Validation of Group B Borderline Resectable Pancreatic Cancer: Retrospective Analysis

BACKGROUND/AIMS: Among borderline resectable pancreatic cancer (BRPC), group B BRPC patients have findings that are suggestive but not diagnostic of metastasis. In this study, we attempted to validate whether group B could truly be categorized as a borderline resectable group. METHODS: We placed the BRPC patients into group A or group B. The survival outcomes were compared between the groups. RESULTS: A total of 53 patients with pancreatic adenocarcinoma was classified as either group A or B borderline resectable. In group A, 23 (60.5%) of 38 patients underwent pancreatectomy after concurrent chemoradiotherapy or chemotherapy, but in group B, only five (33.3%) of 15 patients underwent pancreatectomy, mainly because of the progression of suspected distant metastasis. There was a significant difference in overall survival (OS) between group A and B patients (median OS, 21.2 months vs 10.2 months, respectively; p=0.007). Of the patients who underwent pancreatectomy, group B had a higher recurrence rate compared to group A (recurrence rate: 11 of 23 patients [47.8%] vs five of five patients [100%], respectively; p=0.033). CONCLUSIONS: This report is the first to validate the definition of BPRC. Group B had much worse outcomes, and whether group B BRPC can be categorized as BRPC together with group A is questionable.

Prognostic Factors and Characteristics of Pancreatic Neuroendocrine Tumors: Single Center Experience

PURPOSE: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors. For PNETs, the predictive factors for survival and prognosis are not well known. The purpose of our study was to evaluate the predictive factors for survival and disease progression in PNETs. MATERIALS AND METHODS: We retrospectively analyzed 37 patients who were diagnosed with PNET at Severance Hospital between November 2005 and March 2010. Prognostic factors for survival and disease progression were evaluated using the Kaplan-Meier method. RESULTS: The mean age of the patients was 50.0+/-15.0 years. Eight cases (21.6%) were described as functioning tumors and 29 cases (78.4%) as non-functioning tumors. In univariate analysis of clinical factors, patients with liver metastasis (p=0.002), without resection of primary tumors (p=0.002), or American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage III/IV (p=0.002) were more likely to demonstrate shorter overall survival (OS). Patients with bile duct or pancreatic duct invasion (p=0.031), sized-lesions larger than 20 mm (p=0.036), liver metastasis (p=0.020), distant metastasis (p=0.005), lymph node metastasis (p=0.009) or without resection of primary tumors (p=0.020) were more likely to demonstrate shorter progression-free survival (PFS). In multivariate analysis of clinical factors, bile duct or pancreatic duct invasion [p=0.010, hazard ratio (HR)=95.046] and tumor location (non-head of pancreas) (p=0.036, HR=7.381) were confirmed as independent factors for predicting shorter PFS. CONCLUSION: Patients with liver metastasis or without resection of primary tumors were more likely to demonstrate shorter OS. Patients with bile duct or pancreatic duct invasion or tumors located at body or tail of pancreas were more likely to demonstrate shorter PFS.

Radiologic findings of Mirizzi syndrome with emphasis on MRI

We have reported a case of Mirizzi syndrome preoperatively diagnosed using MR cholangiopancreatography. MRCP and T2-weighted image using a single-shot fast spin-echo sequence accurately depicted all components of Mirizzi syndrome, including impacted stone in the neck of the gallbladder compressing the common hepatic duct and wall-thickening of the gallbladder without any evidence of malignancy. The combination of MRCP and T2-weighted image can be counted on to replace conventional modalities of diagnosing Mirizzi syndrome without any loss of diagnostic accuracy.

