5. Diagnostics – Pancreatic Cancer
5.1 Diagnostics for Newly-onset Symptoms
Newly-onset upper abdominal and back pain should prompt diagnostic tests that allow the diagnosis of pancreatic cancer.
- Recommendation grade
- C: Studien mit Evidenzgrad 4 oder Extrapolationen von Studien mit Evidenzgrad 2 oder 3
- Level of evidence
- 3
- Consensus
- Strong consensus
Background
In principle, newly-onset upper abdominal and back pain that could be caused by pancreatitis or pancreatic cancer requires further diagnosis. There is no literature that answers which symptoms alone and in which combination and at what age should suggest pancreatic cancer. Which diagnostics alone or in combination are sufficient to exclude a pancreatic tumor is also not supported by literature. However, newly-onset back pain that cannot be explained by musculoskeletal changes alone should not trigger diagnostic testing for pancreatic cancer. Table 2 "Age- and Suspicion Level-adapted Diagnostic Approach" presents a suggestion for an age and suspicion level-adapted approach based on expert opinion.
Table 9: Age- and Suspicion Level-adapted Diagnostic Approach to Newly-onset Upper Abdominal and Back Pain
| Suspicion level | Age (years) | Symptoms | Procedure |
| Low | <50 | Pain only* | Sonography for symptom persistence |
| Medium | <50 | Pain plus** | Sonography, CT if necessary |
| >50 | Pain only* | Sonography, CT if necessary | |
| Pain plus** | Sonography, CT if necessary | ||
| High | >50 | Pain plus** | Sonography, if necessary CT/endosonography |
|
* Newly-onset of pain that radiates into the back in a localized/belt-like manner and is perceptible at night requires further clarification on an individual basis, regardless of age. If the level of suspicion is high, complementary CT or endosonography should be used even if sonography is negative. ** Pain plus other symptoms (inappetence, weight loss, weakness) |
|||
Acute pancreatitis of unclear etiology should prompt additional measures to exclude pancreatic cancer in certain cases (patients > 50 years of age with first „idiopathic“ pancreatitis).
Background
The incidence of pancreatic cancer in acute pancreatitis and even more so in an acute episode of chronic pancreatitis appears to be increased but does not exceed 1-2% of all cases of pancreatic cancer or a maximum of 5% in the idiopathic forms. There are few systematic studies on this topic, especially in the idiopathic forms. The data for endosonography in this context are well documented. Therefore, endoscopic ultrasound is primarily recommended and should be performed in the symptom-free interval after acute pancreatitis. Alternatively, a multidetector CT (MD-CT) scan may be considered. A ductal workup seems worth considering if endoscopic ultrasound is negative, although data are only available for ERCP, which carries a risk for post-ERCP pancreatitis. By analogy, performance of MRCP may be recommended [181], [182].
CA19-9 determinations should not be performed for the diagnosis of pancreatic cancer as a matter of principle. There is also no recommended algorithm or diagnostic procedure that should be used to clarify an elevated CA19-9 value. Although pancreatic cancer can occur before the age of 50, the age-dependent incidence curves show an increase only after the age of 50 [176]. Therefore, the above-mentioned diagnostic examinations should only be performed after the age of 50 years
5.2 Imaging Methods for Primary Diagnostics
Different methods such as sonography, endosonography, multidetector CT, MRI with MRCP, or ERCP are suitable for clarifying a suspected tumor.
Background
The above-mentioned procedures are available in different ways and thus cannot be used in an algorithm defined for every situation. There is a consensus that, in principle, upper abdominal ultrasonography should be performed first, which already allows the suspected diagnosis of pancreatic carcinoma and, if necessary, the diagnosis of metastases. All other procedures also allow the detection of pancreatic carcinoma, although ERCP alone is not suitable for the diagnosis of pancreatic ductal carcinoma, as it only detects ductal changes and does not visualize the mass itself [185], [186].
Computed tomography (CT) should be performed as multidetector computed tomography (MD-CT) with at least a biphasic contrast protocol (pancreatic parenchymal phase and portal venous phase). The slice thickness should be ≤ 3 mm. MRI/MRCP should be performed with a field strength of at least 1.5 Tesla and standard weights (T1 and T2 including MRCP). The slice thickness should be 5-7 mm.
Diagnostic procedures of first choice for the detection of pancreatic cancer are upper abdominal sonography, endosonography, multidetector CT, and MRI in combination with MRCP.
- Recommendation grade
- B: Konsistent Studien mit Evidenzgrad 2 oder 3 bzw. Extrapolationen von Studien mit Evidenzgrad 1
- Level of evidence
- 3
- Consensus
- Consent
Background
According to the literature, the two most sensitive methods for detecting pancreatic cancer are multidetector CT and MRI in combination with MRCP. In the hands of experienced examiners, endosonography sometimes achieves even higher sensitivity. A clear evaluation in favour or against one of the procedures cannot be made here. The procedure for which the greatest expertise exists in a given institution should be used. If necessary, the procedures must also be used in a complementary manner.
5.3 Histology, Cytology, and Laboratory Diagnostics
5.3.1 Cytological Diagnostics
Brush cytology from the bile duct has too low a sensitivity in the presence of pancreatic carcinoma. It is also not recommended to take brush cytology samples from the pancreatic duct for the detection of pancreatic cancer. Therefore, ERCP is not indicated for tissue diagnosis of pancreatic cancer.
- Level of evidence
- 5
- Consensus
- Consent
Background
The literature does not allow an adequate statement on the question above. The brushing procedures in the pancreas, but also in the bile duct system are risky and inexpedient.
5.3.2 Laboratory Examinations
Background
Laboratory determination of CA19-9 may be used for differential diagnosis in individual cases. In cases of potential resectability on imaging, a very high preoperative CA19-9 value may give reason to perform a staging laparoscopy, because in such cases there is often a larger tumor burden than suspected on imaging, e.g., disseminated tumor seeding. To date, however, no cost-benefit analyses exist to demonstrate the usefulness of this kind of determination [191], [192], [193], [194].
5.3.3 Tissue Diagnostics: Procedure for Pancreatic Masses
In the presence of a potentially resectable, carcinoma-suspected mass in the pancreas, resection should be the primary approach. Endosonographically guided biopsy can be performed if there is differential diagnostic evidence that would alter the approach, such as suspected metastasis from another malignancy in the medical history.
Background
Endosonographically assisted fine needle aspiration is sensitive and highly specific for histologic or cytologic detection of pancreatic cancer [198], [199], [200]. However, it is dispensable in the vast majority of cases, since in the case of operability, even masses of unclear dignity should be operated on. A bioptic diagnosis of a pancreatic mass with potentially resectable findings is therefore not necessary preoperatively.
If a biopsy is performed nevertheless on the basis of differential diagnostic considerations, preference is given to biopsies of those space lesions whose puncture is associated with the lowest risk of complications.
- Recommendation grade
- D: Expertenmeinung oder inkonsistente bzw. nicht schlüssige Studien jedes Evidenzgrades
- Level of evidence
- 5
- Consensus
- Consent
Prior to the implementation of specific palliative therapy, bioptic diagnostic confirmation is mandatory, regardless of whether the pancreatic cancer is locally advanced, unresectable, or metastatic.
- Recommendation grade
- B: Konsistent Studien mit Evidenzgrad 2 oder 3 bzw. Extrapolationen von Studien mit Evidenzgrad 1
- Level of evidence
- 2a
- Consensus
- Strong consensus
- References
- [201]
Background
Before initiating palliative chemotherapy, the diagnosis must be confirmed cytologically or histologically to exclude possible differential diagnoses and resulting incorrect treatment [201].
The most accessible lesion with the lowest possible risk is to be punctured, regardless of whether it is the primary tumor or a metastasis
- Recommendation grade
- D: Expertenmeinung oder inkonsistente bzw. nicht schlüssige Studien jedes Evidenzgrades
- Level of evidence
- 5
- Consensus
- Strong consensus
5.4 Preoperative Spread Diagnosis
Multidetector CT and endosonography are preferred for preoperative assessment of local tumor extent or resectability.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 1
- Consensus
- Consent
- References
- [202]
Endosonography as a high-quality diagnostic procedure can be used for local evaluation of pancreatic cancer.
