Efficacy of early clip-with-line method for colorectal endoscopic submucosal dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) remains demanding due to technical difficulties and high risk of perforation. Most of the reported traction methods are initiated after creating a mucosal flap, which is time consuming. To obtain a good visualization at the mucosal incision stage, we developed the early clip-with-line (ECL) method. This method was started immediately after injection of sodium hyaluronate solution into the submucosal layer. In this study, we evaluated the efficacy and the safety of the ECL method for colorectal ESD. METHODS: We retrospectively analyzed all cases of colorectal ESDs (41 cases in total) performed from January 2017 to February 2019 in our institution. From January 2017 to August 2018, 27 of these cases were performed using conventional (non-ECL) ESDs, while from September 2018 onwards, the remaining 14 cases were performed using the ECL method. Retrospective comparison between the ECL group and the non-ECL group was conducted in terms of clinical characteristics, treatment outcomes, and adverse events. RESULTS: There were no significant differences in clinical characteristics between two groups. Procedure time (median [range]) was significantly shorter in the ECL group than in the non-ECL group (66 [29-131] min vs 90 [30-410] min; P = 0.03). As for adverse events, no case of perforation occurred in the ECL group, whereas perforation was observed in 7.4% (2/27) cases in the non-ECL group (no significant difference). CONCLUSION: Early clip-with-line method for colorectal endoscopic submucosal dissection reduced procedure time.

Prognostic relevance of apparent diffusion coefficient obtained by diffusion-weighted MRI in pancreatic cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is utilized as a method of oncologic imaging for predicting treatment outcomes. This study explored the role of DW-MRI in the treatment of patients with resected pancreatic cancer by comparing apparent diffusion coefficient (ADC) values with clinicopathological findings and survival rates. MATERIALS AND METHODS: Records of 54 patients in whom DW-MRI at 1.5T was performed (b values: 0 and 1000 mm(2) /s) before macroscopically curative resection were analyzed. ADC values were then calculated and compared with clinicopathological factors including age, gender, serum carcinoembryonic antigen levels, serum carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, differentiation, resectability, and pT stage. A survival analysis of clinicopathological factors and ADC values was performed using the Kaplan-Meier method, and the results were evaluated with the log-rank test. Prognostic significance was assessed using the Cox proportional hazard model. RESULTS: Significant associations were found between tumor differentiation and ADC values (P = 0.001). In a univariate analysis of overall survival, tumor differentiation (P = 0.037) and ADC values (P = 0.002) were identified as significant prognostic factors. However, age, gender, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, resectability, and pT stage were not associated with overall survival. In a multivariate analysis of overall survival, only ADC values were identified as significant prognostic factors (hazard ratio 2.293, 95% confidence interval 1.147-4.585, P = 0.019). CONCLUSION: ADC values were found to be associated with prognosis in patients with resected pancreatic cancer.

Factors affecting the accuracy of endoscopic transpapillary sampling methods for bile duct cancer.

BACKGROUND AND AIM: Various methods for endoscopic transpapillary sampling have been developed. However, the factors affecting the accuracy of these methods for bile duct cancer are unknown. The aim of the present study was to determine the factors affecting the accuracy of endoscopic transpapillary sampling methods. METHODS: We reviewed the results from 101 patients with bile duct cancer who underwent transpapillary sampling by aspiration bile cytology, brushing cytology, and fluoroscopic forceps biopsy. The final diagnosis of bile duct cancer was made on the basis of pathological evaluation of specimens obtained at surgery and the clinical course over at least 1 year in patients not operated on. We carried out subgroup analyses for the factors affecting the accuracy of each transpapillary sampling method. RESULTS: Aspiration bile cytology was carried out 238 times in 77 patients, brushing cytology was carried out 67 times in 60patients, and fluoroscopic forceps biopsy was carried out 64 times in 53 patients. Accuracies of aspiration bile cytology were significantly higher for longer (≥15 mm) biliary cancerous lesions than for shorter (<15 mm) lesions (30% vs 18%, respectively, P = 0.049). Accuracies of brushing cytology and fluoroscopic forceps biopsy were significantly higher for non-flat than for flat-type biliary cancerous lesions (brushing: 58% vs 38%, respectively, P = 0.032; forceps biopsy: 60% vs 33%, respectively, P = 0.043). CONCLUSION: Endoscopic transpapillary sampling methods are more accurate for longer or elevated (non-flat) biliary cancerous lesions than for shorter or flat lesions.

