Branch Duct Intraductal Papillary Mucinous Neoplasms Of The Pancreas Research Articles

Predictors of Malignancy in "Pure" Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas without Enhancing Mural Nodules on CT Imaging: A Nationwide Multicenter Study.

Background/AimsPresence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT.MethodsThis retrospective study included 180 patients with surgically confirmed “pure” BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy.ResultsBD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant.ConclusionsIn patients with “pure” BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs): new insights on clinical outcomes and malignant progression.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic tumors of the pancreas that can progress into invasive carcinomas. Main duct IPMN is usually treated with surgery while branch duct IPMN is surgically resected if it is high risk based on certain features of the tumor (mostly radiographic) that do have some limitations. Predicting the risk of malignant progression has been lately the main focus of research especially that comprehending the molecular pathogenesis of the disease has emerged as a valuable means to better understand the disease and thus guide disease management. We will present two abstracts from the ASCO Annual Meeting. The first compares the clinical outcomes of pancreatic ductal carcinoma and IPMN associated cancer, and the second looks at the pathogenesis of the disease at the cellular and molecular levels to predict high risk disease.

Management Strategy for Multifocal Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas

Branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs) often are composed of multifocal lesions. We aimed to clarify the clinicopathologic features of multifocal BD-IPMNs. Medical records of 211 patients with BD-IPMNs (169 solitary and 42 multifocal) were retrospectively analyzed. We compared the pathological grade of resected IPMNs and the resulting clinical course between solitary and multifocal BD-IPMNs. Sixty-nine patients (54 with solitary and 15 with multifocal BD-IPMNs) underwent pancreatectomy, and of these patients, 62 exhibited at least 1 malignant predictor. There was no significant difference in the prevalence of malignancy in the resected BD-IPMNs between the 2 groups. In the remaining 142 patients who exhibited no malignant predictors, both groups demonstrated no differences in morphologic changes of BD-IPMNs. Seventeen distinct ductal carcinomas were identified in both groups, and there was no difference in the prevalence of ductal carcinoma between the 2 groups. Moreover, there was no significant difference in the disease-specific survival rate between the 2 groups. In patients with multifocal BD-IPMNs, resection is only warranted for lesions that exhibit malignancy predictors; moreover, closer attention to the potential presence or development of distinct ductal carcinoma in patients with multifocal and solitary BD-IPMNs is warranted.

The long term risk of malignancy in patients with branch duct intraductal papillary mucinous neoplasms of the pancreas

In patients (pts) with branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN), the risk of malignant progression is well described at short- and mid-term. Few data beyond 5 years are available. Patients and methodsProspective study in consecutive patients (pts) with BD-IPMN and follow-up (F/U) ≥60 months to assess long term risk of malignant progression. All computed tomographies and magnetic resonance cholangiopancreatographies performed every 1 or 2 years (depending on the maximum size of cyst) were read by the same radiologist. EUS was performed in case of occurrence of main pancreatic duct (MPD) dilation or mural nodule >5 mm. Size increase was considered significant if >5 mm. Size variation, criteria suggestive of malignancy, operative therapy and pathology were recorded. Results53 pts were included (median age at diagnosis: 61 years, median F/U: 84 months (range: 60–132) including 5 F/U >120 months). Lesions were stable in 38 pts (72%). Size increased in 8 pts (15%) (median increase : 11 (5–33) mm) without mural nodule (MN). One of those was operated on (low-grade dysplasia). A MN appeared in 5 pts (9%). ≥5 mm in 2 pts (5 and 15 mm) who were operated on (intermediate-grade dysplasia in both). The 3 remaining pts (MN < 5 mm) were carefully followed-up. Invasive advanced carcinoma occurred in 2 pts, both after 84 months F/U. In one of these, no imaging changes were noted 12 months before diagnosis of malignancy. ConclusionIn BD-IPMN, the risk of malignant evolution persists after 60 months F/U including invasive carcinomas. F/U imaging surveillance is still necessary beyond this delay in patients fit for potential surgery.

Intraductal papillary mucinous neoplasms of the pancreas—a surgical disease

Cystic pancreatic neoplasms are increasingly recognized, with intraductal papillary mucinous neoplasms of the pancreas (IPMNs) being the most frequently observed type. IPMNs are characterized by mucin production and epithelial growth within the pancreatic ducts, and are generally differentiated according to location: main pancreatic duct, its major side branches, or both (mixed type). IPMNs vary from benign to malignant and are considered precursor lesions of pancreatic adenocarcinoma. However, the exact time to neoplastic transformation and whether all IPMNs progress to malignant tumors is unclear. Surgical resection is warranted for all main-duct and mixed-type IPMNs (they harbor a high risk of malignancy of ~70%). By contrast, branch-duct IPMNs progress to cancer in only ~30% of cases. Thus, according to current guidelines (Sendai criteria), asymptomatic side-branch IPMNs <3 cm in size without suspicious radiological features (such as size progression) can be treated conservatively. Lately, even this approach has become controversial, owing to a number of Sendai-negative IPMNs showing malignant transformation. Although most IPMNs should be resected by standard oncological procedures (including lymphadenectomy), small Sendai-negative IPMNs can be treated with limited resections. This Review summarizes current knowledge of the treatment of IPMNs, with a particular focus on surgical approaches to this disease.