- Recommendation grade
- 0: offene Empfehlung (Option) bzgl. einer Maßnahme - verwendete Ausdrucksweise = kann
- Level of evidence
- 1
- Consensus
- Consent
- References
- [203] [204]
Change note
Abdominal ultrasonography is mandatory to assess systemic tumor spread. Abdominal multidetector computed tomography is mandatory when abdominal ultrasonography does not demonstrate systemic metastasis or when imaging according to RECIST criteria (Response Evaluation Criteria In Solid Tumors) is desired in study situations. A chest X-ray examination is an obligatory part of tumor staging. MRI is also considered optional for the study of systemic tumor spread, as is chest CT for staging. Endosonography, ERCP and MRCP, and skeletal scintigraphy are not used for tumor staging. FDG-PET examination, as well as micrometastasis diagnostics from whole blood, is currently of no value in preoperative spread diagnostics.Background
Abdominal ultrasonography can be useful for evaluating systemic tumor spread in the absence of appropriate cross-sectional imaging, as it can be used to include or exclude focal liver lesions [D'Onofrio, M. et al. 2012], [D'Onofrio, M. et al. 2020]. The negative predictive value of abdominal ultrasonography is very high under good conditions and can be chosen as a diagnostic method of exclusion in cases of unclear symptoms. If the sensitivity and specificity of the procedure are limited, contrast-enhanced 2-phase computed tomography (CT) should be performed in cases of diagnostic uncertainty [1]. Alternatively, MRI can be performed in cases of contrast intolerance or renal insufficiency.
CT is the standard procedure for assessing the size of the primary tumor and local tumor spread. CT of the lung and abdomen to determine tumor extension should be performed as a 2-phase examination. A comparison of the literature on preoperative staging of pancreatic cancer by endoscopic ultrasound and CT revealed a slightly higher sensitivity for endoscopic ultrasound [203], [204], but endoscopic ultrasound is not widely available in the quality investigated in studies and the imaging documentation is often insufficient from a surgical point of view, so that cross-sectional imaging is usually necessary for assessment by the surgeon. If sufficient multidetector computed tomography or magnetic resonance imaging examinations are already available pretherapeutically, further procedures can be dispensed with [202].
Contrast-enhanced computed tomography of the lung and abdomen/pelvis shall be performed when evaluation of tumor spread is necessary and there are no contraindications to CT.
- Consensus
- Strong consensus
Change note
Abdominal ultrasonography is mandatory to assess systemic tumor spread. Abdominal multidetector computed tomography is mandatory when abdominal ultrasonography does not demonstrate systemic metastasis or when imaging according to RECIST criteria (Response Evaluation Criteria In Solid Tumors) is desired in study situations. A chest X-ray examination is an obligatory part of tumor staging. MRI is also considered optional for the study of systemic tumor spread, as is chest CT for staging. Endosonography, ERCP and MRCP, and skeletal scintigraphy are not used for tumor staging. FDG-PET examination, as well as micrometastasis diagnostics from whole blood, is currently of no value in preoperative spread diagnostics.Patients with resectable pancreatic cancer should receive liver MRI with diffusion weighting preoperatively after 2-phase thin-slice CT.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 3
4 - Consensus
- Consent
- References
- [209] [210] [211] [212] [213]
Change note
Abdominal ultrasonography is mandatory to assess systemic tumor spread. Abdominal multidetector computed tomography is mandatory when abdominal ultrasonography does not demonstrate systemic metastasis or when imaging according to RECIST criteria (Response Evaluation Criteria In Solid Tumors) is desired in study situations. A chest X-ray examination is an obligatory part of tumor staging. MRI is also considered optional for the study of systemic tumor spread, as is chest CT for staging. Endosonography, ERCP and MRCP, and skeletal scintigraphy are not used for tumor staging. FDG-PET examination, as well as micrometastasis diagnostics from whole blood, is currently of no value in preoperative spread diagnostics.Evidence tables (5)
Chew, Cindy et al. The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography. Singapore Medical Journal. 57. 334-338. 2016; Ito, T. et al. The diagnostic advantage of EOB-MR imaging over CT in the detection of liver metastasis in patients with potentially resectable pancreatic cancer. Pancreatology. 17. 451-456. 2017; Jeon, Sun Kyung et al. Magnetic resonance with diffusion-weighted imaging improves assessment of focal liver lesions in patients with potentially resectable pancreatic cancer on CT. European Radiology. 28. 3484-3493. 2018; Kim, H. W. et al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer. Surgery (United States). 161. 1579-1587. 2017; Kim, H. J. et al. Incremental role of pancreatic magnetic resonance imaging after staging computed tomography to evaluate patients with pancreatic ductal adenocarcinoma. Cancer Research and Treatment. 51. 24-33. 2019Alternatively, they should receive FDG-PET CT to rule out the presence of distant metastases with higher certainty.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 1
2 - Consensus
- Consent
- References
- [214] [215]
Change note
Abdominal ultrasonography is mandatory to assess systemic tumor spread. Abdominal multidetector computed tomography is mandatory when abdominal ultrasonography does not demonstrate systemic metastasis or when imaging according to RECIST criteria (Response Evaluation Criteria In Solid Tumors) is desired in study situations. A chest X-ray examination is an obligatory part of tumor staging. MRI is also considered optional for the study of systemic tumor spread, as is chest CT for staging. Endosonography, ERCP and MRCP, and skeletal scintigraphy are not used for tumor staging. FDG-PET examination, as well as micrometastasis diagnostics from whole blood, is currently of no value in preoperative spread diagnostics.Background
A systematic evaluation of the role of MRI preoperatively could show that the sensitivity of MRI compared to CT for the detection of metastases is higher (especially for lesions < 1 cm) and metachronous metastases were detected significantly later after staging by MRI compared to CT - associated with a longer postoperative survival [210], [212], [209], [211], [213]. From this it is deduced that MRI should be performed preoperatively for locally operable findings. Alternatively, FDG-PET/CT can be used with a sensitivity of up to 93% and a specificity of up to 76% [215], [214], [216], [217], [218], [219], [220], [221], [222], [223]. The data come from a randomized trial from the United Kingdom [215]. PET/CT in this indication is not covered nationwide in Germany and individual cost coverage must be requested from the health insurance company. The lack of nationwide availability of the examination method, which may lead to a delay in curative surgery, should also be critically evaluated. For the British health care system, as published in the NICE guidelines, it has been shown that preoperative staging using PET/CT leads to an increase in QALY (quality-adjusted life years) and is thus assessed as cost-efficient. This assessment cannot be safely transferred to the German health care system.
ERCP, MRCP, and skeletal scintigraphy should not be used for diagnosis of spread.
- Consensus
- Strong consensus
Change note
Abdominal ultrasonography is mandatory to assess systemic tumor spread. Abdominal multidetector computed tomography is mandatory when abdominal ultrasonography does not demonstrate systemic metastasis or when imaging according to RECIST criteria (Response Evaluation Criteria In Solid Tumors) is desired in study situations. A chest X-ray examination is an obligatory part of tumor staging. MRI is also considered optional for the study of systemic tumor spread, as is chest CT for staging. Endosonography, ERCP and MRCP, and skeletal scintigraphy are not used for tumor staging. FDG-PET examination, as well as micrometastasis diagnostics from whole blood, is currently of no value in preoperative spread diagnostics.Table 10: Diagnostic value of magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography combined with CT (PET/CT), endosonography (EUS), and transabdominal ultrasound (US) for the diagnosis of pancreatic cancer
|
Diagnostic Value: Imaging Techniques for Pancreatic Cancer Diagnosis |
|||||
|
Method |
MRI |
CT |
PET/CT |
EUS |
US |
|
Sensitivity |
93% |
90% |
89% |
91% |
88% |
|
Specificity |
89% |
87% |
70% |
86% |
94% |
|
Accuracy |
90% |
89% |
84% |
89% |
91% |
Source: [224]
Background
Staging laparoscopy is of particular interest when, for example, excessive elevated CA19-9 levels or ascites result in suspicion of peritoneal seeding without being detectable on imaging. In up to one-third of patients, staging laparoscopy reveals findings that exclude curative resection [225], [226].