Duodenal tuberculosis with gastric outlet obstruction: a case report of successful diagnosis and treatment, with review of literature.

BACKGROUND: Duodenal tuberculosis (TB) is extremely rare, and its diagnosis is challenging owing to the lack of specific symptoms and radiological or endoscopic findings. When it leads to gastric outlet obstruction (GOO), diagnosing it accurately and providing appropriate treatment is crucial. However, this is often overlooked. CASE PRESENTATION: A 35-year-old man presented with abdominal pain, fullness, vomiting, and weight loss. Upper gastrointestinal endoscopy and radiography revealed nearly pinpoint stenosis with edematous and reddish mucosa in the D1/D2 portion of the duodenum. Computed tomography (CT) showed the duodenal wall thickening, luminal narrowing, multiple enlarged abdominal lymph nodes, and portal vein stenosis. Conventional mucosal biopsy during endoscopy revealed ulcer scars. We initially suspected stenosis due to peptic ulcers; however, chest CT revealed cavitary lesions in both lung apices, suggesting tuberculosis. Due to the suspicion of duodenal TB and the need to obtain deeper tissue samples, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. The tissue sample showed caseating granulomas with multinucleated giant cells, and acid-fast bacilli were positive by Ziehl-Neelsen staining. The patient was diagnosed with duodenal TB and subsequent GOO. Because the patient had difficulty eating, surgical intervention was prioritized over antitubercular drugs, and laparoscopic gastrojejunostomy was performed. The patient started an oral diet on the 3rd postoperative day and began antitubercular treatment immediately after discharge on the 11th day. During the 6th month of treatment, endoscopic examination revealed residual duodenal stenosis; however, the bypass route functioned well, and the patient remained asymptomatic. CONCLUSIONS: An aggressive biopsy should be performed to diagnose duodenal TB. EUS-FNA has proven to be a useful tool in this regard. Both nutritional improvement and antitubercular treatment were achieved early and reliably by performing laparoscopic gastrojejunostomy for duodenal TB with GOO.

Use of F-18 fluorodeoxyglucose positron emission tomography with dual-phase imaging to identify intraductal papillary mucinous neoplasm.

BACKGROUND & AIMS: We investigated the usefulness of dual-phase F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) to differentiate benign from malignant intraductal papillary mucinous neoplasms (IPMNs) and to evaluate branch-duct IPMNs. METHODS: We used FDG-PET/CT to evaluate IPMNs in 48 consecutive patients who underwent surgical resection from May 2004 to March 2012. IPMNs were classified as benign (n = 16) or malignant (n = 32) on the basis of histology analysis. The ability of FDG-PET/CT to identify branch-duct IPMNs was compared with that of the International Consensus Guidelines. RESULTS: The maximum standardized uptake value (SUVmax) was higher for early-phase malignant IPMNs than that for benign IPMNs (3.5 ± 2.2 vs 1.5 ± 0.4, P < .001). When the SUVmax cutoff value was set at 2.0, early-phase malignant IPMNs were identified with 88% sensitivity, specificity, and accuracy. The retention index values for malignant and benign IPMNs were 19.6 ± 17.8 and -2.6 ± 12.9, respectively. When the SUVmax cutoff was set to 2.0 and the retention index value to -10.0, early-phase malignant IPMNs were identified with 88% sensitivity, 94% specificity, and 90% accuracy. In identification of branch-duct IPMNs, when the SUVmax cutoff was set to 2.0, the sensitivity, specificity, and accuracy values were 79%, 92%, and 84%, respectively. By using a maximum main pancreatic duct diameter ≥7 mm, the Guidelines identified branch-duct IPMNs with greater specificity than FDG-PET/CT. The Guidelines criteria of maximum cyst size ≥30 mm and the presence of intramural nodules identified branch-duct IPMNs with almost equal sensitivity to FDG-PET/CT. CONCLUSIONS: Dual-phase FDG-PET/CT is useful for preoperative identification of malignant IPMN and for evaluating branch-duct IPMN.

