Reduced pancreatic parenchymal thickness indicates exocrine pancreatic insufficiency after pancreatoduodenectomy.

BACKGROUND: The aim of this study was to investigate whether perioperative morphologic characteristics are predictive of exocrine pancreatic function after pylorus-preserving pancreatoduodenectomy (PPPD) with pancreaticogastrostomy. MATERIALS AND METHODS: A 13C-labeled mixed triglyceride breath test was performed in 52 patients after PPPD to assess postoperative exocrine pancreatic function. A value of percent 13CO2 cumulative dose at 7 h (%CD-7 h) of less than 5% was considered diagnostic of exocrine pancreatic insufficiency. Pre- and postoperative pancreatic parenchymal thicknesses were calculated using computed tomography (CT) scans, and compared by means of receiver operating characteristic (ROC) analysis. RESULTS: Thirty-four (65.4%) of 52 patients were found to have exocrine pancreatic insufficiency based on the breath test. With ROC analysis for identification of exocrine pancreatic insufficiency, the areas under the ROC curve for the postoperative pancreatic parenchymal thickness were higher than those for the preoperative pancreatic parenchymal thickness (0.904 and 0.702, respectively, P=0.009). When the cut-off value of the postoperative pancreatic parenchymal thickness was set at 13.0 mm, the sensitivity and specificity for identifying exocrine pancreatic insufficiency were 88.2% and 88.9%, respectively. CONCLUSION: Reduced postoperative pancreatic parenchymal thickness is a reliable indicator of exocrine pancreatic insufficiency after PPPD.

Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most deadly cancers, and serum carbohydrate antigen 19-9 (CA19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The purpose of this study was to determine which prognostic factor (preoperative or postoperative serum CA19-9 level) is more useful. METHODS: Pre- and postoperative serum CA19-9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009, and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods. RESULTS: In univariate analysis, tumor location (P = 0.019), postoperative adjuvant chemotherapy (P < 0.001), residual tumor factor status (P < 0.001), UICC pT stage (P = 0.004), lymph node metastasis (P = 0.015), and UICC final stage (P = 0.015) were significantly associated with overall survival. Differences in overall survival were significant between groups divided on the basis of four postoperative CA19-9 cutoff values (37, 100, 200, and 500 U/ml) but not significant between groups divided on the basis of the same four preoperative CA19-9 cutoff values. Pre- to postoperative increase in CA19-9 level also was significantly associated with poor prognosis. In multivariate analysis, postoperative adjuvant chemotherapy (hazard ratio, 1.59; P = 0.004) and postoperative CA19-9 cutoff value of 37 U/ml (HR, 1.64; P = 0.004) remained independent predictors of prognosis. CONCLUSIONS: Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level.

Middle pancreatectomy with pancreaticogastrostomy: a technique, operative outcomes, and long-term pancreatic function.

BACKGROUND AND OBJECTIVES: Middle pancreatectomy is infrequently performed in selected patients. The rationale is to preserve pancreatic function. This study evaluates a technique, operative outcomes, and long-term exocrine and endocrine pancreatic function of the middle pancreatectomy procedure. METHODS: Nineteen patients who underwent middle pancreatectomy between 1996 and 2008 were reviewed. Indications included eight intraductal papillary-mucinous neoplasms, five endocrine tumors, one serous and two mucinous cystadenomas, and three other benign lesions. Reconstruction of the distal pancreatic remnant was performed with pancreaticogastrostomy using the duct-to-mucosa method in 16 patients and with Roux-en-Y end-to-end pancreaticojejunostomy in 3 patients. RESULTS: Median operative time was 215 min. Perioperative mortality was nil. Morbidity was 53%, including 9 (47%) pancreatic fistulas. One patient with hemorrhage, complicated by a pancreatic fistula was successfully treated by endovascular embolization. No patients required postsurgical reoperation. Only one patient had clinical exocrine insufficiency requiring pancreatic enzyme supplementation. None developed postresection new-onset insulin-dependent diabetes. CONCLUSIONS: Middle pancreatectomy with pancreaticogastrostomy is feasible and reasonable technique. Although the incidence of pancreatic fistula formation may still be higher compared to conventional resection, long-term exocrine, and endocrine pancreatic function may be preserved. Thus, careful patient selection and experienced pancreatic surgeons in high-volume centers are of great importance.

