Title: Branch-Duct Intraductal Papillary Mucinous Neoplasms: Observations in 145 Patients Who Underwent Resection
Abstract: Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations. Methods: A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1990 and 2005 was conducted. Results: Sixty-six patients (45.5%) had adenoma, 47 (32%) borderline tumors, 16 (11%) carcinoma in situ, and 16 (11%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). Jaundice was more frequent in patients with cancer (12.5% vs 1.8%, respectively, P = .022) and abdominal pain in patients with benign tumors (45% vs 25%, respectively, P = .025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter ≥30 mm (P < .001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100% and, for invasive cancer, was 63%. Conclusions: This large cohort of resected branch-duct IPMNs shows that cancer is present in 22% of cases and validates the recent guidelines that indicate absence of malignancy in tumors <30 mm, without symptoms or mural nodules. Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations. Methods: A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1990 and 2005 was conducted. Results: Sixty-six patients (45.5%) had adenoma, 47 (32%) borderline tumors, 16 (11%) carcinoma in situ, and 16 (11%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). Jaundice was more frequent in patients with cancer (12.5% vs 1.8%, respectively, P = .022) and abdominal pain in patients with benign tumors (45% vs 25%, respectively, P = .025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter ≥30 mm (P < .001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100% and, for invasive cancer, was 63%. Conclusions: This large cohort of resected branch-duct IPMNs shows that cancer is present in 22% of cases and validates the recent guidelines that indicate absence of malignancy in tumors <30 mm, without symptoms or mural nodules. See editorial on page 345; CME quiz on page 309.See Lahav M et al on page 813 in the July 2007 issue of CGH.Asymptomatic cystic tumors of the pancreas are being identified with increasing frequency, and this has resulted in a dramatic increase in the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) at specialized centers.1Sohn T.A. Yeo C.J. Cameron J.L. Iacobuzio-Donahue C.A. Hruban R.H. Lillemoe K.D. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity.Ann Surg. 2001; 234: 313-322Crossref PubMed Scopus (302) Google Scholar, 2Fernandez-del Castillo C. Targarona J. Thayer S.P. Rattner D.W. Brugge W.R. Warshaw A.L. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients.Arch Surg. 2003; 138: 427-434Crossref PubMed Scopus (525) Google Scholar, 3Sohn T.A. Yeo C.J. Cameron J.L. Hruban R.H. Fukushima N. Campbell K.A. Lillemoe K.D. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience.Ann Surg. 2004; 239: 788-799Crossref PubMed Scopus (769) Google Scholar, 4Conlon K.C. Intraductal papillary mucinous tumors of the pancreas.J Clin Oncol. 2005; 23: 4518-4523Crossref PubMed Scopus (59) Google Scholar Consequently, knowledge of the clinicopathologic characteristics and natural history of specific subtypes of IPMNs has become critical. At the center of the controversy is the observation that IPMNs arising from the branch ducts seem to have a less aggressive clinical course than those arising from the main ducts. This in turn raises the question of whether branch-duct IPMN (Br-IPMNs) may be a distinct tumor type with altogether different biologic behavior than those arising in the main pancreatic duct.5Traverso L.W. Peralta E.A. Ryan Jr, J.A. Kozarek R.A. Intraductal neoplasms of the pancreas.Am J Surg. 1998; 175: 426-432Abstract Full Text PDF PubMed Scopus (168) Google Scholar, 6Matsumoto T. Aramaki M. Yada K. Hirano S. Himeno Y. Shibata K. Kawano K. Kitano S. Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas.J Clin Gastroenterol. 2003; 36: 261-265Crossref PubMed Scopus (201) Google Scholar, 7Sugiyama M. Izumisato Y. Abe N. Masaki T. Mori T. Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas.Br J Surg. 2003; 90: 1244-1249Crossref PubMed Scopus (380) Google Scholar, 8Tanaka M. Kobayashi K. Mizumoto K. Yamaguchi K. Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas.J Gastroenterol. 