Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

57
ITALIAN CONSENSUS GUIDELINES FOR DIAGNOSTIC WORK-UP AND FOLLOW-UP OF CYSTIC PANCREATIC NEOPLASMS Elisabetta Buscarini Raffaele Pezzilli

description

Gastrolearning II modulo/5a lezione Lesioni cistiche pancreatiche: linee guida diagnostiche Prof.ssa E. Buscarini - Crema

Transcript of Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Page 1: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

ITALIAN CONSENSUS GUIDELINES FOR DIAGNOSTIC WORK-UP AND FOLLOW-UP OF

CYSTIC PANCREATIC NEOPLASMS

Elisabetta Buscarini Raffaele Pezzilli

Page 2: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

WHO classification of cystic pancreatic tumors, 2010

CPNs: mostly detected incidentally High prevalence: 2.6% -19.6% Increase of CPNs prevalence with age: 8% below 70 yrs up to 35% >90 yrs

Page 3: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

serousmucinousIPMNpseudopapillary

Pancreatic cystic neoplasms epidemiology

Type Sex Mean age at diagnosis

serous 50

mucinous 50

IPMN >60

pseudopap 30

Page 4: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

AIGO and AISP have fostered consensus guidelines :

– limited to the diagnostic work-up and follow-up of all CPNs according to WHO classification

– based on a sound consensus methodology to allow evaluation of published data and of their quality, and to synthesize them with expert opinion

– clinically oriented– taking into account also the characteristics of Italian Health Care

System, with its inherent availability of different diagnostic techniques– applicable only for patients “fit for treatment” at the time of diagnosis or

along the follow up

Consensus guidelines CPNs

Page 5: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

COHORDINATORSElisabetta Buscarini Raffaele PezzilliRenato CannizzaroMassimo Falconi

CLINICALRenato Cannizzaro Luca Frulloni Stefano Crippa Riccardo Casadei Alessandro Zerbi

EUSClaudio De Angelis Paolo Arcidiacono Paolo Bocus Pietro Fusaroli Luca Barresi

IMAGING Giovanni MoranaSilvia Venturini Mirko D’Onofrio Lucia Calculli Claudio Pasquali

LABORATORYMassimo Gion Daniela Basso Maurizio VentrucciRodolfo Rocca Gabriele Capurso

PATHOLOGYGiuseppe Zamboni Vincenzo Villanacci Vincenzo Canzonieri Gianpaolo Balzano Donatella Pacchioni

Consensus guidelines CPNsTeams

Page 6: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Luca AlbarelloLorenzo CamelliniRita ConigliaroGiuseppe Del Favero Giovanna Del Vecchio BlancoPierluigi Di SebastianoCarlo FabbriNiccola Funel Andrea GalliArmando GabbrielliRossella GrazianiAndrea LaghiGiampiero Macarri Fabrizio MagnolfiGuido ManfrediMarco Marzioni

Consensus Participants

Fabio MonicaNicola MuscatielloMassimiliano MutignaniAntonio PisaniEnrico ScaranoMarco SpadaAlessandro ZambelliRepresentative of SIEDGuido Costamagna Representative of SIGEPaolo CantùRepresentative of SIGENPTiziana GuadagniniRepresentative of SIUMBCarla SerraRepresentative of the GPMarco ViscontiRepresentative of citizen and patient rights Paolo Federici

Page 7: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Levels of evidence Oxford Centre for Evidence-Based Medicine

Medicine

Page 8: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Grades of recommendation The strength of each recommendation depends on

the category of the evidence supporting it Oxford Centre for Evidence-Based Medicine

Page 9: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Consensus Guidelines CPNs Fifty-two questions

1. Clinical framework, 12 statements2. Laboratory, circulating, 5 statements3. Radiology, 5 statements 4. EUS, 13 statements 5. Laboratory, intracystic, 11 statements 6. Pathology, 6 statements

Page 10: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

CLINICAL EVALUATION

Page 11: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

 Statement

All patients with pancreatic cystic neoplasms require a diagnostic work-up

EL 2a, RG B

After exclusion of patients neither suitable for any treatment nor wishing a diagnostic definition, which patient with

pancreatic cystic lesion needs further diagnostic work up?

