Table 2. Significant survival predictors for malignant IPMNs listed.
Figure 2. Kaplan-Meyer survival curves of malignant IPMNs. R0N0 vs R1N1. Log Rank p = 0.02.
5.1. Serous Cystic Neoplasms (SCN)
In accordance with the literature 70% of our SCNs were incidentalomas, and were resected either due to symptoms of pain, weight loss, jaundice, or uncertainty of malignant degeneration at the time of diagnosis in the larger lesions with impression on the stomach.
Asymptomatic patients with classic radiology findings and smaller lesions are suitable for follow-up with reassuring information. Watchful expectation monitors the natural history of the lesions and makes intervention possible on a later stage if needed .
5.2. Intraductal Papillary Mucinous Neoplasms (IPMN)
Neither the natural development of this disease entity over a period of time, nor the exact time frame from benign lesions to malignancy is known. However, according to the literature, patients with malignant IPMNs are 5 - 7 years older on the average than those lodging benign IPMNs [12,13]. Moreover, anatomic site of the lesion in the main duct is associated with malignant transformation and cancer prevalence in approximately 70% of the patients, whereas branch duct lesions are associated with malignancy in approximately 25% of operated cases .
The uncertainty of malignant potential calls for a meticulous work-up that should include a thorough medical history focusing on discrete symptoms easily overseen. Moderate weight-loss and abdominal discomfort often discreetly appear ahead of jaundice and pain. In our material symptom presence itself (p = 0.02), jaundice (p = 0.04), and pain (p = 0.009) were found significantly more often in malignant cases (Table 1).
Pre-operative biochemical tests can be supplemented by tumour markers as KRAS mutations and CEA in cyst fluid, but sensitivity and specificity levels of the latter, at approximately 67% and 79%, respectively, calls for cautious interpretation as all tests might come across as negative even in malignant cases . Considerable scepticism to cyst fluid CEA levels and DNA analysis predicttion capabilities of malignancy was also voiced in accordance with results in the PANDA study . However, upcoming tests like interleukin 1b (IL 1b) in cyst fluid seems promising in predicting the risk of malignancy, but further validation in clinical practice is needed .
In accordance with the literature, and despite our easily available EUS resources, FNA of cyst fluid was not routinely used. Noteworthy however, we found serum median values of bilirubin (p = 0.02) and ALP (p = 0.02) significantly higher in the malignant cases.
As a consequence of imaging findings, FNAC sampling can seem tempting, but again on should be aware of the marginal utility in surgical decision-making cytology alone holds, as it neither represents, nor give trustworthy estimates of the degree of dysplasia that is known to vary throughout the cystic lesions .
With this backdrop, final decision making on treatment is preferably done by a multidisciplinary team, considering all the work-up results of the case, to provide the best subsequent management.
According to the literature, malignancy is verified in 60% - 90% of main duct IPMNs [19,20], which corroborates our finding of cancer prevalence of 70% in this group. We also found 86% symptom presence in malignant versus 33% in benign main duct IPMNs.
All main duct lesions were operated with standard pancreatic resections. High rate of established malignancy when operated and the likelihood of dysplastic lesions to progress, have led to the recommendation that all main duct IPMNs should be resected. Furthermore, the surgical resection should be done at referral centers where per-operative pathology assessment of the resection margins is accessible and guide an extended resection whenever needed .
On the contrary, branch duct IPMNs’ all over less malignant character opens a window of opportunity to watchful expectation for asymptomatic smaller lesions (<3 cm), whereas others are considered suited for resection without delay. The latter group consists of symptomatic patients, patients lodging lesions with mural nodules, or lesions larger than 3 cm [6,22].
In our series, all malignant branch duct IPMNs presented with pain despite the fact that all were smaller than 3 cm, underlining the importance of a meticulous medical history interview.
Non-operative management should be based on an established surveillance program, and consider patient age and co-morbidity as well as willingness and ability to go through with it.
Intra abdominal complications (IAC) were registered in four patients, of whom two had pancreatic juice leakage, but only one eventually needed reoperation. This is well within the leakage rate reported in other series of pancreatic resections [23-25].
The main findings in the group of malignant IPMNs were survival at 2 years of 75% and 5 years of 67%. Our series is too small for multivariate analysis. It should, however, be noted that we found no differences in survival in main duct versus branch duct malignant IPMNs. Peroperative standard lymph node dissection is recommended and differences in survival for RxNx groups are depicted in Figure 2 . Although all over survival for patients suffering malignant IPMNs is considerably better than for conventional pancreatic ductal adenocarcinomas, they are not in the clear when it comes to recurrent disease.
In addition to surveillance of non-operated asymptomatic cases, follow-up is advocated for operated cases who may suffer curable recurrences in the pancreatic remnant, and finally also for cases lodging multifocal lesions with immanent potential for malignant transformation [19,27].
5.3. Solid Pseudopapillary Neoplasms (SPPN)
Solid Pseudopapillary Neoplasms accounts for 1% to 2% of all exocrine pancreatic tumours. SPPN should especially be kept in mind during work-up of incidentalomas found in young females. Even though clinical features are discrete or absent and tumour markers are negative, the tumours lodge a malignant potential and should always be referred to a specialist center for resection.
Patients lodging SCN should not be operated unless worrisome symptoms have surfaced, impression on neighbouring viscera afflicts the patient or malignancy cannot be ruled out.
All main duct IPMNs are recommended resected whereas asymptomatic branch duct lesions, less than 3 cm and without mural nodules can be subjected to watchful expectation of symptoms and up-dated radiology examinations at regular intervals. Supplementary work-up with EUS at specialist centers is recommended and opens the possibility for biochemical analyses following FNA in difficult cases. Patients with SPPN should always be referred to a specialist center for work-up and MDT e-valuation.
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