2005; 40: 669-675Crossref PubMed Scopus (114) Google Scholar, 9Schmidt C.M. Lillemoe K.D. IPMN-controversies in an “epidemic.”.J Surg Oncol. 2006; 94: 91-93Crossref PubMed Scopus (12) Google Scholar Various reports have shown significant differences in the prevalence of cancer in main-duct IPMN (including the mixed type) vs Br-IPMNs (70% vs 25%, respectively).1Sohn T.A. Yeo C.J. Cameron J.L. Iacobuzio-Donahue C.A. Hruban R.H. Lillemoe K.D. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity.Ann Surg. 2001; 234: 313-322Crossref PubMed Scopus (302) Google Scholar, 3Sohn T.A. Yeo C.J. Cameron J.L. Hruban R.H. Fukushima N. Campbell K.A. Lillemoe K.D. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience.Ann Surg. 2004; 239: 788-799Crossref PubMed Scopus (769) Google Scholar, 4Conlon K.C. Intraductal papillary mucinous tumors of the pancreas.J Clin Oncol. 2005; 23: 4518-4523Crossref PubMed Scopus (59) Google Scholar, 5Traverso L.W. Peralta E.A. Ryan Jr, J.A. Kozarek R.A. Intraductal neoplasms of the pancreas.Am J Surg. 1998; 175: 426-432Abstract Full Text PDF PubMed Scopus (168) Google Scholar, 7Sugiyama M. Izumisato Y. Abe N. Masaki T. Mori T. Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas.Br J Surg. 2003; 90: 1244-1249Crossref PubMed Scopus (380) Google Scholar, 8Tanaka M. Kobayashi K. Mizumoto K. Yamaguchi K. Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas.J Gastroenterol. 2005; 40: 669-675Crossref PubMed Scopus (114) Google Scholar, 9Schmidt C.M. Lillemoe K.D. IPMN-controversies in an “epidemic.”.J Surg Oncol. 2006; 94: 91-93Crossref PubMed Scopus (12) Google Scholar, 10Bernard P. Scoazec J.Y. Joubert M. Kahn X. Le Borgne J. Berger F. Partensky C. Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases.Arch Surg. 2002; 137: 1274-1278Crossref PubMed Google Scholar, 11Irie H. Yoshimitsu K. Aibe H. Tajima T. Nishie A. Nakayama T. Kakihara D. Honda H. Natural history of pancreatic intraductal papillary mucinous tumor of branch duct type: follow-up study by magnetic resonance cholangiopancreatography.J Comput Assist Tomogr. 2004; 28: 117-122Crossref PubMed Scopus (107) Google Scholar, 12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google Scholar, 13Salvia R. Fernandez-del Castillo C. Bassi C. Thayer S.P. Falconi M. Mantovani W. Pederzoli P. Warshaw A.L. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.Ann Surg. 2004; 239: 678-687Crossref PubMed Scopus (641) Google Scholar Consequently, some authors have recommended nonsurgical management with close observation for IPMNs that arise from branch ducts and that fail to meet certain “high-risk” criteria.6Matsumoto T. Aramaki M. Yada K. Hirano S. Himeno Y. Shibata K. Kawano K. Kitano S. Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas.J Clin Gastroenterol. 2003; 36: 261-265Crossref PubMed Scopus (201) Google Scholar, 7Sugiyama M. Izumisato Y. Abe N. Masaki T. Mori T. Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas.Br J Surg. 2003; 90: 1244-1249Crossref PubMed Scopus (380) Google Scholar, 10Bernard P. Scoazec J.Y. Joubert M. Kahn X. Le Borgne J. Berger F. Partensky C. Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases.Arch Surg. 2002; 137: 1274-1278Crossref PubMed Google Scholar, 11Irie H. Yoshimitsu K. Aibe H. Tajima T. Nishie A. Nakayama T. Kakihara D. Honda H. Natural history of pancreatic intraductal papillary mucinous tumor of branch duct type: follow-up study by magnetic resonance cholangiopancreatography.J Comput Assist Tomogr. 2004; 28: 117-122Crossref PubMed Scopus (107) Google Scholar, 12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google Scholar, 13Salvia R. Fernandez-del Castillo C. Bassi C. Thayer S.P. Falconi M. Mantovani W. Pederzoli P. Warshaw A.L. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.Ann Surg. 2004; 239: 678-687Crossref PubMed Scopus (641) Google Scholar, 14Kobayashi G. Fujita N. Noda Y. Ito K. Horaguchi J. Takasawa O. Akaishi S. Tsuchiya T. Kobari M. Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS.J Gastroenterol. 