Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma

BACKGROUND: Although the prognosis in malignant resectable intraductal papillary mucinous tumours of the pancreas (IPMT) is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma, the long term outcome remains ill defined. AIMS: To assess prognostic factors in patients with malignant IPMT after surgical resection, and to compare long term survival rates with those of patients surgically treated for ductal adenocarcinoma. METHODS: Seventy three patients underwent surgery for malignant IPMT in four French centres. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with invasive malignant IPMT were matched with patients with pancreatic ductal adenocarcinoma, according to age and TNM stages; survival rates after resection were compared. RESULTS: Surgical treatment for IPMT were pancreaticoduodenectomy (n=46), distal (n=14), total (n=11), or segmentary (n=2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n=22) or invasive carcinoma (n=51). In the latter group, 17 had lymph node metastases. Overall median survival was 47 months. Five year survival rates in patients with in situ and invasive carcinoma were 88% and 36%, respectively. On univariate analysis, abdominal pain, preoperative high serum carbohydrate antigen 19.9 concentrations, caudal localisation, invasive carcinoma, lymph node metastases, peripancreatic extension, and malignant relapse were associated with a fatal outcome. Using multivariate analysis, lymph node metastases were the only prognostic factor (OR 7.5; 95% CI: 3.4 to 16.4). Overall five year survival rate was higher in patients with malignant invasive IPMT compared with those with pancreatic ductal carcinoma (36 v 21%, p=0.03), but was similar in the subset of stage II/III tumours. CONCLUSIONS: The prognosis of patients with resected in situ/invasive stage I malignant IPMT is excellent. In contrast, prognosis of locally advanced forms is as poor as in patients with pancreatic ductal adenocarcinoma.     

Surgical treatment of intraductal papillary-mucinous tumors of the pancreas

BACKGROUND/AIMS: IPMT (Intraductal papillary-mucinous tumor of the pancreas) is increasingly recognized. The aim of this study was to investigate the appropriate surgical treatment for these tumors. METHODOLOGY: Between January 1981 and September 1998, 62 patients with IPMT underwent surgery. We retrospectively examined the clinicopathological features and surgical outcomes of the patients. RESULTS: The types of IPMT were as follows: hyperplasia (20); adenoma (31); and carcinoma, both invasive (5) and noninvasive (6). Lymph node metastasis was found in 36% of the carcinomas. The size of mural nodules was more than 3 mm in all adenoma or carcinoma cases, while the percentage of hyperplasia less than 3 mm was 75%. Intraoperative pancreatoscopy and annular array ultrasonography were very useful, because they detected 10 lesions that could not be found by preoperative examinations, such as computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography. All patients underwent surgical resection, including 10 pancreaticoduodenectomies (Whipple's procedure), 10 pylorus-preserving pancreaticoduodenectomies, 13 pancreatic head resections with segmental duodenectomies, 17 distal pancreatectomies, 9 segmental resections of the pancreas, 2 duodenum-preserving pancreatic head resections, and 1 total pancreatectomy. No operative or hospital death was observed. The postoperative survival rate at 5 years was 71.6% for carcinoma in IPMT. All of the cases with hyperplasia, adenoma and noninvasive carcinoma survived. Only two of the patients with invasive carcinoma died. CONCLUSIONS: IPMT had a favorable prognosis, as compared with pancreatic duct carcinoma. When selecting a surgical procedure for treating these tumors, it is important to confirm the tumor extent, as well as the diagnosis of invasion or noninvasion. In cases with invasion, radical resection is required. On the other hand, organ-function-preserving procedures should be selected for diseases without invasion.     

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas

OBJECTIVE: Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery. METHODS: The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status. RESULTS: The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p<0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence. CONCLUSIONS: IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.     

