLOGICAL HISTORY (Check drug and dose) 

 
 
 
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Pharmacological therapy at diagnosis: 
☐ Aspirin use for prolonged periods: 
☐Cardioaspirin 100 mg 
☐Cardirene 75 mg / 100 mg / 160 mg / 300 mg 
☐Aspirin 325 mg / 400 mg / 500 mg 
Dose: ____ | Times/day: ____ | Total years: ____ 
☐ NSAID use: ☐ No | Drug: ____ | Dose: ____ | Times/day: ____ | Total years: ____ 
☐ Statins use: ☐ No | ☐ Atorvastatin | ☐ Fluvastatin | ☐ Lovastatin | ☐ Pravastatin | ☐ Rosuvastatin | ☐ 
Simvastatin | ☐ Simvastatin + Ezetimibe | Dose: ____ mg | Times/day: ____ | Total years: ____ 
☐ PPI use ☐ No | Drug: ____ | Dose: ____ | Times/day/week: ____ | Total years: ____ 
☐ACE Inhibitors: 
☐Lisinopril (Zestril, Prinivil) 5 mg/20 mg 
☐Enalapril (Enapren, Converten) 5 mg/20 mg 
☐Ramipril (Triatec, Unipril) 1.25 mg/2.5 mg/5 mg 
☐Quinapril (Accupril, Acequin) 5 mg/20 mg 
☐Perindopril (Coversyl) 4 mg 
☐Trandolapril (Gopten) 0.5 mg/2 mg 
☐Zofenopril (Zantipress) 7.5 mg/30 mg 
☐Fosinopril (Eliten, Fosipres) 10 mg/20 mg 
Frequency: ____ times/day for ____ years 
☐ARB (Angiotensin Receptor Blockers) use: 
☐Valsartan (Tareg) 80 mg/160 mg 
☐Telmisartan (Micardis) 20 mg/40 mg/80 mg 
☐Losartan (Loartan) 12.5 mg/50 mg/100 mg 
☐Irbesartan (Aprovel) 75 mg/150 mg/300 mg 
☐Olmesartan (Olmetec) 20 mg/40 mg 
☐Candesartan (Blopress) 8 mg/16 mg/32 mg 
☐Eprosartan (Teveten) 600 mg 
Frequency: ____ times/day for ____ years 
DIAGNOSTIC SYMPTOMS or ☐ Incidental Diagnosis (Specify) 
Diagnosis date (first imaging with mass detected): ____ | First symptom date: ____ 
Symptoms leading to diagnosis (Specify onset date and severity): 
☐ Weight loss (____ kg in ____ time) | 
☐ Diabetes /☐ Worsening diabetes 
☐ Pain (Location: ____) 
☐ Diarrhea 
☐ Jaundice ☐ Fatigue (ASTHENIA) ☐ Appetite loss ☐ Acute pancreatitis ☐ Other: ____ 
DIAGNOSTIC-THERAPEUTIC PATHWAY 
IMAGING at DIAGNOSIS (Specify date and details or attach report) 
☐ Abdominal ultrasound ☐ No ☐ in OSR 

 
 
 
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☐ CT ☐ No __________☐ in OSR 
☐ MRI ☐ No ☐ in OSR 
☐ PET ☐ No☐ in OSR 
☐ EUS ☐ No __________☐ in OSR 
☐ EUS-FNA/FNB  ☐ No ________☐ in OSR 
Cytology/Histology report: _______ 
☐ Biopsy: ☐ Hepatic metastasis (Date: ) | ☐ Pancreatic (CT-guided, Date: ___) 
☐ **Laparoscopic (Date: ) | Histology: ____ (in OSR ☐) 
☐ Clinical/Imaging diagnosis only ☐ No | TNM Stage: T N M 
Primary Tumor Location: ☐ Head ☐ Body-Tail ☐ Uncinate Process ☐ Disseminated | Max Tumor Size 
(mm): CT EUS 
☐ No local invasion ☐ Vascular invasion (Specify: ____) 
CA19-9 at diagnosis: ____ u/ml (During jaundice? ☐ Yes ☐ No) 
CEA at diagnosis: ____ | Other markers: ____ 
Lab Tests: Neutrophils: ____ /mm³ | Lymphocytes: ____ /mm³ | CRP: ____ g/L | Albumin: ____ 
☐ Biliary drainage performed? ☐ No Date: ____ 
☐ ERCP ☐ Choledochoduodenostomy ☐ Hepaticogastrostomy ☐ PTC 
SURGERY WITH CURATIVE INTENT: ☐ Yes ☐ No Date: ____ ☐ Performed at OSR 
TYPE OF SURGERY: 
☐ DCP ☐ PD ☐ SPD ☐ Enucleation ☐ Vascular resection ☐ Other: _____ 
HISTOLOGY: 
• 
Grade: G 1 ☐ 2 ☐ 3 ☐ 
• 
Resection margin: R 0 ☐ 1 ☐ 
• 
T: _____ 
• 
N1 ratio: ___ 
• 
N2 ratio: ___ 
• 
Vascular invasion: _____ 
• 
Perineural invasion: _____ 
Non-radical surgery performed? (Specify type) ☐ Yes ☐ No Date: _____ 
CHEMOTHERAPY (specify type, start and end date, duration) 
☐ Yes ☐ No ☐ Performed at ORS ☐ Performed at _____ 
• 
Drug: _____ Period: _____ 
☐ Neoadjuvant/palliative ☐ Adjuvant post-surgery 
• 
Drug: _____ Period: _____ 
☐ Neoadjuvant/palliative ☐ Adjuvant post-surgery 