Endoscopic sphincterotomy combined with large balloon dilation for removal of large bile duct stones.

BACKGROUND/AIMS: Recently, there have been sporadic reports of lithotomy using endoscopic sphincterotomy combined with large balloon dilation (EPLBD) against large or multiple bile duct stones. However, there are not many reports so far concerning this procedure. Therefore, we decided to discuss the results of EPLBD against large or multiple bile duct stones. METHODOLOGY: Stone retrieval using EPLBD was performed with 59 patients of choledocholithiasis, A) with 13 mm or more in shortest dimension, or B) multiple (≥3) bile duct stones, with the smallest more than 10 mm in shortest dimension. The papilla treated with endoscopic sphincterotomy (EST) was dilated using a 12-20 mm balloon suitable for the biliary ductal size. RESULTS: The success rate for the first lithotomy for choledocholithiasis was 83.1% (49/59). The final lithotomy rate was 100% (59/59). The time required for lithotomy was 43.7 (12-125) minutes and the number of treatment was 1.3 (1-4) on average. Lithotripsy was needed in 13.6% (8/59). The incidence of coincidental events associated with the procedure was 6.8% (4/59). No pancreatitis was noted. CONCLUSIONS: An endoscopic treatment using EST plus large balloon dilation against large or multiple bile duct stones was suggested to be safe and effective.

Current situation of endoscopic treatment for common bile duct stones.

BACKGROUND/AIMS: The progression of endoscopy and devices as well as newly developed treatment methods have enabled endoscopic lithotomy. In this study, we examined to what degree is it possible to endoscopically treat patients who are diagnosed as having common bile duct stones. METHODOLOGY: Lithotomy was conducted using a backward side-viewing endoscope for patients without surgical history of upper gastrointestinal tract and patients with stomach reconstructed with Billroth-I method, using an ordinary endoscope for patients with stomach reconstructed with Billroth-II method (Bil-II) and using a double balloon endoscope for patients with difficulty in reaching the papilla or patients of Roux-en-Y anastomosis (R-Y). As for treatment methods, we selected endoscopic sphincterotomy as the first choice for papilla treatment and selected endoscopic papillary balloon dilation for patients with bleeding tendency or patients of Bil-II or R-Y. For patients with multiple stones or giant stones, lithotripsy was selected depending on judgment of the endoscopist. RESULTS: Endoscopic complete lithotomy was successful in 97.7% (168/172). An accidental disease was observed in 2.9% (5/172). In one patient with the perforated gastrointestinal tract, a surgery was performed but others were mild. CONCLUSIONS: Common bile duct stones can be endoscopically treated safely with high rate.

A long-term controlled trial of endoscopic pancreatic stenting for treatment of main pancreatic duct stricture in chronic pancreatitis.

BACKGROUND/AIMS: Endoscopic pancreatic stenting (EPS) has been used to treat main pancreatic duct (MPD) stricture in chronic pancreatitis (CP), with favourable reported results. However, most studies were retrospective and uncontrolled. We conducted a longterm prospective controlled study of EPS for treatment of MPD stricture in CP. METHODOLOGY: Consecutive patients with CP were treated to remove pancreatic stones by extracorporeal shock-wave lithotripsy or endoscopic basket extraction. After treatment, 41 patients were enrolled in the study upon meeting the criteria of complete removal of stones, pain relief after the treatment, and dominant stricture of the MPD. Twenty patients chose EPS, while 22 control patients did not. We compared recurrence of pain and pancreatic function between groups for over 3 years of follow-up. RESULTS: The mean follow-up period was 62.5 ± 20.9 months. Pain recurred in 15% of EPS patients (3/20) and in 50.0% of control patients (11/22), a significant difference (p<0.05). Progression of exocrine insufficiency in the EPS group was significantly slower than in the control group (p<0.05), while endocrine function showed no difference between groups. CONCLUSIONS: EPS reduced pain recurrence and slowed down the progression of exocrine insufficiency in CP patients with MPD stricture.