Total pancreatectomy in six patients with intraductal papillary mucinous tumour of the pancreas: the treatment of choice

BackgroundIntraductal papillary mucinous tumours (IPMT) were described as a distinct entity in l982.The extent of surgical resection remains controversial.MethodsSix patients with a diffuse dilatation of the main pancreatic duct were treated with total pancreatectomy for cure of IPMT.ResultsHistological examination showed one IPM adenoma, four IPM non-invasive carcinomas and one IPM invasive carcinoma. In all but one case multifocal extensive intraductal changes were found, affecting either most of the pancreas or the whole organ. All patients survived the operation and remain alive 5–56 months later. Post-pancreatectomy diabetes has been moderately well controlled.DiscussionIPMTs represent a subgroup of pancreatic neoplasms with a favourable prognosis, and the resection should aim at removing all dysplastic foci. In cases with diffuse dilatation of the main pancreatic duct, widespread tumour involvement of the duct system can be expected, so total pancreatectomy should be the operation of choice.     

IHPBA in Tokyo, 2002: surgical treatment of IPMT vs MCT: a Japanese experience

The differences and similarities between intraductal papillary mucinous tumor (IPMT) and mucinous cystadenoma or carcinoma (mucinous cystic tumor; MCT) of the pancreas have been noted. The similarities include: (1) both tumors originate from pancreatic duct cells, (2) massive mucin production is found in both tumors, and (3) papillary projection is a common histological characteristic. However, there are also many differences. IPMT is most frequently found in men in their sixties, and originates in the head of the pancreas, with 62% (123/199) of tumors reported to be found in the head of the pancreas. This tumor sometimes spreads throughout the entire pancreas. The tumor itself basically is of the dilated pancreatic duct type, and the prognosis is generally good. In contrast, MCT frequently develops in women in their forties. This tumor is usually large, round, and almost totally encapsulated by fibrous tissue, with no communication with the pancreatic duct. The tumor histologically has an ovarian-like stroma. It most often develops in the body or tail of the pancreas. Invasion is often present and the operative prognosis is not good. IPMT resembles the shape of a bunch of grapes and MCT resembles that of an orange. From the differences between these two types of tumors, they are classified into different categories. With regard to therapeutic strategies for MCT, the tumor should be resected with lymph node dissection immediately when it is detected. In contrast, some patients with branch-type IPMT can be followed without surgical procedures. Because IPMT shows good prognosis and little tendency for infiltration, some kinds of organ-preserving procedures would be possible for some patients with this tumor. Such organ-preserving procedures are: duodenum-preserving pancreas head resection, spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, and so on.     

Total pancreatectomy for intraductal papillary-mucinous tumor of the pancreas: reappraisal of total pancreatectomy

BACKGROUND/AIMS: Total pancreatectomy is rarely performed as the treatment of pancreatic carcinoma because of markedly impaired quality of life and poor prognosis. Intraductal papillary-mucinous tumor (IPMT) of the pancreas is characterized by extensive intraductal spread and favorable outcome even in its invasive stage. The role of total pancreatectomy was reappraised in the treatment of IPMT. METHODOLOGY: A total of five Japanese patients with IPMT underwent total pancreatectomy and their clinical follow-up data were reviewed. RESULTS: Total pancreatectomy was performed due to massive involvement of the entire pancreas in two patients, positive surgical margins on frozen section in one, benign IPMT with concomitant pancreatic cancers in one and recurrent IPMT in the remnant pancreas after distal pancreatectomy for IPMT in the other. Three of them underwent total pancreatectomy of the Whipple type, another underwent total gastrectomy and the other underwent the pylorus-preserving method. Surgical margins were negative by histology and no lymph node metastases were evident. Two patients had severe infection including liver abscess in one and pneumonia in the other. The former died on postoperative day 82 and the latter was controlled by medical treatment and discharged on postoperative day 73. The other three patients had an uneventful postoperative course and were discharged from 29 to 62 days after the operation. Long-term follow-up of the four patients revealed that three patients had hypoglycemic attacks, two diabetic retinopathy and two fatty liver. The four patients were doing well from 683 to 4,140 days after the operation without signs of recurrence. CONCLUSIONS: Total pancreatectomy would be indicated as a treatment of benign or malignant IPMT with extensive involvement when patients' condition permits and gives a chance of cure, although careful long-term medical care and follow-up are essential.     

