Influence of microscopically positive resection margins on long-term (>5-year) survival after resection of pancreatic ductal adenocarcinoma.

CONTEXT: The impact of R1 resection on outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear, with most studies assessing survival for up to 5 years. OBJECTIVE: The aim of this study was to evaluate the prognostic influence of R1 and R0 resection on >5-year survival in patients with PDAC. MATERIAL AND METHODS: Of the 271 patients with PDAC who underwent pancreatic resection over a 26-year period, 33 had survived for ≥5 years. R1 status was defined as the presence of tumor tissue ≤1 mm from a circumferential margin surface. Patients were followed-up for 61 to 288 months. RESULTS: Of the 33 long-term survivors, 19 and 14 underwent R0 and R1 resection, respectively. The percentage of male patients was significantly higher in the R1 than in the R0 group. The R0 group tended to show a weaker relationship between R status and stage than the R1 group. Multivariate analysis showed that R status was an independent prognostic marker (P=0.0071), and Kaplan-Meier curves showed that >5-year survivors in the R1 group had significantly poorer prognoses (P=0.002). CONCLUSIONS: Patients who have survived >5 years following R1 resection for PDAC can experience tumor recurrence in the resected area.

Knowledge discovery for pancreatic cancer using inductive logic programming.

Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

Long-term outcomes after endoscopic sphincterotomy versus endoscopic papillary balloon dilation for bile duct stones.

OBJECTIVE: Endoscopic sphincterotomy (ES) is a well-established standard method for treating common bile duct stones. However, biliary sphincter function is impaired after the treatment, and this may influence the long-term outcomes. In this study, we aimed to compare the long-term outcomes after ES with those after endoscopic papillary balloon dilation (EPBD) because the latter procedure is expected to preserve biliary sphincter function better than ES. DESIGN: A prospective follow-up of the original cohort in a previously randomized, controlled trial to compare the early outcomes after ES and EPBD. SETTING: Eleven centers, including 6 clinical practices and 5 academic institutions. PATIENTS: A total of 282 patients with common bile duct stones were randomly selected to undergo ES (n = 144) or EPBD (n = 138) in the previous study. INTERVENTIONS: ES or EPBD. MAIN OUTCOME MEASUREMENTS: Complications after ES or EPBD occurring during long-term follow-up. RESULTS: The patients were followed up annually after the treatment. The median duration of the follow-up was 6.7 years. Morbidity was observed in 36 (25.0%) and 14 (10.1%) of the patients who underwent ES and EPBD, respectively (P = .0016). Kaplan-Meier analysis revealed a significantly higher incidence of biliary complications in the ES group than in the EPBD group (P = .0011). Multivariate analysis showed that ES, periampullary diverticulum, and in situ gallbladder stones were independent risk factors for stone recurrence. CONCLUSIONS: During long-term follow-up, patients who underwent ES had significantly more biliary complications than those who underwent EPBD. The biliary sphincter dysfunction after ES results in additional late complications.

FU-MK-1 expression in human gallbladder carcinoma: an antigenic prediction marker for a better postsurgical prognosis.

Gallbladder carcinoma is an aggressive type of neoplasm difficult to cure by conventional procedures. Because of the lack of reliable markers for assessing the prognosis, this retrospective study was designed to investigate the prognostic significance of MK-1 overexpression in human carcinoma of the gallbladder. Immunohistochemical staining using monoclonal antibody FU-MK-1 (MK-1 antigen) was performed on paraffin-embedded tissues from 63 patients who had undergone surgical resection for gallbladder carcinoma. Expression of MK-1 was found in 50 (79%) of 63 tumor samples. All 21 papillary and 12 of 13 well-differentiated tubular adenocarcinomas but only 1 of 8 poorly differentiated adenocarcinomas were positive for FU-MK-1. Multivariate analysis showed that only MK-1 expression was an independent prognostic marker (P = .0473), and Kaplan-Meier curves showed that MK-1 expression was significantly related to increased overall survival (P < .0001). These results suggest that MK-1 expression is a prognostic marker in gallbladder carcinoma.

Diagnosis of small pancreatic cancer by endoscopic balloon-catheter spot pancreatography: an analysis of 29 patients.