Page 12: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

 

Statement

Signs/symptoms include: abdominal pain, acute pancreatitis, nausea and vomiting, weight loss also due to exocrine pancreatic insufficiency with steatorrhea, anorexia, recent onset or worsening diabetes, obstructive jaundice, and palpable mass

EL 4, RG D

After setting definition on the basis of the presence/absence of sign/symptoms, depict accordingly clinical scenarios.

 In symptomatic patients which are signs/symptoms due to a

pancreatic cystic lesion?

Page 13: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Symptomatic Lesions

Page 14: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

In the setting of symptomatic patients, high resolution imaging techniques including MRI with MRCP and/or MDCT scan with pancreas protocol represent the first diagnostic step

EL 1a, RG A

In the setting of symptomatic patients which diagnostic technique/s is/are necessary before treatment? 

Page 15: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Asymptomatic Lesions

Page 16: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

 Statement

A family history for pancreatic cancer and/or other malignancies and a personal and familial history consistent with Von Hippel-Lindau disease have to be searched

Serum CA19-9 and glucose level have to be evaluated as well

EL 2a, RG B

Which data regarding personal or familial history, and which laboratory findings have to be searched for in asymptomatic

patients?

Page 17: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

An enhancing solid component within the cyst represents an indication for treatment

For IPMNs the presence of a main duct > 10 mm is another indication for treatment

EL 2a, RG B

In asymptomatic patients are there morphological findings of the cystic pancreatic neoplasms which can address

straightforward to treatment?

Page 18: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

In asymptomatic patients which technique/s is/are necessary to address the patient with pancreatic cystic

lesion either to treatment or to follow-up?

Statements

In this setting pan exploring high resolution imaging techniques including MRI with MRCP and/or MDCT scan with pancreas protocol represent the first diagnostic step

EL 4, RG C

When “worrisome” morphological features are identified or in patients with uncertain radiologic diagnosis (i.e. small branch-duct IPMN versus small SCN) EUS with FNA for cytology is recommended

EL 4, RG C

Page 19: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Regarding the follow-up of patients where observation has been chosen, and bearing in mind that follow-up aims to: 1) demonstrate the size variations over the time (either as cystic lesion increase or decrease in size or disappears);

2) diagnostic confirmation (test of time), we need to answer to the following questions:Which is the test

of choice for follow-up?

Statement

The test of choice for follow-up is MRI with MRCP.

At any follow-up evaluation a careful clinical examination to look for symptoms and laboratory tests including, CA 19.9 and glucose levels has to be performed, especially in mucinous lesions

EL 2a, RG B

Page 20: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the timing?

Statement

Follow-up timing should be carried out at least yearly and be related with morphological characteristics of the cystic lesion, family history of pancreatic cancer, diabetes mellitus and serum CA 19-9 levels

EL 3, RG B

Page 21: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Suggested follow-up timing according to the type of cystic lesion

Page 22: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

TEST 1

F, 32 yo, incidental discovery

F, 38 yo, incidental discovery during pregnancy

Page 23: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Do cystic lesions of the pancreas exclude the patient from organ transplantation?

Statement

No

EL 4, RG C

Page 24: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which diagnostic work-up is required in organ transplant candidates with evidence of a cystic lesion of the pancreas

without morphological characteristics of malignancy?

StatementMRI/ MRCP and EUS with FNA are recommended. Laboratory tests including CA 19.9 and glucose level and a careful clinical evaluation for cyst-related symptoms should be carried out.

EL 4, RG C

Page 25: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

In the organ transplanted patient does the presence of an asymptomatic cystic lesion of the pancreas without morphological aspects of malignancy require alternative follow-up strategies in

diagnostic tests and timing?

StatementNoEL 4, RG C

Page 26: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

LABORATORY &CIRCULATING MARKERS

Page 27: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the post-test probability that an abnormal serum CA19.9 level recognizes a malignant behavior of a

pancreatic cystic neoplasm?

