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We previously published a nomogram for prediction of carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). The objective of the current study was to validate this nomogram in an external cohort of patients at multiple institutions.

Inflammatory myofibroblastic tumor (IMT), which expresses cyclooxygenase-2 (COX-2), can be effectively treated with COX-2 inhibitor. Here, we report a case of urinary bladder IMT in a 13-year-old boy. Although total cystectomy was initially planned for complete resection of the tumor, neoadjuvant treatment with COX-2 inhibitor and prednisolone reduced the size of the tumor and enabled complete resection of the tumor by partial cystectomy. Neoadjuvant treatment with COX-2 inhibitor and prednisolone for IMT of the bladder allowed a more conservative surgical procedure that preserved bladder function.

This study aimed to elucidate the natural history of intraductal papillary mucinous neoplasm (IPMN) of the pancreas with mural nodules (MNs) in branch duct IPMN (BD-IPMN).

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

Since 1981, the Japan Pancreas Society has been hosting a nationwide pancreatic cancer registry. To commemorate its 30th anniversary, we review its history and latest achievement.

There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet.

The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan.

The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs).

With the aim of improving early detection of pancreatic carcinoma, we attempted to make correlations among positive immunohistochemical detection of p53 expression, mutations in the p53gene, and detailed histologic features of pancreatic carcinoma.

Background/Aims:From 1992 to 2003, 7 carcinomata in situ (CIS) were incidentally discovered during microscopical observation of resected materials for advanced carcinomas of peripancreatic organs, of which 4 had undergone endoscopie retrograde cholangiopancreatography (ERCP) or postoperative pancreatography of the resected specimen (POP). In addition, 7 of 79 invasive ductal carcinomata (IDC) of the pancreas were accompanied by CIS = 2 cm long. A total of 11 patients were reviewed here for pancreatographic findings for CIS of the pancreas. Methods:All resected pancreatobiliary materials were sliced serially at 5-to 8-mm intervals in a plane at right angles to the main pancreatic duct, referring to POP images. Results:Irregularity (I), non-continuous narrowing (N), granular defects (G), and dilatation (D) were seen in 78, 67, 33 and 22% on ERCP, respectively, and in 90, 70, 60 and 40% on POP, respectively. Conclusions:I, N, G,and D are most important pancreatographic findings in ERCP and highly suggestive of CIS of the pancreas, so that whenever they are encountered, cytological and/or pathological examination of the pancreatic duct should be actively performed.

To analyze the early state and the mode of advancement of IPDACs.

The goal of this study was to evaluate the consistency of distinction between pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary-mucinous neoplasms (IPMN) and the hypothesis that guidelines for their distinction might be inadequate.

Abstract

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.

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.

: Abstract Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Little is known about the clinical characteristics and outcome of surgical treatment in patients with tumor thrombus in the portal vein. Medical charts of 142 consecutive patients who underwent hepatic resection for colorectal metastasis were reviewed retrospectively. Of the 142 patients, 4 (2.8%) had macroscopic portal vein invasion. The most prominent characteristic on preoperative imaging was segmental staining in the arterial phase shown by dynamic computed tomography (CT) or by CT arteriography. This finding was positive in all four of the patients. All patients underwent anatomic liver resection and were alive with no evidence of disease for an average of 52.3 months (range 21–102 months). Macroscopic tumor thrombus in the portal vein is rare with colorectal metastasis. It is accurately detected by CT by checking for signs of segmental staining. In this setting, anatomic major resection of the liver is essential for curative treatment.

Parathyroid hormone‐related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor‐burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. Bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25‐dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human.