2005; 40: 744-751Crossref PubMed Scopus (101) Google Scholar A recent consensus conference supports this view.12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google Scholar However, the majority of contemporary series has only recently begun to distinguish between main-duct IPMN and those of the side-branch variety when describing experiences managing these 2 important neoplasms.15Serikawa M. Sasaki T. Fujimoto Y. Kuwahara K. Chayama K. Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment strategy based on morphologic classification.J Clin Gastroenterol. 2006; 40: 856-862Crossref PubMed Scopus (93) Google Scholar, 16Fernandez-del Castillo C. Intraductal papillary mucinous neoplasms of the pancreas: a plea for prospective differentiation between main-duct and side-branch tumors.Ann Surg Oncol. 2005; 12: 98-99Crossref PubMed Scopus (15) Google ScholarWe recently reported the combined experience of the Massachusetts General Hospital (MGH) and the University of Verona (UV) comprising 140 patients with resected IPMNs of the main duct and the combined type.13Salvia R. Fernandez-del Castillo C. Bassi C. Thayer S.P. Falconi M. Mantovani W. Pederzoli P. Warshaw A.L. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.Ann Surg. 2004; 239: 678-687Crossref PubMed Scopus (641) Google Scholar The purpose of the current study is again to combine the experiences of these 2 pancreatic centers with resected IPMNs exclusively of the branch-duct variety to help elucidate their clinicopathologic characteristics and long-term survival and to compare these with main-duct IPMNs.Materials and MethodsPatientsThe MGH and UV institutional review boards approved this study. Patients with surgically resected, pathologically confirmed IPMNs between January 1990 and December 2005 were identified from prospectively collected databases. The absence of a stromal layer was used as criterion to distinguish Br-IPMNs from mucinous cystic neoplasms.12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google Scholar, 17Zamboni G. Kloppel G. Hruban R.H. Longnecker D.S. Adler G. Mucinous cystic neoplasms of the pancreas World Health Organization classification of tumors.in: Hamilton S.R.A.L. Pathology and genetics of tumors of the digestive system. IARC Press, Lyon2000: 237-240Google Scholar, 18Zamboni G. Scarpa A. Bogina G. Iacono C. Bassi C. Talamini G. Sessa F. Capella C. Solcia E. Rickaert F. Mariuzzi G.M. Kloppel G. Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors.Am J Surg Pathol. 1999; 23: 410-422Crossref PubMed Scopus (550) Google Scholar Three hundred sixty-three patients were identified during this time period (203 MGH and 160 UV). Of these, 145 (40%) were determined to have pure Br-IPMNs, with the remaining being main-duct or combined IPMNs. Information including demographics, clinical history and presentation, diagnostic workup, type of surgical procedure, details of the pathology report, hospital course, and short- and long-term follow-up were obtained. Perioperative mortality was defined as in-hospital or 30-day death. For the analysis, Br-IPMNs with adenoma or borderline neoplasms were grouped as “benign” and Br-IPMNs with carcinoma in situ and invasive carcinoma as “malignant.”All patients had follow-up evaluations consisting of clinical examination, serologic assessment including fasting glucose blood levels and tumoral markers, and imaging. Imaging procedures included contrast-enhanced abdominal ultrasound (US), computer tomography (CT), and magnetic resonance imaging (MRI). In most patients, recurrences were diagnosed by CT and were confirmed histologically whenever possible. Patients with benign IPMN usually had a yearly follow-up evaluation for the first 5 years and then underwent imaging evaluation in the case of abdominal symptoms. Patients with invasive carcinoma were seen every 6 months for the first 2 years and yearly thereafter.Worsening diabetes was defined as deterioration in the metabolic control of previously diagnosed diabetes, requiring modification of the medical treatment. No specific exocrine function tests were performed. New onset of exocrine insufficiency was defined as steathorrea and weight loss requiring pancreatic enzymes supplementation.Statistical AnalysisDescriptive data are presented as mean ± standard deviation unless otherwise specified. Normally distributed continuous variables were compared using a 2-sample