Lesioni cistiche pancreatiche: linee guida diagnostiche - Gastrolearning®
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Transcript of 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
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
serousmucinousIPMNpseudopapillary
Pancreatic cystic neoplasms epidemiology
Type Sex Mean age at diagnosis
serous 50
mucinous 50
IPMN >60
pseudopap 30
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
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
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
Levels of evidence Oxford Centre for Evidence-Based Medicine
Medicine
Grades of recommendation The strength of each recommendation depends on
the category of the evidence supporting it Oxford Centre for Evidence-Based Medicine
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
CLINICAL EVALUATION
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?
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?
Symptomatic Lesions
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?
Asymptomatic Lesions
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?
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?
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
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
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
Suggested follow-up timing according to the type of cystic lesion
TEST 1
F, 32 yo, incidental discovery
F, 38 yo, incidental discovery during pregnancy
Do cystic lesions of the pancreas exclude the patient from organ transplantation?
Statement
No
EL 4, RG C
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
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
LABORATORY &CIRCULATING MARKERS
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
CROSS SECTIONAL IMAGING &
NUCLEAR MEDICINE
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
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
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
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
ENDOSONOGRAPHY & ERCP
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?
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?
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?
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?
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?
TEST 2F, 74 yo, recurrent epigastric pain & recent diabetes onset
M, 64 yo, incidental discoveryTEST 3
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?
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?
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?
LABORATORY- MARKERS IN CYST FLUID
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
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
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
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
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
PATHOLOGY
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
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
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
TEST 4
TEST 5F, 75 yo, incidental discovery
TEST 5
CEA > 150,000 ng/mlAmylase 84 U/mlNo malignant cells
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