Background/Aims: Clinicopathological features and postoperative results from mucinous cystic tumors of the pancreas (MCTs) were reviewed. MCTs with ovarianlike stroma (MCTs-OLS+; n = 6) and those lacking ovarianlike stroma (MCTs-OLS–; n = 4) were compared to elucidate the oncogenesis of MCT without OLS. Patients and Methods: Ten patients with MCT were studied. Results: The 6 MCTs-OLS+ cases occurred in females and were located in the body and tail of the pancreas. The mean tumor size was 6.5 cm (range 2–11 cm). The majority (5/6) of MCTs-OLS+ were multilocular and exhibited tiny loculi on the cyst wall and septum characteristic of MCTs-OLS+. Pathological classifications were adenoma in 4 patients and noninvasive adenocarcinoma in 2 patients. All 6 patients were alive without tumor recurrence 6–124 months after tumor resection. Of the 4 MCTs-OLS– cases, 2 were males and 2 females; MCTsOLS– were located in the tail of the pancreas. The mean tumor size was 6.9 cm (range 4–8.4 cm). Invasive cancer in the pancreatic parenchyma or extrapancreatic tissue was recognized in all 4 patients, and the pathological classification of epithelia of the cyst wall were adenocarcinomas. These findings were also compatible with common invasive ductal carcinomas of the pancreas with secondary retention cyst on pseudocyst. All patients died of the disease (15, 27, 31 and 80 months after resection, respectively). Whether or not OLS is specific for MCTs of the pancreas should be clarified in future studies. Conclusion: The results of our study led to three hypotheses regarding the oncogenesis of MCTs-OLS–: (1) MCTs in which OLS disappears during the development of invasive carcinoma; (2) advanced cancer derived from intraductal papillary mucinous tumor of the pancreas, and (3) invasive ductal carcinoma of the pancreas with secondary cyst.

Abstract.: Although anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, a few patients survive for a fairly long time after modern intensive treatment. We tried to identify prognostic factors of ATC to assist in deciding on the proper therapeutic strategy in individual patients. Of 47 patients with ATC (1976–1999), 3 patients with “incidental” ATC (largely differentiated thyroid carcinoma with a small region of ATC) were excluded because they had a favorable outcome. The 1-year survival rate of the remaining 44 patients with clinically distinct ATC was 16%. The presence of acute symptoms, large tumor (> 5 cm), distant metastasis, and leukocytosis (white blood cell count ≥ 10,000/mm3) proved to be significant risk factors. Multivariate analysis by the Cox proportional hazard model showed that these four factors were independent factors for predicting death from ATC. We devised a novel prognostic index (PI) based on the number of these four unfavorable characteristics the patient possessed. Patients with a PI of ≤1 had a 62% survival rate at 6 months, whereas no patients with a PI of ≥3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Nine patients received multimodal treatment with a combination of surgery, external irradiation, and chemotherapy and had a long survival (mean 333 ± 68 days; one patient is still alive and tumor-free), with a mean PI of 0.6. Our PI is useful as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results; if it is high most patients are too seriously ill to tolerate intensive treatment and palliative therapy is recommended.

With carcinoma of the thoracic esophagus, clinical evidence of invasion of adjacent organs (T4) indicates a highly advanced stage, and most surgeons avoid esophagectomy. Although the therapeutic strategy for such disease is generally selected based on preoperative evaluation and intraoperative inspection, their accuracy and the relation to survival outcomes after esophagectomy have seldom been analyzed on the basis of exact histopathologic evidence. We performed esophagectomy, with perioperative adjuvant therapy when possible, on patients with clinical-T4 tumors unless absolutely unresectable conditions were detected. Among the 500 patients who underwent esophagectomy, the 78 patients whose tumors were confirmed to be T4 pathologically were compared with patients whose tumors were assessed as T4 preoperatively or intraoperatively to evaluate the role of esophagectomy for clinical-T4 carcinoma. Esophagectomy was possible for 99% of the pathologic-T4 tumors preoperatively assessed as resectable, but the resection was grossly incomplete in 35%. The true-positive rates in tumors preoperatively and intraoperatively assessed as T4 were 51% and 84%, respectively. The hospital mortality rate in patients with pathologic-T4 tumors was 4%. The overall 5-year survival rate for patients with pathologic-T4 tumors was 14%, compared with 60% for those with tumors assessed as T4 intraoperatively but not pathologically. Esophagectomy with perioperative adjuvant therapy yielded occasional cure with an acceptable mortality rate for patients with pathologic-T4 tumors assessed as technically resectable. Preoperative assessment and intraoperative macroscopic inspection had limitations for predicting pathologic-T4 disease and incomplete resection. Only patients with definitive evidence of unresectability should be excluded from esophagectomy.