Acute Pancreatitis in Patients Operated on for Intraductal Papillary Mucinous Neoplasms of the Pancreas

Acute pancreatitis (AP) may reveal intraductal papillary mucinous neoplasms of the pancreas (IPMN). The aims were to describe the characteristics of AP associated with IPMN and to compare patients with AP with those without AP. All patients who underwent surgery for IPMN between 1995 and 2006 were retrospectively studied. Clinical, imaging, and histological data were collected. The clinical and radiological severity of AP, the number of episodes, and recurrence after surgery were assessed. One hundred eighty-five patients were included. Sixty-four (34.6%) had at least 1 AP (median, 2; range, 1-10). The median Balthazar score was 1 (0-6). Imaging analysis showed no difference between the 2 groups except for the presence of a mass. Branch duct IPMNs were more frequent in the AP group (74.4% vs 45.3%, P = 0.001), whereas combined IPMNs were more frequent in the non-AP group (45.3% vs 21.5%, P = 0.001). There was no difference in the grade of dysplasia between AP and non-AP groups: carcinoma, 45.3% versus 56.2%; benign IPMN, 54.7% versus 43.8% (P = NS), respectively. Acute pancreatitis occurs in 34.6% of patients with IPMNs. Acute pancreatitis is not severe and often recurs. Histology showed no difference between the 2 groups.

Incidence of Synchronous and Metachronous Pancreatic Carcinoma in 168 Patients with Branch Duct Intraductal Papillary Mucinous Neoplasm

Background/Aims: Although branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency, the incidence of concomitant pancreatic carcinoma (PC) is not well known. We investigated the incidence and clinical features of synchronous and metachronous PC in patients with BD-IPMN. Methods: We studied 168 BD-IPMN patients diagnosed by various imaging modalities, including endoscopic retrograde pancreatography, between 1990 and 2008. We reviewed the medical records and clinical features in both patients developing and not developing PC. The diagnosis of PC was histologically verified in all patients. Results: PC was observed in 9 (5.4%) of 168 patients. Five were synchronously detected at the time of BD-IPMN diagnosis, whereas four were metachronously identified during the follow-up period. All PCs occurred in regions separate from the BD-IPMN lesion. All PCs represented histologically invasive ductal adenocarcinomas, whereas the BD-IPMN lesion was diagnosed as adenoma. Patients developing PC were significantly older than patients not developing PC (p = 0.017). The diameters of the BD-IPMN lesions and main pancreatic ducts were significantly smaller in patients developing PC than patients not developing PC (p = 0.013 and p<0.001, respectively). Conclusions: It was not infrequent for PC to occur in the pancreas with BD-IPMN. Particular attention should therefore be paid to the development of PC, even in low-risk BD-IPMN, as well as to changes in BD-IPMN.

Utility of Multidetector Row CT in Diagnosing Branch Duct IPMNs of the Pancreas Compared with MR Cholangiopancreatography and Endoscopic Ultrasonography

This study aimed to compare the usefulness of multidetector row CT (MDCT), MR cholangiopancreatography (MRCP), and endoscopic ultrasonography (EUS) in diagnosing branch duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Imaging and pathological findings were retrospectively evaluated for 25 patients with branch duct IPMNs of the pancreas who underwent surgical resection (13 adenomas, 4 borderline lesions, and 8 carcinomas). MDCT and MRCP were performed on all 25 patients, whereas EUS was performed on 22 patients. MDCT and MRCP were used to identify features predictive of malignancy, including carcinoma, borderline lesions, and the presence of thickened irregular walls/septa or a solid mass. EUS was used to identify the presence of intramural nodules or a solid mass. Correlations between histopathology and maximum diameter of the main pancreatic duct (MPD) or cyst size detected by MDCT and MRCP were also examined. Presence of a solid mass was highly correlated with malignancy with all imaging methods (MDCT; P=0.001, MRCP; P=0.008, EUS; P<0.001, respectively). Presence of thickened irregular walls/septa on MDCT correlated well with malignancy (P=0.019). In contrast, presence of thickened irregular walls/septa on MRCP and intramural nodules on EUS did not correlate with malignancy. No significant correlation was found between malignancy and average maximum MPD diameter or cyst size (P>0.05), though values tended to be larger in malignant tumors. Our results suggest that the presence of thickened irregular walls/septa or a solid mass on MDCT are highly correlated with malignancy, and that MDCT is useful for diagnosis of branch duct IPMNs of the pancreas.

