The International Consensus Guidelines for the Management of Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms have given us a classification scheme, diagnostic criteria, and treatment strategies of the IPMN at present. However, there remain several problems to be clarified further. These include, for instance : 1) How should we manage the mixed type of IPMN, as the branch duct type or main duct type? 2) Should an adenoma of IPMN be resected or followed up? 3) Is the definitive preoperative diagnosis of malignancy possible or not? 4) How can we determine the proper site of resection of main duct or mixed type IPMN? Japanese investigators are expected to solve these problems by meticulous and careful studies of their patients.

View full abstract

We report the strategy for treatment of main duct intraductal papillary-mucinous neoplasms (IPMN) of the pancreas based on our experience of 70 patients with IPMN and international consensus guidelines. The proportion of malignant IPMN in the main duct IPMN was significantly (p < 0.01) higher than in the branch duct IPMN. A positive preoperative cytological examination of pancreatic juice and the presence of jaundice were useful markers for the diagnosis of malignant and invasive IPMN, respectively. However, imaging examination could not definitely distinguish benign from malignant IPMN or non-invasive from invasive IPMN. All main duct IPMNs should be resected because of high frequency of malignancy in the main duct IPMN and the difficulty of preoperative differentiation between benign and malignant IPMN. Pancreatectomy with lymph node dissection, rather than pancreatectomy alone, is recommended for main duct IPMN because it is difficult to differentiate between non-invasive and invasive IPMN preoperatively and the frequency of extrapancreatic invasion, including lymph node metastasis, is high in invasive IPMN. Frozen section of the surgical pancreatic margin is mandatory in the intraoperative management of main duct IPMN. If invasive carcinoma, carcinoma in situ and PanIN 3 are detected at the surgical margin, further resection is recommended.

View full abstract

Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas can be divided into two distinct clinical subtypes ; main duct type and branch duct type. Each subtype of IPMNs should be treated adequately because the branch type IPMN has less malignant potential than the main duct type. Preoperative differentiation between malignant and benign branch type IPMNs requires conventional imaging studies, which allow prediction of malignancy based on tumor diameter, mural nodules and main pancreatic duct diameter, as well as cytological examination of the pancreatic juice. Prognostic factors of branch type IPMN include malignant potential of IPMNs, concomitant pancreatic ductal carcinomas, extrapancreatic malignancies, recurrent IPMNs of the residual pancreas, development of diabetes and underlying diseases. The proposed International Consensus Guideline for Management of IPMN and MCN of the pancreas (Tanaka M, et al. Pancreatology 2006 ; 6 : 17-32.) should standardize the treatment of IPMNs in the near future. Any treatment strategy for branch type IPMNs should take into consideration the general condition of the patient, prognosis of underlying diseases, possible concomitant pancreatic or extrapancreatic carcinoma, and endocrine/exocrine pancreatic function, in addition to the status of the pancreas.

View full abstract

Intraductal papillary mucinous neoplasms (IPMNs) are of various histological types, ranging form benign adenomas to invasive carcinoma. It is well known that the majority of branch duct IPMNs are benign lesions. Although IPM carcinomas should be resected, it is often difficult to distinguish malignant IPMNs from benign ones preoperatively. Tumor size over 30 mm, presence of mural nodules, and dilatation of the main pancreatic duct are significant predictors of malignancy in branch duct IPMNs. Patients with IPMNs have a favorable outcome and a variety of limited pancreatectomies have been performed. Limited resection is effective for the preservation of exocrine and endocrine pancreatic function, although postoperative complications including pancreatic leakage occurs in some patients.

View full abstract

Our strategy of surgical treatment of multiple IPMNs includes only borderline lesions (moderate dysplasia) or malignant ones, while the remaining tumors are observed closely without any surgical interventions as long as possible. Multiple non-invasive and benign tumors should be excised with combinations of some minimized surgical procedures. In such procedures, it is important to achieve complete resection of the tumor. A limited indication of total pancreatectomy remains for patients with apparently diffuse IPMNs because of the compromised postoperative insulin management and deterioration of quality of life. The utilization of intra-operative ultrasound with precise preoperative information about the tumor enhances a complete resection of tumor. Reconstruction of the pancreatic duct must be performed in pancreaticogastrostomy, which could allow the use of endoscopic investigations for recurrent or new IPMNs.