Utility of placement of pancreatic duct spontaneous dislodgement stent for prevention of post-ERCP pancreatitis in patients with difficulty in selective biliary cannulation.

BACKGROUND/AIMS: To examine the utility of placement of pancreatic duct spontaneous dislodgement stents for prevention of post-ERCP pancreatitis in patients with difficulty in selective biliary cannulation. METHODOLOGY: The incidence of pancreatitis was compared between the group with P(+) pancreatic duct spontaneous dislodgement stent placed for prevention of post-ERCP pancreatitis and the group without P(-) in patients with difficulty in selective biliary cannulation. RESULTS: The final success rate of selective biliary cannulation was 94.45%. Post-ERCP pancreatitis was observed at 7.07%. The success rate of placement of pancreatic duct stent in the P(+) group was 99.0%. The incidence of pancreatitis in 99 patients in the P(+) group was 3.0%, that of abdominal pain was 3.0%, that of hyperamylasemia was 16.2%, and the mean post-ERCP amylase level was 353.031 +/- 520.792 IU/L. The incidence of pancreatitis in the P(-) group was 11.1%, that of abdominal pain was 20.2%, that of hyperamylasemia was 33.3%, and the mean post-ERCP amylase level was 541.204 +/- 771.843 IU/L. Comparing between the P(+) group and P(-) group, the incidence of pancreatitis, that of abdominal pain, that of hyperamylasemia and the mean post-ERCP amylase level were significantly decreased in the P(+) group (p<0.05). CONCLUSION: Placement of pancreatic duct spontaneous dislodgement stent in patients with difficulty in selective biliary cannulation could be useful for prevention of post-ERCP pancreatitis.

Transpancreatic precut papillotomy in patients with difficulty in selective biliary cannulation.

BACKGROUND/AIMS: Transpancreatic precut papillotomy (TPPP) is considered as an effective method in patients with difficulty in selective biliary cannulation. However, the use of placing a pancreatic duct stent as a measure against post-ERCP pancreatitis has not been clarified. Here we examine the methods of implementing TPPP safely. METHODOLOGY: TPPP was conducted on patients with difficulty in selective biliary cannulation. The incidence of pancreatitis was compared between group P(+) in which a spontaneous dislodgement type pancreatic duct stent was placed and group P(-) without a duct stent. RESULTS: The success rate of biliary cannulation was 83.3% at the first ERCP and finally 93.9%. Post-ERCP pancreatitis was observed in 9.09% of patients. The success rate of placement of pancreatic duct stent in the P(+) group was 100%. The incidence of pancreatitis in the P(+) group was 4.1% and the mean post-ERCP amylase level was 340.071 ±420.035IU/L. The incidence of pancreatitis in the P(-) group was 23.5% and the mean post-ERCP amylase level was 661.250±772.285IU/L. The incidence of pancreatitis and the mean post-ERCP amylase level were significantly lower in the P(+) group (p<0.05). CONCLUSIONS: In the patients with difficulty in selective biliary cannulation, TPPP is a useful technique for biliary cannulation. The placement of a spontaneous dislodgement type pancreatic duct stent after TPPP may be useful for prevention of post-ERCP pancreatitis.

Quantitative analysis of vascular endothelial growth factor in liver metastases from pancreatic carcinoma as a predictor of chemotherapeutic effect and prognosis.

