Current roles of endoscopy in the management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin‐producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS‐guided fine‐needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed.     

Clinicopathological features and medical management of intraductal papillary mucinous neoplasms

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are a clinicopathological entity that is being diagnosed with increasing frequency. However, the best approach to medical management of IPMN needs to be clarified. The aim of the present study was to identify preoperative features that may be predictors of malignant IPMN, and to define the medical management of IPMN of the pancreas. METHODS: A total of 23 patients who underwent surgical resection for IPMN of the pancreas at Kochi Medical School between 1982 and 2004 were examined. Multivariate Cox regression analysis was used to identify factors independently associated with IPM carcinoma. RESULTS: Among the 23 patients, 12 had IPMN adenoma, three had borderline IPMN, four had IPMN with carcinoma in situ, and four had IPMN with invasive carcinoma. In multivariate analysis, elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels were found to be preoperative predictors of malignant IPMN. These results suggest that the following IPMN of the pancreas should be resected: (i) IPMN of the pancreas situated in the main duct; (ii) IPMN located in the branch duct if the size of the cystic lesion is >30 mm and the mural nodules are >5 mm in height by endoscopic ultrasound (EUS); and (iii) the diameter of the main pancreatic duct is >10 mm by endoscopic retrograde pancreatography (ERP). Careful observation of patients with branch-type IPMN with small cysts and/or without mural nodules is recommended as a management strategy. CONCLUSION: The present study reinforces the need for immediate surgical resection of malignant IPMN and suggests indicators for IPMN that should assist physicians in making decisions on treatment options.     

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.     

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.     

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.     

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.     

Localized type 1 autoimmune pancreatitis superimposed upon preexisting intraductal papillary mucinous neoplasms

A 70-year-old woman was found to have 2 cystic lesions in the head of the pancreas on abdominal ultrasonography during a routine medical examination.Endoscopic ultrasonography(EUS)and magnetic resonance cholangiopancreatography showed multilocular cysts in the head of the pancreas without dilation of the main pancreatic duct.The patient was followed-up semiannually with imaging studies for suspected branch duct-type intraductal papillary mucinous neoplasm(IPMN).At 3 years after initial presentation,hypoechoic lesions were observed around each pancreatic cyst by EUS.Diffusion-weighted imaging showed high-intensity regions corresponding to these lesions.Therefore,a diagnosis of invasive carcinoma derived from IPMN could not be excluded,and subtotal stomach-preserving pancreaticoduodenectomy was performed.The macroscopic examination of the surgical specimen showed whitish solid masses in the head of the pancreas,with multilocular cysts within each mass.Microscopically,each solid mass consisted of inflammatory cells such as lymphocytes and plasma cells.Furthermore,immunochemical staining revealed immunoglobulin G4-positive cells,and many obliterating phlebitides were observed.The cysts consisted of mucus-producing epithelial cells and showed a papillary growth pattern.Based on these findings,we diagnosed multiple localized type 1 autoimmune pancreatitis occurring only in the vicinity of the branch ducttype 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.     

A case of minimal invasive carcinoma from intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas]

A 69-year-old man was referred to our hospital for epigastralgia. He was found to have elevation of serum amylase and CA19-9. Ultrasonography, abdominal CT, MRCP, ERCP and EUS showed the cystic lesion and a possibility of an other tumor. There was a stenosis of the main pancreatic duct (MPD) at the pancreas head and dilatation of the MPD from the body to the tail. Intraductal papillary mucinous neoplasm (IPMN) of the branch pancreatic duct was diagnosed, and there was a likelihood of ductal carcinoma of the pancreas. We therefore performed pancreatoduodenectomy. Pathological finding showed invasive carcinoma from an intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas.     

谐波造影增强超声内镜技术在胰腺占位性疾病中的诊断作用研究

目的探讨谐波造影增强超声内镜技术（CEH—EUS）在胰腺占位性疾病中的诊断作用。方法选择胰腺疾病患者为检查对象,以EUS—FNA或组织病理学结果以及随访结果为最终诊断,评价CEH—EUS诊断胰腺疾病的准确性,并分析CEH—EUS检查下受检部位的增强情况,包括增强顺序、增强时向特点、增强模式分级以及静脉洗脱程度。结果共23例胰腺疾病患者入选本研究,经FNA和（或）组织病理确诊,13例为胰腺癌,7例为慢性胰腺炎,2例为胰管内乳头状产黏蛋白肿瘤,1例为胰腺微囊型浆液性囊腺瘤。CEH—EUS诊断准确率为95．65％,明显高于普通EUS诊断准确率（78．2％）。其中CEH—EUS显示13例胰腺癌病灶增强晚于周围组织或与周围组织同步,呈不均匀低增强或存在充盈缺损区域,无显著达峰表现,消退明显早于周围组织。慢性胰腺炎等良性胰腺疾病病灶处增强与周围组织基本同步,充盈均匀,消退与周围组织同步。结论CEH—EUS在胰腺疾病的诊断中可以安全、简便、准确地显示病灶血供情况,不仅可成为EUS—FNA的有力补充,同时为胰腺疾病的鉴别诊断提供了直接且有效的帮助。     

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.     

