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.     

A case of intraductal papillary-mucinous carcinoma of the pancreas with the onset of acute pancreatitis

Intraductal papillary-mucinous carcinoma of the pancreas has been reported with increasing frequency. We report a case with intraductal papillary-mucinous carcinoma of the pancreas and discuss surgical treatment and current imaging modalities. A case with intraductal papillary-mucinous carcinoma was analyzed by radiological findings and clinical course. A 47-year-old man developed abdominal pain and nausea. Computed tomography showed a diffusely dilated main pancreatic duct. Duodenoscopy showed a patulous orifice of the pancreas with massive mucus secretion, but the pancreatic juice was not positive for malignant cells. Endoscopic retrograde cholangiopancreatography revealed a markedly dilated pancreatic duct extending from the body to the tail of the pancreas. Distal pancreatectomy was performed with splenectomy and lymph nodes dissection. Histopathological diagnosis was intraductal papillary-mucinous carcinoma. Endoscopic retrograde cholangiopancreatography is useful for diagnosing intraductal papillary mucin-producing tumors. To avoid unnecessary total pancreatectomy and preserve pancreatic function, intraoperative frozen section examination is widely available for the surgical treatment of intraductal papillary mucin-producing tumors.     

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.     

Role of endoscopic ultrasonography in the diagnosis and treatment of cystic tumors of the pancreas

Endoscopic ultrasound (EUS) allows high resolution imaging of the pancreas. EUS is a very useful technique for evaluating morphological features of a cystic tumors of the pancreas. These features include thick wall type, tumor protruding type, thick septal type, microcystic type, thin septal type and simple type. Malignant cystic lesions may present as a hypoechoic cystic/solid mass or as a complex cyst and are frequently associated with a dilated main pancreatic duct. There is some overlap between EUS appearances of non-neoplastic and neoplastic cystic pancreatic lesions. EUS guided FNA of cystic pancreatic lesions can play an important role in the differential diagnosis of these lesions and deciding about the need for surgery by evaluating cytology and tumor markers such as CEA in cyst fluid. There is some emerging data on EUS guided treatment of cystic pancreatic tumors by injection of alcohol.     

Inferior head resection of the pancreas for noninvasive intraductal papillary mucinous adenocarcinoma

We report inferior head resection of the pancreas for noninvasive intraductal papillary mucinous cancer. A 77-year-old man was admitted to our hospital complaining of epigastric pain. Contrast-enhanced computed tomographic scan and magnetic resonance imaging showed a multilocular cystic tumor 3.5 cm in diameter in the head of the pancreas. We performed inferior head resection of the pancreas with partial resection of the duct of Santorini. The duodenum, the common bile duct, and most of the duct of Santorini were preserved. He is presently alive and well without any evidence of recurrent disease 49 months after the operation. Partial pancreatic resection has the advantage of preserving pancreatic parenchyma. Inferior head resection of the pancreas would play an important role in surgical management of low-grade malignant neoplasm.     

Mucin-producing tumor of the pancreas — surgical treatment

To evaluate appropriate surgical treatment and to predict prognosis for mucin-producing tumors (MPTs) of the pancreas, we conducted a retrospective clinicopathological study in 25 patients with MPT. Eight patients who had mild dysplasia of the pancreas were diagnosed with benign disease and 17 patients with ductal lesions of the pancreas with severe dysplasia/carcinoma in situ or with invasive foci were diagnosed as malignant. Clinical symptoms and histories, tumor markers, cytological examination, and radiological and gross pathological features were compared in the benign and malignant groups. Clinical symptoms, history, and tumor markers were of no value for predicting prognosis. Cytological examination results were ambiguous because of too many falsenegatives. Radiological features, including the diameters of the cystic space and of the main pancreatic duct (MPD) were shown to be valuable. The significant maximal diameters, above which malignancy was seen, were 30mm for the diameter of the cystic space and 10mm for the MPD. In regard to gross features, the uniformly dilated main duct-type and focally dilated main duct-type were significant indicators of malignancy. Long term follow-up was available in 22 patients. Seven patients died of recurrence of the tumor or other malignancies. We could have predicted prognosis by the radiological features and gross appearance. Surgical treatment should be considered the primary choice for MPT. Total pancreatectomy would be ideal for patients with the uniformly dilated main duct-type. Because of the probability of multicentricity and the transforming potential of mild dysplasia, very careful follow-up is necessary for patients with MPT.     