 
 
 
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• 
Drug: _____ Period: _____ 
☐ Neoadjuvant/palliative ☐ Adjuvant post-surgery 
RADIOTHERAPY (specify type, start and end date, duration) 
☐ Yes ☐ No ☐ Performed at ORS ☐ Performed at _____ 
EUS-GUIDED ABLATIVE THERAPY ☐ Yes ☐ No Date: _____ 
PSYCHO-ONCOLOGICAL SUPPORT ☐ Yes (Performed at ORS) ☐ No 
NUTRITIONAL SUPPORT ☐ Yes (Performed at ORS) ☐ No With: _____ 
FECAL ELASTASE AT DIAGNOSIS: ____________ 
PERT: ☐ Yes ☐ No Start date: ____________ Dosage: ____________ 
Modifications or interruptions: ____________ 
DEATH: ☐ Yes Date: ____________ ☐ No Date of last contact: ____________ 
 
Classification of Resectability of PDAC (Pancreatic Ductal Adenocarcinoma) According to NCCN 
Guidelines (Modified) 
Vessel 
Involvement 
Resectable 
Borderline Resectable 
Unresectable 
Arterial 
vessels 
No contact 
Contact with common hepatic artery 
without contact to the celiac trunk or 
hepatic artery bifurcation (resection 
possible) 
Distant metastasis or non-regional 
lymph node metastasis 
Venous 
vessels 
No contact 
without vessel 
alteration 
Contact with SMA ≤ 180°, celiac 
trunk ≤ 180°, SMV/portal vein ≤ 
180° (resection possible) 
SMA or celiac trunk contact > 180°, 
aorta infiltration, non-
reconstructable SMV or portal vein 
invasion 
 
 
 
 
 
 
Appendix B. Questionnaire for subjects enrolled as controls. 
 
PHYSIOLOGICAL HISTORY 

 
 
 
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1. Sex: _____ 
2. Age: _____ 
3. Weight (kg): _____ 
4. Height (cm): _____ 
5. BMI: _____ 
6. Smoking: 
o YES 
o NO 
o FORMER SMOKER 
If former, specify for how many years: ___ 
If yes, indicate:  
o 
Cigarettes/day: ______ 
o 
Years of smoking: ______ 
7. Alcohol Consumption: 
o YES 
o NO 
o FORMER DRINKER 
If former, specify for how many years: ___ 
If yes, indicate:  
o 
Units/day: ______ 
o 
Years of alcohol consumption: ______ 
 
FAMILY MEDICAL HISTORY (Specify relative and age of onset) 
1. Pancreatic Neoplasia: 
o YES 
o NO 
If yes, indicate: 
o 
Relation: ____________ 
o 
Age of onset: _________ 
o 
Relation: ____________ 
o 
Age of onset: _________ 
2. Breast Neoplasia: 
o YES 
o NO 
If yes, indicate: 
o 
Relation: ____________ 
o 
Age of onset: _________ 
o 
Relation: ____________ 

 
 