Diagnosis of Pancreatic Tumors: Comparison of MR Pancreatograp hy (MRP )and Endoscopic Retrograde Pancreatography(ERP)

PURPOSE: Magnetic resonance pancreatography(MRP) is a non-invasive imaging technique for visualization of the pancreatic duct system, and is similar to those obtained by means of endoscopic retrograde pancreatography (ERP). To determine the role of MRP in the diagnosis of pancreatic tumors, the diagnostic confidence and imaginal difference of MRP and ERP were compared. MATERIALS AND METHODS: Twenty patients (13 male and 7 female, mean age 59 years) with pancreatic tumors underwent MRP and ERP. The former involved the use of a single shot fast spinecho sequence on a 1.5T system. All images were retrospectively reviewed by a radiologist and a gastroenterologist, working together. Both MRP and ERP were compared for separate visualization of the head, body and tail portion of the pancreatic duct, and scored as excellent (4), good (3), fair (2), poor (1), or no visualization (0). In addition, the overall diagnostic confidence of both modalities was graded subjectively from non-diagnoses (0) to definite information (4). The final diagnoses derived from surgical findings (n=9) or imaging findings and clinical follow-up (n=7) were as follows : pancreatic cancer (n=12), mucin-producing pancreatic cancer (n=2), mucinous ductectatic tumor (n=4), serous cystadenoma (n=2). To assess the statistical significance of difference, the paired t-test was used. RESULTS: Mean scores of visualization of the pancreatic duct by MRP and ERP were 2.91 and 3.15 in the pancreatic head (p=NS), 3.11 and 2.18 in the pancreatic body (p=NS), and 3.07 and 1.09 in the pancreatic tail (p<0.01). The mean score of diagnostic confidence was 4.03 for MRP and 2.51 for ERP, a statistically significant difference (p <0.05). In 11 patients with obstruction of the pancreatic duct due to malignant lesions, MRP visualized the duct both proximally and distally to the site of obstruction, while ERP visualized only the distal duct to the site of obstruction. MRP was also better at defining the extent of tumor by visualization of surrounding pancreatic parenchyma. In two cases of serous cystadenoma with lack of communication between the pancreatic duct and cystic neoplasm, MRP depicted the lesion clearly whereas ERP showed no information. CONCLUSION: MRP is better than ERP at visualizing the of pancreatic duct proximal to obstruction, assessment of tumoral extent, and diagnosis of a cystic neoplasm which does not communicate with the pancreatic duct.

Utility of Single Shot Fast Spin Echo Technique in Evaluating Pancreaticobiliary Diseases : T 2 - weighted Image and Magnetic Resonance Cholangiopancreatography

PURPOSE: To evaluate the accuracy of T2-weighted imaging and MR cholangiopancreatography using the single shot fast spin-echo technique for evaluating pancreaticobiliary disease. MATERIALS AND METHODS: B e t ween March and July 1997, axial and coronal T2-weighted images ( T E : 8 0 -2 00 msec) and MR cholangiopancreatograms(TE:800 -1 2 00 msec) were obtained in two ways [single slab (thickness:30 -50 mm) and multislice acquisition under chemical fat saturation] using SSFSE pulse sequencing in 131 cases of suspected pancreati-cobiliary disease. The accuracy of SSFSE MR imaging was assessed in 89 lesions of 74 patients [male,48; female,26; age range, 3 0 -86 (mean,59)years] confirmed surgicopathologically(50 lesions in 39 patients) and clinically (39 lesions in 35 patients). Two radiologists reviewed the MR images and diagnosis was determined by consensus. RESULTS: Correct diagnosis was confirmed in 84 of 89 lesions (94 %). Seven lesions were falsely interpreted, false positive and false negative results accounting for two and five cases, respective l y. Two pancreatic cancers were misdiagnosed as pancreatitis and a cancer of the proximal common bile duct(CBD) was interpreted as a distal CBD cancer. The sensitivity of SSFSE MR imaging for malignancy was 93 %. One CBD stone revealed by endoscopic retrograde cholangiopancreatography (ERCP) was not detected on MR images. In contrast, a stone in the CBD seen on MR images was not apparent on subsequent ERC P. Sensitivity and specificity for calculous disease were 96 % and 99.7 %, respective l y. A benign stricture of the ampulla of Vater was falsely interpreted as normal, and correct diagnosis was possible in two falsely diagnosed cases when MR images were rev i ewed retrospectively. CONCLUSION: The combination of T2-weighted and cholangiographic images using SSFSE is an accurate method for diagnosing pancreaticobiliary diseases.