Student t test; the Mann–Whitney U test was used for nonnormally distributed variables. Categorical variables were compared using a Pearson χ2 test and Fisher exact test when cell counts were <5. Survival analysis was done using the Kaplan–Meier function, comparing histologic groups with the log-rank test. A P value of less than .05 was considered statistically significant.ResultsOf the 145 patients with resected Br-IPMNs, 66 had adenomas (45.5%), 47 borderline neoplasms (32.4%), 16 carcinoma in situ (11%), and 16 invasive carcinoma (11%). One hundred thirteen patients had benign Br-IPMNs, and 32 had malignant neoplasms.Clinical CharacteristicsClinical characteristics are described in Table 1. There was a nonsignificant slight preponderance of females in both benign and malignant subgroups (58% vs 53%, respectively), and the median age at presentation was also similar in the 2 groups (66 vs 68 years, respectively).Table 1Clinical Characteristics of 145 Patients With Branch-Duct IPMNBenign (n = 113)Malignant (n = 32)Total (n = 145)P value (benign vs malignant)Male, n (%)47 (41.6)15 (46.9)62 (42.8)NSFemale, n (%)66 (58.4)17 (53.1)83 (57.2)NSMedian age, yr (range)66 (39−90)67.5 (35−84)67 (35−90)NSHistory of smoking, n (%)44 (38.9)8 (25)52 (35.9)NSPrevious diagnosis of chronic pancreatitis, n (%)13 (11.5)4 (12.5)17 (11.7)NSSymptoms, n (%)64 (56.6)23 (71.9)87 (60)NS Median duration of symptoms in weeks (range)19 (2−520)18 (4−572)18 (4−572)NS Abdominal pain, n (%)52 (46)8 (25)60 (41.4).025 Jaundice, n (%)2 (1.8)4 (12.5)6 (4.1).022 Weight loss, n (%)aLoss of >5% of body weight.28 (24.8)7 (21.9)35 (24.1)NS Acute pancreatitis, n (%)17 (15)5 (15.6)22 (15.2)NS Deterioration of diabetes, n (%)9 (8)4 (12.5)13 (9)NS Asymptomatic, n (%)49 (43.4)9 (28.1)58 (40)NS Median cancer antigen 19-9, U/L, range10 (1−156)10 (1−1774)10 (1−1774)NS Other tumor (synchronous or metachronous)6 (5.3)2 (6.3)8 (5.5)NSa Loss of >5% of body weight. Open table in a new tab Overall, 58 patients (40%) were asymptomatic, and there was no significant difference in the frequency of incidentally discovered tumors between benign and malignant (43% vs 28%, respectively, P = .12). Females were more likely to be symptomatic than males (68% vs 32%, respectively, P = .002). Differences in presentation that reached statistical significance included a higher incidence of jaundice in patients with malignant tumors and a higher incidence of abdominal pain in patients with benign tumors.Eight patients (5.5%), 6 with adenoma and 2 with malignant IPMNs (1 carcinoma in situ and 1 invasive carcinoma), presented with synchronous or metachronous neoplasms. In 2 cases, Br-IPMNs with in situ carcinoma and adenoma were incidentally found in the surgical specimen after resection for ductal adenocarcinoma and ampullary carcinoma, respectively. Three patients with branch-duct adenoma were unexpectedly found to have a secondary tumor (1 neuroendocrine microadenoma, 1 mucinous cystadenoma, and 1 small bowel lymphoma), and another patient with Br-IPMNs with invasive carcinoma had a neuroendocrine microadenoma. Two patients with Br-IPMNs adenoma developed metachronous squamous cell carcinoma of the lung.Tumor Location and SizeThe anatomic locations are described in Table 2. Two thirds of Br-IPMNs were located in the head or uncinate process of the pancreas. The mean diameter of the lesions, as determined by preoperative radiologic studies, was 30.6 ± 15.7 mm (median, 30; range, 10–90 mm), and multifocality was described in 21 patients (14.5%). There was no significant difference in the incidence of malignancy when comparing the location of benign and malignant neoplasms.Table 2Location Of The Tumor According To Preoperative Radiologic StudiesBenign (n = 113)Malignant (n = 32)Total (n = 145)P value (benign vs malignant)Head, n (%)44 (38.9)17 (53.1)61 (42.1)NSUncinate process, n (%)17 (15)5 (15.6)22 (15.2)NSBody, n (%)24 (21.2)3 (9.4)27 (18.6)NSTail, n (%)10 (8.8)4 (12.5)14 (9.7)NSMultifocal, n (%)18 (15.9)3 (9.4)21 (14.5)NSMean radiologic size (mm)aRadiologic size was available in 120 patients (benign, 94; malignant, 26).27.9 (10–84)40.5 (10–90)30.5 (10–90).0001NOTE. Radiologic studies include abdominal US, CT, MRI, magnetic