Mucin-producing tumors (MPTs) of the pancreas accompanied by carcinomas usually include various grades of dysplasia in the ductal epithelium, and invasive areas are histologically similar to those of common invasive ductal carcinomas, suggesting that MPTs provide a good tool to investigate early stages of pancreatic carcinogenesis. Thus, to clarify genetic alterations in the early stage of pancreatic carcinogenesis, we analyzed K-rasgene mutations and loss of heterozygosity (LOH) at the p53gene locus using 37 cases of MPTs harboring dysplastic epithelium. Further, we conducted an extended, multifocal microdissection analysis focusing on the histological features of ductal epithelium and the distribution of genetic alterations for 3 cases of MPT positive for LOH of the p53gene to determine the relation to tumor progression. K-rasgene mutations were detected with high frequency in 50% or more cases of the adenomas (14 of 19), borderline tumors (4 of 7), and carcinomas (8 of 11), whereas LOH of the p53gene was limited to carcinomas (3 of 5 informative cases, 60%) and always accompanied by K-rasgene mutation. Investigation of a total of 126 microdissection sites from 3 cases showed the presence of K-rasgene mutations in mild dysplasia and all (100%) regions of moderate or more marked dysplasia, whereas LOH of the p53gene showed more gradual tendency to increase with grade from moderate dysplasia. In addition, the multifocal genetic analysis showed K-rasgene mutations to be widely distributed throughout tumors, whereas LOH of the p53gene was localized to 1 or a few areas. Further, topographically delimited areas with the same histology in the same tumor did not always show the same genetic alteration. In conclusion, we could confirm that both the K-rasand p53gene alterations occur in the intraductal stage of MPT, and the latter is superimposed on the former during the course of tumor progression. However, the pattern of association of histological features with genetic alteration differs from tumor to tumor. HUMPATHOL31:795-803.

Abstract: Purpose: This present study aimed to investigate the genetic changes in gallbladder carcinogenesis. Methods: Eleven intramucosal gallbladder carcinomas were compared with 31 invasive lesions for loss of heterozygosity (LOH) on chromosomes 5q, 9p, 17p and 18q, frame-shift mutations in a ten-adenine repeat site within the gene encoding the transforming growth factor β type II receptor (TGFβRII) and an eight-guanine repeat site within BAX, and point mutations in codon 12 of Ki-ras. Results: The incidences of LOH in intramucosal and invasive carcinomas were 14% and 17% on 5q, 9% and 52% on 9p, 64% and 65% on 17p, and 13% and 32% on 18q. No frame-shift mutations were found at TGFβRII or BAX, and point mutations in codon 12 of Ki-ras were present in only 8% of the samples. Thus, LOH on 17p was by far the most frequent lesion with similar results in both intramucosal and invasive carcinomas. In contrast, the frequency of LOH on 9p and 18q was distinctly higher in invasive lesions. Conclusion: The present data suggest that LOH on 17p may play an important role in the evolution of gallbladder carcinoma from a relatively early phase, while LOH on 9p and 18q may play roles in progression.