Prognosis of cancer with branch duct type IPMN of the pancreas

To examine the coexistence of metachronous and synchronous cancer in branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMN). We reviewed the records of 145 patients with branch duct IPMN between January 1991 and April 2008 and assessed the relationship between IPMN and intra- or extra-pancreatic carcinoma and the outcome of IPMN. The mean observation period was 55.9 +/- 45.3 mo. Among the 145 patients, the frequency of extra-pancreatic cancer was 29.0%. The frequency of gastric cancer, colon cancer, breast cancer, and pancreatic cancer were 25.5%, 15.7%, 13.7%, and 9.8%, respectively. Twenty (13.8%) of the patients died. The cause of death was extra-pancreatic carcinoma in 40%, pancreatic cancer in 25%, IPMN per se in 20%, and benign disease in 15% of the patients. The prognosis for IPMN depends not on the IPMN per se, but on the presence of intra- or extra-pancreatic cancer.

Risk of additional pancreatic cancer in patients with branch duct intraductal papillary-mucinous neoplasm.

Branch duct intraductal papillary-mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency. Although BD-IPMN outcomes are generally good, pancreatic ductal adenocarcinoma (PDA) is found distant from the original BD-IPMN in about 3.3-9.2% of cases. These reports raise the question of whether a possible association exists between BD-IPMN and PDA. Recent findings from follow-up studies suggest that pancreases with BD-IPMNs have a high risk of developing additional pancreatic cancer, with standardized incidence ratios (SIRs) of 15.8- to 26-fold. These studies suggest that special attention should be paid to BD-IPMN patients who are ≥70years. Furthermore, molecular evidence supports the hypothesis that field cancerization causing multiple primary neoplastic lesions exists in pancreases harboring IPMNs. Although more extensive studies are required to clarify the magnitude of this increased risk, clinicians should pay close attention to the development of PDA in patients with BD-IPMN, as well as to changes in BD-IPMN lesions.

Outcome of Invasive and Noninvasive Intraductal Papillary‐Mucinous Neoplasms of the Pancreas (IPMN): A 10‐year Experience

Intraductal papillary-mucinous neoplasms (IPMN) were officially introduced into the TNM classification in 1996. Based on a two-center database, we reevaluated histopathological findings, clinicopathological pattern, predictive markers for malignancy, and outcome. Between 1996 and 2006, a total of 1424 pancreatic resections were performed in the University Hospitals Dresden and Mannheim. Pathologists of both institutions reviewed the IPMN diagnoses and other with cystic or solid tumor diagnoses. All possible markers, such as diabetes, jaundice, etc., were analyzed for prediction of malignancy. We performed a survival analysis based on the morphologic classification to determine the prognosis of IPMN. There were 43 patients of primarily diagnosed IPMN along with 1174 patients with diagnoses, such as ductal adenocarcinoma. In 207 patients, the diagnoses revealed other cystic or small solid tumors. A histopathological review of the latter patients revealed 54 IPMNs, resulting in a total of 97 IPMN patients (29 noninvasive, 68 invasive). All IPMN patients had a median survival of 36 months. Recurrence occurred more frequently in invasive IPMN. Predictive markers of malignancy were pain, preoperative weight loss, jaundice, and elevated CA 19.9. The strongest independent prognostic factor was invasive growth. The survival analysis revealed excellent prognosis for noninvasive IPMN. Since the introduction of IPMN in 1996, even specialized centers have had to deal with a learning curve. By reevaluating all cystic or small solid tumors, centers can improve and their patients' treatment can be optimized. Because the preoperative diagnostic methods are not sensitive enough to differentiate between benign and malignant lesions, surgery is advocated for all main duct IPMN, because they have a high malignant potential. For branch duct IPMN, surgery is advocated if the lesion is symptomatic, >3 cm, or has enlarged nodules.

Intraductal papillary mucinous neoplasms (IPMNs): is it time to (sometimes) spare the knife?

A study by Tanno et al 1 published in this issue of Gut (see page 10.1136/gut.2007.129684) shows that a branch-duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs) without mural...

NATURAL HISTORY OF BRANCH-DUCT TYPE INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS OF THE PANCREAS

Background/Aims: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) consist of two types; branch-duct and main-duct. Branch-duct type is more common and follows a better course than main-duct type, the exact natural history of branch-duct type IPMN has not verified yet. The aim of this study was to investigate the natural course of branch-duct type IPMN. Methods: The medical records of forty five patients with branch-duct type IPMN diagnosed by pancreatogram was reviewed retrospectively. The mean age was 62.9±8.3 years and the mean follow-up duration was 27.4 ±18.9 months. Demographic, clinical and radiologic characteristics were evaluated. The histological findings of resected specimens during the follow-up were also evaluated. Results: Ten patients (22.2%) out of 45 showed enlargement of the cysts during follow-up. Initial size of the cyst in patients with cyst enlargement was smaller than in patients without enlargement in univariate analysis (p < 0.01). The cyst size less than 1.0cm was significantly associated with enlargement of the cyst with odds ratio of 4.48 in multivariate analysis. Ten patients underwent surgical resection and pathology revealed one carcinoma in situ and another invasive adenocarcinoma. The presence of mural nodule was associated with malignant change of IPMNs (p = 0.02). None of unresected cases showed any metastasis or disease-related death. Conclusions: Natural history of branch-duct type IPMNs is generally good. The occurrence of mural nodule but not the speed of size increase was associated with the malignant change of the cyst.