Hepatic angiomyolipoma: a case report.

We experienced a rare case of hepatic angiomyolipoma (AML). A 66-year old Japanese female presented inhomogeneous echogenic lesion in the lateral segment of the liver on ultrasonography. Contrast computed tomography (CT) revealed early arterial enhancement within the lesion that stayed hyperdense in the equilibrium phase. Magnetic resonance imaging (MRI) demonstrated a non-homogeneous and partially high intensity mass on both T1- and T2-weighted images. Selective hepatic digital subtraction angiography (DSA) showed the lesion to be inhomogeneously hypervascular, supplied via branches of the left hepatic artery. The patient underwent elective left hemihepatectomy. Microscopic findings demonstrated that the tumor was composed of fat cells, blood vessels, and smooth muscle cells. Most of the spindle cells were immunoreactive to homatropine methylbromide 45 (HMB-45), alpha-smooth muscle actin and Melan-A/MART-1. Morphological pattern and immunophenotype were consistent with hepatic angiomyolipoma.

Adjuvant gemcitabine plus S-1 chemotherapy improves survival after aggressive surgical resection for advanced biliary carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine plus S-1 chemotherapy after aggressive surgical resection for advanced biliary carcinoma. SUMMARY BACKGROUND DATA: No effective adjuvant therapy for advanced biliary carcinoma has been reported although its prognosis is extremely poor. METHODS: Medical records were reviewed for 103 patients with International Union Against Cancer (UICC) stage II biliary carcinoma who underwent aggressive surgical resection. About 50 patients received 10 cycles of adjuvant gemcitabine plus S-1 chemotherapy and 53 patients did not. Clinicopathological factors and patient survival were compared between the 2 groups using univariate and multivariate analysis. A cycle of chemotherapy consisted of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 50 mg/m(2) for 7 consecutive days, followed by a 1-week break from chemotherapy. RESULTS: Patient demographics, tumor characteristics, and surgical procedures did not differ between the 2 groups. Aggressive surgical procedures including major hepatectomy or pancreatoduodenectomy were performed for 94 of 103 patients. In the chemotherapy group, 37 patients (74%) were given the full number of 10 cycles. The use of postoperative adjuvant chemotherapy (P < 0.001) and surgical margin status (P = 0.003) were independently associated with long-term survival by multivariate analysis. Five-year survival rates of patients who did or did not receive postoperative adjuvant chemotherapy were 57% and 24%, respectively (P < 0.001). Toxicity during chemotherapy was mild. CONCLUSIONS: Adjuvant gemcitabine plus S-1 chemotherapy may be one of several factors contributing to improved outcomes after aggressive surgical resection of advanced biliary carcinoma in recent years.

Invasive intraductal papillary-mucinous neoplasm of the pancreas: comparison with pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the clinicopathological differences between patients with invasive intraductal papillary-mucinous neoplasm (IPMN) of the pancreas and pancreatic ductal adenocarcinoma. METHODS: The medical records of 16 patients with invasive IPMN and 106 patients with pancreatic ductal adenocarcinoma, who underwent surgical resection, were retrospectively reviewed, and the clinicopathological factors and survival were compared between the two groups. RESULTS: The presence of retroperitoneal tissue invasion, portal or splenic vein invasion, nodal involvement, and positive surgical margins were significantly lower in patients with invasive IPMN than in those with ductal adenocarcinoma (P < 0.05). The actuarial 5-year overall survival rates in patients with invasive IPMN and ductal carcinoma were 40% and 18%, respectively (P = 0.008). However, the actuarial 5-year survival rate of patients with invasive IPMN was only 27% for UICC stage II disease, although this was significantly higher than that of patients with UICC stage II ductal adenocarcinoma (P = 0.049). CONCLUSIONS: Invasive IPMN has a favorable prognosis compared with pancreatic ductal adenocarcinoma that is likely due to the less aggressive nature of the disease. However, the prognosis for cases of advanced invasive IPMN is not always favorable despite complete tumor resection.

Analysis of fat digestive and absorptive function after subtotal gastrectomy by a 13C-labeled mixed triglyceride breath test.