PURPOSE: In pancreatic carcinoma, vascular endothelial growth factor (VEGF) expression at the primary site has been suggested to be a prognostic parameter. We quantitatively analyzed VEGF expression in liver metastases from pancreatic carcinoma and examined the correlation among VEGF expression in liver metastases, clinicopathologic factors, and clinical outcome. EXPERIMENTAL DESIGN: The subjects consisted of 23 patients with pancreatic adenocarcinoma who had liver metastases and were treated with S-1 and gemcitabine as the first-line treatment. VEGF expression was quantitated by enzyme immunoassay in biopsy specimens of liver metastases and nontumorous liver tissue, and in plasma. In 10 of the 23 patients, VEGF expression was also quantitated in biopsy specimens of the primary pancreatic tumor. All samples were collected before treatment. RESULTS: The VEGF level in nontumorous liver tissue was 36.6 +/- 10.0 pg/mg protein versus 376.8 +/- 106.1 pg/mg protein in liver metastases (P = 0.0016). Pretreatment VEGF levels in plasma and in primary pancreatic carcinoma did not correlate with VEGF levels in the corresponding liver metastases. The median VEGF level in liver metastases (138.9 pg/mg protein) was used as the cutoff value between high and low VEGF expression in liver metastases. Patients showing high VEGF expression had a significantly longer progression-free survival and overall survival than patients showing low VEGF expression in liver metastases (P = 0.0219 and P = 0.0074, respectively). CONCLUSIONS: Evaluation of VEGF levels in liver metastases might be useful in assessing the prognosis of patients with metastatic pancreatic carcinoma who are under systemic chemotherapy.

Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer.

PURPOSE: The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer. METHODS: Patients were randomly assigned to receive GS (oral S-1 60 mg/m(2) daily on days 1-15 every 3 weeks and gemcitabine 1,000 mg/m(2) on days 8 and 15) or gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and one patients were randomly assigned. PFS was significantly longer in the GS arm with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43-0.98; P = 0.039; median 5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months for GEM (HR 0.93; 95 % CI 0.61-1.41; P = 0.714). Grade 3-4 neutropenia (44 vs 19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more frequent in the GS arm. CONCLUSIONS: GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer.

Clinical usefulness of repeated pancreatic juice cytology via endoscopic naso-pancreatic drainage tube in patients with pancreatic cancer.

BACKGROUND: Cytological examination of pancreatic juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) is well established, but its sensitivity for pancreatic cancer has not been satisfactory. The aim of this study was to evaluate the usefulness of repeated pancreatic juice cytology (PJC) via the endoscopic naso-pancreatic drainage (ENPD) tube in patients with pancreatic cancer compared with conventional PJC. METHODS: We retrospectively investigated 139 patients with pancreatic disease. Between April 2004 and November 2007, conventional PJC was performed in 56 patients with pancreatic cancer and 23 with benign pancreatic stricture. Between January 2008 and November 2010, ENPD was used in 40 patients with pancreatic cancer and 20 with benign pancreatic stricture. The ENPD tube was placed into the main pancreatic duct for up to 3 days, and cytological samples of pancreatic juice were collected up to 6 times in total. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ENPD method for pancreatic cancer were 80, 100, 100, 71, and 87 %, respectively, revealing significantly higher sensitivity than the conventional method (p = 0.0001). Sensitivities according to tumor location and size were 90 % (19/21), 69 % (9/13), and 67 % (4/6) in the head, body, and tail of the pancreas, 88 % (7/8), 79 % (19/24), and 75 % (6/8) in tumors with a diameter less than 20 mm including carcinoma in situ, 21-40, and greater than 41 mm, respectively. CONCLUSIONS: The ENPD method was found to have high diagnostic yield, especially for tumors less than 20 mm or located in the pancreatic head, and might be useful for the diagnosis of early-stage pancreatic cancer.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PURPOSE: Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. METHODS: Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. RESULTS: Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. CONCLUSIONS: This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

Evaluation of pancreatic intraepithelial neoplasia and mucin expression in normal pancreata.