OBJECTIVES: The diagnosis of small pancreatic cancer remains difficult. The present study describes the diagnostic value of endoscopic balloon-catheter spot pancreatography for small pancreatic cancer. METHODS: Since April 1984, balloon spot pancreatography has been used to detect small-sized pancreatic cancer in patients having possible symptoms or findings of obstructive pancreatitis. RESULTS: A resection was performed on 175 of 416 patients with conditions diagnosed as pancreatic cancer. Of the 175 patients, 23 (13%) had invasive carcinoma 2 cm or smaller based on histological measurements, 3 intraductal papillotubular adenocarcinoma, and 3 carcinoma in situ (CIS). Regarding invasive carcinoma, balloon pancreatography displayed duct abnormalities diagnosed as carcinoma in 20 of 22 patients, whereas carcinoma was suggested in 2. A definite diagnosis was obtained based on the findings of main duct stenosis or obstruction with marked stricture of the branch ducts (n = 18) and a filling defect in the main duct (n = 2). Moreover, this pancreatogram demonstrated an intraductal filling defect in 2 of 3 with intraductal carcinoma and dead twiglike findings in the branch ducts in 1 of 3 with CIS. CONCLUSIONS: Balloon spot pancreatography is an essential tool for the diagnosis of small ductal pancreatic cancer, and it also makes it possible to locate CIS lesions of the branch ducts.

An endoscopic sphincterotomy of the minor papilla in the management of symptomatic pancreas divisum.

BACKGROUND/AIMS: The efficacy of endoscopic treatment in pancreas divisum remains controversial. This study evaluated the results of an endoscopic sphincterotomy of the minor papilla and temporary transpapillary pancreatic stenting in patients with pancreas divisum. METHODOLOGY: Pancreas divisum was diagnosed in four patients between 1994 and 2004. All patients demonstrated episodes of recurrent upper abdominal and back pain were with a median follow-up period of 14.5 months. One patient was treated by a sphincterotomy of the minor papilla alone, while three others also underwent transpapillary pancreatic stent insertion for seven days. RESULTS: A Sphincterotomy of the minor papilla could be successfully achieved in all patients. There was no instance of bleeding, perforation or sepsis after the procedure. The postoperative serum amylase level in the patients without stent insertion (1352 IU/L) was higher than that the patients with stents (mean level 515 IU/L, range 358 to 680). The dilatated dorsal pancreatic ducts were found to improve after a sphincterotomy in all patients. None of the patients had any further episodes of pancreatitis. In addition, all patients demonstrated a considerable improvement in their upper abdominal or back pain symptoms, which did not require either analgesic medication or hospitalization. CONCLUSIONS: An endoscopic sphincterotomy and temporary transpapillary pancreatic stenting were therefore suggested to be a beneficial treatment modality for patients with pancreas divisum.

Balloon-catheter endoscopic retrograde pancreatography-compression study for diagnosis of early-stage pancreatitis.

Endoscopic retrograde pancreatography (ERP) is considered by many as the gold standard imaging method in the diagnosis of chronic pancreatitis (CP). However, conventional ERP usually has a limited ability to accurately diagnose early-stage CP, in which only the branch ducts are involved and the main pancreatic duct (MPD) is unaffected. To visualize precisely the branch ducts, we have developed a more sophisticated ERP method, called balloon ERP-compression study (balloon ERP-CS). In this procedure, a catheter equipped with a balloon at its tip is placed first into the MPD via the papilla with the aid of conventional ERP, followed by the removal of the endoscope, leaving the catheter behind. Then, the balloon is inflated, and the contrast medium is injected slowly. The balloon serves to block the back flow of the injected contrast medium from the MPD to the duodenum, enabling visualization of the branch ducts. The compression study affords further precise pancreatography of the corresponding area. Thus, balloon ERP-CS has now become an essential procedure for diagnosis of pancreatic lesions, including CP. So far (April 1984 to April 2005), we have performed the procedure in 1012 cases, for a total of 1562 examinations. In this study, we focus on the role of balloon ERP-CS in diagnosis of early-stage CP to elucidate its characteristic features in association with histological findings. This presentation will clarify the usefulness as well as the limitations of balloon ERP-CS for the diagnosis of CP, especially cases without the involvement of the MPD.

Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases.

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.

[Interventional treatment of biliary stricture].