A total of 69 gastric carcinomas of very old people (aged ≥85) were collected and pathologically analyzed in comparison with those of young to middle‐aged (30–39) and elderly (65–69) people, with special attention to their phase. In the very old, almost all (34/35) carcinomas in the early phase belonged to well‐differentiated categories. In the advanced phase, half of them (17/34) were classified into poorly differentiated categories when determined from the predominant pattern, but a well‐differentiated pattern almost always coexisted in the superficial site. Thus, the gastric carcinomas in the very old may principally develop as well‐differentiated carcinomas which then progress to poorly differentiated carcinomas with time, in contrast to those of the young to middle‐aged, most of which emerged from the very early phase as poorly differentiated lesions. The gross features of the carcinomas were also in line with these histological observations. The carcinomas of the elderly showed distinct similarity to those of the very old. The results suggest that poorly differentiated carcinomas of the young to middle‐aged and the old may be better classified and analyzed separately in view of the generally recognized etiological (e.g., specifically close causal relationship with environmental factors of the intestinal‐type carcinoma of the old) and biological (e.g., practically no tendency for hematogenous metastasis of the diffuse‐type carcinoma of the young to middle‐aged) differences, although in the General Rules for Gastric Cancer Study of Japan, both are placed in the same category, por (por2).

PURPOSE: Lymph node metastasis in the hepatoduodenal ligament is known as one of the most significant prognostic factors after liver resection for colorectal metastasis. However, there have been very few articles on the clinical features of node-positive patients and on detailed distribution of positive nodes. Further, there has been no established strategy on how to handle hepatic lymph nodes during liver resection. To address these subjects, a retrospective study was conducted. METHODS: During the period of 1980 through April 1998, 182 hepatic resections were performed for metastatic colorectal carcinoma. Of these, 78 cases had hepatic lymph node sampling during the operation. Distribution of positive nodes, location of liver metastasis, stage of the primary lesion, and outcome after liver resection were analyzed. RESULTS: Nine cases (12 percent) had secondary lymph node metastases in the hepatoduodenal ligament. The incidence was slightly higher (13.5 percent) in the most recent 44 consecutive cases. There was a tendency for liver metastases in the right lobe to metastasize to No. 12b (or node of the foramen of Winslow, lymph nodes along the common bile duct) and liver metastases in the left lobe to metastasize to No. 8a (anterosuperior group of the lymph nodes along the common hepatic artery). Outcome of node-positive patients (n=9) was extremely poor (P<0.001) compared with that of node-negative patients (n=66), and the most common site of recurrence in the node-positive patients was remnant liver and hepatic lymph nodes. Preoperatively, there were no significant predicting factors for positive hepatic lymph nodes. CONCLUSIONS: No. 8a and No. 12b nodes are principal nodes that should be palpated and sampled during liver resection to check the secondary lymphatic spread from liver metastases. Hepatic nodal involvement indicates the progression of disease beyond simple liver metastases and may not be the indication for simple surgical removal. Further study, including hepatoduodenal dissection and systemic adjuvant chemotherapy, may elucidate the survival benefit, if any, of liver resection in node-positive patients.

Abstract: Purpose: Although preoperative chemotherapy for advanced gastric cancer is now commonly applied with favorable results, convincing evidence for life prolongation and predictive markers for a good prognosis are both lacking. We report here 5 cases that have shown a distinct positive effect of preoperative chemotherapy together with the results of a precise histological examination of materials indicating features predicting a favorable outcome. Patients and methods: A total of 18 patients with a far-advanced gastric carcinoma subjected to gastrectomy after FLEP (5-fluorouracil, leucovorin, etoposide, cisplatin) in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, could be divided into two distinct groups: 5 surviving over 5 years (group A) and 13 who died within 13 months (group B). Histological features (subtypes) of the carcinomas and chemotherapeutic effects were studied with reference to biopsy materials and resected stomachs and lymph nodes. Results: In group A, 3 of 5 patients had solid-type poorly differentiated adenocarcinomas. In contrast, in group B, 9 had tubular adenocarcinomas (well or moderately differentiated) and 3 non-solid or diffuse-type poorly differentiated adenocarcinomas and there was only one solid-type tumor. In group A, remarkable therapeutic effects were apparent histologically in 4 of the 5 patients with almost complete disappearance of cancer cells from metastases in lymph nodes, whereas no such changes were evident in group B. Conclusion: FLEP is distinctly beneficial for certain types of advanced gastric carcinoma, especially solid-type poorly differentiated adenocarcinomas, and favorable results can be predicted, to a certain extent, on the basis of findings for the material resected after chemotherapy.