resonance cholangiopancreatography.a Radiologic size was available in 120 patients (benign, 94; malignant, 26). Open table in a new tab Surgical ResectionsSurgical resections comprised 97 (67%) pancreaticoduodenectomies (with pylorus preservation in 28 cases), 29 (20%) distal pancreatectomies (14 with splenic preservation), 15 (10%) middle pancreatectomies, and 2 (1.4%) total pancreatectomies. One patient (0.7%), in the early period of the series, underwent enucleation and another (0.7%) underwent a combined pancreaticoduodenectomy and distal pancreatectomy because of the presence of a multifocal lesion in the head and tail. The number of resections has increased over time, notwithstanding that more selective criteria for resection have been applied over the last years (Figure 1A). This policy has resulted in a notable decrease in the number of resections for incidentally discovered lesions (Figure 1B). At present, both of our institutions subscribe to the recommendations of the consensus conference of Sendai.12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google ScholarPathologyThe diagnosis of Br-IPMN relies on the presence of 1 or more cystic neoplastic lesions communicating with the main pancreatic duct (but not involving it) and lacking an ovarian-like stromal layer.12Tanaka M. Chari S. Adsay V. Fernandez-del Castillo C. Falconi M. Shimizu M. Yamaguchi K. Yamao K. Matsuno S. International Association of PancreatologyInternational consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32Abstract Full Text PDF PubMed Scopus (1633) Google Scholar, 17Zamboni G. Kloppel G. Hruban R.H. Longnecker D.S. Adler G. Mucinous cystic neoplasms of the pancreas World Health Organization classification of tumors.in: Hamilton S.R.A.L. Pathology and genetics of tumors of the digestive system. IARC Press, Lyon2000: 237-240Google Scholar, 18Zamboni G. Scarpa A. Bogina G. Iacono C. Bassi C. Talamini G. Sessa F. Capella C. Solcia E. Rickaert F. Mariuzzi G.M. Kloppel G. Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors.Am J Surg Pathol. 1999; 23: 410-422Crossref PubMed Scopus (550) Google Scholar The pathologic features of the tumors are described in Table 3. The mean diameter (as measured by the pathologist) was 26.4 ± 16.8 mm (median, 20; range, 5–100 mm), with a statistically significant difference between benign and malignant (mean, 23.8 vs 40 mm, respectively, P = .003; median, 20 [range, 5–50 mm] vs 30 [range, 8–100 mm], respectively, P = .003). Pathologic examination revealed the presence of a higher frequency of multifocality compared with the radiologic assessment (25.6% vs 14.5%, respectively, P = .028). Moreover, there was a statistically significant difference in tumor size between radiologic and pathologic examination (mean radiologic size, 30.6 ± 15.7 mm vs mean pathologic size, 26.4 ± 16.8 mm, P = .01 [median radiologic size, 30 mm vs median pathologic size, 20 mm, P = .001]).Table 3Pathological Characteristics of 145 Branch-Duct IPMNBenign (n = 113)Malignant (n = 32)Total (n = 145)P value (benign vs malignant)Size <30 mm, n (%)aPathologic size was available in 140 patients (benign, 110; malignant, 30).86 (77.5)12 (41.4)98 (70).0001Presence of thick wall, n (%)bThick wall was defined as a cyst wall with a thickness greater than 3 mm.2604 (12.5)4 (2.8).0001Presence of nodules/papillae, n (%)4 (3.5)19 (59.4)23 (15.9).0001Presence of septae, n (%)17 (15)3 (9.4)20 (13.8)NSMultifocal lesions, n (%)28 (24.8)9 (28.1)37 (25.5)NSUnifocal lesions, n (%)85 (75.2)23 (71.9)108 (74.5)NSMean size (mm)aPathologic size was available in 140 patients (benign, 110; malignant, 30).23.8 (5−50)40 (8−100)26.4 (5−100).003a Pathologic size was available in 140 patients (benign, 110; malignant, 30).b Thick wall was defined as a cyst wall with a thickness greater than 3 mm.26Chiu S.S. Lim J.H. Lee W.J. Chang K.T. Oh D.K. Lee K.T. Lee J.K. Choi S.H. Intraductal papillary mucinous tumour of the pancreas: differentiation of malignancy and benignancy by CT.Clin Radiol. 