BACKGROUND/AIM: In the choice of reconstructions, digestive and absorptive disturbances, resulting in weight loss after subtotal gastrectomy, remain a problem. The aim of this study was to compare fat absorptive function after Billroth I (B-I) and Roux-en-Y (RY) reconstructions after subtotal gastrectomy for gastric cancer. METHODS: A (13)C-labeled mixed triglyceride breath test was performed in 31 patients after subtotal gastrectomy and in 15 healthy volunteers to assess fat digestive and absorptive function. Seventeen B-I reconstructions and 14 RY reconstructions were performed after subtotal gastrectomy. Fat digestive and absorptive function was determined by percent (13)CO(2) cumulative dose at 7 h. Relationship between fat absorptive function and perioperative factors were analyzed. RESULTS: Gender distribution, mean age, pathological staging, level of lymph node dissection, preservative procedure of the vagus nerve and mean follow-up period in the two surgical groups did not differ significantly. Only the type of reconstruction (p = 0.024) was associated with differences in fat digestive and absorptive function by univariate analysis: B-I reconstruction was superior to RY reconstruction. CONCLUSIONS: Fat digestive and absorptive function after B-I reconstruction was superior to that after RY reconstruction, probably because the B-I reconstruction was the procedure that permitted food passage through the duodenum.

Combination of polyglicolic acid felt and fibrin glue for prevention of pancreatic fistula following pancreaticoduodenectomy.

The most frequent cause of morbidity following pancreaticoduodenectomy is pancreatic fistula. An appropriate technique to minimize pancreatic fistula is very important. Polyglicolic acid felt combined with fibrin glue has been applied in other organ surgery with excellent results and without any notable adverse reactions. We herein describe a new technique for prevention of pancreatic fistula using the combination of polyglicolic acid felt and fibrin glue as an adjunct of pancreaticoenterostomy following pancreaticoduodenectomy. Polyglicolic acid felt combined with fibrin glue as an adjunct of pancreaticoenterostomy was applied prospectively to 25 consecutive patients undergoing pancreaticoduodenectomy. Drain amylase was measured daily after the surgery and the incidences of complications were recorded. Median drain amylase on day 1 after surgery was 745 IU/L, on day 2 it was 427 IU/L, on day 3 it was 97 IU/L, and on day 5 it was 38 IU/L. Three patients (12%) developed grade A pancreatic fistula. No grade B or C pancreatic fistula was observed. No re-do operations, no postoperative percutaneous drainage, and no surgical mortality occurred. The combination of polyglicolic acid felt and fibrin glue was extremely favorable for prevention of pancreatic fistula following pancreaticoduodenectomy.

Main pancreatic duct obstruction due to a small nonfunctioning endocrine tumor of the pancreas.

A 65-year-old Japanese male was referred to our hospital for evaluation of a main pancreatic duct obstruction. Two months previously, he had suffered an attack of acute pancreatitis that was resolved with conservative treatment. Dynamic contrast-enhanced study by multidetector row computed tomography revealed a well-enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main pancreatic duct in the body and tail. On endoscopic retrograde pancreatography, obstruction of the main pancreatic duct in the head of the pancreas was noted. Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main pancreatic duct dilatation. The patient underwent elective pylorus-preserving pancreaticoduodenectomy. Pathological examination revealed a well-differentiated endocrine tumor of the pancreas of uncertain behavior, 5 mm in size. Immunohistochemically, the tumor was diffusely positive for chromogranin A and synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it was negative for gastrin. The final diagnosis was main pancreatic duct obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the pancreas is important in the differential diagnosis of main pancreatic duct obstruction demonstrated by radiographic examinations.

Randomized clinical trial to assess the efficacy of ulinastatin for postoperative pancreatitis following pancreaticoduodenectomy.

