Introduction
Over the past several years, there have been significant advances in imaging techniques that have resulted in marked improvement in pancreatic imaging. These advances are not limited to a single imaging modality but have occurred in a broad spectrum of modalities that include CT scan, MRI and ultrasound techniques. Such progress has had a very noticeable impact in leading to better diagnosis and staging of pancreatic malignant neoplasms as well as a significant decrease in the number of unnecessary exploratory and staging surgery for those patients with unresectable or metastatic malignant disease. Furthermore, in experienced centers today, it is quite uncommon to start a pancreatic resective procedure for cancer of the pancreas without a definite diagnosis of malignancy. The inherent consequence of the development of more sensitive imaging studies however, is the incidental discovery of lesions that are asymtpomatic. Hence the term of “pancreatic incidentaloma” which refers to those lesions in the pancreas that are diagnosed incidentally when obtaining an imaging study of the abdomen not intended to look for a pancreatic pathologic process. This phenomena is not new to the pancreas and it has been observed with adrenal tumors. The solution for the adrenal incidentaloma has been to develop clear guidelines of how to deal with them once diagnosed. The task of developing clear guidelines to deal with an incidentally found pancreatic lesion however, is much more complex and controversial that with the adrenal equivalent. This is because of the presence of a wider array of pathologic process that occurs in the pancreas. There is also a significant difference in the incidence of malignant lesions between adrenal (6%) and pancreatic incidentalomas (up to 50%) (1). The presence of pre-malignant lesions in pancreatic incidentalomas has also been reported to be quite significant, as high as 60% in some series (2). The present discussion should serve as a general guidance and not applied as a strict rule. We will discuss some general principles and then concentrate in the treatment of incidentally discovered IPMN, an area that appears more controversial and that has become much more common in recent years.
General Principles
History
Each patient that presents with a pancreatic incidentaloma should be asked for prior history of pancreatitis, family history of pancreatic cancer and directly asked to remember if they had undergone any imaging study of the abdomen in the past. In some instances, the patient may have had an imaging study several years earlier that failed to report the presence of a small cystic lesion of the pancreas. When the old images are compared to the newer study, the absence of changes in size or characteristics of a benign appearing lesion may suffice to decide for a conservative follow-up avoiding further expensive and invasive diagnostic procedures In the presence of a cystic lesion, the past history of a diagnosed acute or chronic pancreatitis or a symptomatic event that could have been explained. It is not uncommon to have patients with pancreatitis that have not been followed with imaging studies in regular basis that come to surgical referral for an incidentally found cystic lesion.
Diagnostic Procedures
The incidentally found pancreatic lesion requires careful evaluation an in many instances that would imply referral to a tertiary care center that counts with a multidisciplinary pancreatic team and where a large volume of pancreatic disease is dealt with.
The performance and evaluation of imaging studies such as a pancreatic protocol CT scan and particularly a pancreatic protocol MRI varies significantly among different centers across the country and a well performed and interpreted study is crucial in the decision making process. The surgeon should review and discuss the images of the study with an experience radiologist as a crucial step in the decision making process. An experience radiologist would understand his/her role in the process and not simply report an array of differential diagnosis. The radiologist needs to be vested in reaching to a diagnosis as a part of a multidisciplinary team dealing with this type of disease processes.
Endoscopic ultrasonography and fine needle (FNA) sampling have revolutionized the diagnosis and treatment of pancreatic lesions. The study is markedly operator dependant however, and the gastroenterologist performing the study should be equally part of the multidisciplinary team and discuss the particulars of each case with the surgeon and if necessary with the radiologist. A non-experienced operator will often end with a non-diagnostic FNA and a description of the lesion that may not be of help to the surgeon. On the other hand the experience endo-ultrasonographer plays a vital role in the decision making process. ERCP may be of help in patients with a pseudocyst but with the advent of MRI/MRCP and endoscopic ultrasonography its use has significantly decreased in frequency. Pancreatoscopy however is a modality that may prove to be useful in diagnosis patients with certain pathologic processes as for example IPMN.