Intraductal papillary or mucinous tumors (IPMT) of the pancreas: report of a case series and review of the literature

OBJECTIVE: Despite a better understanding of these conditions, intraductal papillary or mucinous tumors (IPMT) of the pancreas still present difficulty relating to the predictive factors of malignancy and the risk of relapse after surgical resection. The aim of this study was to report on our experience and to compare it to previously published cases. METHODS: We studied retrospectively 26 patients (mean age 60.3 yr) presenting with IPMT. Of the 26 patients, 19 had surgical resection and seven did not. The main clinical feature was acute pancreatitis occurring in 38% of the patients. Segmental pancreatectomy was performed in all the cases. At pathological assessment of resection margins, tumor resection was considered as complete in 17 cases. Margins exhibited benign mucinous involvement, and resection was considered to be incomplete in one multifocal case and in one case with diffuse spread of the tumor. RESULTS: A total of 11 tumors were benign and five were malignant. Carcinomas were invasive in four cases (two invading the pancreatic parenchyma, one the duodenum, and one the peripancreatic nodes) and in situ in one case. Malignancy was not diagnosed preoperatively except when invasion was evident (duodenal spread). Although main pancreatic duct type and obstructive jaundice appeared as suggestive features for the risk of malignancy, no reliable preoperative predictive factors for malignancy could be identified as regarding to clinical parameters, biological examinations, carcinoembryonic antigen or CA19-9 levels in serum or in pure pancreatic juice, imaging, and cytological methods. Within 40.8 months mean follow-up after surgery (range 2-96 months), three patients (16%), two with malignant and one with benign tumor, had tumor relapse after respectively 7, 27, and 14 months. Margins were positive without malignant features in the two malignant cases and negative in the other case. Tumor relapse was malignant with diffuse spreading in the three cases, and the patients died within 34 months after surgical resection. CONCLUSIONS: Our series and the review of the literature indicate that preoperative indicators of malignancy in IPMT are still lacking. Concerning resection margins, complete tumor resection is usually possible by segmental pancreatectomy. Malignant relapses are not exceptional. Incomplete resection and diffuse or multifocal tumor represent poor prognostic factors. Total pancreatectomy should be considered in such cases.     

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.     

Invasive cancer and survival of intraductal papillary mucinous tumors of the pancreas

OBJECTIVES: Intraductal papillary mucinous tumor (IPMT) is frequently associated with pancreatic cancer. We hypothesized that IPMT progresses to invasive cancer with K-ras mutations as an early event, and that invasive cancer affects survival. We compared survival after resection and determined whether K-ras mutations predicted survival in IPMT patients without or with invasive cancer. METHODS: Records of 47 patients with IPMT who were seen between 1983 and 1998 were reviewed retrospectively in 15 cases and prospectively in 32. All histological material was reviewed to confirm the diagnosis of IPMT and to assess invasion. Kaplan-Meier survival curves were analyzed by the log-rank test. The chi2 test was used for differences in K-ras between groups. RESULTS: There were 30 men and 17 women, with a mean age of 65 yr (range 36-90 yr). Of the patients, 26 had IPMT without invasive cancer and 19 had IPMT with invasion. Tissue diagnosis was available in 45 patients. K-ras was analyzed in 40 patients. Mutations were present in 15 of 23 patients (65%) without invasive cancer and in 14 of 17 patients (82%) with invasive cancer (p = ns). At 2.5 yr, the overall cumulative survival of IPMT patients without invasive cancer was 94% compared to 24% of patients with invasive cancer (p < 0.001). The 5-yr survival of IPMT patients without invasive cancer was 94%. K-ras mutations did not correlate with survival. CONCLUSIONS: Invasive cancer in IPMT reduces the 2.5-yr survival after surgery from 93% to 24%. K-ras mutations occur before invasive cancer, and do not predict postoperative survival.     