BACKGROUND AND OBJECTIVES: Ulinastatin, an intrinsic trypsin inhibitor, has proved to be effective for the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography. The aim of this study was to assess the efficacy of ulinastatin for postoperative pancreatitis following pancreaticoduodenectomy in a randomized clinical trial. METHODS: Patients undergoing pancreaticoduodenectomy were randomized to receive perioperative ulinastatin or placebo. Levels of serum amylase, drain amylase, and urine trypsinogen-2 were measured. RESULTS: A total of 42 patients were enrolled (20 in the ulinastatin group, 20 in the placebo group, 2 excluded). Two patients in the ulinastatin group and nine patients in the placebo group developed hyperamylasemia (P = 0.013) No patient in the ulinastatin group and five patients in the placebo group developed pancreatitis (P = 0.016). One patient in the ulinastatin group and two patients in the placebo group developed grade A pancreatic fistula (P = 0.548). Serum amylase levels at 4 hr and postoperative days 1, 2, and 3, and drain amylase levels on days 2 and 3 were significantly lower in the ulinastatin group than in the placebo group. CONCLUSIONS: Prophylactic administration of ulinastatin reduced the levels of serum and drain amylase and the incidence of postoperative pancreatitis following pancreaticoduodenectomy.

Postoperative adjuvant chemotherapy improves survival after surgical resection for pancreatic carcinoma.

Pancreatic carcinoma is one of the most aggressive types of gastrointestinal malignancy, and its prognosis remains extremely dismal. The aim of this study was to identify useful prognostic factors for patients undergoing surgical resection for pancreatic carcinoma. Medical records of 89 patients with pancreatic carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival. There were no operative deaths. Overall 1-, 2-, and 5-year survival rates were 59, 28, and 7%, respectively (median survival time, 12.1 months). Univariate analysis revealed that postoperative adjuvant chemotherapy, portal vein invasion, lymph node metastasis, extrapancreatic nerve plexus invasion, surgical margin status, UICC pT factor, and UICC stage were significantly associated with long-term survival (P<0.01). Furthermore, use of postoperative adjuvant chemotherapy and absence of extrapancreatic nerve plexus invasion were found to be significant independent predictors of a favorable prognosis using a Cox proportional hazard regression model (P<0.05). These results suggest that postoperative adjuvant chemotherapy may improve survival after surgical resection for pancreatic carcinoma and that extrapancreatic nerve plexus invasion indicates a poor prognosis for long-term survival.

An antecolic Roux-en Y type reconstruction decreased delayed gastric emptying after pylorus-preserving pancreatoduodenectomy.

The aim of this study was to identify a preferable procedure reducing the incidence of delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PPPD). Data on 132 consecutive patients with pancreatobiliary disease, who underwent PPPD, were collected retrospectively. A retrocolic Billroth I type reconstruction (B-I group) and an antecolic Roux-en Y type reconstruction (R-Y group) were performed for 54 and 78 patients after PPPD, respectively. Clinical measures of DGE were compared between the two groups. The incidence of DGE was 81% in B-I group and 10% in R-Y group (P < 0.001). The type of reconstruction (P < 0.001), operative time (P = 0.016), and postoperative complications (P = 0.001) were significantly associated with DGE by univariate analysis. Only the type of reconstruction (P < 0.001) was identified as an independent factor, which was associated with DGE by multivariate analysis. An antecolic Roux-en Y type duodenojejunostomy could be a useful reconstruction method after PPPD to prevent the occurrence of DGE.

Telomere shortening and telomerase expression during multistage carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been increasingly identified as a precursor to infiltrating ductal adenocarcinoma. Telomerase activation in response to telomere crisis followed by telomere shortening is thought to be a crucial event in the development of most human cancers. The aim of this study was to determine when this event occurs in the context of histologically defined IPMN progression. We analyzed telomerase expression in 68 IPMN samples and assessed telomere length by quantitative fluorescence in situ hybridization in samples taken from 17 sequential IPMN patients that included 37 individual loci. Samples from pancreatic ductal adenocarcinomas (PDACs, n=15) and chronic pancreatitis patients (n=10) were also examined. Telomeres were significantly shortened in 36 (97.3%) of 37 IPMN loci, with average telomere length decreasing with IPMN progression. Notably, even adenoma IPMNs demonstrated a 50% reduction of telomere length in 7 of 14 foci examined. Marked telomere shortening was observed from the in situ IPMN carcinoma stage (P<0.001; vs borderline IPMNs) through the invasive stage, although telomerase had been activated, indicating that telomeres had shortened to a critical length by this histological grade. Up-regulated human telomerase reverse transcriptase expression was detectable and increased gradually with cancer development and was primarily observed at the borderline IPMN stage and then in more advanced histopathologies. Progressive telomere shortening predominantly occurs during early IPMNs carcinogenesis before telomerase activation and progression from borderline to carcinoma in situ IPMNs is the critical stage of IPMNs carcinogenesis at which telomere dysfunction occurs.