5.5 Cystic Processes
Out of all sectioning techniques, MRI with MRCP should be used preferrentially for the differential diagnosis of a cystic lesion of the pancreas.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 5
- Consensus
- Strong consensus
- References
- [227]
For further differential diagnosis, endosonography should be performed in addition to cross-sectional imaging if a lesion > 1 cm is diagnosed or if diagnostic uncertainty exists.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 5
- Consensus
- Strong consensus
- References
- [227]
An endosonographic puncture to obtain cells or cyst fluid and differential diagnosis of the lesion (histopathological or cytopathological analysis, determination of lipase/amylase and CEA, molecular pathological analysis) can be performed.
Background
The diagnostic accuracy of MRI with MRCP is 40-95% for cystic lesions of the pancreas. For CT, diagnostic accuracy is reported to be 40-81%. The imaging prevalence of cystic lesions of the pancreas in CT examinations is 2.1-2.6% and 13.5-45% for MRI/MRCP examinations. MRI/MRCP has a significantly higher sensitivity for detection. Differential diagnostic confidence is inadequate for both examination methods, especially for lesions < 1cm. PET/CET is reported to have a sensitivity of 95% (95% CI 80-97%) and a specificity of 65% (95% CI 39-84%). Endosonography has a sensitivity of 95% (95% CI 84-99%) and a specificity of 53% (95% CI 31-74%). Contrast-enhanced endosonography can increase sensitivity to 60-100% and specificity to 75%-93%. Diagnostic puncture may be indicated for differential diagnosis. Diagnostic cyst puncture allows detection of infection of the cyst contents and thus indicates drainage. In addition, diagnostic puncture of a cystic lesion by EUS helps to differentiate between cystic neoplasms and pseudocysts or non-neoplastic cysts. In this regard, the sensitivity of an EUS-guided FNA is 50% (95% CI 1-100%) and the specificity is 95% (95% CI 67-100%) [229]. If additional methods, such as the determination of lipase/amylase and CEA and molecular pathological analyses using highly sensitive NGS (next-generation sequencing) are added, the diagnostic accuracy can be increased. Using NGS, a sensitivity of 100% (95% CI 74-100%) can be achieved for the diagnosis of mucinous cystic neoplasia (MCN) and 76% (95% CI 66-84%) for the diagnosis of intraductal papillary mucinous neoplasia (IPMN) [230].
Briefly summarized: If EUS-assisted puncture of a cyst yields a CEA > 400 ng/ml, variably elevated or low amylase (lipase), high viscosity, mucin, or mucus-forming epithelia in the cyst contents, the presence of mucinous neoplasia must be assumed. If lipase/amylase is negative and the clinical constellation is appropriate, the diagnosis is usually a mucinous cystic neoplasia (MCN), which occurs frequently in women aged 30-50 years, is usually localized in the tail of the pancreas and has mural nodules on imaging. The so-called „eggshell pattern“ is typical in this case. If the growth is noninvasive, the prognosis after surgery is good. However, if invasive growth is demonstrated, the median survival is 45 months. The cyst punctate of MCN differs little from that of intraductal papillary mucinous neoplasia (IPMN), although in this case amylase/lipase is usually elevated in punctate due to ductal connection. IPMN should also be considered a precancerous lesion. The malignant potential depends on the location (main duct or lateral duct) and the size of the lesion as well as the solid portions. An IPMN originating from the main duct should always be resected, as carcinoma develops from this lesion in 52-92% of cases over an 8-year period. For lesions of the lateral duct, this is true in 6-46%. Malignant/invasive carcinomas develop from lesions with negative Sendai/Fukuoka criteria in 0.025% of cases. If malignancy is detected, surgical therapy should be initiated. For further diagnostic procedures, please refer to the European guideline for diagnosis and therapy of cystic lesions [227], as well as the revised Fukuoka consensus recommendations [231].
If a cystic lesion is suspected clinically or on imaging at the time of initial diagnosis or during its course to require intervention, endosonography should be performed for risk assessment and/or intervention planning.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 5
- Consensus
- Strong consensus
- References
- [227]
Endosonography in cystic pancreatic lesion should be performed to identify morphological characteristics that help to better assess the risk for malignant degeneration.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 5
- Consensus
- Strong consensus
- References
- [227]
Background
The spatial resolution of endosonography to evaluate the cyst wall and detect wall perfused nodules (nodules, > 5 mm) is higher than on MRI or CT. Because nodules are the only independent predictor of invasive carcinoma or higher grade dysplasia [232] and endosonography has an additional diagnostic value for perfused nodules of 7.5% over CT, EUS should be performed [233]. Risk factors for malignancy independent of nodules are a size greater than 3 cm and a ductus wirsungianus dilated to > 5 mm [233].
For therapy of symptomatic or asymptomatic pseudocysts or WOPN, we refer to the S3 guideline on pancreatitis from 2020.
Background
High-quality current European and international guidelines are available on this topic. Diagnosis and therapy should follow the recommendations contained in these guidelines. To summarize, the following approach is recommended: According to the international consensus guidelines, all main duct IPMN, mixed (main duct and side duct) IPMN, symptomatic IPMN, and IPMN with malignancy predictors should be surgically removed. The extent of resection depends on the location and intraoperative frozen section analysis. Total pancreatectomies have also been described due to multifocal occurrence. Another therapeutic problem is the postoperative recurrence rate of about 20%. Therefore, annual control examinations by CT or MRI are recommended. If carcinoma is detected, these should be performed every 6 months. Patients may benefit from resection if recurrence is detected.
The guidelines for therapy of IPMN further suggest that tumors < 3 cm arising from side branches known to rarely transform malignantly can be closely monitored. This approach is supported by prospective case series (Table 4: "Recommended approach in the presence of a side branch IPMN" and Algorithm for therapy Monitoring and therapy of a cystic lesion of the pancreas).
Table 11: Recommended Procedure in the Presence of a Side-branch IPMN
|
Size of the Lesion |
Recommended Procedure |
|
< 1 cm |
MRI/CT/EUS after 2 years |
|
> 1–2 cm without malignancy criteria* |
Imaging 6 months after initial diagnosis, if constant: control after 2 years |
|
> 2-3 cm without malignancy criteria* |
Imaging 6 months after initial diagnosis, if constant: follow-up after 1 year |
|
> 1–3 cm with suspected invasive growth |
Resection |
|
*Malignancy criteria include mural nodules with a size ≥ 10 mm and a ductal width of ≥ 10 mm, cystic side branch dilation > 30 mm, higher grade dysplasia on cytology |
|
5.6 Therapy Evaluation in the Palliative Situation
The investigation of tumor response in the course of palliative chemotherapy should principally be conducted with upper abdominal sonography. Computed tomography should only be used if required in study situations (RECIST criteria) or if upper abdominal sonography does not allow a statement on the course.