Cystic neoplasm of the pancreas: a Japanese multiinstitutional study of intraductal papillary mucinous tumor and mucinous cystic tumor

The Japan Pancreas Society performed a multiinstitutional, retrospective study of 1379 cases of intraductal papillary mucinous tumor (IPMT) and 179 cases of mucinous cystic tumor (MCT) of the pancreas. Clinicopathologic features and postoperative long-term outcomes were investigated. IPMT were most frequently found in men and in the head of the pancreas. In contrast, all patients with MCT were women. Ovarian-type stroma were found in only 42.2% of the MCT cases. Prognostic indicators of malignant IPMT included advanced age, positive symptoms, abundant mucous secretion, presence of large nodules and/or large cysts, remarkable dilatation of the main pancreatic duct, and main duct- or combined-type IPMT. Advanced age, positive symptoms, and presence of large nodules and/or large cysts were predictive of malignant MCT. The 5-year survival rate of IPMT patients was 98%-100% in adenoma to noninvasive carcinoma cases, 89% in minimally invasive carcinoma cases, and 57.7% in invasive carcinoma cases. The 5-year survival rate of MCT patients was 100% in adenoma to minimally invasive carcinoma cases and 37.5% in invasive carcinoma cases. In conclusion, IPMT and MCT show distinct clinicopathologic and prognostic differences. The results from this study may contribute to the diagnosis and treatment of IPMT and MCT.     

Intraductal papillary-mucinous tumors of the pancreas: Clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18)     

Invasive carcinoma derived from intraductal papillary mucinous carcinoma of the pancreas

BACKGROUND/AIMS: Most patients with intraductal papillary mucinous tumors of the pancreas have a favorable prognosis after surgical treatment. However, recurrent disease frequently occurs in patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma. The objective of this study was to clarify the clinicopathological features of invasive carcinoma derived from intraductal papillary mucinous carcinoma. METHODOLOGY: We performed a retrospective review of the 29 patients with intraductal papillary mucinous tumor including 10 patients with invasive carcinoma who underwent pancreatic resection between June 1995 and December 2001 at the National Cancer Center Hospital East. RESULTS: Of 10 patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma, 7 patients had lymph node involvement and 8 patients had retroperitoneal invasion. The overall 1-, 2-, 4-year actuarial survival rate for invasive carcinoma derived from intraductal papillary mucinous carcinoma was 39%, 26%, 13%. Recurrence occurred as liver metastasis in 3 patients, carcinomatous peritonitis in 3, local recurrence in 3, and lung metastasis in 1. All patients with adenoma, non-invasive carcinoma, and minimally invasive carcinoma are alive without recurrent disease after pancreatic resection. CONCLUSIONS: Patients with invasive carcinoma derived from intraductal papillary mucinous carcinoma had a worse prognosis. Margin-negative pancreatic resection is essential for treating this disease.     

Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma

BACKGROUND AND AIMS: Intraductal papillary mucinous tumours (IPMT) of the pancreas constitute a unique pathological entity with an overall incidence of associated invasive malignancy of 20%. The malignant potential of an individual IPMT cannot be accurately predicted. Preoperative estimation of the risk of associated invasive malignancy with IPMT would be of significant clinical benefit. As aberrations in cell cycle regulatory genes are associated with the progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor beta/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT. METHODS: Sections of formalin fixed paraffin embedded pancreatic tissue from a cohort of 18 patients with IPMT were examined using immunohistochemistry for protein expression of cell cycle regulatory genes p16(INK4A), p21(CIP1), p27(KIP1), cyclin D1, pRb, and p53, as well as the cell signalling molecule Smad4. A comparison of expression levels was made between adenoma/borderline IPMT (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight patients, four of whom harboured invasive carcinoma). Statistical analysis was performed using the chi(2) and Fisher's exact tests. RESULTS: Aberrant expression of the proteins examined increased in frequency from adenoma/borderline IPMT to IPMC. Specifically, there was a significantly greater incidence of loss of p16(INK4A) expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%) adenoma/borderline IPMT (p<0.001). Similarly, loss of Smad4 expression was associated with IPMC: 3/8 (38%) versus adenoma/borderline IPMT 0/10 (p<0.03). Loss of Smad4 expression within the IPMT was the best marker for the presence of invasive carcinoma (p<0.001). CONCLUSIONS: These data indicate that loss of p16(INK4A) and Smad4 expression occur more frequently in IPMC alone, or with associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.     