 
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o 
Age of onset: _________ 
3. Other Neoplasms: 
o YES 
o NO 
If yes, indicate: 
o 
Organ: _____________ 
o 
Relation: ____________ 
o 
Age of onset: _________ 
o 
Organ: _____________ 
o 
Relation: ____________ 
o 
Age of onset: _________ 
o 
Organ: _____________ 
o 
Relation: ____________ 
o 
Age of onset: _________ 
 
PAST MEDICAL HISTORY 
4. Diabetes: 
o YES 
o NO 
If yes, indicate: 
o 
Type I 
o 
Type II 
Additionally, indicate type of therapy: 
o 
Insulin: 
o YES, for _____ years 
o NO 
o 
Metformin: 
o YES, for _____ years 
o NO 
5. Periodontitis (Have you ever been diagnosed with periodontitis or pyorrhea? Do your gums bleed 
easily, retract, or form abscesses near teeth?): 
o YES 
o NO 
o DO NOT VISIT DENTIST 
If yes, indicate: 
o 
For how many years: ____________ 
o 
Tooth loss (number): _________ 
o 
Oral surgery (year): __________ 

 
 
 
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6. Hypertension: 
o YES 
o NO 
If yes, indicate: 
o 
Since year: ____________ 
o 
Therapy: __________________ 
7. Chronic Pancreatitis: 
o YES 
o NO 
If yes, indicate: 
o 
Since year: ____________ 
o 
Therapy: __________________ 
8. Ulcer: 
o YES 
o NO 
If yes, indicate: 
o 
Ulcer type: 
o Gastric 
o Duodenal 
o 
Since year: ____________ 
o 
Therapy: __________________ 
9. Helicobacter pylori (Hp) Infection: 
o YES 
o NO 
If yes, indicate: 
o 
Year of Hp diagnosis: ____________ 
o 
Eradication: 
o YES 
o NO 
o 
Year of eradication: ___________ 
o 
Therapy: __________________ 
10. Gastroresection: 
o YES 
o NO 
If yes, indicate: 
o 
Since year: ____________ 
o 
Type: _______________________ 
o 
Indication: __________________ 

 
 
 
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11. Cholecystectomy: 
o YES 
o NO 
If yes, indicate: 
o 
Since year: ____________ 
o 
Indication: __________________ 
 
PHARMACOLOGICAL HISTORY (Check drug and dose) 
12. Prolonged Aspirin Use: 
o YES 
o NO 
If yes, indicate: 
o 
Which: 
o Cardioaspirin 100 mg – _____ times/day 
o Cardirene 75 mg/100 mg/160 mg/300 mg – _____ times/day 
o Aspirin 325 mg/400 mg/500 mg – _____ times/day 
o 
Total years: __________ 
13. Prolonged NSAID Use: 
o YES 
o NO 
If yes, indicate: 
o 
Drug type: ___________________ 
o 
Dose: _____________________ 
o 
Times/day or times/week: ____________ 
o 
Total years or within the last year: __________ 
14. Statin Use: 
o YES 
o NO 
If yes, indicate: 
o 
Which: 
o Atorvastatin (Torvast, Totalip) 
o Fluvastatin (Lescol, Lipaxan, Primesin) 
o Lovastatin (Lovinacor, Rextat, Tavacor) 
o Pravastatin (Aplactin, Prasterol, Pravaselect, Sanare, Selectin) 
o Rosuvastatin (Crestor, Provisacor, Simestat) 
o Simvastatin (Liponorm, Medipo, Sindaco, Sivastin, Zocor) 
o Simvastatin + Ezetimibe (Inegy, Goltor, Vytorin) 
o 
Dosage: 10 mg/20 mg/40 mg/60 mg/80 mg/100 mg/120 mg 
o 
Times/day: __________ 
o 
Total years: __________ 

 
 
 
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15. Prolonged PPI Use: 
o YES 
o NO 
If yes, indicate: 
o 
Drug type: ___________________ 
o 
Dose: _____________________ 
o 
Times/day or times/week: ____________ 
o 
Total years or within the last year: __________ 
16. Prolonged ACE Inhibitor Use: 
o YES 
o NO 
If yes, indicate: 
o 
Which: 
(List of ACE inhibitors as per original) 
o 
Times/day or times/week: ____________ 
o 
Total years or within the last year: __________ 
17. Prolonged ARB (Sartans) Use: 
o YES 
o NO 
If yes, indicate: 
o 
Which: 
(List of ARBs as per original) 
o 
Times/day or times/week: ____________ 
o 
Total years or within the last year: __________