- Recommendation grade
- D: Expertenmeinung oder inkonsistente bzw. nicht schlüssige Studien jedes Evidenzgrades
- Consensus
- Consent
Evidence tables
Chew, Cindy et al. The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography. Singapore Medical Journal. 57. 334-338. 2016
| Chew, Cindy et al. The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography. Singapore Medical Journal. 57. 334-338. 2016 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | Population | Outcomes/Results | ||
| Evidence level: 3 Study type: prospektive Kohorte, unizentrisch, UK |
Number of patients / samples: Number of Patients n=69 resektabel nach MDCT n=16 Lebermetastasen (LM(+)) nach MRT n=47 Keine Lebermetastasen (LM(-)) nach MRT Recruiting Phase 04/2012-12/2013 Inclusion Criteria 1. Pankreaskarzinom 2. resektabel nach MDCT und EUS/FNA Exclusion Criteria nicht angegeben Reference standard: Index Test (Intervention) MRT der Leber Reference Standard (Comparison) MDCT Reference Standard bei allen Patienten angewandt Alle Patienten erhielten vor dem MRT ein MDCT, in Studie keine Angaben zu Sensitivität, Spezifität, PPV, NPV des MDCT Validation: Sensitivität Spezifität positiver Vorhersagewert (PPV) negativer Vorhersagewert (NPV) Mittleres Überleben Medianes Überleben Blinding: nicht angegeben Inclusion of clinical information: nicht angegeben Dealing with ambiguous clinical findings: nicht angegeben |
Results: Follow-up Median 6 Monate MRT Sensitivität: 76,2 % Spezifität: 95,8 % PPV: 88,9% (95%CI: 67,2–95,9) NPV: 90.2% (95%CI: 79,0–95,4) Mittleres Überleben LM(+) vs. LM(-) nach MRT statistisch signifikant höher bei LM(-) LM(+): 9,64 Monate (95%CI: 5,22–14,05) LM(-):16,22 Monate (95%CI: 14,33–18,10) p=0,001 Medianes Überleben LM(+) vs. LM(-) nach MRT LM(+): 6,0 Monate (95%CI: 2,42–9,58) LM(-): Endpunkt in follow-up nicht erreicht Author conclusions: In conclusion, the present study has demonstrated that liver MR imaging with DWI using hepatocyte-specific contrast upstages patients who have findings of resectable pancreatic cancer on CT and adds valuable information to the diagnostic process, thus allowing clinicians to determine the most appropriate treatment for patients. Nevertheless, the findings of this study need to be confirmed by multicentre assessments and comparisons with other staging modalities such as PET/CT. |
||
| Methodical Notes | ||||
| Funding Sources: nicht angegeben COI: nicht angegeben Notes: Gesamtqualität: abgewertet (-) Studiendesign: prospektive Kohorte Repräsentative Patientengruppe: unklar Referenz- und Indexstandard bei allen Patienten angewendet: ja Vergleich unabhängig und verblindet: unklar Reproduzierbarkeit: ja |
||||
Ito, T. et al. The diagnostic advantage of EOB-MR imaging over CT in the detection of liver metastasis in patients with potentially resectable pancreatic cancer. Pancreatology. 17. 451-456. 2017
| Ito, T. et al. The diagnostic advantage of EOB-MR imaging over CT in the detection of liver metastasis in patients with potentially resectable pancreatic cancer. Pancreatology. 17. 451-456. 2017 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | Population | Outcomes/Results | ||
| Evidence level: 4 Study type: retrospektive Kohorte, unizentrisch, Japan |
Number of patients / samples: Number of Patients n=201 Recruiting Phase 2011 – 2015 Inclusion Criteria 1. potentiell resektables Pankreaskarzinom (MDCT/ Ultraschall) 2. präoperatives MRT mit leberspezifischem Kontrastmittel (EOB-MRT) und Verdacht auf Lebermetastasen Exclusion Criteria 1. neoadjuvante Chemotherapie Reference standard: Index Test (Intervention) EOB-MRT Reference Standard (Comparison) CT (MDCT) und Ultraschall Reference Standard bei allen Patienten angewandt Ja, keine Angaben zu den Outcomes der Reference Standards in der Studie Validation: Sensitivität Spezifität Präzision (Accuracy) Positiver Vorhersagewert (PPV) Negativer Vorhersagewert (NPV) Blinding: einfach verblindet Inclusion of clinical information: nicht angegeben Dealing with ambiguous clinical findings: nicht angegeben |
Results: EOB-MRT Sensitivität: 77,5% Spezifität: 94,7% Präzision: 90,2% PPV: 83,8% NPV: 92,3% Author conclusions: In conclusion, EOB-MR imaging is superior to CT in the detection of tiny liver metastasis from pancreatic cancer. However, whether EOB-MR examination should be performed in all patients remains unclear in terms of its cost and limited availability. |
||
| Methodical Notes | ||||
| Funding Sources: No funding was received for this study. COI: The authors have no conflicts of interest to declare. Notes: Gesamtqualität: ausreichend Studiendesign: retrospektive Kohorte Repräsentative Patientengruppe: ja Referenz- und Indexstandard bei allen Patienten angewendet: ja Vergleich unabhängig und verblindet: ja Reproduzierbarkeit: ja |
||||
Jeon, Sun Kyung et al. Magnetic resonance with diffusion-weighted imaging improves assessment of focal liver lesions in patients with potentially resectable pancreatic cancer on CT. European Radiology. 28. 3484-3493. 2018
| Jeon, Sun Kyung et al. Magnetic resonance with diffusion-weighted imaging improves assessment of focal liver lesions in patients with potentially resectable pancreatic cancer on CT. European Radiology. 28. 3484-3493. 2018 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | Population | Outcomes/Results | ||
| Evidence level: 4 Study type: retrospektive Kohorte, unizentrisch, Korea |
Number of patients / samples: Number of Patients n=167 Recruiting Phase 01/2011 – 12/2014 Inclusion Criteria 1. pathologisch bestätigtes und potenziell resektables PDAC 2. MDCT und MRT(mit DWI) von guter diagnostischer Qualität (präoperativ) 3. keine präoperative lokale oder systemische Therapie 4. keine koexistierenden oder früheren malignen Erkrankungen 5. follow-up von mindestens 12 Monaten Exclusion Criteria nicht angegeben Reference standard: Index Test (Intervention) MRT (mit DWI)+MDCT Reference Standard (Comparison) MDCT Reference Standard bei allen Patienten angewandt ja Validation: Reader-averaged figure-of-merit (FOM) (JAFROC-Analyse) Sensitivität Spezifität Präzision (Accuracy) Blinding: einfach verblindet Inclusion of clinical information: nicht angegeben Dealing with ambiguous clinical findings: Interobserver-Variabilität MRT+MDCT: κ = 0,904 („excellent agreement“) MDCT: κ = 0,638 („substantial agreement“) |
Results: Reader-averaged figure-of-merit (FOM) (JAFROC-Analyse) MRT(DWI)+MDCT vs MDCT statistisch signifikant höher bei MRT+MDCT MRT+MDCT 0,94 (95%CI 0,86-1,02) MDCT 0,86 (95%CI 0,79-0,92) p=0,028 Sensitivität MRT(DWI)+MDCT vs MDCT kein statistisch signifikanter Unterschied Reviewer 1: MRT+MDCT 100% MDCT 87,5% p=0,500 Reviewer 2: MRT+MDCT 100% MDCT 81,3% p=0,250 Spezifität MRT(DWI)+MDCT vs MDCT statistisch signifikant höher bei MRT+MDCT Reviewer 1: MRT+MDCT 98;7% MDCT 86,8% p<0,001 Reviewer 2: MRT+MDCT 97,4% MDCT 86,1% p=0,001 Präzision MRT(DWI)+MDCT vs MDCT statistisch signifikant höher bei MRT+MDCT Reviewer 1: MRT+MDCT 98,8% MDCT 86,8% p=0,002 Reviewer 2: MRT+MDCT 97,6% MDCT 85,6% p=0,013 Author conclusions: In conclusion, in patients with potentially resectable PDACs, the addition of MR imaging with DWI to MDCT can provide significantly better diagnostic performance and greater interobserver reliability in the characterization of focal liver lesions. Although the diagnostic yield of adding MR imaging with DWI for hepatic metastasis was low in patients with benign-on-CT findings, additional MR imaging with DWI was demonstrated to provide significantly better diagnostic performance in the characterization of focal liver lesions in indeterminate- or suspicious metastasis-on-CT cases, especially in small-sized lesions (≤ 1 cm), thereby aiding in the determination of appropriate operation candidates |