Statement

CA19.9 is not a marker of CPNs malignancy. However serum CA19.9 determination provides additional information within the diagnostic work up since a positive result is associated with the presence of an invasive carcinoma with a SP ranging from 79 to 100% and a PPV of 74%. Conversely a negative result does not exclude the presence of a malignancy (SS 37-80%)

EL 4, RG C

Page 28: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

CROSS SECTIONAL IMAGING &

NUCLEAR MEDICINE

Page 29: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the best imaging modality among US/CEUS, MDCT, MRI - MRCP, secretin MRCP, FDG-PET for differentiating

between benign and malignant cystic pancreatic lesions?

StatementConventional US of the pancreas is not able to definitively diagnose CPNsEL 5; RG C

The different dynamic imaging modalities (CEUS, MDCT, MR) have similar high accuracy.EL 1b; RG A

Available data do not support the use of S-MRCP in the differential diagnosis of benign versus malignant CPNsEL 5; RG D

The accuracy of FDG-PET-CT is highEL 1b; RG B

Page 30: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the best imaging modality among US/CEUS, MDCT, MRI - MRCP, secretin MRCP, FDG-PET for differentiating between mucinous and non-mucinous cystic pancreatic

lesions?

Statement

MDCT and MR are the best imaging modalities for differentiating mucinous and non-mucinous CPNs, both with high accuracy

EL 1b; RG A

There are no corresponding detailed data on CEUS and 18FDG-PET Data supporting the use of S-MRCP are not available

EL 5; RG D

Page 31: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the role of different imaging techniques in patients with CPNs (diagnostic algorithm)?

Statement

MR and MDCT are first level techniques in the differentiating benign from malignant CPNs. CEUS has similar performances than MR and MDCT, when CPNs is visible at US

MR with MRCP is the best imaging modality to evaluate the communication of CPNs with the main pancreatic duct

EL 1b; RG A

Based on the above statements, MR with MRCP is the imaging method of choice for the study of CPNs

18FDG-PET must be considered as a second level, if clinical suspicion for malignancy is high and other imaging modalities are inconclusive or if other imaging modalities are suspicious for malignancy but with a low level of confidence.

EL 5; RG D

Page 32: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the role of different imaging techniques (US/CEUS, MDCT, MRI - MRCP, secretin MRCP, 18FDG-PET-CT) for the

follow up of patients with asymptomatic CPNs?

StatementThe role of single method is depending on both the size and the number of CPNsSingle cyst:Small (< 1 cm)• visible at US: US preferred until size change occurs. • not visible at US: MR/MRCPLarge (≥ 1 cm)• visible at US: US preferred until size change occurs. If size change occurs,• not visible at US: MR with MRCP or MDCT (the latter with the above limitations).In case of strict follow-up (e.g. 3 months), MDCT should be used only in older patients without renal insufficiency or in patients with absolute contraindications to MR

Multiple cysts: •MR with MRCP

Page 33: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

ENDOSONOGRAPHY & ERCP

Page 34: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

StatementEUS can identify morphological features which increase the suspicion for malignancy in CPNs. However EUS morphologic features alone cannot exclude the presence of malignancy in CPNs

EL 2b, RG B

What is the role of EUS in differentiating between benign and malignant CPNs?

Page 35: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

StatementAlthough EUS morphology alone cannot provide a definite differential diagnosis between mucinous and non-mucinous CPNs, some EUS features offer useful information on the type of lesion

EL 4, RG C

What is the role of EUS in differentiating between mucinous and non-mucinous pancreatic cystic lesions?

Page 36: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

Contrast enhanced EUS may be helpful in differential diagnosis of CPNs and in ruling out neoplastic degeneration. Analysis of intracystic nodules at contrast enhanced EUS may help in differentiating neoplastic vegetations from mucus and debris

EL 4, RG C

Does the use of contrast during EUS increase the diagnostic accuracy of EUS for CPNs?

Page 37: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

EUS-FNA is indicated when a previous diagnostic modality has depicted CPNs with worrisome features other than an enhancing solid component or when the other diagnostic modalities fail to give either a definite diagnosis or in cases of advanced malignant cystic lesions when chemotherapy is considered

EL 2a, RG B

When is EUS-FNA recommended for differentiating between benign and malignant CPNs?

Page 38: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

EUS-FNA is indicated when the other diagnostic modalities fail to give a definite differential diagnosis

EL 2a, RG B

When is EUS-FNA recommended for differential diagnosis between mucinous and non–mucinous CPNs?

