Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas

BACKGROUND: Mucin-producing tumor of the pancreas is an increasingly recognized clinical entity. However, the differentiation of benign from malignant mucin-producing tumors of the pancreas is challenging. Peroral pancreatoscopy as recently developed may have potential for the diagnosis of mucin-producing tumors of the pancreas. METHODS: The subjects were 41 patients with clinically diagnosed mucin-producing tumors of the pancreas, 40 of whom underwent surgical resection. Autopsy findings were available in another patient with unresectable disease. Histologically, hyperplasia was identified in 3 patients, mildly atypical adenoma in 11, severely atypical adenoma in 16, and adenocarcinoma in 11. Peroral pancreatoscopy was performed before surgery or pathologic examination. The findings were retrospectively evaluated and compared with the histopathologic diagnosis. RESULTS: Pancreatoscopic observation was successful in 30 patients (73.2%). Elevated lesions were identified in 22 (73.3%). Villous or vegetative elevations and red color markings were frequently found in severely atypical adenoma or adenocarcinoma. Tumor location (main or branch duct type) did not correlate with survival after resection. Partial resection was performed in 7 of 30 patients with nonmalignant tumors and resulted in favorable outcomes. CONCLUSION: Peroral pancreatoscopy can be used to differentiate benign mucin-producing tumors of the pancreas (hyperplasia and mildly atypical adenoma) from the more dysplastic lesions (severely atypical adenoma and adenocarcinoma) and may provide useful information for determining the type of surgery to be performed.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM USING PERORAL PANCREATOSCOPY WITH NARROW BAND IMAGING

A 77‐year‐old man was diagnosed with a pancreas cyst at another hospital. Abdominal ultrasonography revealed a cyst in the head of the pancreas and a small protrusion. These findings suggested intraductal papillary mucinous neoplasm. Cytologic finding of the pancreatic juice revealed a Class III lesion, and intraductal ultrasonography and peroral pancreatoscopy (PPS) were performed. An abnormal course of main pancreatic duct (MPD) prevented the insertion of an ultrasonography probe into the MPD, and PPS was performed. The mucosal surface of the MPD near the papillary area was normal, and narrow band imaging (NBI) clearly showed the vascular structure. When the PPS was inserted more deeply, many small protrusions were observed and NBI delineated the protrusions more clearly. Papillary protrusions were observed in the cyst, but NBI did not reveal any tumor vessels. These findings led to a diagnosis of benign intraductal papillary mucinous neoplasm lesion. Since then, follow‐up examinations have been made. Changes in the cyst and protrusion have not been observed.     

Differential diagnosis of intraductal papillary‐mucinous tumor of the pancreas by endoscopic ultrasonography and intraductal ultrasonography

Background: Intraductal papillary‐mucinous tumor (IPMT) of the pancreas has a broad spectrum of histology ranging from hyperplasia to adenocarcinoma. Therefore, it is important to differentiate between the malignant and benign lesions to determine the therapeutic strategy for IPMT. Patients and Methods: Thirty‐nine patients with IPMT (27 men and 12 women, mean age: 63.3 years) underwent surgery between January 1985 and March 2002. The size of the cystic lesion, the maximum diameter of the main pancreatic duct (MPD), and the height of the papillary tumor inside the cyst were investigated by endoscopic ultrasonography (EUS) and/or intraductal ultrasonography (IDUS) before operation. These preoperative clinical findings were compared with the pathological findings of the resected specimen. Results: The size of the cystic lesion, the diameter of MPD, and the height of the papillary tumor in cases with malignant IPMT (invasive and non‐invasive carcinoma) were larger than those in cases with benign IPMT (adenoma and hyperplasia). Analysis of the images of the lesions revealed that the following three factors are important for diagnosing IPMT: (i) the size of the cystic lesion is ≥ 30 mm; (ii) the diameter of MPD is ≥ 8 mm; (iii) the height of the papillary tumor inside the cyst is ≥ 3 mm. It was not significant to differentiate between benign and malignant IPMT based on factor (i), but statistically significant (P < 0.001) based on factors (ii) and (iii). Conclusions: EUS and IDUS are useful in the differential diagnosis of IPMT, especially in the differentiation between malignant and benign IPMT.     