Surgical treatment of intraductal papillary-mucinous tumor (IPMT) of the pancreas: operative indications based on surgico-pathologic study focusing on invasive carcinoma derived from IPMT

Background/Purpose. Between 1979 and 2000, 51 patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas underwent surgical resection. Methods. The patients were reviewed to disclose the surgical pathology of invasive carcinoma derived from IPMT and to determine the surgical indications for IPMT on the basis of the pathologic findings. Results. The incidence of invasive carcinoma derived from IPMT according to the localization of the tumor was as follows: 4/9 (44%) in the main pancreatic duct (MPD type), 4/9 (44%) showing ductal spread from the MPD to branch ducts (mixed type), and 2/33 (6%) in the 2 branch duct (branch type). The maximal size of the intraductal spread of invasive carcinomas (8 of 18 cases in the MPD and mixed type together and 2 of 33 cases in the branch type) was as follows: 6/8 (75%) in the MPD and mixed type were over 6?cm in size, and the 2-branch-type invasive carcinomas were within the 3-cm size range. Conclusions. We concluded that for both invasive and noninvasive IPMTs, surgical resection was necessary for any MPD or mixed-type IPMTs, and that surgical resection was appropriate for branch-type lesions larger than or equal to 3?cm in diameter, or for lesions smaller than 3?cm showing rapid growth on clinical images.     

胰腺间变癌的临床病理特点——附6例报告

目的胰腺间变癌是少见的胰腺外分泌恶性肿瘤，本文探讨其临床病理学特点。方法回顾性分析6例胰腺间变癌的临床特点并结合文献讨论。结果本组6例，其中男5例，女1例，年龄4j～74岁。肿瘤位于胰头3例，胰体尾3例。行胰头十二指肠切除术3例，其中1例作肠系膜上静脉切除重建术，另1例同时行肠系膜上动、静脉切除重建术。3例胰体尾肿块，2例行胰体尾切除、脾切除术．另1例肿瘤已侵犯周围脏器，行全胃、结肠脾曲、腹腔动脉切除术。病理检查：肿瘤细胞呈多形性．可见圆形、卵圆形、多边形和梭形的肿瘤细胞，核大深染，异型明显，也可见巨核或多核的瘤巨细胞及破骨细胞样巨细胞。随访5例，术后平均生存5．5月．均死于肿瘤腹腔内和肝脏转移。结论胰腺间变癌组织学特点为肿瘤细胞的多形性，并可见巨核或多核的巨细胞或破骨细胞样巨细胞．呈侵袭性生长，易侵犯周围脏器、大血管和发生肝脏、淋巴结转移，恶性程度高，预后差。     

Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas

BACKGROUND & AIMS: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. METHODS: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. RESULTS: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23-75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). CONCLUSIONS: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete "curative" resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.     

Positron emission tomography with 2-deoxy-2-[<Superscript>18</Superscript>F] fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose for diagnosis of intraductal papillary mucinous tumor of the pancreas with parenchymal invasion

We used positron emission tomography with 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG-PET) in the diagnosis of two cases of malignant intraductal papillary mucinous tumor (IPMT) of the pancreas. A 56-year-old man and a 72-year-old man, both with tumors in the pancreatic head, were referred to Akita University Medical Center. Computed tomography revealed tumors with multiple cystic components in both patients. FDG-PET images showed markedly high FDG uptake in the area corresponding to a solid component found in one patient and diffuse faint uptake, higher than that of the surrounding tissue, in the other patient, who had no solid component. Histological examination of the resected specimens after pancreatectomy showed invasive carcinoma involving the pancreatic parenchyma in both patients. Although our experience is limited and preliminary, FDG-PET seems to be useful for the detection of malignancy in IPMT, especially in patients not showing any solid component on conventional diagnostic images such as computed tomography.     