||
| Methodical Notes | ||||
| Funding Sources: The authors state that this work has not received any funding. COI: The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Notes: Gesamtqualität: ausreichend Studiendesign: retrospektive Kohorte Repräsentative Patientengruppe: ja Referenz- und Indexstandard bei allen Patienten angewendet: ja Vergleich unabhängig und verblindet: ja Reproduzierbarkeit: ja |
||||
Kim, H. W. et al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer. Surgery (United States). 161. 1579-1587. 2017
| Kim, H. W. et al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer. Surgery (United States). 161. 1579-1587. 2017 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | Population | Outcomes/Results | ||
| Evidence level: 4 Study type: retrospektive Kohorte, unizentrisch, Korea |
Number of patients / samples: Number of Patients n= 65 CT plus MRT der Leber n=102 CT Recruiting Phase 01/2006-12/2014 Inclusion Criteria 1. potenziell resektables PDAC 2. präop. CT im Rekrutierungszeitraum 3. unklare Leberläsionen im CT Exclusion Criteria 1. bereits diagnostizierte Lebermetastasen 2. Ablehnung einer Resektion 3. vorherige Chemotherapie 4. weitere aktuelle, primäre Krebserkrankung 5. Mortalität im ersten Monat nach Resektion 6. makroskopisch unvollständige Resektion Reference standard: Index Test (Intervention) CT+MRT der Leber Reference Standard (Comparison) CT Reference Standard bei allen Patienten angewandt Ja Validation: medianes Gesamtüberleben krankheitsfreies Überleben (DFS) Auftreten von hepatischem Rezidiv Blinding: einfach verblindet Inclusion of clinical information: nicht angegeben Dealing with ambiguous clinical findings: nicht angegeben |
Results: Follow-up CT: Median 17,6 Monate CT+MRT: Median 18,7 Monate medianes Gesamtüberleben CT+MRT vs. CT statistisch signifikant länger bei CT+MRT CT+MRT: 24,7 Monate CT: 18,2 Monate p=0,020 DFS CT+MRT vs. CT statistisch signifikant länger bei CT+MRT CT+ MRT: 10,0 Monate CT: 8,5 Monate p=0,016 Auftreten von hepatischem Rezidiv Kumulative Inzidenz nach 12 Monaten CT+MRT vs. CT signifikant geringer bei CT+MRT CT+MRT: 18% CT: 43% p<0,001 Kumulative Inzidenz nach 24 Monaten CT+MRT vs. CT signifikant geringer bei CT+MRT CT+MRT: 25% CT: 56% p<0,001 Author conclusions: In conclusion, the combination of hepatic MRI with pCT provides incremental value for detecting PDAC hepatic metastasis. Furthermore, patients with PDAC who undergo resection after a negative hepatic MRI and pCT have a lesser rate of hepatic recurrence and better survival than those who undergo pCT alone. Therefore, preoperative hepatic MRI should be considered for patients with potentially resectable PDAC, especially for those with greater tumor burdens. Future randomized, controlled, and prospective studies are warranted to study this topic further. |
||
| Methodical Notes | ||||
| Funding Sources: The authors declare no sources of funding. COI: The authors declare no conflicts of interest. Notes: Gesamtqualität: ausreichend Studiendesign: retrospektive Kohorte Repräsentative Patientengruppe: ja Referenz- und Indexstandard bei allen Patienten angewendet: ja Vergleich unabhängig und verblindet: ja Reproduzierbarkeit: ja |
||||
Kim, H. J. et al. Incremental role of pancreatic magnetic resonance imaging after staging computed tomography to evaluate patients with pancreatic ductal adenocarcinoma. Cancer Research and Treatment. 51. 24-33. 2019
| Kim, H. J. et al. Incremental role of pancreatic magnetic resonance imaging after staging computed tomography to evaluate patients with pancreatic ductal adenocarcinoma. Cancer Research and Treatment. 51. 24-33. 2019 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | Population | Outcomes/Results | ||
| Evidence level: 4 Study type: retrospektive Kohorte, unizentrisch, Korea |
Number of patients / samples: Number of Patients n=216 Recruiting Phase 1/2005-12/2012 Inclusion Criteria 1. PDAC, histopathologisch bestätigt 2. potenziell resektabel nach CT Exclusion Criteria 1. unvollständige klinische oder radiologische Daten 2. unresektabel laut CT 3. vorherige CT oder MRT Untersuchung 4. Alter >80Jahre Reference standard: Index Test (Intervention) CT+MRT Reference Standard (Comparison) CT Reference Standard bei allen Patienten angewandt Ja Validation: Geänderte Einschätzung der Resektabilität nach MRT Blinding: einfach verblindet Inclusion of clinical information: Daten zu klinischer Information im Verblindungsverfahren ausgeschlossen Dealing with ambiguous clinical findings: Konsensusfindung |
Results: Follow-up CT+MRT: Median 1,4 Jahre CT: Median 1,6 Jahre Geänderte Bewertung der Resektabilität nach MRT: CT+MRT-Kollektiv, gesamt: von potenziell resektabel zu unresektabel: 31 Patienten (14,4%) aufgrund von im MRT zusätzlich gefundenen: Lebermetastasen: 16 Patienten Bedeutende Vaskuläre Invasion: 13 Patienten Vergrößerte Paraaortale Lymphknoten: 1 Patient Peritoneale Streuung: 1 Patient Author conclusions: In conclusion, additional MRI resulted in changes of resectability and treatment modification in a significant proportion of patients who had potentially resectable state on CT and delay in time to liver metastases in patients after curative surgery. Additional MRI to standard staging CT can be recommended for surgical candidates of PDA. |
||
| Methodical Notes | ||||
| Funding Sources: nicht angegeben COI: Conflict of interest relevant to this article was not reported. Notes: Gesamtqualität: ausreichend Studiendesign: retrospektive Kohorte Repräsentative Patientengruppe: ja Referenz- und Indexstandard bei allen Patienten angewendet: ja Vergleich unabhängig und verblindet: ja Reproduzierbarkeit: ja |
||||
Wang, L. et al. Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: A meta-analysis. International Journal of Surgery. 46. 119-125. 2017
| Wang, L. et al. Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: A meta-analysis. International Journal of Surgery. 46. 119-125. 2017 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | P - I - C | Outcomes/Results | Literature References | |
| Evidence level: 1 Study type: Systematisches Review + Metaanalyse Databases: PubMed, EMBASE, SCI, Cochrane Search period: nicht angegeben Inclusion Criteria: 1. klinische Studien an Patienten mit Pankreaskarzinom 2. veröffentlicht auf Englisch 3. PET/CT und CT präoperativ bei allen Patienten 4. pathologisch bestätigtes Pankreaskarzinom 5. Informationen zur Sensitivität von PET (PET und PET/CT) und CT bei der Erkennung regionalen Lymphknotenbefalls und Metastasen (einschließlich Lebermetastasen und andere Fernmetastasen) Exclusion Criteria: 1. Stichprobengröße < 20. 2. Abstracts, Übersichtsarbeiten, Fallberichte und Kommentare 3. fehlende Daten über regionale Lymphknoten und Metastasen 4. fehlende Informationen zur Operation |