Predictive factors of malignant or invasive intraductal papillary-mucinous neoplasms of the pancreas.

The aim of this study was to identify useful preoperative diagnostic findings indicative of malignant or invasive intraductal papillary-mucinous neoplasms (IPMN) of the pancreas to determine an optimal operative procedure for IPMN. Sixty-two IPMNs, which consisted of 29 adenomas, 10 borderline tumors, 11 adenocarcinomas in situ, and invasive adenocarcinomas were reviewed from 1990 to 2003. Preoperative predictive factors of malignant or invasive IPMN were analyzed among 10 factors by univariate and multivariate analysis. Diameter of the main pancreatic duct (> or =6 mm) and cytological examination of the pancreatic juice (the presence of malignant cells) were identified as independent predictive factors of malignant IPMN, and only cytological examination of the pancreatic juice (the presence of malignant cells) was identified as an independent predictor of invasive IPMN by multivariate analysis (P < 0.05). There was no recurrent disease in patients with adenoma and adenocarcinoma in situ, whereas recurrences occurred in 6 of 12 patients with invasive IPMN. Patient survival in noninvasive IPMN was significantly (P = 0.018) better than that in invasive IPMN (The overall 5-year survival rates were 87.2% and 49.2%, respectively). These results might be useful for selecting an optimal surgical procedure for IPMN.

Intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms of the pancreas differentiated by ovarian-type stroma.

BACKGROUND: Intraductal papillary-mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) of the pancreas have similar clinicopathologic findings. This study was intended to clarify clinicopathologic characteristics in IPMNs and MCNs differentiated by ovarian-type stroma. METHODS: Medical records for 77 patients with pancreatic cystic neoplasms with mucin secretion were reviewed. Patients were divided into IPMN (n = 70) or MCN (n = 7) according to the presence of ovarian-type stroma, and clinicopathologic parameters were compared between groups. RESULTS: IPMNs consisted of 32 adenomas, 12 borderline neoplasms, 13 adenocarcinomas in situ, and 13 invasive adenocarcinomas; MCNs included 6 adenomas and 1 invasive adenocarcinoma. The mean age of IPMN patients (66 years) was significantly older than that of MCN patients (55 years). The male:female ratio in IPMN (53/17) was significantly greater (P < .001) than in MCN (0/7). The location of the pancreatic mass differed, with 76% 0f IPMNs occurring in the head, while 86% of MCNs occurred in the body or tail. Mass mean size was significantly smaller (28 mm vs 78 mm, P < .001), and mean diameter of the main pancreatic duct was larger (6.8 mm vs 3.1 mm, P < .001) in IPMN than in MCN. Patulous papilla was present in 44% (31/70) of IPMNs, but none was present in MCNs. Communication between the cyst and main pancreatic duct was more frequent in IPMNs (67/70) than in MCNs (1/7). Overall 5-year survival rates were 84% (IPMN) and 100% (MCN). CONCLUSIONS: Clinicopathologic differences between IPMN and MCN are much clearer when differentiated by presence of ovarian-type stroma. Favorable prognosis for both neoplasms is offered by complete resection.

Relapsing acute pancreatitis due to ampullary adenoma in a patient with familial adenomatous polyposis.

A patient with familial adenomatous polyposis (FAP) presented with a relapsing attack of acute pancreatitis. Evaluation using computed tomography, ultrasonography, and duodenoscopy revealed an ampullary adenoma, which was classified as Spigelman's stage III according to Spigelman's criteria. The patient underwent a pylorus-resected pancreatoduodenectomy, and has had no abdominal pain suggesting acute pancreatitis for 1 year after surgery. Only a few reports of acute pancreatitis due to ampullary neoplasms in patients with FAP are available. Relapsing acute pancreatitis is another surgical indication for premalignant periampullary neoplasms in FAP.

[A case of recurrent esophageal cancer responding to second-line chemotherapy of TS-1/docetaxel combination].

