European experts consensus statement on cystic tumours of the pancreas

Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6 mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.     

Air in the main pancreatic duct associated with a pancreatic intraductal papillary mucinous neoplasm

A 62-year-old man was referred to our hospital after ultrasonographic mass screening detected a pancreatic cyst that proved to be an intraductal papillary mucinous neoplasm. Computed tomography additionally demonstrated air in the main pancreatic duct. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography delineated a filling defect in the main pancreatic duct in the body of the pancreas. The sphincter of Oddi was open. The main pancreatic duct was dilated by viscous mucin; air in the duct was attributed to consequent dysfunction of the sphincter. Laboratory findings included no significant abnormality. The patient has remained asymptomatic during follow-up. Of 25 previously reported cases with air in the duct, only 1 involved an intraductal papillary mucinous neoplasm.     

Long-term follow-up of intraductal papillary adenoma of the pancreas

Intraductal papillary mucinous tumors of the main pancreatic duct are often considered to be premalignant or malignant, and therefore surgical resection is recommended. We report two autopsy cases of intraductal papillary mucinous tumor of the pancreas following long-term observation. The first patient was an 84-year-old man with early gastric cancer treated by endoscopic mucosectomy. The second patient was a 77-year-old man with hepatocellular carcinoma treated by percutaneous pure ethanol injection and transarterial embolization. In both patients, endoscopic retrograde pancreatography showed a diffusely dilated main pancreatic duct, with intraductal filling defects expressing mucus, as well as dilated side branches. Obvious intramural nodules were not detected. Due to their advanced age and personal requests, both patients were managed conservatively and followed nonoperatively. In the first patient, serial pancreatograms showed progression of the pancreatic duct dilatation. Both patients died of gastric cancer, the first patient 7¹/₂ years and the second, 10 years after first presentation, respectively. Autopsies revealed extensive intraductal papillary adenoma throughout the dilated mucus-filled main pancreatic duct. However, there was no evidence of progression to adenocarcinoma. Based on these observations, we suggest that, in patients with intraductal papillary mucinous tumor of the pancreas without obvious intramural nodules, even if the tumor is in the main pancreatic duct, pancreatectomy may not be mandatory, particularly in the elderly. Received: March 21, 2001 / Accepted: July 6, 2001 Reprint requests to: T. Kamisawa     

Recurrent cholangitis as the first manifestation of an intraductal papillary mucinous tumor of the pancreas

Intraductal papillary mucinous tumor is a rare pancreatic tumor originating from the epithelium of the pancreatic duct and exhibiting papillary proliferation of tall columnar epithelial cells. The usual clinical presentation is recurrent episodes of pancreatitis due to hypersecretion of mucin and obstruction of a markedly dilated pancreatic duct. We describe a 74-year-old man who presented recurrent attacks of cholangitis, due to a common bile duct obstruction from thick pancreatic mucus reflux, as the first manifestation of intraductal papillary mucinous tumor.     

A case of mixed adenoneuroendocrine carcinoma of the pancreas mimicking intraductal papillary mucinous carcinoma

A previously healthy 52-year-old man was referred to our hospital for further evaluation of main pancreatic duct dilatation. The preoperative work-up was consistent with intraductal papillary mucinous carcinoma (IPMC) derived from a mixed type intraductal papillary mucinous neoplasm (IPMN), because multilocular cysts with enhancing thickened pancreatic head walls and dilated pancreatic ducts lined with dysplastic mucinous epithelium, with papillary proliferation from the pancreatic body to the tail, were observed; in addition, the pancreatic juice cytology was class V, which is suggestive of adenocarcinoma. Total pancreatectomy was performed because a definite mass was not found before surgical resection and the tumors could have spread to the tail. The pathological diagnosis was mixed adenoneuroendocrine carcinoma of the pancreatic head. IPMN with high- or low-grade dysplasia was not observed anywhere in the pancreatic duct. The pancreatic ductal adenocarcinoma consisted of large caliber malignant glands with intraluminal flat or papillary structures; therefore, we were unable to recognize a definite pancreatic mass before surgical resection, and suspected an IPMC derived from a mixed type IPMN.     