BACKGROUND/PURPOSE: It has been suggested that pancreatic ductal adenocarcinoma (PDAC) and pancreatic intraepithelial neoplasia (PanIN) are closely related, but several reports indicate PanIN lesions can also be found in normal pancreata (normal PanINs). We examined differences in mucin expression between normal PanIN lesions and PanINs in PDACs (PDAC PanINs). METHODS: We examined 54 autopsied normal pancreata and eight autopsied PDACs for PanIN lesions; graded the pancreata specimens as PanIN-1A (non-papillary hyperplasia), PanIN-1B (papillary hyperplasia), PanIN-2 (atypical hyperplasia) or PanIN-3 (carcinoma in situ); and tested the PanIN lesions for expression of MUC1 (pan-epithelial membrane-associated mucin) and MUC5AC (gastric secretory mucin) which were both previously detected in PDACs. RESULTS: In normal PanIN-1A, PanIN-1B and PanIN-2 specimens, MUC1 was expressed in 2.8, 10.5 and 9.1%, respectively, compared to 19.1, 27.6 and 13.0% in PDAC PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively. MUC5AC was expressed in 41.0, 65.7 and 36.4% of normal PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively, and in 80.9, 75.8 and 78.3% of PDAC PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively. Differences in the frequency of MUC1 expression were significant between normal and PDAC PanIN-1A (p < 0.0001) and PanIN-1B (p < 0.05); and differences in the frequency of MUC5AC expression were significant between normal and PDAC PanIN-1A (p < 0.0001) and PanIN-2 (p < 0.05). CONCLUSIONS: Normal PanIN and PDAC PanIN lesions differed in the rates of MUC1 and MUC5AC expression.

New cannulation method for pancreatic duct cannulation-bile duct guidewire-indwelling method.

The patient was a 58-year-old male with symptomatic alcoholic chronic pancreatitis. Since a 10 mm calculus was observed in the pancreatic body and abdominal pain occurred due to congestion of pancreatic juice, endoscopic retrograde cholangiopancreatography was conducted for assessment of the pancreatic duct and treatment of pancreatic calculus. Pancreatogram was slightly and insufficiently obtained by injecting the contrast media via the common channel of the duodenal main papilla. We tried to cannulate selectively into the pancreatic duct for a clear image. However, the selective cannulation of the pancreatic duct was difficult because of instability of the papilla. On the other hand, selective cannulation of the bile duct was relatively easily achieved. Therefore, after the imaging of the bile duct, a guidewire was retained in the bile duct to immobilize the duodenal papilla and cannulation of the pancreatic duct was attempted. As a result, selective pancreatic duct cannulation became possible. It is considered that the bile duct guidewire-indwelling method may serve as one of the useful techniques for cases whose selective pancreatic duct cannulation is difficult ("selective pancreatic duct difficult cannulation case").

Phase II study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.

PURPOSE: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m(2)/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. RESULTS: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. CONCLUSIONS: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

Changes in tumor vascularity depicted by contrast-enhanced ultrasonography as a predictor of chemotherapeutic effect in patients with unresectable pancreatic cancer.

OBJECTIVES: This study was conducted to assess changes in tumor vascularity using contrast-enhanced ultrasonography in patients with pancreatic carcinoma under systemic chemotherapy and to examine the correlation among vascular change, clinicopathologic factors, and outcome. METHODS: Forty-one consecutive patients with histopathologically confirmed pancreatic carcinoma who had distant metastases and were under systemic chemotherapy were recruited. Contrast-enhanced ultrasonography was performed before and after 1 and 2 cycles of treatment.The vascular signals from the tumor were continuously recorded,and the highest signal intensity was selected and classified into 5 categories by their intensity. RESULTS: As for the tumor response determined by dynamic computed tomography after 2 cycles, 6 patients showed a partial response, 25 remained stable, and in 10 patients, the disease progressed. A significant relationship was observed between vascular change after 1 cycle and tumor response (P G 0.001). Progression-free survival and overall survival were significantly short in the case of patients showing increased vascularity after 1 and 2 cycles of chemotherapy, compared with those who did not (P G 0.001). CONCLUSIONS: Contrast-enhanced ultrasonography was useful to evaluate tumor vascular changes and thereby the effect of systemic chemotherapy, as well as the prognosis of patients with advanced pancreatic carcinoma.