Intraductal papillary mucinous tumors and mucinous cystic tumors of the pancreas: imaging

Most cystic lesions of the pancreas are nonneoplastic and inflammatory in nature. However, approximately 5%–15% of cystic pancreatic masses may be neoplastic. Among the cystic neoplasms are the mucin-producing tumors, both the intraductal papillary mucinous neoplasms and the mucinous cystic neoplasms. Their imaging features on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) can assist in the differentiation of these lesions. The imaging findings of both intraductal papillary mucinous neoplasm and mucinous cystic neoplasm are reviewed with attention to CT and MRI.     

Mucin-Producing Tumor of the Pancreas: A Unique Clinical Entity

We report our experience with nine patients with "mucin-producing tumor of the pancreas," in which abundant mucin secreted by the tumor cells played a major role in the characteristic alterations of the pancreatic duct system. Four of nine patients presented with pancreatitis. Ultrasound and computed tomography demonstrated a well-defined cystic mass and dilated main pancreatic duct. Endoscopic retrograde pancreatography showed ductectatic character, i.e., diffuse dilatation of main duct and/or cystic dilatation of the branch ducts with filling defects of mucin. Ultrasound proved to be a good screening test. However, the diagnosis was confirmed on endoscopic retrograde pancreatography. Nine of our cases had no peripancreatic invasion or metastasis, resulting in a good prognosis after pancreatectomy. Mucin-producing tumor of the pancreas is a unique clinical entity that should be distinguished from "common" pancreatic carcinomas, and a favorable prognosis can be expected after surgical operation.     

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     

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.     

Virtual CO2 MDCT pancreatography: a new feasible technique for minimally invasive pancreatectomy in intraductal papillary mucinous neoplasms

BACKGROUND/AIMS: Less invasive pancreatic head resection, such as duodenum-preserving pancreatic head resection (DPPHR) has been introduced for the treatment of pancreatoduodenal lesions, especially for benign conditions, for reducing surgical stress and maintaining exocrine and endocrine function of the residual pancreas in consideration of postoperative quality of life (QOL). METHODOLOGY: We investigated the feasibility of a new technique employing three-dimensional (3D) virtual pancreatography using multi-detector CT (MDCT) with carbon dioxide (CO2) gas as a negative contrast agent for detection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas requiring minimally invasive surgery. Branch IPMN is subjected in this study. RESULTS: Contrast-enhanced MDCT scan of the abdomen diagnosed 4- to 20-mm multilocular septated cysts in the head-uncinate process of the pancreas. Endoscopic retrograde pancreatography (ERP) showed multiple cystic lesions in the head-uncinate process with mild dilatation in the remaining pancreatic duct. For localizing diagnosis of these small and multiple pancreatic cysts, we placed an endoscopic pancreatic stent (EPS), and MDCT with injection of CO2 via EPS was examined for the virtual CO2 pancreatography, consisting of OsiriX software system employing 3D virtual anatomic reconstruction with CO2 gas as a negative contrast agent. Virtual CO2 MDCT pancreatography demonstrated that all cystic lesions of the pancreas were contained within the area of the head-uncinate process of the pancreas. We performed DPPHR, and surgical margin of the patient's remnant pancreas was determined as non-malignant by intraoperative histology. There was no residual pancreatic cyst and tumor after surgery. The resected tumor was diagnosed as branch duct type intraductal papillary mucinous adenocarcinoma. According to our minimally invasive DPPHR obtained by virtual CO2 pancreatography, the pancreatic endocrine and exocrine functions of this patient were maintained at almost the same levels as those in his preoperative status. With respect to preservation of the endocrine and exocrine functions of the pancreas, DPPHR is a highly effective surgical procedure due to limited surgical resection. CONCLUSIONS: Our new technique of virtual CO2 MDCT pancreatography is a feasible procedure for preservation of the remnant pancreatic function. This is the first report of virtual CO2 pancreatography providing minimally invasive pancreatic surgery.     