Outcomes of intraductal papillary mucinous neoplasm with “Sendai-positive” criteria for resection undergoing non-operative management

BackgroundThere are few data on the outcome of patients with intraductal papillary mucinous neoplasms of the pancreas meeting criteria for resection (Sendai-positive), and not operated.AimTo evaluate outcome of patients with a resectable, Sendai-positive intraductal papillary mucinous neoplasm, and not operated.MethodsMulticentre, retrospective analysis of prospectively enrolled patients, with resectable Sendai-positive, not-operated intraductal papillary mucinous neoplasm. Overall-survival and disease-specific survival were the primary end-point, and progression-free survival secondary.ResultsThirty-five patients (60% male, median age 77) enrolled: 40% main-duct, 60% branch-duct intraductal papillary mucinous neoplasms. In 19 patients surgery was ruled out due to comorbidities, in 7 because aged > 80, 9 refused surgery. Twelve (34.3%) patients died after a mean of 32.5 months, 8 due to disease progression, 4 due to comorbidities. The median overall, disease-specific and progression-free survival were 52, 55, and 44 months respectively. Main duct involvement and age at diagnosis were associated with worse overall and progression-free survival, only main duct involvement with worse disease-specific survival (52 months main duct vs. 64 branch duct; P = 0.04).ConclusionThese results suggest that in elderly and comorbid patients with Sendai-positive intraductal papillary mucinous neoplasms, especially of the branch duct, a conservative approach could be reasonable, as associated with a relatively good outcome, and should be carefully discussed with the patients.     

Intraductal mucinous tumors occurring simultaneously in the liver and pancreas

A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a 67-year-old man is described. Abdominal ultrasonography and computed tomography (CT) revealed the presence of cystic lesions with intraluminal septae both in the caudate lobe of the liver and in the uncinate process of the pancreas; these cystic lesions communicated with the hepatic duct and pancreatic duct, respectively. Mucin retention was observed in the cysts, and cholestasis was induced by mucin secretion into the common bile duct. The lesions were resected by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy. Both lesions were multilocular cystic tumors with no papillary projections or focal mass effect in their walls. Histologically, both cystic lesions were a mixture of hyperplasia and adenoma lined by low papillary columnar epithelium. There were no cellular or histological features to suggest malignant change. The fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma. The hepatic lesion was considered to be of a similar nature to intraductal papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions occurred simultaneously in the liver and pancreas. This case is of interest in regard to the diagnosis and management of mucinous hepatopancreatobiliary lesions. Received: March 16, 2001 / Accepted: September 14, 2001     

Familial intraductal papillary mucinous neoplasms of the pancreas

The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described.MethodsThree families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for.ResultsSymptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n = 3) or fortuitous discovery (n = 5). Number of cystic lesions was ≤3 (n = 4) or >3 (n = 4). Intraductal papillary mucinous neoplasms involved branch ducts (n = 7) or both main pancreatic duct and branch duct (n = 1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes).ConclusionA familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.     

The role of pancreatoscopy in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas

BACKGROUND: Intraductal papillary mucinous tumor of the pancreas is a rare neoplasm managed by operative resection of the affected segment of the pancreas. GOALS: To evaluate the role of peroral pancreatoscopy in the diagnosis and preoperative localization of the affected region of the pancreatic duct and to undertake the appropriate operation for each patient. STUDY: Five patients with suspected intraductal papillary mucinous tumor of the pancreas were studied using endoscopic retrograde cholangiopancreatography, computed tomography of the abdomen, endoscopic ultrasonography, and peroral pancreatoscopy. The findings from these studies were compared, and operative resection was performed in each patient based on pancreatoscopic findings. RESULTS: Of the five patients with suspected intraductal papillary mucinous tumor, only four had histologically confirmed tumor, and the remaining one patient had a retention cyst of the pancreas. Pancreatoscopy correctly identified all four patients with the tumor while excluding the diagnosis of papillary tumor in one. CONCLUSION: Peroral pancreatoscopy is valuable in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas, especially in the localization of such tumor.     

Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas

Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.     

Intraductal papillary and mucinous tumor of the pancreas: a case report of successful surgical treatment with decompression

Intraductal papillary mucinous tumor of the pancreas is commonly regarded as histopathologically low-grade malignancy. As yet, no fixed strategy of treatment for the advanced aged patient with intraductal papillary mucinous tumor exists. An 80-year-old woman was admitted to our hospital in July 1996 because of back pain due to pancreatitis. Examinations showed a widely opened orifice of the ampulla of Vater, the mural nodule in the cystic lesion of the pancreas uncus, and a mucinous plug in the diffusely dilated main pancreatic duct, so the patient was diagnosed as having intraductal papillary mucinous tumor in the pancratic head. However, in view of the patient's advanced age and the fact that intraductal papillary mucinous tumor is commonly regarded as a slow growing and histopathologically low-grade malignancy, we refrained from radical operation and selected the best supportive care. Four years subsequent to this, her symptoms became uncontrollable and she returned to our hospital. In consideration of her age, side-to-side pancreaticojejunostomy as minimally invasive surgery was employed. The postoperative course was uneventful. The symptoms, biochemical profiles and images improved and she was discharged from the hospital 28 days after the operation. No event has been observed in the patient for one year after operation. Surgical decompression is considered to be effective minimally invasive surgery for intraductal papillary mucinous tumor.     