Biliary stenting is a well-established intervention in pancreatic-biliary disease. Although interventional therapy is an excellent less-invasive method that can improve the quality of life of patients with stricture of the bile duct, inappropriate application can be harmful. The procedure includes the endoscopic as well as percutaneous transhepatic approach. The indications for each procedure depend upon the characteristics of the lesion, and technical feasibility must also be considered. Two types of prosthesis, the plastic tube stent (TS) and expandable metallic stent(EMS), are available. Since the former costs less and has the advantage of removability compared with the latter, it can be used in the treatment of benign strictures and for temporary stenting of resectable malignant strictures. However, the TS has a short patency period because it is likely to become occluded by clogging. In contrast, the EMS has a long patency period due to its large diameter, and multiple stents can be placed in hepatic hilar strictures. Tumor ingrowth is a major late complication of EMS. To maintain patency, other procedures such as radiation, microwave coagulation therapy, and hyperthermia can be considered in combination with EMS, which may contribute to further improvement in survival and quality of life in patients with unresectable malignant biliary strictures. Those procedures should not be performed in patients with benign biliary strictures since the EMS cannot be removed, and the long-term outcome after placement remains to be clarified.

Endoscopic sphincterotomy and endoscopic papillary balloon dilatation for bile duct stones: A prospective randomized controlled multicenter trial.

BACKGROUND: Endoscopic papillary balloon dilatation may be an alternative to endoscopic sphincterotomy in the treatment of bile duct stones. However, there is a controversy as to the effectiveness and safety of endoscopic papillary balloon dilatation. METHODS: Two hundred eighty-two patients with bile duct stones were enrolled and randomized to an endoscopic sphincterotomy or endoscopic papillary balloon dilatation group. The success rate for duct clearance as well as the frequency and types of complications were evaluated prospectively. Endoscopic sphincterotomy was performed in a standard manner. Endoscopic papillary balloon dilatation was carried out with gradual inflation of a 4-, 6-, or 8-mm diameter balloon. RESULTS: Complete duct clearance was achieved in 100% in the endoscopic sphincterotomy group and 99.3% in the endoscopic papillary balloon dilatation group (not significant). Complications occurred in 11.8% of patients in the endoscopic sphincterotomy group and 14.5% of those in the endoscopic papillary balloon dilatation group (not significant). No complication was severe; there was no mortality. The frequency of acute pancreatitis was higher in the endoscopic papillary balloon dilatation group than the endoscopic sphincterotomy group (respectively, 10.9% vs. 2.8%; p < 0.045). Hemorrhage occurred only in the endoscopic sphincterotomy group. CONCLUSIONS: Endoscopic sphincterotomy and endoscopic papillary balloon dilatation were approximately equal in terms of successful clearance of bile duct stones. They were also similar with respect to overall complications. Endoscopic papillary balloon dilatation is an alternative to endoscopic sphincterotomy as a treatment of bile duct stones.

[Evaluation of diagnostic imagings of liver metastases].

With the advent of various therapeutic modalities for the management of metastatic liver tumor, the task of pretreatment imaging has become more demanding. US and CT are non-invasive, and the most widely used techniques for pretreatment imaging, but they are far from optimal. Recently, the most sensitive pretreatment imaging modality for the depiction of focal liver lesions is CT during arterial portography (CTAP); however, it is an invasive procedure with an established risk of false-positive results. CT and MRI are the sensitivities of these techniques have recently been improved with the development of multidetector CT, contrast agents for MRI that specifically accumulate in the liver, and other advances. Superparamagnetic iron oxide (Feridex) has been developed as a liver-specific particulate MRI contrast agent that is taken up by the Kupffer cells of the liver. Rational selection of appropriate modalities for a given purpose requires familiarity with the characteristics of each modality. The aim of the present study was to evaluate the sensitivities of diagnostic modalities in the pre- and post-treatment periods of metastatic liver tumor. Feridex-enhanced MRI (Ferumoxide MRI) is more sensitive than enhanced CT and MRI in the depiction of metastatic liver tumor. In terms of the ability to visualize residual tumor after MCT, dynamic MRI was superior to enhanced CT and Ferumoxide MRI. In conclusion, combined Ferumoxide MRI and dynamic MRI is a noninvasive method and clinically useful since it can change the therapeutic approach.