2006; 61: 776-783Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Open table in a new tab Significant factors associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter equal to or greater than 30 mm (P < .001). The likelihood of malignancy increased significantly with the presence of nodules. Nodules were absent in all 66 cases of adenoma, whereas they were identified in 4 of 47 borderline tumors (8.5%), 7 of 16 in situ carcinomas (43.8%), and 12 of 16 invasive carcinomas (75%). The pathologist described thick walls only in invasive carcinomas (n = 4 cases). Multifocality and septae were not significantly different between benign and malignant subgroups. Figure 2 is a scatter plot of radiologic tumor size as a function of histologic subtype and presence or absence of symptoms and nodules.Figure 2Scatter plot of radiologic tumor size as a function of histologic subtype and presence or absence of symptoms and nodules.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Of the 16 patients with invasive carcinoma, 19% had positive lymph nodes. The mean number of nodes resected in these patients was 20, and the mean number of positive nodes was 4. Vascular invasion was present in 1 (6%) and neural invasion was present in 3 (19%) patients. The mean tumor size of Br-IPMN with invasive cancer was 50 ± 24 mm. Only 3 patients with invasive carcinoma had carcinoma with a diameter of ≤30 mm, and 2 out of 3 patients had only small foci of invasive carcinoma in the context of adenoma or borderline tumors. These 3 patients had also nodules or symptoms present.Data on pancreatic transection margins were unavailable in 7 patients (5 affected by adenoma, 1 by borderline neoplasm, and 1 by in situ carcinoma). In 133 (96.4%) patients, the transection margin was negative (the presence of mucinous metaplasia was considered as a negative margin). Of the remaining patients, 4 had adenoma and 1 had borderline dysplasia in the side branches of the transection margin (by definition, the main pancreatic duct was without any atypia). No patient with a positive transection margin developed a neoplastic recurrence.Perioperative CourseTable 4 shows perioperative complications. Thirty-nine patients (27%) developed abdominal complications, the most common of which was pancreatic fistula, occurring in 17% of cases. Forty-seven patients (32.4%) had extra-abdominal complications. The median postoperative length of stay was 9 days (range, 4–77; mean, 12 ± 10 days). Seven patients (4.8%) required readmission for perioperative complications. There were no operative deaths and no surgical reexplorations.Table 4Perioperative Results in 145 Patients Undergoing Pancreatic Resection for Branch-Duct IPMNsPerioperative ComplicationsNo. (%)Overall morbidity74 (51)Abdominal complicationsaAbdominal complication is defined as the occurrence of pancreatic or biliary fistula, abscess, collection, hemorrhage, wound infection, and delayed gastric emptying.39 (27)Pancreatic fistula25 (17)Biliary fistula4 (2.8)Delayed gastric emptying9 (6)Intrabdominal collections/abscess13 (9)Nonsurgical complicationsbNonsurgical complications is defined as the occurrence of cardiopulmonary, neurologic, urologic, and septic complications.45 (31)Perioperative Readmission7 (4.8)Reoperation0 (0)Mortality0 (0)a Abdominal complication is defined as the occurrence of pancreatic or biliary fistula, abscess, collection, hemorrhage, wound infection, and delayed gastric emptying.b Nonsurgical complications is defined as the occurrence of cardiopulmonary, neurologic, urologic, and septic complications. Open table in a new tab Long-Term Follow-Up, Recurrence, and SurvivalFollow-up was available in 98% of patients, and the mean duration of follow-up was 45.9 ± 34.2 months (median, 38.7; range, 1–180 months). Ten patients had tumor recurrence (6.9%). Four patients had only local recurrence, and they all had an IPMA with a negative pancreatic transection margin. These recurrent (or metachronous) lesions were asymptomatic and discovered after a mean follow-up of 34.7 months. In all cases, they were small in size (<30 mm), without nodules or thick walls, and are being managed conservatively with close clinicoradiologic observation. Six of the 16 patients (38%) with invasive carcinoma developed metastases. Three patients developed both local and distant recurrence, whereas the other 3 had only distant recurrence. All cases of distant recu