Role of SpyGlass-DStm in the preoperative assessment of pancreatic intraductal papillary mucinous neoplasm involving the main pancreatic duct

Background/Objectives

It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DS^tm in the preoperative assessment of intraductal papillary mucinous neoplasm involving the main pancreatic duct.

Biliopancreatic fistula associated with intraductal papillary-mucinous pancreatic cancer: institutional experience and review of the literature

Intraductal papillary-mucinous tumour is clinicopathologically characterized by papillary growth and mucin production within the pancreatic duct system. The category includes a wide range of dysplasia, ranging from adenoma to carcinoma, the latter designated as intraductal papillary-mucinous cancer. In general, the tumor renders a favorable prognosis after complete resection. However, intraductal papillary-mucinous tumor with overt invasion outside the gland has been reported to have a poor prognosis, as is the case with the usual type of duct cell cancer of the pancreas. We experienced two cases of intraductal papillary-mucinous cancer with obstructive jaundice due to impaction of thick mucus protruding from the pancreas via a "spontaneous" biliopancreatic fistula. Preoperative examinations of both patients showed a large intraductal papillary-mucinous tumor in the head of the pancreas with fistula formation between the intrapancreatic portion of the common bile duct and the main pancreatic duct. Histopathological investigation of the two resected specimens suggested that the fistula may not have developed from invasion by papillary or tubular adenocarcinoma, but from compression and destruction of the intercalating tissues by abundant mucinous secretion. The first patient died of peritoneal carcinomatosis with clinicopathologic features of pseudomyxoma peritonei 6 years after surgery. The second patient is alive and has been well for 2 years postoperatively. Review of the world literature showed that half of the patients with intraductal papillary-mucinous cancer plus biliopancreatic fistula had no stromal invasion around the fistula, indicating that the fistula might have been caused by mechanical pressure. However, the other half of the cases did have stromal invasion around the fistula. Two-thirds of these cases, including our own patients, had foci of mucinous carcinoma in the stroma around the fistulization, implying that mucinous lakes in the stroma may have served as part of the "waterway" from the pancreatic duct to the bile duct, assisted by increased pressure by mucus production. Since intraductal papillary-mucinous cancer with biliopancreatic fistula has a comparatively favorable prognosis, surgical resection should be considered.     

COMPARISON OF THE HEIGHT OF PAPILLARY TUMOR IN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS BETWEEN MEASURED PREOPERATIVE IMAGES AND RESECTED MATERIAL

The height of the mural nodules and papillary tumors in main pancreatic duct or dilated branch duct is the most important factor for diagnosis of intraductal papillary mucinous neoplasm (IPMN). In this study, the authors compared the height of the papillary lesions and mural nodules between the height of resected tissues and the height detected by the preoperative imaging tools (endoscopic ultrasonography [EUS] and intraductal ultrasonography [IDUS]) in 38 patients with IPMN. In 21 out of 23 cases of adenoma, and in cases with the non‐invasive cancer, the difference of the height of operative and preoperative analysis measured by EUS and IDUS was within 1–2 mm. EUS and IDUS are useful for diagnosis of degree of malignancy in IPMN.     

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.     

Precursors to pancreatic cancer

Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment.     

Cystic Lesions of the Pancreas

Opinion statement Pancreatic cystadenomas are a group of benign, premalignant, and malignant cystic tumors of the pancreas. Serous cystadenomas are benign lesions that often do not require surgical excision unless they are complicated by bleeding, obstruction, or pain. Mucinous cystadenomas are premalignant lesions that may be surgically excised if there is a concern regarding malignant degeneration. However, it may be difficult to predict the timing and risk of malignant change. Also, it is controversial whether all mucinous cystadenomas should be resected. Cystadenocarcinomas should be surgically managed if they are resectable, that is, there is no evidence of metastatic disease. Intraductal papillary mucinous tumors share many features with mucinous cystadenomas. However, intraductal papillary mucinous tumors arise from the pancreatic duct and are often associated with a dilated pancreatic duct. These lesions are often managed with surgical resection, including total pancreatectomy for diffuse lesions with evidence of localized malignancy.     