Population: Patienten mit Pankreaskarzinom Intervention: PET (PET und PET/CT) Comparison: CT |
Primary: Nachweis entfernter Metastasen Secondary: Nachweis regionaler Lymphknoteninvasionen Results: n=17 Studien (6 prosp., 11 retrosp.) n=1343 Patienten 1. Nachweis entfernter Metastasen PET (PET und PET/CT) vs. CT (17 Studien) statistisch signifikant höher bei PET und PET/CT als bei CT allein OR=1,52 (95%CI: 1,23-1,88) Subgruppenanalyse: PET vs. CT (5 Studien) kein statistisch signifikanter Unterschied OR=0,96 (95%CI: 0,56-1,65) PET/CT vs. CT (12 Studien) statistisch signifikant höher bei PET/CT als bei CT allein OR=1,66 (95%CI: 1,31-2,08) 2. Nachweis regionaler Lymphknoteninvasionen PET (PET und PET/CT) vs. CT (6 Studien) kein statistisch signifikanter Unterschied OR=0,97 (95%CI: 0,63-1,47) Author's Conclusion: PET, especially for PET/CT, provides extensive possibility for avoiding futile radical resection by detecting occult distant metastasis of pancreatic cancer preoperatively. From current published data, it is beneficial for pancreatic cancer patients and should be recommended before PD. However, further well-designed, larger randomized control trials that assess the value of PET/CT for surgical decision are needed. |
A. Asagi, K. Ohta, J. Nasu, M. Tanada, S. Nadano, R. Nishimura, N. Teramoto, K. Yamamoto, T. Inoue, H. Iguchi, Utility of contrast-enhanced FDG-PET/CT in the clinical management of pancreatic cancer: impact on diagnosis, staging, evaluation of treatment response, and detection of recurrence, Pancreas 42 (1) (2013) 11-19. M.E. Burge, N. O'Rourke, D. Cavallucci, R. Bryant, A. Francesconi, K. Houston, D. Wyld, M. Eastgate, R. Finch, G. Hopkins, P. Thomas, D. Macfarlane, A prospective study of the impact of fluorodeoxyglucose positron emission tomography with concurrent non-contrast CT scanning on the management of operable pancreatic and peri-ampullary cancers, HPB Oxf. 17 (7) (2015) 624-631. J.M. Farma, A.A. Santillan, M. Melis, J. Walters, D. Belinc, D.T. Chen, E.A. Eikman, M. Malafa, PET/CT fusion scan enhances CT staging in patients with pancreatic neoplasms, Ann. Surg. Oncol. 15 (9) (2008) 2465-2471. S. Heinrich, G.W. Goerres, M. Schafer, M. Sagmeister, P. Bauerfeind, B.C. Pestalozzi, T.F. Hany, G.K. von Schulthess, P.A. Clavien, Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness, Ann. Surg. 242 (2) (2005) 235-243. O. Javery, P. Shyn, K. Mortele, FDG PET or PET/CT in patients with pancreatic cancer: when does it add to diagnostic CT or MRI? Clin. Imaging 37 (2) (2013) 295-301. W. Jung, J.Y. Jang, M.J. Kang, Y.R. Chang, Y.C. Shin, J. Chang, S.W. Kim, The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in follow-up of curatively resected pancreatic cancer patients, HBP 18 (1) (2016) 57-64. S.P. Kauhanen, G. Komar, M.P. Seppanen, K.I. Dean, H.R. Minn, S.A. Kajander, I. Rinta-Kiikka, K. Alanen, R.J. Borra, P.A. Puolakkainen, P. Nuutila, J.T. Ovaska, A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer, Ann. Surg. 250 (6) (2009) 957-963. R. Kim, G. Prithviraj, N. Kothari, G. Springett, M. Malafa, P. Hodul, J. Kim, B. Yue, B. Morse, A. Mahipal, PET/CT fusion scan prevents futile laparotomy in early stage pancreatic cancer, Clin. Nucl. Med. 40 (11) (2015) 501-505. X.X. Li, N.B. Liu, L. Zhu, X.K. Yuan, C.W. Yang, P. Ren, L.L. Gong, L.J. Zhao, W.G. Xu, P. Wang, Consequences of additional use of contrast-enhanced (18) F-FDG PET/CT in target volume delineation and dose distribution for pancreatic cancer, Br. J. Radiol. 88 (1051) (2015) 20140590. D. Lytras, S. Connor, L. Bosonnet, R. Jayan, J. Evans, M. Hughes, C.J. Garvey, P. Ghaneh, R. Sutton, S. Vinjamuri, J.P. Neoptolemos, Positron emission tomography does not add to computed tomography for the diagnosis and staging of pancreatic cancer, Dig. Surg. 22 (1-2) (2005) 55-61. [K. Maemura, S. Takao, H. Shinchi, H. Noma, Y. Mataki, H. Kurahara, S. Jinnouchi, T. Aikou, Role of positron emission tomography in decisions on treatment strategies for pancreatic cancer, J. Hepatobiliary Pancreat. Surg. 13 (5) (2006) 435-441. H.R. Mertz, P. Sechopoulos, D. Delbeke, S.D. Leach, EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma, Gastrointest. Endosc. 52 (3) (2000) 367-371. M. Picchio, E. Giovannini, P. Passoni, E. Busnardo, C. Landoni, G. Giovacchini, V. Bettinardi, C. Crivellaro, L. Gianolli, N. Di Muzio, C. Messa, Role of PET/CT in the clinical management of locally advanced pancreatic cancer, Tumori 98 (5) (2012) 643-651. C. Sperti, C. Pasquali, S. Bissoli, F. Chierichetti, G. Liessi, S. Pedrazzoli, Tumor relapse after pancreatic cancer resection is detected earlier by 18-FDG PET than by CT, J. Gastrointest. Surg. 14 (1) (2010) 131-140. H. Wakabayashi, Y. Nishiyama, T. Otani, T. Sano, S. Yachida, K. Okano, K. Izuishi, Y. Suzuki, Role of 18F-fluorodeoxyglucose positron emission tomography imaging in surgery for pancreatic cancer, World J. Gastroenterol. 14 (1) (2008) 64-69. X.Y. Wang, F. Yang, C. Jin, D.L. Fu, Utility of PET/CT in diagnosis, staging, assessment of resectability and metabolic response of pancreatic cancer, World J. Gastroenterol. 20 (42) (2014) 15580-15589. J. Zhang, C.J. Zuo, N.Y. Jia, J.H. Wang, S.P. Hu, Z.F. Yu, Y. Zheng, A.Y. Zhang, X.Y. Feng, Cross-modality PET/CT and contrast-enhanced CT imaging for pancreatic cancer, World J. Gastroenterol. 21 (10) (2015) 2988-2996. |
|
| Methodical Notes | ||||
| Funding Sources: None COI: All authors have no conflict of interests related to this article. Study Quality: Bewertungsinstrument: Newcastle-Ottawa-Skala (NOS) Ergebnisse der eingeschlossenen Studien: Lytras et al. 6 alle anderen 7 oder 8 Sterne = hohe Qualität Heterogeneity: Heterogenität wurde mit I2 gemessen: geringe Heterogenität wurde definiert als I2 <33%. 1. Nachweis entfernter Metastasen PET (PET und PET/CT) vs. CT (17 Studien) I2=28,9%; p=0,127 Subgruppenanalyse a) PET vs. CT (5 Studien) I2=55,4%, p=0,062 b) PET/CT vs. CT (12 Studien) I2=0,0%, p=0,452 2. Nachweis regionaler Lymphknoteninvasionen PET (PET und PET/CT) vs. CT (6 Studien) I2=0,0%, p=0,897 Publication Bias: Bewertungsverfahren: Funnel-Plot-Analyse Ergebnis: Es gab keine starken Hinweise auf einen Publikationsbias. Notes: Gesamtqualität: keine methodischen Mängel PICO Frage klar formuliert: ja Ausreichende Suchstrategie: ja Ein- und Ausschlusskriterien klar definiert: ja Qualitätsbewertung der eingeschlossenen Studien erfolgt: ja Metanalyse erfolgt: ja Prüfung der Heterogenität: ja |
||||
References
[175] rBjornsson, E., Ismael, S., Nejdet, S., Kilander, A., Severe jaundice in Sweden in the new millennium: causes, investigations, treatment and prognosis, Scand J Gastroenterol, 2003. 38(1): p. 86-94., https://pubmed.ncbi.nlm.nih.gov/12608470/
[176] Reisman, Y., Gips, C. H., Lavelle, S. M., Wilson, J. H., Clinical presentation of (subclinical) jaundice--the Euricterus project in The Netherlands. United Dutch Hospitals and Euricterus Project Management Group, Hepatogastroenterology, 1996. 43(11): p. 1190-5., https://pubmed.ncbi.nlm.nih.gov/8908550/
[177] Watanabe, I., Sasaki, S., Konishi, M., Nakagohri, T., Inoue, K., Oda, T., et.al. Onset symptoms and tumor locations as prognostic factors of pancreatic cancer, Pancreas, 2004. 28(2): p. 160-5., https://pubmed.ncbi.nlm.nih.gov/15028948/