Intraductal papillary-mucinous adenoma developed in the ventral pancreas in a patient with pancreas divisum

A 34-year-old man was admitted to our hospital with the chief complaints of back pain and epigastralgia. The physical examinations on admission disclosed no abdominal tumor. The serum concentration of total bilirubin was 1.4?mg/dl. The serum elastase-1 level was elevated to 526?ng/dl. Computed tomography showed a cystic lesion, 1?cm in diameter, in the head of the pancreas, without dilatation of the main pancreatic duct. Endoscopic retrograde cholangiopancreatography via the papilla of Vater and the accessory papilla revealed an enlarged ventral pancreatic duct and pancreas divisum. The preoperative diagnosis was mucin-producing pancreatic tumor in the ventral pancreas of a patient with pancreas divisum. A pylorus-preserving pancreatoduodenectomy was performed. The gross findings of the cut surface of the resected specimen disclosed mural nodules in the dilated duct of the ventral pancreas. A histological examination of the mural nodules in the ventral pancreas revealed mucin and intraductal papillary adenoma. Benign tumors associated with pancreas divisum are rare; to the best of our knowledge, only three cases have been reported. Although in these three patients the tumor developed in the dorsal pancreas, the tumor developed in the ventral pancreas in our patient.     

Operative indications for cystic lesions of the pancreas with malignant potential--our experience

BACKGROUND/AIMS: There are still many important but unclear points regarding the differential diagnosis and operative indications of cystic lesions of the pancreas with malignant potential. Studies of the clinicopathological and molecular biological characteristics of such diseases are necessary. In this paper, we discuss operative indications for this condition based on a review of the literature and our own experience. METHODOLOGY: Seven cases of serous cystadenoma and 9 cases of mucinous cystadenoma or cystadenocarcinoma of the pancreas that were operated on or autopsied in our department from 1980 to 1996 were analyzed clinicopathologically. Small cystic lesions incidentally found in 300 autopsied cases were also studied. Finally, mucin-producing tumors described in several reports were reviewed, and the branch type of this tumor was especially investigated. RESULTS: A marked disappearance of pancreatic acini in the upstream pancreas was found when serous cystadenoma became large. Papillary projection was histologically found in all of the cases. Tumorous invasion to the interstitium was suspected in tumors more than 5 cm in diameter, and malignancy was reported when tumors were larger than 6 cm. As for mucinous cystadenocarcinoma, the patients had a poor prognosis. In 2 of 42 cases with a pseudocyst, small duct cell carcinoma was incidentally found adjacent to the pseudocyst on the duodenal side. With regard to branch-type intraductal papillary neoplasm, 80% of the tumors larger than 4 cm were malignant. Most of the small cystic lesions found in elderly autopsy cases were accompanied by hyperplastic epithelia without evidence of malignancy. CONCLUSIONS: Based on our experience, an operation should be considered and resection is recommended under the following circumstances: 1) cystic lesions in the body and tail of the pancreas in middle-aged women; 2) typical serous cystadenoma larger than 4 cm; 3) mucinous cystadenoma of any size; 4) branch-type intraductal papillary neoplasm larger than about 3 cm; and, 5) pseudocysts of unknown cause. Small cystic lesions in elderly patients should not necessarily be operated on, but should be followed-up carefully.     

Intraductal papillary-mucinous tumor of the pancreas: a historical review of the nomenclature and recent controversy.

A number of studies on mucin-producing cystic neoplasm of the pancreas have been reported since the first report of the tumor in 1982. There has been some controversy about nomenclatures and clinicopathologic entities of mucin-producing cystic tumor, mucinous cystic tumor, and intraductal papillary tumor of the pancreas. In 1996 and 1997, new classifications of pancreatic neoplasms were published by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP). According to the new WHO and AFIP classifications, mucin-producing cystic neoplasm of the pancreas corresponds mainly to intraductal papillary-mucinous tumor and mucinous cystic tumor of the pancreas. and these two diseases are independent conditions. Intraductal papillary-mucinous tumor is regarded as a unique clinical entity, but controversy remains about the term and clinicopathologic entity. Some confusion and problems remain betweeen the two lesions. In this review, we review their historical background, terminology, WHO and AFIP classification, and problems with classification.     

A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct

We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor.Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas,accompanied with severe dilatation of the main pancreatic duct,which was diagnosed as an intraductal papillary-mucinous neoplasm.We performed distal pancreatectomy and splenectomy.The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma(giant cell type)and adenocarcinoma in the pancreas.There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct.The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery.In this case,we could observe a remarkable intraductal tumor growth into the main pancreatic duct.We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.     