Page 39: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

TEST 2F, 74 yo, recurrent epigastric pain & recent diabetes onset

Page 40: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

M, 64 yo, incidental discoveryTEST 3

Page 41: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

Diagnostic ERCP for the evaluation of CPNs is indicated only if endoscopic views of the papillary area, pancreatoscopy, or intraductal ultrasound are still required at the end of the diagnostic work-up for a definite diagnosis in patients with suspected IPMN

EL 4, RG C

Which is the diagnostic role of ERCP in patients with CPNs?

Page 42: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

EUS-FNA of CPNs entails a rate of intra-cyst hemorrhage around 4%. Usually bleeding is self-limiting. No death has been reported after EUS-FNA performed in the standard modality with standard needles. Different risks of complications have been reported with different technical modalities of FNA or using different devices.

EL 4, RG C

Which is the expected complication rate due to EUS-FNA?

Page 43: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Statement

There are not sufficient data to show that antibiotic prophylaxis reduces the rate of infectious complications.

EL5, RG D

Does antibiotic prophylaxis reduce the infectious complication rate of EUS-FNA of CPNs?

Page 44: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

LABORATORY- MARKERS IN CYST FLUID

Page 45: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Is the determination of intracystic CEA useful in the differential diagnosis between benign and malignant cystic

pancreatic lesions?

Statement

Intracystic CEA is not accurate in recognizing malignant from non-malignant lesions

EL 2a, RG B

Page 46: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Is the determination of intracystic CEA useful in the differential diagnosis between mucinous and non-mucinous

cystic pancreatic lesions?

Statement

Increased CEA levels in cyst fluid are helpful in distinguishing mucinous from not mucinous CPNs

EL 2a, RG B

Page 47: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Is the determination of intracystic amylase useful in the differential diagnosis of cystic pancreatic lesions?

Statement

The determination of amylase in cyst fluid is helpful to determine the differential diagnosis among CPNs. High amylase levels are usually associated with a communication between pancreatic duct and cystic lesion, as for the majority of IPMNs

EL 2c, RG B

Page 48: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

How much does a combination of intracystic tests increase their performances?

Statement

The determination of both CEA and amylase is recommended to help in distinguishing mucinous from non-mucinous cyst lesions

EL 2c, RG B

Page 49: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Are there specific recommendations for the assessment of positive/negative cutoff point of CEA, Amylase and CA19.9

in cyst fluid ?

Statement

No evidence exist on cutoff to be used in the clinical practice. In addition, cutoff values are partially related to the used assay method

EL 5, RG D

Page 50: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

PATHOLOGY

Page 51: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Can cytological examination differentiate between benign and malignant cystic pancreatic lesions?

Statement

The cytological examination is useful in the differential diagnosis between benign and malignant cystic pancreatic lesions

EL 2a, RG B

Page 52: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

How could be differentiated a mucinous from a non-mucinous cystic lesion by cytological examination?

Statement

The presence of extracellular, thick mucus, and the recognition of an atypical epithelial cell component with intracytoplasmic mucin, represent the diagnostic hallmark of mucinous cystic lesions

EL 2c, RG B

Page 53: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Which is the diagnostic value of high-grade cellular atypia?

Statement

The presence of cells with high grade atypia is the best cytological marker of a malignant cystic neoplasms

EL 2b, RG B

Page 54: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

TEST 4

Page 55: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

TEST 5F, 75 yo, incidental discovery

Page 56: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

TEST 5

CEA > 150,000 ng/mlAmylase 84 U/mlNo malignant cells

Page 57: Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®

Future developments

The consensus process has highlighted some areas particularly in need of study:

1. Available data on natural history of CPNs are still very limited

2. Studies of CPNs with transcutaneous imaging are barely comparable to EUS studies as the latter generally deal with smaller CPNs or more difficult to interpret: studies comparing the yield and impact of these techniques in similar CPNs are thus desirable

3. The laboratory examination of CPN fluid still requires a standardization

4. AIGO and AISP will validate present guidelines with a prospective data collection in order to evaluate the improvement of both patient management and efficiency in resource utilization