Accuracy of MR Imaging for Resectability of Extrahepatic Bile Duct Carcinoma

PURPOSE: To determine the accuracy of preoperative MR imaging for evaluation of resectability of extrahepaticbile duct carcinoma. MATERIALS AND METHODS: Thirty-four patients with proven extrahepatic bile duct carcinomaunderwent pre-operative MR imaging. All MR examinations were performed with a 1.5 T system, using a phased-arraymulticoil. Tumor resectability was prospectively determined by two radiologists who reached consensus. Tenpatients did not undergo surgery because the preoperative MR imaging, CT and endoscopic findings all indicatedunresectability. Twenty-five patients subsequently underwent surgical exploration, and their imaging andpathologic and laparotomic findings were compared. RESULTS: Twenty-two of 34 cases (65%) were resectable. Amongthe 22 cases resectable in laparotomy, pre-operative MR imaging had suggested that 20 were resectable, andsensitivity for resectability was thus 91%. Among the 22 cases in which MR imaging had suggested resectability,macroscopic clearance was complete in 20, giving a positive value of 91%. MR imaging underestimated portal venousor hepatic arterial invasion, and in one case missed small (<1 cm) hepatic metastases. In two cases, MR imagingoverestimated portal venous or hepatic arterial encasement. CONCLUSION: MR imaging is a useful diagnosticmodality for preoperative assessment of resectability of extrahepatic bile duct cancer.

Combined use of tamoxifen, cyclosporin A, and verapamil for modulating multidrug resistance in human hepatocellular carcinoma cell lines

The intensive use of chemotherapeutic agents for the treatment of cancer has resulted in the cure or improved survival of many patients. But unfortunately, many cancers including human hepatocellular carcinoma (HCC) don't respond to chemotherapy. One of the major mechanisms for the drug resistance in the HCC is an elevated MDR1 RNA expression which makes cells become multidrug resistant. To overcome the multidrug resistance (MDR) phenotype, a high dose of verapamil is required both clinically and experimentally. Accordingly we have examined the MDR modulating effects with combinations of tamoxifen, cyclosporin A, and verapamil in vitro with the physiologically achievable concentrations of each agent, i.e., 2.0 microM/L for tamoxifen, 1.6 microM/L for cyclosporin A, and 2.5 microM/L for verapamil respectively in HCC lines. As expected, verapamil alone with the physiologically achievable concentration at which we tested didn't enhance the doxorubicin cytotoxicity in the HCC lines. Furthermore, any verapamil combination with cyclosporin A or tamoxifen was not effective in overcoming the doxorubicin resistance in the high MDR1 expressor (Hep-G2) line. However tamoxifen reduced the IC50 of doxorubicin by a factor of 1.9 in the low MDR1 expressor (SK-Hep1) and 1.1 in the high MDR1 expressor line (p< 10(-5) respectively). Of interest, combinations of tamoxifen and cyclosporin A showed a significant reduction in the IC50 of doxorubicin in both HCC lines. The IC50 of doxorubicin was reduced by a factor of 3.9 and 1.3, i.e., from 0.023943 micrograms/ml to 0.006157 micrograms/ml (p< 10(-5)) in the SK-Hep1 cell line, and 0.068819 micrograms/ml to 0.052442 micrograms/ml (p< 10(-5)) in Hep-G2 respectively when tamoxifen and cyclosporin A were administered together. Both the estrogen and progesterone receptors in the SK-Hep1 and Hep-G2 lines were less than 0.01 fmol/mg of cytosol protein, respectively. It is therefore suggested that the reversal of doxorubicin resistance is unrelated to their anti-estrogenic activity in the HCC lines. Three modulator combinations of tamoxifen, cyclosporin A, and verapamil were not more effective than the combination of tamoxifen and cyclosporin A on the sensitivity to doxorubicin. MDR modulators of tamoxifen, cyclosporin A, and verapamil didn't reduce the IC50 of cisplatin to the clinically achievable concentration range in HCC lines. In summary, the combination of tamoxifen and cyclosporin A at the concentrations normally seen after clinical administration of these modulators showed significant synergism on the sensitivity to doxorubicin in both low and high MDR1 expressor HCC lines. These data indicate the need for in vivo trials.