PROSPECTIVE STUDY OF THE EVALUATION OF THE USEFULNESS OF TUMOR TYPING BY NARROW BAND IMAGING FOR THE DIFFERENTIAL DIAGNOSIS OF GASTRIC ADENOMA AND WELL‐DIFFERENTIATED ADENOCARCINOMA

Background and Aim: Presently, the differential diagnosis of gastric adenoma and well‐differentiated adenocarcinoma by endoscopy is very difficult. We carried out magnifying endoscopy with narrow band imaging (NBI) in lesions that required discrimination between gastric adenoma and well‐differentiated adenocarcinoma, and prospectively evaluated whether the tumor typing that we propose is useful for their differential diagnosis. Methods: The materials were 93 lesions that required differential diagnosis between gastric adenoma and well‐differentiated adenocarcinoma among the gastric epithelial tumors for which endoscopic treatment was planned at three facilities during the 14 months between November 2008 and December 2009. According to the typing method proposed by our facility based on images of the mucosal ultrastructure and microvessels obtained by magnified endoscopy combined with NBI, type I‐II and type III‐V lesions were diagnosed as gastric adenoma and well‐differentiated adenocarcinoma, respectively, before endoscopic treatment, and the accuracy of the diagnoses were prospectively examined by comparing them with the postoperative pathological findings. Results: Of the 93 lesions, 87 could be typed into the five types of our typing method, but six lesions could not be classified. The 87 lesions consisted of 16 type I, 12 type II, 29 type III, 27 type IV, and three type V lesions. The percentages of accurate preoperative diagnoses of types I‐II as adenoma and types III‐V as well‐differentiated adenocarcinoma were 79% and 93%, respectively. Conclusions: The tumor typing based on NBI was useful for the endoscopic differentiation of gastric adenoma and well‐differentiated adenocarcinoma.     

PERORAL PANCREATOSCOPY: CURRENT STATUS AND FUTURE EXPECTATIONS USING NARROW BAND IMAGING

Peroral pancreatoscopy (POPS) under duodenoscopic assistance provide direct visual assessment of the pancreatic duct, tissue sampling, and therapeutic interventions. Sometimes, pancreatoscopy can confirm accurate diagnosis, such as differential diagnosis of filling defects between intraductal tumors and stones. However, it is often difficult to differentiate malignant from benign strictures solely on pancreatoscopy. It is currently considered that intraductal papillary mucinous neoplasm (IPMN) is the most suitable indication of POPS. POPS has several problems: image resolution, fragility and maneuverability. Concerning image resolution, the quality has been improved with the development of a video pancreatoscope. Moreover, the recently developed endoscopic optical technology of narrow band imaging (NBI) is now available to video pancreatoscopy. This will allow direct visual assessment. Although currently POPS has several problems, further improvement will assist POPS to become a useful modality in combination with NBI.     

CLINICAL SIGNIFICANCE OF INTRADUCTAL ULTRASONOGRAPHY FOR DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS

Intraductal ultrasonography (IDUS) is useful for evaluating the horizontal spread along the main pancreatic duct in cases of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, thus providing valuable information for the determination of the resection line at surgery. Differentiation between benign and malignant IPMN is also indispensable for management decisions. Measurement of the height of mural nodules by IDUS is expected to be useful for differential diagnosis of IPMN. Because IDUS cannot always demonstrate whole lesions, especially in branch duct IPMN, endoscopic ultrasonography plays a complementary role in such cases.     

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors,i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian‐type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low‐grade PanINs. Mucin expression profiles suggest intestinal‐type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB‐type IPMNs progress toward ductal adenocarcinoma. It is a well‐described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step‐wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.     

Endoscopic diagnosis of cystic lesions of the pancreas

Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS‐guided fine‐needle aspiration cytology and EUS‐guided fine needle‐based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non‐mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast‐enhanced harmonic EUS (CH‐EUS), as an add‐on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH‐EUS has a sensitivity of 60–100% and a specificity of 75–92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta‐analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.     

