Molecular profile of apomucin and p53 protein as predictors of malignancy in intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND/AIMS: Invasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show poor prognosis similar to ductal adenocarcinomas. The aim of this study was to evaluate the molecular indicators of invasion and risk factors of recurrence of IPMNs. METHODOLOGY: For 46 curative resections of IPMNs, we analyzed the expression of apomucin antigens (MUC1, MUC2 and MUC5AC), p53 and Ki67 using resected specimens. RESULTS: All 46 IPMNs were classified into 4 groups; MUC1+/p53+, MUC1+/p53-, MUC2+ and MUC1-/MUC2-. The incidence of MUC1 expression increased according to the grade of dysplasia and all of 5 invasive carcinomas expressed MUC1. None of the invasive carcinoma, but almost half of IPMNs of non-invasive carcinoma and sever dysplasia expressed MUC2. Additionally, p53 expression was limited to invasive IPMNs and a non-invasive IPMN which recurred after the operation. The Ki67 labeling index was increased according to the grade of dysplasia and was highest in the MUC1+/p53+ group. In the MUC2+ cases, Ki67 labeling index was significantly higher than that in the MUC1-/MUC2- cases. MUC5AC was expressed in all IPMNs. CONCLUSIONS: The expression of MUC1, MUC2 and p53 might be indicators of malignancy and the expressions of MUC1 and p53 were the predictors of tumor invasion and recurrence.

Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial.

PURPOSE: Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. METHODS: Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. RESULTS: The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P<0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. CONCLUSION: Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Preoperative evaluation of malignancy in intraductal papillary mucinous neoplasms of the pancreas, especially in relation to dysplastic epithelial changes.

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms have a better prognosis than ductal adenocarcinomas of the pancreas. The aim of this study was to evaluate the malignant potential of IPMNs by their preoperative images. METHODOLOGY: Forty-three intraductal papillary mucinous neoplasms were divided into 3 duct ectatic types using preoperative images (the main duct type, the branch duct type, and the mixed type), and into 2 groups using resected specimens (the malignant group including severe dysplasia based on the WHO classification and the benign group). The diameters of the tumor, main pancreatic duct and mural nodule were measured on the images. RESULTS: Two thirds of main duct type cases were in the malignant group. For the branch duct and mixed types, the diameters of the tumor and detectable mural nodules were larger in the malignant group than in the benign group. A tumor diameter larger than 3.5cm and a mural nodule diameter larger than 6mm were risk factors for malignancy (p < 0.05). CONCLUSIONS: The main duct type, a tumor larger than 3.5cm of the branch duct or mixed type, and a mural nodule larger than 6mm were all indicators of malignancy risk.

Treatment results of radiotherapy for carcinoma of the cervical esophagus.

The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.

Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma.

PURPOSE: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer. PATIENTS AND METHODS: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. RESULTS: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. CONCLUSION: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.

Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary-mucinous tumors.

Pancreatic intraepithelial neoplasia (PanIN) is a recently proposed nomenclature for putative precursor lesions of pancreatic cancer, which are designated as PanIN-1 through -3 according to their increasing grade of dysplasia. A stepwise progression model of PanINs has been proposed, and multistep genetic alterations in PanINs are being investigated. PanIN-1A and PanIN-1B may remain unchanged for a long period. PanIN-3 potentially progresses toward invasive ductal carcinoma (IDC), and there are several case reports suggesting such progression. In these reported patients, PanIN-3 was found in specimens from partial pancreatectomies, and IDC manifested in the pancreatic remnant 17 months to 29 years after the surgery. We describe herein a patient with PanIN-3, in whom IDC manifested in the distal remnant pancreas 69 months after segmental pancreatectomy. Of the reported cases, including the present one, four of the patients were male and three were female, and the age at the first operation ranged from 46 to 70 years. Intraductal papillary-mucinous tumor (IPMT) is an entity that is distinct from PanIN. However, IPMTs of small size resemble PanINs morphologically. Loss of Dpc4 expression has been reported in the invasive component of IPMT, as well as in PanIN-3 and IDC. Analysis of mucin expression patterns has been reported, suggesting that, in practice, MUC1-positive MUC2-negative IPMTs may not be distinguishable from PanINs. There may be overlapping lesions between PanINs and IPMTs. Should the paradigm of the ductal origin of IDC be accepted, PanINs and a fraction of IPMTs would represent precursors of IDC.