Previous studies of Japanese patients showed that distal gastric carcinomas (of the corpus or the antrum) were associated with histologic changes in the non-neoplastic gastric mucosa. These changes (cells with ciliated metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular cysts, and extensive intestinal metaplasia) were often found in carcinomas of intestinal type.Previous studies of Japanese patients showed that distal gastric carcinomas (of the corpus or the antrum) were associated with histologic changes in the non-neoplastic gastric mucosa. These changes (cells with ciliated metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular cysts, and extensive intestinal metaplasia) were often found in carcinomas of intestinal type.

Abstract. Although most papillary thyroid microcarcinomas (PMCs) are of little clinical significance, patients with PMCs occasionally have an unfavorable outcome, especially when they present with bulky nodal metastasis or distant metastasis. We have attempted to identify “high-risk” PMCs by evaluating clinical, pathologic, and immunohistochemical prognostic factors. Among 190 patients with a PMC, 156 without clinically apparent nodal metastasis had a benign course. The remaining 34 patients, who presented with cervical lymphadenopathy of at least 1 cm, were studied. Three of the four patients who developed distant metastasis died of the disease, and the other died of local recurrence. All patients who developed distant metastasis or died of the disease had both nodal metastasis of at least 3 cm and a nonencapsulated type of primary lesion. All patients who developed distant metastasis showed both extracapsular extension of the metastatic lesions in lymph nodes and positive staining for transforming growth factor-β3 (TGFβ3) (a potent growth inhibitor) in the primary lesion. The Ki-67 (an indicator of cell proliferation) labeling indices in the primary and metastatic nodal lesions of patients who died of cancer were significantly higher than those of the others with nonfatal disease. None of the patients showed P53 (nuclear tumor-suppressor phosphoprotein) overexpression. In conclusion, patients with PMC who have both 3 cm or larger lymphadenopathy and a nonencapsulated type of primary lesion may be regarded as high-risk patients. Immunohistologic positivity for Ki-67 and TGFβ3 in cancer cells is a potential indicator of aggressively malignant PMC.:

To evaluate the effects of aggressive operation for esophageal cancer invading the trachea and main bronchi, we investigated retrospectively 62 patients with proven tracheobronchial involvement who underwent thoracotomy for esophagectomy between 1973 and 1993. We operated unless the tumor was assessed to be definitely unresectable. Esophagectomy was possible in 55 patients, and the resectability rate was 95% after preoperative computed tomography and bronchoscopy became routine. After esophagectomy, no residual cancer lesion was recognizable macroscopically in 53% of patients. The hospital mortality rate in esophagectomy cases was 7% in the past 8 years. The outcome in patients who underwent curative resection was significantly favorable (p< 0.0001), and the 2-year survival was 51%. The patients with nonresectable cancer all died within 6 months compared with a 23% 1-year survival rate for palliative esophagectomy cases (p< 0.006). Among patients with tracheobronchial involvement assessed as resectable on computed tomography and bronchoscopy, a considerable proportion benefited from aggressive therapy with esophagectomy. The possibility of complete cure was high, especially when the cancer responded well to preoperative therapy and no lymph nodes were involved.