Endosonographic diagnosis of intraductal papillary‐mucinous pancreatic tumors by intraductal ultrasonography

Background: Intraductal papillary‐mucinous pancreatic tumors (IPMT) are intraductal lesions formed by mucin‐producing epithelium, which proliferates in a papillary pattern, and presents a spectrum from hyperplasia to adenocarcinoma. The value of intraductal ultrasonography (IDUS) for excluding malignancy has not been assessed in a case series previously. Methods: Intraductal ultrasonography was performed in 17 patients with IPMT (12 with adenocarcinoma and five with adenoma) between November 1993 and June 2002. Intraductal ultrasonography was used to determine the maximum height and maximum cross‐sectional area of protruding lesions. Results were compared after dividing the tumors into three groups: a benign lesion group, a non‐invasive cancer group, and an invasive cancer group. The resection line was located over 10 mm from the edge of the protruding lesion visualized by intraductal ultrasonography. Results: All adenocarcinomas had a height ≥ 5 mm and all benign lesions had a height ≤ 3 mm, with this difference being significant (P = 0.0034). The height of non‐invasive and invasive cancer was similar. The maximum cross‐sectional area of the protrusion was smaller for benign lesions (≤ 15 mm²) than for non‐invasive cancer (≥ 34 mm², P = 0.0034). The cross‐sectional area of the protrusion was greater in patients with invasive cancer than in those with non‐invasive cancer (P = 0.0367). All surgical margins have remained clear and no patient has suffered from a recurrence during 1 to 8 years of follow‐up computed tomography and ultrasonography. Conclusions: Intraductal ultrasonography can distinguish benign from malignant IPMT based on the height and maximum cross‐sectional area of the protruding tumor.     

DIRECT PERORAL CHOLANGIOSCOPY AND PANCREATOSCOPY FOR DIAGNOSIS OF A PANCREATOBILIARY FISTULA CAUSED BY AN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS: A CASE REPORT

Here, we report a case of a pancreatobiliary (PB) fistula caused by an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The PB fistula was suspected after endoscopic retrograde cholangiopancreatography (ERCP) and diagnosed after direct visualization with a direct peroral cholangioscopy and pancreatoscopy by using an ultra‐slim endoscope. No previous reports exist on the precise diagnosis of a PB fistula with direct peroral cholangioscopy and pancreatoscopy. In our case report, a 69‐year‐old man underwent an ERCP because of a pancreatic head mass and biliary tract obstruction. During ERCP, a fistula between the common bile duct (CBD) and main pancreatic duct (MPD) was suspected. After endoscopic sphincterotomy, we examined both the CBD and MPD with an ultra‐slim videoendoscope (GIF‐N260; Olympus Optical Co, Tokyo, Japan) under direct visualization and biopsy of the mass. The analysis of the biopsy specimen confirmed this mass to be an IPMN of the pancreas. When we examined the CBD, one fistula with copious mucin secretion was identified at the distal CBD. In conclusion, direct peroral cholangioscopy and pancreatoscopy using the ultra‐slim endoscope is an efficient tool for diagnosis of PB fistula and pancreatic IPMN.     

Immunohistochemical study of genetic alterations in intraductal and invasive ductal tumors of the pancreas.

BACKGROUND/AIMS: Multiple genetic alterations are involved in the development of pancreatic neoplasm. Here we investigated the incidence of p53, ras, bcl-2 and c-erbB-2 gene alterations in intraductal papillary-mucinous tumors and invasive ductal adenocarcinoma of the pancreas by immunohistochemical method to identify and analyze their relationship in terms of these genetic alterations. METHODOLOGY: Fifty-four pancreatic lesions, including 18 benign (hyperplasia (3) and intraductal papillary adenoma (15)), and 16 malignant (carcinoma in situ (2) and intraductal papillary adenocarcinoma (14)) cases of intraductal papillary-mucinous tumor; and 20 cases of invasive ductal adenocarcinoma, were immunostained by avidin-biotin peroxidase conjugate method. RESULTS: p53 and rasp21 expressions were significantly greater in malignant intraductal (P < 0.01, P < 0.05) and invasive ductal (P < 0.01, P < 0.01) tumors than in benign intraductal papillary-mucinous tumors; while bcl-2 and c-erbB-2 expressions were significantly greater in invasive ductal adenocarcinoma than both benign (P < 0.01, P < 0.05) and malignant (P < 0.05, P < 0.05) intraductal papillary-mucinous tumors. CONCLUSIONS: Different groups of genetic alterations are involved in different phases of pancreatic tumorigenesis. p53 and ras gene alterations occur at an early stage during the development of intraductal papillary-mucinous tumor, while additional alterations of bcl-2 and c-erbB-2 occur during the development of invasive ductal adenocarcinoma of the pancreas.     