Ventral pancreas-preserving pancreatic head and body resection

A new procedure that included ventral pancreas-preserving pancreatic head and body resection for a huge mucinous cystic neoplasm was performed to preserve pancreatic function. A 45-year-old man was diagnosed as having a huge mucin-producing pancreatic neoplasm. The ventral pancreas-preserving pancreatic head and body resection was performed. The stumps of the caudal pancreas and the uncinate process were negative for cancer by frozen-section histology. The remaining pancreas was anastomosed by a method of double pancreatojejunostomy with a Roux-en-Y loop. The resected specimen was 15 x 10 cm in size and contained mucin. The papillary tumor was 5.0 x 4.5 x 3.0 cm in size, which was an intraductal papillary adenocarcinoma without pancreatic invasion microscopically. The postoperative course was uneventful and the patient was discharged 14 days after surgery. Glucose tolerance test was normal 24 months after surgery and both sides of the pancreatic duct were patent confirmed by magnetic resonance. The patient is well now two years after surgery. A new limited pancreatic resection, ventral pancreas-preserving pancreatic head and body resection, was safely applied to a huge mucinous cystic neoplasm of the pancreas.     

The spectrum of mucin-producing adenocarcinoma of the pancreas

The clinical distinction between cystic and mucinous carcinomas of the pancreas has been poorly defined. Therefore we sought to stratify the entity known as pancreatic mucinous adenocarcinoma based on pathologic and clinical criteria. Clinical data and pathology specimens were reviewed for patients (n = 40) who had been diagnosed as having mucin-producing pancreatic adenocarcinoma and had undergone either resection or intraoperative biopsy of their pancreatic tumor during a 40-year period at the UCLA Medical Center. Based on histologic criteria, three distinct classes of pancreatic adenocarcinoma were identified: mucinous noncystic (colloid) adenocarcinoma (group I), mucinous cystadenocarcinoma (group II), and ductal adenocarcinoma (group III). Based on clinical behavior, groups I and III were indistinguishable. Compared to patients from groups I and III, those from group II were younger, more likely to be female, and had a better prognosis. Among mucin-producing adenocarcinomas of the pancreas, mucinous noncystic adenocarcinoma and ductal adenocarcinoma share similar clinical features, whereas true cystic lesions represent a distinct clinical entity.     

Usefulness of selective endoscopic retrograde pancreatography (selective ERP) and endoscopic pancreatic biopsy (EPB) in the diagnosis of mucin-producing tumor of the pancreas]

Selective ERP and EPB were employed in the diagnosis of mucin-producing tumor (MPT) of the pancreas and their usefulness was evaluated. Thirty five cases of MPTs were subdivided into three subtypes, i.e., 1) main duct type, 2) branch duct type and 3) peripheral type (mucinous cystadenoma/cystadenocarcinoma). Selective ERP was proved to be useful in demonstrating precise and whole pancreatograms, especially in revealing multiple lesions, when compared with standard ERP. Selective ERP could demonstrate communication between cystic tumors of the peripheral type and the pancreatic duct in seven (88%) of eight cases of the peripheral type, which suggests high frequency of the communication in the peripheral type. For preoperative tissue diagnosis, EPB was shown to be a useful method to yield sufficient tissue materials for histopathological evaluation and may be used as an adjunction method to diagnose the intraductal extent of the tumorous lesion.     

An apparent idiopathic case of relapsing acute pancreatitis

We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.     

Intraductal papillary mucinous tumors of the pancreas

Cystic neoplasms of the exocrine pancreas are a small fraction of pancreatic tumors. Within that group of cystic neoplasms, intraductal papillary mucinous tumors (IPMTs) can be distinguished from mucinous cystic neoplasms, serous cystic neoplasms, and pseudopapillary cystic tumors. Awareness of IPMTs has increased since the World Health Organization classified these tumors as its own group in 1996. Because of their favorable prognosis, an extensive diagnostic workup for IPMTs should be performed in patients presenting with cystic lesions of the pancreas. This workup often leads to the diagnosis and the predominant tumor location and size, although the extent of the ductal changes can only be established by histopathology. Surgical resection is the therapy of choice for IPMTs. The type of resection depends upon the extent of the quantitative and qualitative ductal involvement. Total pancreatectomy is currently the treatment for an IPMT that comprises the entire main duct.