[178] Reisman, Y., Gips, C. H., Lavelle, S. M., Wilson, J. H., Clinical presentation of (subclinical) jaundice--the Euricterus project in The Netherlands. United Dutch Hospitals and Euricterus Project Management Group, Hepatogastroenterology, 1996. 43(11): p. 1190-5., https://pubmed.ncbi.nlm.nih.gov/8908550/
[179] Balthazar, E. J., Pancreatitis associated with pancreatic carcinoma. Preoperative diagnosis: role of CT imaging in detection and evaluation, Pancreatology, 2005. 5(4-5): p. 330-44., https://www.ncbi.nlm.nih.gov/pubmed/16015017
[180] Mujica, V. R., Barkin, J. S., Go, V. L., Acute pancreatitis secondary to pancreatic carcinoma. Study Group Participants, Pancreas, 2000. 21(4): p. 329-32., https://pubmed.ncbi.nlm.nih.gov/11075985/
[181] Balthazar, E. J., Pancreatitis associated with pancreatic carcinoma. Preoperative diagnosis: role of CT imaging in detection and evaluation, Pancreatology, 2005. 5(4-5): p. 330-44., https://pubmed.ncbi.nlm.nih.gov/16015017/
[182] Mujica, V. R., Barkin, J. S., Go, V. L., Acute pancreatitis secondary to pancreatic carcinoma. Study Group Participants, Pancreas, 2000. 21(4): p. 329-32., https://pubmed.ncbi.nlm.nih.gov/11075985/
[183] Adamek, H. E., Albert, J., Breer, H., Weitz, M., Schilling, D., Riemann, J. F., Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study, Lancet, 2000. 356(9225): p. 190-3., https://www.ncbi.nlm.nih.gov/pubmed/10963196
[184] Hanninen, E. L., Ricke, J., Amthauer, H., Rottgen, R., Bohmig, M., Langrehr, J., et.al. Magnetic resonance cholangiopancreatography: image quality, ductal morphology, and value of additional T2- and T1-weighted sequences for the assessment of suspected pancreatic cancer, Acta Radiol, 2005. 46(2): p. 117-25., https://www.ncbi.nlm.nih.gov/pubmed/15902884
[185] Adamek, H. E., Albert, J., Breer, H., Weitz, M., Schilling, D., Riemann, J. F., Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study, Lancet, 2000. 356(9225): p. 190-3., https://pubmed.ncbi.nlm.nih.gov/10963196/
[186] Hanninen, E. L., Ricke, J., Amthauer, H., Rottgen, R., Bohmig, M., Langrehr, J., et.al. Magnetic resonance cholangiopancreatography: image quality, ductal morphology, and value of additional T2- and T1-weighted sequences for the assessment of suspected pancreatic cancer, Acta Radiol, 2005. 46(2): p. 117-25., https://pubmed.ncbi.nlm.nih.gov/15902884/
[187] Forsmark, C. E., Lambiase, L., Vogel, S. B., Diagnosis of pancreatic cancer and prediction of unresectability using the tumor-associated antigen CA19-9, Pancreas, 1994. 9(6): p. 731-4., https://www.ncbi.nlm.nih.gov/pubmed/7846016
[188] Nazli, O., Bozdag, A. D., Tansug, T., Kir, R., Kaymak, E., The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma, Hepatogastroenterology, 2000. 47(36): p. 1750-2., https://pubmed.ncbi.nlm.nih.gov/11149048/
[189] Ritts, R. E., Jr., Nagorney, D. M., Jacobsen, D. J., Talbot, R. W., Zurawski, V. R., Jr., Comparison of preoperative serum CA19-9 levels with results of diagnostic imaging modalities in patients undergoing laparotomy for suspected pancreatic or gallbladder disease, Pancreas, 1994. 9(6): p. 707-16., https://pubmed.ncbi.nlm.nih.gov/7846013/
[190] Tessler, D. A., Catanzaro, A., Velanovich, V., Havstad, S., Goel, S., Predictors of cancer in patients with suspected pancreatic malignancy without a tissue diagnosis, Am J Surg, 2006. 191(2): p. 191-7., https://pubmed.ncbi.nlm.nih.gov/16442944/
[191] Forsmark, C. E., Lambiase, L., Vogel, S. B., Diagnosis of pancreatic cancer and prediction of unresectability using the tumor-associated antigen CA19-9, Pancreas, 1994. 9(6): p. 731-4., https://pubmed.ncbi.nlm.nih.gov/7846016/
[192] Nazli, O., Bozdag, A. D., Tansug, T., Kir, R., Kaymak, E., The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma, Hepatogastroenterology, 2000. 47(36): p. 1750-2., https://pubmed.ncbi.nlm.nih.gov/11149048/
[193] Ritts, R. E., Jr., Nagorney, D. M., Jacobsen, D. J., Talbot, R. W., Zurawski, V. R., Jr., Comparison of preoperative serum CA19-9 levels with results of diagnostic imaging modalities in patients undergoing laparotomy for suspected pancreatic or gallbladder disease, Pancreas, 1994. 9(6): p. 707-16., https://pubmed.ncbi.nlm.nih.gov/7846013/
[194] Tessler, D. A., Catanzaro, A., Velanovich, V., Havstad, S., Goel, S., Predictors of cancer in patients with suspected pancreatic malignancy without a tissue diagnosis, Am J Surg, 2006. 191(2): p. 191-7., https://pubmed.ncbi.nlm.nih.gov/16442944/
[195] Agarwal, B., Abu-Hamda, E., Molke, K. L., Correa, A. M., Ho, L., Endoscopic ultrasound-guided fine needle aspiration and multidetector spiral CT in the diagnosis of pancreatic cancer, Am J Gastroenterol, 2004. 99(5): p. 844-50., https://pubmed.ncbi.nlm.nih.gov/15128348/
[196] Klapman, J. B., Chang, K. J., Lee, J. G., Nguyen, P., Negative predictive value of endoscopic ultrasound in a large series of patients with a clinical suspicion of pancreatic cancer, Am J Gastroenterol, 2005. 100(12): p. 2658-61., https://pubmed.ncbi.nlm.nih.gov/16393216/
[197] Varadarajulu, S., Wallace, M. B., Applications of endoscopic ultrasonography in pancreatic cancer, Cancer Control, 2004. 11(1): p. 15-22., https://pubmed.ncbi.nlm.nih.gov/14749619/
[198] Agarwal, B., Abu-Hamda, E., Molke, K. L., Correa, A. M., Ho, L., Endoscopic ultrasound-guided fine needle aspiration and multidetector spiral CT in the diagnosis of pancreatic cancer, Am J Gastroenterol, 2004. 99(5): p. 844-50., https://pubmed.ncbi.nlm.nih.gov/15128348/
[199] Klapman, J. B., Chang, K. J., Lee, J. G., Nguyen, P., Negative predictive value of endoscopic ultrasound in a large series of patients with a clinical suspicion of pancreatic cancer, Am J Gastroenterol, 2005. 100(12): p. 2658-61., https://pubmed.ncbi.nlm.nih.gov/16393216/
[200] Varadarajulu, S., Wallace, M. B., Applications of endoscopic ultrasonography in pancreatic cancer, Cancer Control, 2004. 11(1): p. 15-22., https://pubmed.ncbi.nlm.nih.gov/14749619/
[201] David, O., Green, L., Reddy, V., Kluskens, L., Bitterman, P., Attal, H., et.al. Pancreatic masses: a multi-institutional study of 364 fine-needle aspiration biopsies with histopathologic correlation, Diagn Cytopathol, 1998. 19(6): p. 423-7., https://www.ncbi.nlm.nih.gov/pubmed/9839131
[202] Bipat, S., Phoa, S. S., van Delden, O. M., Bossuyt, P. M., Gouma, D. J., Lameris, J. S., et.al. Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis, J Comput Assist Tomogr, 2005. 29(4): p. 438-45., https://www.ncbi.nlm.nih.gov/pubmed/16012297
[203] James, P. D., Meng, Z. W., Zhang, M., Belletrutti, P. J., Mohamed, R., Ghali, W., et.al. The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis, PLoS One, 2017. 12(3): p. e0173687., https://pubmed.ncbi.nlm.nih.gov/28319148/
[204] Krishna, Somashekar, Rao, Bhavana, Ugbarugba, Emmanuel, Shah, Zarine, Blaszczak, Alecia, Hinton, Alice, et.al. Diagnostic performance of endoscopic ultrasound for detection of pancreatic malignancy following an indeterminate multidetector CT scan: a systemic review and meta-analysis, Surgical Endoscopy, 2017. 31(11): p. 4558-4567., https://pubmed.ncbi.nlm.nih.gov/28378082/
[1] Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften - Ständige Kommission, Leitlinien, AWMF-Regelwerk "Leitlinien", 2. Auflage, 2020., http://www.awmf.org/leitlinien/awmf-regelwerk/awmf-regelwerk.html