A 70-year-old man suffering from advanced esophageal cancer (Stage II) underwent subtotal esophagectomy in December 2000. He then had postoperative chemotherapy, called low-dose FP, and was followed in an ambulatory setting. In December 2003, he was diagnosed as a recurrence of esophageal cancer with multiple liver metastases and upper mediastinum lymph node, so he was treated by combined chemotherapy consisting of TS-1 and docetaxel as a second-line chemotherapy. After 3 courses of this therapy, CT scan showed that the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. PR continued for about 6 months. This chemotherapy made it possible to treat liver and lymph node metastasis in an ambulatory setting. It is conceivable that this combination chemotherapy might be a promising regimen for a short period.

Duodenal cancer arising from the remaining duodenum after pylorus-preserving pancreatoduodenectomy for ampullary cancer in familial adenomatous polyposis.

We herein report a rare occurrence of duodenal cancer arising from the remaining duodenum after pylorus-preserving pancreatoduodenectomy for ampullary cancer in familial adenomatous polyposis (FAP). In this patient, proctocolectomy and ileoanal anastomosis for FAP had been performed 11 years earlier. During the current admission, the patient was diagnosed with adenocarcinoma in the Vater's ampulla using imaging and pathological examinations. In addition, a pylorus-preserving pancreatoduodenectomy was performed. The tumor was a well-differentiated tubular adenocarcinoma and no other polyps were identified in the duodenum by pathological examination. However, 1 year after surgery, a polypoid lesion measuring 15 x 15 mm was indicated in the remaining duodenum by endoscopic surveillance. This lesion was completely resected by endoscopic mucosal resection and the resected specimen revealed well-differentiated tubular adenocarcinoma in an adenomatous lesion. This report suggests that resection of the total duodenum is essential for duodenal neoplasms in FAP to prevent a recurrence in the remaining duodenum.

Attenuation of telomerase activity by hammerhead ribozymes targeting human telomerase RNA and telomerase reverse transcriptase in pancreatic carcinoma cells.

In cancer gene therapies, it is ideal to target tumor-specific genes. Since telomerase is activated in almost all cancer cells but not most somatic cells, it is considered as one of the favorite targets for cancer gene therapies. Ribozymes are catalytic RNA molecules with site-specific endoribonuclease activity. In the present study, we designed hammerhead ribozymes against human telomerase RNA (hTR) and human reverse transcriptase subunit (hTERT) to evaluate their effect on the attenuation of telomerase in the pancreas cancer cell line, PK-8. Hammerhead ribozyme targeting hTR depressed the level of telomerase activity in PK-8 cells. pRc-hTR vector with ribozyme targeting hTR and pRc-hTERT vector with ribozyme targeting hTERT mRNA were transfected into PK-8 cells and depressed telomerase activity and target RNA, but in pRc-hTR transfectant, hTERT mRNA expression was slightly upregulated and in pRc-hTERT transfectant hTR expression was also slightly upregulated. These findings indicate the co-regulation of hTR and hTERT mRNA expression in cancer cells. Extrachromosomal replicational vector, pCEP4, containing ribozyme targeting hTERT mRNA showed the most effective inhibition of telomerase activity, suggesting that the continuous effect of ribozyme is necessary to inhibit telomerase activity. Since the level of hTERT mRNA expression is less than that of hTR expression in cancer cells, ribozyme targeting hTERT mRNA might be a more useful therapeutic strategy for cancer gene therapy. Moreover, the co-regulation of hTR and hTERT mRNA expression in cancer cells to maintain the levels of telomerase activity suggested that the strategy of inhibiting hTERT mRNA and hTR simultaneously has a powerful potential as a gene therapy for targeting human telomerase.

Pancreatic metastasis of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare skin tumor that is considered to have intermediate malignancy; it demonstrates frequent local recurrence, but systemic metastasis is rare. We report a 49-year-old woman with pancreatic metastasis of DFSP who underwent total pancreatectomy with partial resection of the portal vein. Except for our patient, only two other cases of pancreatic metastasis of DFSP have been reported in the literature, to our knowledge. Radical resection may be considered for pancreatic metastasis of DFSP when there are no other metastatic lesions.