MANAGEMENT OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) consist of main duct (MD) type and branch duct (BD) type. The authors describe their way of thinking regarding diagnostic modalities and management for BD type IPMNs. Endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS) provide high resolution images of main and branch pancreatic ducts. The cases with nodules demonstrated by EUS and/or IDUS regardless of the size are the indication of operation. There were 235 cases with BD type IPMN who underwent EUS and IDUS between April 1991 and June 2005. A total of 94 patients underwent surgical resection and were histopathologically diagnosed (carcinoma, 10 cases; adenoma, 64 cases; hyperplasia, 20 cases). Diagnoses of 79 cases with nodules detected by EUS or IDUS preoperatively were 10 carcinomas, 61 adenomas and eight hyperplasias. Diagnoses of 15 cases without nodules but with symptoms were three adenomas, 12 hyperplasias and no carcinoma. The authors think that the combination of EUS and IDUS is the best way for diagnosing BD type IPMNs in the present state.     

Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia

Background

Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes.

Methods

Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN; n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression.

Results

Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions.

Conclusions

These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.     

Pancreatic juice cytology in IPMN of the pancreas.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.     

Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment strategy based on morphologic classification

GOALS: The aim of this study was to examine and clarify the preoperative markers that are useful for differentiating between benign and malignant lesions of intraductal papillary-mucinous neoplasms (IPMN) of the pancreas, grouped according to morphologic classification. BACKGROUND: There are various stages of pathology in IPMN, ranging from benign to malignant lesions. Although the determination of appropriate treatment guidelines to deal with IPMN is a critical issue, no such guidelines have been established. PATIENTS AND METHODS: One hundred twenty cases of IPMN were classified morphologically into either main or branch duct types. We compared the morphologic classification with histopathologic diagnosis using indicators of malignancy detected by imaging such as main duct diameter, the number and diameter of cysts, and the presence or absence of mural nodules. We also examined the usefulness of pancreatic juice cytology and measurement of telomerase activity as indicators of malignancy. Finally, we performed a survival analysis on the basis of morphologic classification to determine prognosis of IPMN. RESULTS: Whereas a high incidence (64%) of malignant lesions was seen in main duct type IPMN, benign lesions were dominant (80.5%) in branch duct type IPMN. Survival analysis showed that the prognosis was significantly worse in main duct type than in branch duct type IPMN. The lesions were aggravated in all patients with main duct type who did not undergo resection, resulting in death due to progression of the pancreatic lesion. The incidence of mural nodules was a useful indicator in main duct type, whereas main duct diameter and incidence of mural nodules were useful indicators in branch duct type. Although pancreatic juice cytology showed a high accuracy rate with low sensitivity for determining malignancy, measurement of telomerase activity in this juice was very effective for differentiating between benign and malignant lesions. CONCLUSIONS: The incidence of malignant lesions was extremely high in main duct type IPMN, indicating that surgery is required in all these patients. However, to determine whether surgery is indicated in branch duct type IPMN it is necessary to obtain an appropriate image diagnosis focusing on main duct diameter and mural nodules and also to carry out cytology and measurement of telomerase activity in samples of pancreatic juice.     

IDUS IN THE DIAGNOSIS OF IPMT

Intraductal papillary mucinous tumor of the pancreas (IPMT) is considered as having low‐grade malignant potential, and malignancy is not infrequent. Therefore, accurate diagnosis is indispensable for appropriate patient care. IPMT is classified mainly into two categories based on the distribution of tumor, the main duct type and the branch duct type. In the diagnosis of IPMT, there are four important points: differentiation of IPMT from other pancreatic pathologies; differentiation of malignancy from benign lesions; evaluation of tumor extent along the MPD; and investigation of duct cell carcinoma coexistent with or derived from IPMT. IPMT should be distinguished from chronic pancreatitis, ductal adenocarcinoma, or cystic neoplasms. IPMT often requires pancreaticoduodenectomy for cure, but such invasive surgery should be avoided in patients with benign hyperplasia. Mural nodules in the MPD can be clearly visualized by intraductal ultrasonography (IDUS). Measurement of the height of the tumor mass by IDUS is useful in distinguishing benign from malignant IPMT. Intraductal spread of IPMT along the MPD is demonstrated by IDUS as irregular thickening of the MPD wall. To achieve a tumor‐free margin in surgery, evaluation by IDUS of the extent of the tumor along the MPD is important. The expected accuracy of IDUS in the diagnosis of invasive IPMT is reportedly over 90%.     

Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS

Background We investigated the mode of progression of intraductal papillary-mucinous neoplasm of the pancreas (IPMN) in patients who underwent follow-up in order to elucidate the characteristics of malignancy and to establish an effective treatment strategy.Methods Fifty-one patients with IPMN (branch-duct type, 47; main-duct type, 4) who had undergone follow-up study by endoscopic ultrasonography (EUS) were included (mean follow-up duration, 41.0 ± 32.3 months; average number of EUS examinations performed during follow-up, 4.4). Chronological changes in EUS findings and histological findings of resected specimens were evaluated.Results Of the patients with the branch-duct type, only 2% showed enlargement of the dilated branches. In the main-duct-type group, an increase in size of the main pancreatic duct (MPD) was observed in 75% of the patients. In 14 patients with papillary protrusions, an increase in size and lateral spread was observed in 71% and 43%, respectively. No patients developed invasive cancer. In 15 patients who had thick septum-like structures (TSS), the development of papillary protrusions and that of invasive cancer were observed in 53% and 13%, respectively. Twenty-nine patients who had thin septum-like structures showed no change. Two patients with dense multilocular large cysts and TSS developed invasive cancer without change in the cystic lesions. One patient developed carcinoma with multifocal stromal invasion.Conclusions Patients with branch-duct type IPMNs without papillary protrusions or TSS are not immediate candidates for surgery. Those who have small papillary protrusions have a benign course. It is recommended that patients with the large branch-duct type with TSS should undergo surgery. Attention should be paid to the entire pancreas when performing follow-up examinations in patients with branch-duct type IPMN, as invasive ductal adenocarcinoma can develop at a site in the pancreas different from that of the IPMN.     

LATERAL SPREAD ALONG THE MAIN PANCREATIC DUCT IN BRANCH‐DUCT INTRADUCTAL PAPILLARY‐MUCINOUS NEOPLASMS OF THE PANCREAS: USEFULNESS OF INTRADUCTAL ULTRASONOGRAPHY FOR ITS EVALUATION

Background: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend to spread intraepithelially along the pancreatic duct wall. We evaluated histopathological intraductal lateral spread (LS) along the main pancreatic duct (MPD) from branch‐duct IPMN and investigated the usefulness of intraductal ultrasonography (IDUS) for its preoperative diagnosis. Patients and Methods: Twenty‐four patients with branch‐duct IPMN who had undergone preoperative IDUS and surgery were reviewed clinicopathologically. The prevalence and histological length of LS along the MPD from branch‐duct IPMN, characteristics of the patients with LS, and efficacy of LS assessment by IDUS were examined. Results: LS along the MPD was observed in 54% of the subjects. In the group of patients with LS, its mean length was 25.2 ± 16.8 mm (5–50 mm) and the diameter of the MPD was 6 mm or greater. Of the patients with LS, those in whom the length of LS along the MPD was longer than the diameter of the cystically dilated branch accounted for 30%. The diameter of the MPD in the group with LS was significantly greater than that in the group without LS (P = 0.03). The sensitivity, specificity, and overall accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively. Conclusion: LS along the MPD was detected in about half of the resected cases of branch‐duct IPMN. Preoperative transpapillary IDUS may be beneficial for the determination of the resection line, especially in those branch‐duct IPMN patients in whom the MPD is 6 mm or greater in diameter.     

Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a spectrum of neoplasia in the pancreatic duct epithelium characterized by cystic dilation of the main and/or branch pancreatic duct. According to the site of involvement IPMNs are classified into three categories, i.e., main duct type, branch duct type, and combined type. Most branch duct IPMNs are benign, whereas the other two types are often malignant. A large size of branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least. The additional existence of large mural nodules increases the possibility of malignancy in all types. Of recent interest is the relatively high prevalence of synchronous and/or metachronous malignancy in various organs, including the pancreas. The prognosis is favorable after complete resection of benign and noninvasive malignant IPMNs. Malignant IPMNs acquiring aggressiveness after parenchymal invasion necessitate adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs without mural nodules can be observed without resection for a considerably long time. This review addresses available data, current understanding, controversy, and future directions.