Positron emission tomography with 2-deoxy-2-[18f] fluoro-D-glucose in the detection of malignancy in intraductal papillary mucinous neoplasms of the pancreas

A 79-year-old Indian male was admitted with upper abdominal discomfort of 1-year duration which was associated with loss of weight and appetite. Serum tumor markers, including carcinoembryonic antigen and carbohydrate antigen 19-9, were within normal limits. A computed tomographic scan demonstrated a cystically dilated and tortuous pancreatic duct measuring 1.9 cm, suggestive of an intraductal papillary mucinous neoplasm. Fusion positron emission tomography/computed tomography with 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography (FDG-PET/CT) which was subsequently performed confirmed a metabolically active focus within the pancreatic head mass with a standard uptake value (SUVmax) of 3.5 compatible with carcinoma. A total pancreatectomy was performed and the final histology demonstrated a main-duct type intraductal papillary mucinous neoplasm with a focus of high-grade dysplasia compatible with carcinoma-in-situ. These images illustrate the emerging utility of FDG-PET/CT in the preoperative detection of malignancy in intraductal papillary mucinous neoplasm.     

Endoscopic ultrasound characteristics of mucinous cystic neoplasms of the pancreas

OBJECTIVE: Mucinous cystic neoplasms of the pancreas have a more favorable prognosis than ductal adenocarcinoma. Management of a subgroup, intraductal papillary-mucinous neoplasms, is controversial. Endoscopic ultrasound (EUS) with fine-needle aspiration biopsy may emerge as the imaging modality of choice. There are few studies describing the EUS features of these tumors. METHODS: A total of 35 consecutive cases of cystic tumors of the pancreas with an established pathological diagnosis were analyzed for characteristic EUS features. RESULTS: Mucinous cystadenocarcinomas (n = 14) were more likely to be characterized by hypoechoic cystic/solid mass or complex cyst and were frequently associated with a dilated main pancreatic duct. Benign mucinous duct ectasia (n = 6) were characterized by a dilated main pancreatic duct in conjunction with hyperechoic thickening of the duct wall. The two cases of intraductal mucinous hyperplasia additionally showed a hypoechoic mass. Intraductal papillary carcinoma (n = 11) had features in common with mucinous cystadenocarcinoma but also had echogenic foci in the mass and intraductal hyperechoic lesions. The two cases of microcystic cystadenoma showed either a mixed hypoechoic solid/cystic mass or a complex cyst without the additional features seen in mucinous cystadenocarcinoma. CONCLUSIONS: EUS features seem to exist that may help to differentiate cystic neoplasms from adenocarcinoma of the pancreas and, thus, to establish the preoperative diagnosis of cystic tumors of the pancreas.     

Pancreatoscopy: An update

Per-oral pancreatoscopy(POPS) is an endoscopic procedure to visualize the main pancreatic duct. POPS specifically has the advantage of direct visualization of the pancreatic duct, allowing tissue acquisition and directed therapies such as stones lithotripsy. The aim of this review is to analyze and summarize the literature around pancreatoscopy. Pancreatoscopy consists of the classic technique of the mother-baby method in which a mini-endoscope is passed through the accessory channel of the therapeutic duodenoscope. Pancreatoscopy has two primary indications for diagnostic purpose. First, it is used for visualization and histological diagnosis of intraductal papillary mucinous neoplasms. In these cases, POPS is very useful to assess the extent of malignancy and for the study of the intraductal papillary mucinous neoplasm in order to guide the surgery resection margins. Second, it is used to determine pancreatic duct strictures,particularly important in cases of chronic pancreatitis, which is associated with both benign and malignant strictures. Therefore POPS allows differentiation between benign and malignant disease and allows mapping the extent of the tumor prior to surgical resection. Also tissue sampling is possible, but it can be technically difficult because of the limited maneuverability of the biopsy forceps in the pancreatic ducts. Pancreatoscopy can also be used for therapeutic purposes, such as pancreatoscopy-guided lithotripsy in chronic painful pancreatitis with pancreatic duct stones. The available data for the moment suggests that, in selected patients, pancreatoscopy has an important and promising role to play in the diagnosis of indeterminate pancreatic duct strictures and the mapping of main pancreatic duct intraductal papillary mucinous neoplasms. However, further studies are necessary to elucidate and validate the pancreatoscopy role in the therapeutic algorithm of chronic pancreatitis.