[207] Sohal, Davendra P. S., Kennedy, Erin B., Khorana, Alok, Copur, Mehmet S., Crane, Christopher H., Garrido-Laguna, Ignacio, et.al. Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update, Journal of Clinical Oncology, 2018. 36(24): p. 2545-2556., https://pubmed.ncbi.nlm.nih.gov/29791286/
[208] Sohal, Davendra P.S., Kennedy, Erin B., Cinar, Pelin, Conroy, Thierry, Copur, Mehmet S., Crane, Christopher H., et.al. Metastatic Pancreatic Cancer: ASCO Guideline Update, Journal of Clinical Oncology, 2020. 38(27): p. 3217-3230., https://ascopubs.org/doi/abs/10.1200/JCO.20.01364
[209] Chew, C., O'Dwyer, P. J., The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography, Singapore Med J, 2016. 57(6): p. 334-8., https://www.ncbi.nlm.nih.gov/pubmed/27353741
[210] Ito, T., Sugiura, T., Okamura, Y., Yamamoto, Y., Ashida, R., Aramaki, T., et.al. The diagnostic advantage of EOB-MR imaging over CT in the detection of liver metastasis in patients with potentially resectable pancreatic cancer, Pancreatology, 2017. 17(3): p. 451-456., https://pubmed.ncbi.nlm.nih.gov/28298257/
[211] Jeon, Sun Kyung, Lee, Jeong Min, Joo, Ijin, Lee, Dong Ho, Ahn, Su Joa, Woo, Hyunsik, et.al. Magnetic resonance with diffusion-weighted imaging improves assessment of focal liver lesions in patients with potentially resectable pancreatic cancer on CT, European Radiology, 2018. 28(8): p. 3484-3493., https://pubmed.ncbi.nlm.nih.gov/29352379/
[212] Kim, H. J., Park, M. S., Lee, J. Y., Han, K., Chung, Y. E., Choi, J. Y., et.al. Incremental Role of Pancreatic Magnetic Resonance Imaging after Staging Computed Tomography to Evaluate Patients with Pancreatic Ductal Adenocarcinoma, Cancer Res Treat, 2019. 51(1): p. 24-33., https://pubmed.ncbi.nlm.nih.gov/29397657/
[213] Kim, H. W., Lee, J. C., Paik, K. H., Kang, J., Kim, Y. H., Yoon, Y. S., et.al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer, Surgery (United States), 2017. 161(6): p. 1579-1587., https://pubmed.ncbi.nlm.nih.gov/28237643/
[214] Wang, L., Dong, P., Wang, W. G., Tian, B. L., Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: A meta-analysis, International Journal of Surgery, 2017. 46: p. 119-125., https://pubmed.ncbi.nlm.nih.gov/28890410/
[215] Ghaneh, P., Hanson, R., Titman, A., Lancaster, G., Plumpton, C., Lloyd-Williams, H., et.al. PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer, Health Technol Assess, 2018. 22(7): p. 1-114., https://www.ncbi.nlm.nih.gov/pubmed/29402376
[216] Yoneyama, Tomohiro, Tateishi, Ukihide, Endo, Itaru, Inoue, Tomio, Staging accuracy of pancreatic cancer: comparison between non-contrast-enhanced and contrast-enhanced PET/CT, European Journal of Radiology, 2014. 83(10): p. 1734-1739., https://pubmed.ncbi.nlm.nih.gov/25043494/
[217] Santhosh, S., Mittal, B. R., Bhasin, D. K., Rana, S. S., Gupta, R., Das, A., et.al. Fluorodeoxyglucose-positron emission tomography/computed tomography performs better than contrast-enhanced computed tomography for metastasis evaluation in the initial staging of pancreatic adenocarcinoma, Annals of Nuclear Medicine, 2017. 31(8): p. 575-581., https://pubmed.ncbi.nlm.nih.gov/28689356/
[218] Rijkers, A. P., Valkema, R., Duivenvoorden, H. J., Van Eijck, C. H. J., Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: A meta-analysis, European Journal of Surgical Oncology, 2014. 40(7): p. 794-804., https://pubmed.ncbi.nlm.nih.gov/24755095/
[219] Kim, M. J., Lee, K. H., Lee, K. T., Lee, J. K., Ku, B. H., Oh, C. R., et.al. The value of positron emission tomography/computed tomography for evaluating metastatic disease in patients with pancreatic cancer, Pancreas, 2012. 41(6): p. 897-903., https://pubmed.ncbi.nlm.nih.gov/22699202/
[220] Kim, H. R., Seo, M., Nah, Y. W., Park, H. W., Park, S. H., Clinical impact of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in patients with resectable pancreatic cancer: Diagnosing lymph node metastasis and predicting survival, Nuclear Medicine Communications, 2018. 39(7): p. 691-698., https://pubmed.ncbi.nlm.nih.gov/29893751/
[221] Hillner, B. E., Siegel, B. A., Shields, A. F., Liu, D., Gareen, I. F., Hunt, E., et.al. Relationship between cancer type and impact of PET and PET/CT on intended management: Findings of the national oncologic PET registry, Journal of Nuclear Medicine, 2008. 49(12): p. 1928-1935., https://pubmed.ncbi.nlm.nih.gov/18997054/
[222] Einersen, Peter, Epelboym, Irene, Winner, Megan D., Leung, David, Chabot, John A., Allendorf, John D., Positron emission tomography (PET) has limited utility in the staging of pancreatic adenocarcinoma, Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2014. 18(8): p. 1441-1444., https://pubmed.ncbi.nlm.nih.gov/24928186/
[223] Buchs, N. C., Buhler, L., Bucher, P., Willi, J. P., Frossard, J. L., Roth, A. D., et.al. Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: a prospective study, J Gastroenterol Hepatol, 2011. 26(4): p. 657-62., https://www.ncbi.nlm.nih.gov/pubmed/21155879
[224] Toft, J., Hadden, W. J., Laurence, J. M., Lam, V., Yuen, L., Janssen, A., et.al. Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy, Eur J Radiol, 2017. 92: p. 17-23., https://pubmed.ncbi.nlm.nih.gov/28624015/
[225] Schachter, P. P., Avni, Y., Shimonov, M., Gvirtz, G., Rosen, A., Czerniak, A., The impact of laparoscopy and laparoscopic ultrasonography on the management of pancreatic cancer, Arch Surg, 2000. 135(11): p. 1303-7., https://pubmed.ncbi.nlm.nih.gov/11074885/
[226] Vollmer, C. M., Drebin, J. A., Middleton, W. D., Teefey, S. A., Linehan, D. C., Soper, N. J., et.al. Utility of staging laparoscopy in subsets of peripancreatic and biliary malignancies, Ann Surg, 2002. 235(1): p. 1-7., https://pubmed.ncbi.nlm.nih.gov/11753036/
[227] European Study Group on Cystic Tumours of the, Pancreas, European evidence-based guidelines on pancreatic cystic neoplasms, Gut, 2018. 67: p. 789-804., https://gut.bmj.com/content/67/5/789.long
[228] van der Waaij, L. A., van Dullemen, H. M., Porte, R. J., Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis, Gastrointest Endosc, 2005. 62(3): p. 383-9., https://pubmed.ncbi.nlm.nih.gov/16111956/
[229] Gillis, A., Cipollone, I., Cousins, G., Conlon, K., Does EUS-FNA molecular analysis carry additional value when compared to cytology in the diagnosis of pancreatic cystic neoplasm? A systematic review, HPB (Oxford), 2015. 17(5): p. 377-86., https://www.ncbi.nlm.nih.gov/pubmed/25428782
[230] Ngamruengphong, S., Lennon, A. M., Analysis of Pancreatic Cyst Fluid, Surg Pathol Clin, 2016. 9(4): p. 677-684., https://pubmed.ncbi.nlm.nih.gov/27926366/
[231] Tanaka, M., Fernández-Del Castillo, C., Kamisawa, T., Jang, J. Y., Levy, P., Ohtsuka, T., et.al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas, Pancreatology, 2017. 17(5): p. 738-753., https://pubmed.ncbi.nlm.nih.gov/28735806/
[232] Marchegiani, G., Andrianello, S., Borin, A., Dal Borgo, C., Perri, G., Pollini, T., et.al. Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas, Surgery, 2018. 163(6): p. 1272-1279., https://pubmed.ncbi.nlm.nih.gov/29454468/
[233] Han, Y., Lee, H., Kang, J. S., Kim, J. R., Kim, H. S., Lee, J. M., et.al. Progression of Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasm Associates With Cyst Size, Gastroenterology, 2018. 154(3): p. 576-584., https://www.ncbi.nlm.nih.gov/pubmed/29074452