内镜诊治胰腺导管内乳头状粘液性肿瘤的应用

目的探讨胰腺导管内乳头状粘液性肿瘤(IPMN)的诊断、内镜下治疗,以提高对该疾病的认识及内镜对其诊断及治疗的意义。方法回顾性分析经内镜诊治的IPMN患者12例,总结并分析他们的一般情况、临床症状、影像学检查、实验室检查、内镜下治疗等方面资料。结果 12例IPMN患者以老年男性为主,无特异性临床表现,主要发生部位为胰头或钩突部,CT主要表现为囊实性低密度影,其内可有壁结节,胰管扩张伴或不伴胆管扩张,2例侵及胰腺实质。磁共振胰胆管造影(MRCP)主要表现为胰管扩张,胰腺萎缩,胰头部圆形高信号影。内镜下逆行胰胆管造影(ERCP)显示十二指肠乳头膨大,开口扩张,可见胶冻样粘液流出,胰管造影显示胰管全程扩张或胰头部囊状扩张,3例伴胆总管、肝内胆管扩张。9例行ERCP治疗,清除粘液栓并置入胰管支架,3例同时置入胆管支架。结论 IPMN是一种特殊类型的胰腺囊性疾病,影像学检查有其独特的表现,ERCP对其诊断及治疗有重要意义。     

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.     

Growth process of small pancreatic carcinoma： A case report with imaging observation for 22 months

This report describes serial observations of the growth process of a small invasive ductal carcinoma （IDC） of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the lowechoic mass as a benign intraductal mucinous-papillary neoplasm （IPMN） based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.     

Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas

AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.     

Prognosis of cancer with branch duct type IPMN of the pancreas

AIM:To examine the coexistence of metachronous and synchronous cancer in branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMN).METHODS: We reviewed the records of 145 patients with branch duct IPMN between January 1991 and April 2008 and assessed the relationship between IPMN and intraor extra-pancreatic carcinoma and the outcome of IPMN.RESULTS: The mean observation period was 55.9 &#177; 45.3 mo. Among the 145 patients, the frequency of extra-pancreatic cancer was 29.0%. The frequency of ...     

Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas

Aims:  The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN).
Methods:  During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN.
Results:  Patients from the mixed IPMN group ( n  = 52) displayed a greater rate of symptoms (83% vs 55%, P  = 0.004), pancreatic resection (67% vs 38%, P  = 0.007), malignancy (35% vs 13%, P  = 0.017) and death (15% vs 4%, P  = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom-free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases.
Conclusion:  Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed.     

Experience of limited pancreatic head resection for management of branch duct intraductal papillary mucinous neoplasm in a single center

AIM： To share our surgical experience and the outcome of limited pancreatic head resection for the management of branch duct intraductal papillary mucinous neoplasm （IPMN）.
METHODS： Between May 2005 and February 2008, nine limited pancreatic head resections （LPHR） were performed for IPMN of the pancreatic head. We reviewed the nine patients, retrospectively.
RESULTS： Tumor was located in the uncinate process of the pancreas in all nine patients. Three patients had stents inserted in the main pancreatic duct due to inju- ry. The mean size of tumor was 28.4 mm. Postoperative complications were found in five patients： 3 pancreatic leakages, a pancreatitis, and a duodenal stricture. Pancreatic leakages were improved by external drainage. No perioperative mortality was observed and all patients are recorded alive during the mean follow-up period of 17.2 mo.
CONCLUSION： In selected patients after careful evaluation, LPHR can be used for the treatment of branch duct type IPMN. In order to avoid pancreatic ductal injury, pre- and intra-operative definite localization and careful operative techniques are required.     

Intraductal papillary mucinous neoplasm and acute pancreatitis

Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic tumors that arise from the pancreatic ducts and are increasingly reported worldwide. Both benign and malignant tumors of the pancreas are thought to contribute to recurrent pancreatitis possibly by pancreatic duct obstruction, and IPMNs contribute to a major share of this burden. The rate of acute pancreatitis (AP) in IPMN patients in the largest published surgical series has varied from 12% to 67%. IPMN may be categorized into 3 forms on the basis of the areas of involvement: main pancreatic duct (MD-IPMN), side branch (SB-IPMN), or combined. Both MD-IPMN and SB-IPMN may be the cause of pancreatitis. The risk of AP seems to be similar with both main duct IPMN and SB-IPMN, although data are controversial. AP in IPMN patients is not severe and often recurs without treatment. The rate of AP does not seem to differ among benign and malignant IPMNs, and the correlation between the malignant potential and the occurrence of AP is ill defined. AP seems to occur more often in patients with IPMN that in those with usual pancreatic adenocarcinoma possibly because of obstruction of the main duct by thick, abundant mucus secretion. Although the Sendai guidelines recommend surgical resection in patients with SB-IPMN with AP, data are controversial. Moreover, in patients with an episode of pancreatitis, the finding of pancreatic cysts is often attributed to pseudocysts or fluid collections that make the diagnosis of IPMN less suspicious. Future longitudinal and prospective studies to understand the natural history of AP in patients with IPMN are required to better manage patients with recurrent AP in the setting of IPMN.     

Pancreatic adenosquamous carcinoma, 9 mm in size,diagnosed preoperatively by transpapillary biopsy. Report of a case

Adenosquamous carcinoma of the pancreas is a rare variant of pancreatic cancer, which is known to be difficult to diagnose. We herein report a case diagnosed by transpapillary biopsy of the pancreatic duct. A 73‐year‐old man was referred to our department with suspicion of pancreatic cancer. Ultrasound showed a hypoechoic mass, 9 mm in diameter, in the body of the pancreas. Endoscopic retrograde cholangiopancreatography demonstrated a stenosis of the main pancreatic duct in the body with upstream dilatation and a shift of the bile duct to the left. Histological examination of the specimens obtained by transpapillary biopsy of the pancreatic duct revealed both adenocarcinoma and squamous cell carcinoma. Pancreatoduodenectomy was performed and, histopathologically, the tumor was diagnosed as adenosquamous carcinoma of the pancreatic body, 9 mm in size. This is the first case of adenosquamous carcinoma of the pancreas preoperatively diagnosed by transpapillary biopsy of the pancreatic duct, and the smallest stage I (TNM classification) case of such carcinoma detected to date.