View full abstract

IPMNs are less invasive than main duct IPMNs, and in many of the cases, they do not progress even over a long period of time. For this reason, treatment for branch duct IPMNs is either surgery or follow-up observation. The decision to resect or not is based on imaging findings such as the status of elevated mural nodules, and the diameters of the main pancreatic duct and dilated branch duct. According to the International Consensus Guidelines, the diameter of the dilated branch duct is the most important, followed by the presence of mural nodules and dilation of the main pancreatic duct, as indicators of malignancy. In Japan, on the other hand, the majority considers the height of mural nodules the most important, followed by dilation of the main pancreatic duct. Regarding decision for treatment or follow-up, evaluations of both the pancreatic duct and elevation of mural nodules are necessary ; for the former, US, CT and MRCP should be used, and for the latter, EUS is indispensable. It is noted recently that IPMN is often accompanied by common type pancreatic cancer. For this reason, it is essential to examine the entire pancreas at follow-up visits. Furthermore, regular whole-body examination is also important since distant metastases are frequent in IPMN patients.

View full abstract

Surveillance of IPMN is quite controversial. IPMN is a slow-growing tumor and non-neoplastic lesions (hyperplasia) sometimes show clinical manifestations similar to those of adenoma or adenocarcinoma. IPMN frequently develops in the elderly. When surgical treatment is indicated, such an invasive procedure as pancreaticoduodenectomy or total pancreatectomy is often required. Furthermore, an increase in the prevalence of comorbid diseases and a decrease in tolerability for surgery with aging are also problematic. In branch duct IPMN, patients having cysts with smooth walls and containing thin septum-like structures do not have to undergo frequent follow-up examinations. Those with papillary protrusions less than 5 mm in height can be followed up, while in cases with protrusions greater than that, surgery is recommended. Association of dilation of the main pancreatic duct is regarded as an indicator of malignancy. Recently, several papers have reported synchronous or heterochronous development of common-type duct cell adenocarcinoma of the pancreas in patients with IPMN. Therefore, it is necessary to assess the entire pancreas at the time of follow-up. In addition, the prevalence of malignancies of other organs is also high in IPMN patients. These issues should be taken into account when planning a surveillance program for IPMN patients.

View full abstract

A total of 217 patients who underwent pancreatectomy for intraductal papillary mucinous neoplasm (IPMN) were investigated to evaluate the method of follow-up after surgical resection. The 5-year survival rate was 39% in patients with invasive IPMN. Liver metastasis and peritoneal dissemination were often recognized as the mode of tumor recurrence. Five patients (2.3%) underwent pancreatectomy again for a metachronous multifocal IPMN lesion in the remaining pancreas and 4 of these had a main duct IPMN. Furthermore, 32 patients (15%) had other malignant tumors in addition to synchronous or metachronous IPMN. We consider a close follow-up after surgical resection for IPMN is important, with special attention to tumor recurrence, especially invasive IPMN, metachronous multifocal IPMN in the remnant pancreas, and possible other malignant tumors associated with synchronous or metachronous IPMN.

View full abstract

The patient was a 62-year-old man with multiple lung metastases appearing thirteen months after pancreaticoduodenectomy for pancreatic head cancer. Administration of gemcitabine hydrochloride was started at a dose of 1000mg/m² with a cycle consisting of three continuous weeks of infusion followed by one week of rest. We found little toxicity to the gastrointestinal tract and finding on hematologic examination were good. Therefore, chemotherapy was carried out in an outpatient setting from the second cycle. The effect of chemotherapy was evaluated as NC (no change) by CT imaging technique after two cycles. Thus, the dose of gemcitabine was decreased to 700mg/m² from the third cycle with an aim of conserving QOL during prolonged administration. Few side effects were observed, and the chemotherapy could be continued for fourteen months in an outpatient setting without change in the disease state until the appearance of carcinomatous thoracic fluid retention. Though the prognosis of lung metastases after pancreatectomy is very poor, some patients can become long-term survivers by administration of gemcitabine, while maintaining QOL in an outpatient setting.

View full abstract

A 51-year-old man was admitted to our hospital for treatment of advanced pancreatic carcinoma. During surgery, several small liver metastases were discovered, and intraoperative electron beam irradiation (20 Gy) was performed for the main tumor with microwave coagulation carried out for the metastatatic sites. Postoperatively, the patient received gemcitabine 800 mg as a 10 mg/m²/min infusion followed by oxaliplatin 100 mg as a 1-hour infusion every 2 weeks. As the incidence of neurosensory disorders such as paresthesia of the lip or extremities increased with the number of courses administered, the gemcitabine-oxaliplatin regimen (GemOx) had to be stopped after ten courses. Neither nephrotoxicity nor hematologic toxicity was observed. The outpatient GemOx regimen was well tolerated by the patient. We believe that this case report demonstrates both the potential efficacy and side effects of GemOx for treatment of pancreatic carcinoma.

View full abstract