Reply to the Letter to the Editor: “Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms”

by Ihab R. Kamel (ikamel@jhmi.edu)

Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms

Dear Editor,

We would like to thank Dr. Menu for the opportunity to respond to some interesting comments made in the letter by Dr. Sbeit and his colleagues with regards to our manuscript entitled “Added value of apparent diffusion coefficient distinguishing between serous and mucin-producing pancreatic cyst neoplasms” [1] and to clarify aspects related to our methodology related to these comments. We would also like to thank Dr. Sbeit and his colleagues for showing immense interest in our manuscript with the goal of shedding further light on evolving non-invasive evaluation methods of pancreatic cystic neoplasms (PCNs) in an attempt to make it clearer to all audiences.

The aim of our study was to evaluate the added value of Diffusion weighted imaging (DWI) as a complementary tool to routine morphological magnetic resonance imaging (MRI) protocol. DWI has been reported to be useful in distinguishing between different types of PCNs in difficult cases [2] and is quantifiable as apparent diffusion coefficient (ADC) maps [3]. A study from our center concluded that DWI is a helpful tool in distinguishing between mucin-producing and serous PCNs [4]. This study showed that an ADC of 3 × 10−3 mm²/s resulted in correct classification of cysts in 77% to 81% of cases by three readers, with sensitivity and specificity ranging between 84 and 88% and between 66 and 72%, respectively. Previous studies, however, did not compare the performance of DWI with conventional morphological MRI alone. Our current study explored the added value of DWI (over morphological imaging sequences) in differentiating between serous and mucin-producing PCNs.
Sbeit et al. commented on the “Introduction” section stating that the statement “resection is recommended for all patients with worrisome features including cyst > 3 cm, thickened /enhancing cyst walls, main duct size 5-9 mm, non-enhancing mural nodule and abrupt change in caliber of the pancreatic duct with distal pancreatic atrophy according to International consensus guidelines from 2012” is misleading [1]. The guidelines (both the International consensus guidelines from 2012 as well as American Gastroenterology Association guidelines from 2015) seem to have equivocal recommendations in the subset of patients with worrisome features, especially those with main duct size 5–9 mm and non-enhancing mural nodule. The International consensus guidelines suggest that the younger patients (< 65 years) with a cyst size > 2 cm may be candidates for resection owing to the cumulative risk of malignancy and recommend individualization of the decision based not only on the risk of malignancy but also on the patient’s conditions and cyst location, without providing further clarification on these suggestions. They recommend observation for elderly patients with branch duct-Intraductal papillary mucinous neoplasm of > 3 cm without mural nodules and negative cytology [5]. Similarly, the AGA guidelines suggest that patients with both a solid component and a dilated pancreatic duct should undergo surgery to reduce the risk of mortality from carcinoma. However, they specify that these should be confirmed on both endoscopic ultrasound and MRI [6]. We agree with Dr. Sbeit et al that the guidelines seem to favor the important role of EUS-FNA in this subset of patients with worrisome features alone and the overall consensus seems to favor resection only in the presence of “findings suggestive of malignancy” including cytology positive or suspicious of malignancy, definite mural nodule, thickened cyst wall or intraductal mucin suggestive of main duct involvement.

Dr. Sbeit et al suggested that we show all the cysts characteristics including imaging findings, cyst fluid analysis, and cytology that were part of multidisciplinary pancreatic cyst clinic (MPCC) evaluation for the confirmation of diagnosis in 68 patients. The details of the MPCC evaluation utilized for the diagnosis and determining the type of PCN were beyond the scope of this manuscript but have been described in detail previously [7]. Also, while we collected the MPCC impression for each of the 68 patients who did not have histological diagnosis, individual cysts characteristics including imaging findings, cyst fluid analysis and cytology were not recorded as part of this study’s dataset.

The authors have mentioned that although histology is the gold standard for cyst type diagnosis, Carcino Embryonic Antigen (CEA) plays a major role in routine daily practice in differentiating mucinous from other pancreatic cyst types and have suggested that we compare the results of DWI with CEA values, to strengthen the conclusion of this paper. We agree with the authors; however, our study dataset did not include the specific CEA values for each study subject. Rather, we collected the final diagnosis and type of PCN ascertained by the multidisciplinary pancreatic cyst clinic (MPCC) evaluation among the 68 patients who did not have histological confirmation of their diagnosis. Since the MPCC evaluation included but was not limited to the specific CEA values in some of these subjects, the CEA values were not collected. However, future studies could be undertaken to look into the comparison of CEA values with DWI assessment among PCNs.