General characteristics of the lesion
Even when not corresponding to a clearly malignant process, often an incidentally found solid lesion of the pancreas will correspond to a neuroendocrine tumor, an islet cell tumor or a pre-malignant lesion that will require some type of resective procedure. (1-2)
Cystic lesions are in general of a more benign nature but will require further investigation or intervention depending on their size, characteristics and contents. Larger lesions (>2 cm), lesions with mural nodules on endoscopic ultrasonography, lesions with solid components and mucin producing lesions will most likely require intervention. (1-3) Benign cystic process such as microcystic adenomas and cystic lesions associated with pancreatitis may reach 2-3 cm and require no intervention. IPMN
The diagnosis of intrapapillary mucinous neoplasm (IPMN) is often made in a patient referred for a pancreatic incidentaloma. IPMN was first described by Ohhashi in Japan in 1982. (4). It is therefore not a new disease but just newly defined and over recent years has been detected much more frequently (5-6). In fact, in some high volume centers, IPMN is the second most common indication for pancreatic surgery. Its cumulative incidence has been described as 2/100,000 and its prevalence as 26/100,000. For patients older than 60 years of age, the prevalence increases to 99/100,000 (7)
The WHO classifies the different degrees of IPMN as: Adenoma, Borderline, High Grade Dysplasia and Invasive Carcinoma
The 5-year survival for Invasive IPMN is 24% and for Non-invasive IPMN is 94% (8) Since it appears clear that the disease has the potential for progression from adenoma to malignancy prevention by surgical resection is critical. However, in many instances the disease may take decades to progress and a pancreatic resection may not be necessary.
IPMN is generally classified as main duct IPMN (M) when the main pancreatic duct is dilated > 1cm and side branch IPMN(Br) when the disease is confined to a side duct. There is also a mixed type. The prevalence for cancer in main duct IPMN is estimated 57-92% and 6-46% in side branch IPMN.
In a Consensus conference in Japan in 2004 (9), guidelines for the treatment of IPMN were developed as follow:
Surgery should be offered to surgical candidates with: – IPMN-M – IPMN-Br > 3 cm – IPMN-Br < 3 cm with symptoms Non-surgical management for: – IPMN-Br < 3 cm with no symptoms or mural nodules
In a large multicenter study from Japan (10) 1024 patients underwent surgical resection of a total of 1379. Of the resected patients 44% had invasive cancer and 48% adenoma. Risks factors were identified (Table 1). From the 355 patients that were observed, none developed invasive cancer at 40 months follow-up. It’s interesting to note though that 31 out of these 355 patients had main duct IPMN. The type of surgical procedure when surgery is decided for main duct IPMN is usually a total pancreatectomy if the duct is compromised in its entirety with a dilation > 1cm. A partial pancreatectomy is done for patients that have well localized main duct IPMN and for those selected patients with side branch IPMN that require surgery. In the main duct partial pancreatectomy group however, a conversion to a total pancreatectomy is to be considered if intraoperative frozen section reports the presence of high grade dysplasia at the margin.
Conclusions
Pancreatic incidentalomas have become a more frequent problem presented to the surgeon and need to be dealt in a multispecialty fashion. In modern pancreatic surgery, the surgeon plays a role as one more member of the multidisciplinary team and depends on the close interaction with the other members of the team to provide the best care for the patient with an incidentally found mass. A diagnosis should be reached if not always with certainty, with a high degree of probability. Observation with follow-up imaging studies should be considered as part of the evaluation process for selected patients in whom the lesions do not show any evidence of malignancy. For those lesions in which the diagnosis of IPMN is made, there are general guidelines that can be follow and are helpful in the management of these patients but as for all of this cases the decision making process should be tailored to the patient’s baseline condition, age and location of the lesion.
References
1. Bruzoni M. et al. Pancreatic incidentalomas: clinical and pathologic spectrum Am J Surg 195 (2008) 329 –332
2. Lahat G – Pancreatic Incidentalomas: High Rate of Potentially Malignant Tumors J Am Coll Surg – 01-SEP-2009; 209(3): 313-9
3. Fernandez-del Castillo et al. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg 2003; 138:427-34
4. Ohhashi K., Murakami Y., Maruyama M., Four cases of mucin-producing cancer of the pancreas on specific findings of the papilla of Vater . [in Japanese] Prog Dig Endosc (1982) 20 : pp 348-351.
5. Wada, Traverso. et al. Outcomes following resection of invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas Am J Surg 2005;189:632-37
6. Tollefson et al. Intraductal papillary mucinous neoplasm: did it exist prior to 1980? Pancreas 2003;26:55-8
7. Reid-Lombardo et al. Incidence, prevalence, and management of IPMN in Olmsted County, Minnesota, 1984-2005. Pancreas 2008; 37: 139-44
8. Raimondo M et al; Invasive cancer and survival of intraductal papillary mucinous tumors of the pancreas Am J Gastroenterol 2002 Oct; 97(10):2553-8
9. Tanaka et al. International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas. Pancreatology 2006; 6:17:17-32 10. Suzuki: Cystic neoplasm of the pancreas: a Japanese multiinstitutional study of intraductal papillary mucinous tumor and mucinous cystic tumor. Pancreas, 2004;28:241-246