Radical resection for pancreatic cancer

Ductal adenocarcinoma of the pancreas is still characterized by (1) poor prognosis after surgery and (2) extreme difficulty in early diagnosis, and we need a breakthrough. For the first problem, we have performed a wide range of lymphatic and connective tissue clearance (extended pancreatectomy) which has succeeded in improving the 5-year survival rate from 8% to 24% via decreasing the incidence of locoregional recurrence. When liver perfusion chemotherapy via the hepatic artery and the portal vein was added to the patients who had received extended pancreatectomy, the 5-year survival rate was further elevated to 40% via decreasing the incidence of hepatic metastasis. We conclude that pancreatic cancer should be treated by the better-balanced treatments between locoregional control and prevention of hepatic metastasis. For the second problem, we have more actively collected pancreatic juice to perform cytodiagnosis even though no obvious tumor was delineated by the conventional imaging diagnoses. When cancer cells were detected in the pancreatic juice, our method of intraoperative cytology was very useful in precisely locating the occult lesion indicating an appropriate range of pancreatectomy. The resected pancreas was proven to have included borderline malignancy and in situ or minimally-invasive carcinoma by the postoperative histology, and disease-free 5-year survival rate was 100%. In the future, we need to detect patients with a high risk of pancreatic cancer and develop a less-painful method to collect the pancreatic juice.     

Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas

OBJECTIVE: Intraductal papillary mucinous tumor (IPMT) of the pancreas has a favorable prognosis. Non-pancreatic primary neoplasms have potential prognostic significance in patients with IPMT. This study focused on the incidence and characteristics of nonpancreatic neoplasms in IPMT patients. METHODS: Forty-two patients (mean age, 64 yr) with IPMT underwent surgery; 16 had adenoma and 26 adenocarcinoma. Preoperative and postoperative, nonpancreatic neoplasms were investigated. The mean postoperative follow-up period was 4.2 yr (range, 0.2-13 yr). Furthermore, 46 patients with pancreatic ductal adenocarcinoma were analyzed for nonpancreatic neoplasms. RESULTS: Five-year survival rates were 100% for benign and 82% for malignant IPMT. Twenty patients (48%) had nonpancreatic neoplasms, before (n = 11), at (n = 4), and after (n = 10) surgery for IPMT. Fifteen patients (32%) had nonpancreatic malignancies. Nonpancreatic neoplasms included colorectal adenomas (21%) and adenocarcinomas (12%), and gastric carcinomas (10%). One patient died of subsequent bile duct carcinoma. Development of nonpancreatic neoplasms was related to age but not to gender, family history, adjuvant chemotherapy, or IPMT pathology. The incidences of nonpancreatic neoplasms and malignancies were significantly higher in patients with IPMT than in those with pancreatic ductal adenocarcinoma (11% and 7%, respectively). CONCLUSIONS: IPMT is associated with a high incidence of nonpancreatic neoplasms, particularly colorectal neoplasms. In IPMT patients, systemic surveillance may allow early detection of second tumors. In preoperative screening and postoperative follow-up of patients with nonpancreatic neoplasms, the possibility of IPMT should be considered.     

Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis of intraductal papillary mucinous tumors

The aim of this study was to investigate mutations of the K-ras oncogene and the p53 tumor suppressor gene in pancreatic juice and to evaluate our method for the diagnosis of intraductal papillary mucinous tumors (IPMT). Pancreatic juice was collected endoscopically from 12 patients with IPMT who underwent surgical resection (eight carcinomas and four adenomas) and eight cases without evident pancreatic diseases. DNA was extracted and both genes were examined by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. In addition, surgically resected specimens were analyzed for both genes by the same methods, and p53 overexpression was investigated immunohistochemically. K-ras point mutations were detected in pancreatic juice from all 12 patients (100%) and p53 mutations were detected in five of 12 (42%). They were detected not only in carcinoma but also in adenoma and there was no difference between the mutations detected in pancreatic juice and surgical specimens. No mutations were found in any cases without pancreatic diseases. These findings suggest that alterations of K-ras and p53 gene are common events in the development of IPMT and that genetic analysis of them in pancreatic juice can be a useful tool for the clinical diagnosis of IPMT before surgery.