Recent advances in diagnostic techniques allow detection of relatively small ductal cancers and mucinous cystic neoplasms of the human pancreas. The histopathological characteristics of a series of such small pancreatic carcinomas encountered in our hospital were: 1) all were invasive ductal carcinomas accompanied by fibrosis, 2) four of seven carcinomas were thought to originate in the branch ducts, 3) no precancerous lesions were found, and 4) lymph node metastasis was detected in only one patient. Mucinous cystic neoplasms were of two types: megacystic and ductectatic. The megacystic type is the classical mucinous cystic neoplasm. The ductectatic type is characterized by the presence of multilocular cysts (reminiscent of bronchiectasia of the lung), and papillary proliferation of the lining epithelium—differing from typical ductal carcinomas as well as from megacystic lesions in terms of morphological features, intrapancreatic location, patient age, and sex. The ductectatic type occurs exclusively in the head and body of the pancreas, and is found predominantly in aging males. Semin. Surg. Oncol. 15:8–14, 1998. © 1998 Wiley-Liss, Inc.

A case of a surgically resectable solitary metastasis to the pancreas from a lung cancer, confirmed by immunohistochemical staining (PE-10), is reported. ERCP revealed meniscoid interruption of the main pancreatic duct, which is uncommon in patients with primary pancreatic cancers of the pancreas in our hospital. This patient lived for 29 mo after the surgical resection of the pancreatic lesion. Therefore when metastasis limited to the pancreas is evident on clinical imaging, surgical management may be more optimal than other treatment approaches.

IMPORTANCE: Invasive intraductal papillary mucinous carcinoma has aggressive malignant behavior, including lymph node metastasis. It is important to identify factors associated with invasive intraductal papillary mucinous carcinoma to determine operative procedures, but they remain unclear. OBJECTIVE: To identify the specific factors associated with invasive intraductal papillary mucinous neoplasms for branch duct, main duct, and mixed type carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 286 consecutive patients who underwent surgical resection for intraductal papillary mucinous neoplasm from July 1999 to December 2015 at a tertiary institute. We compared clinical features between 96 patients (33.6%) with invasive intraductal papillary mucinous carcinoma and 190 patients (66.4%) with noninvasive intraductal papillary mucinous neoplasm for each morphological type. MAIN OUTCOMES AND MEASURES: Factors associated with invasive intraductal papillary mucinous carcinoma. Mural nodule size was measured by endoscopic ultrasonography. RESULTS: Of the 286 patients included in the cohort, the median (range) age was 71 (28-86) years, and 162 (56.6%) were male. High mural nodule size was independently associated with invasive intraductal papillary mucinous carcinoma in all types (branch duct: odds ratio [OR], 1.992; 95% CI, 1.177-3.367; P = .01; main duct: OR, 1.443; 95% CI, 1.094-1.905; P = .01; and mixed: OR, 1.178; 95% CI, 1.057-1.312; P = .04). The cutoff values for intraductal papillary mucinous neoplasms, determined by a receiver operating characteristic, were 9 mm for branch duct and 6 mm for mixed and main duct carcinoma. A high carcinoembryonic antigen level in the pancreatic juice was independently associated with mixed (OR, 1.002; 95% CI, 1.000-1.003; P = .01) and main duct (OR, 1.002; 95% CI, 1.000-1.003; P = .048) carcinomas, and the cutoff values were determined to be 150 and 300 ng/mL, respectively (to convert to micrograms per liter, multiply by 1). In addition, both being female and having an elevated serum carbohydrate antigen 19-9 level were also found to be independently associated with mixed type invasive intraductal papillary mucinous carcinoma, and using any 2 among 4 identified factors yielded the highest accuracy (79.0%) for mixed type carcinomas. For all types, the accuracy for these factors was 86.0% for differentiating between invasive and noninvasive intraductal papillary mucinous neoplasms, which was superior to the accuracies using the “high-risk stigmata” factors or “worrisome features” suggested by the international consensus guideline in 2012 (66.1% and 39.9%, respectively). CONCLUSIONS AND RELEVANCE: The measurement of mural nodule size in all types of carcinomas and carcinoembryonic antigen level in the pancreatic juice in mixed and main duct carcinomas might play important roles in predicting invasive intraductal papillary mucinous carcinoma, but further large studies are needed to confirm these results.

Kuroda: Bristol Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Astra Zeneca: Research Funding; Janssen: Honoraria.