Kentaro Sudo

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.

Preoperative histological subtype classification of intraductal papillary mucinous neoplasms (IPMN) by pancreatic juice cytology with MUC stain.

Objective:To prospectively evaluate the diagnostic value of preoperative histological subtyping of intraductal papillary mucinous neoplasms (IPMNs) by pancreatic juice cytology (PJC) with mucin (MUC) stain. Background:IPMNs are classified into four subtypes based on their histomorphology and mucin phenotype, and varied degrees of malignant nature and prognosis among these subtypes have been shown. Methods:The subjects were 36 patients with surgically confirmed IPMNs, who underwent PJC preoperatively by endoscopic retrograde cholangiopancreatography. Histological subtyping of cytological samples with or without MUC stain (MUC1, MUC2, and MUC5AC) was compared with that of resected specimens. Results:Histologically, low-grade dysplasia was found in 4 patients, intermediate in 10, high grade in 11, and invasive carcinoma in 11. Gastric, intestinal, pancreatobiliary, and oncocytic subtypes corresponded to 16, 14, 5, and 1 patient, respectively. The rate of high-grade dysplasia (HGD) and/or invasive IPMNs was 25% for gastric subtype, 85.7% for intestinal subtype, and 100% for both pancreatobiliary and oncocytic subtypes, showing a significant correlation between histological subtype and rate of HGD and/or invasive IPMN (P < 0.01 for gastric vs nongastric).Histological subtype was successfully diagnosed by PJC in 42% (15/36) without MUC stain, and the rate was significantly improved to 89% (32/36) with MUC stain (P < 0.01). The sensitivity, specificity, and overall accuracy of PJC with MUC stain were 86%, 100%, and 94% for intestinal subtype, respectively. When cytological grade was combined with MUC stain, the diagnosis of HGD/invasive IPMN showed 77.2% sensitivity, 85.7% specificity, and 80.5% accuracy. Conclusions:Preoperative PJC with MUC stain proved to be highly reliable for identifying the histological subtype of IPMN and may provide useful information for deciding surgical indication.

Usefulness of multidetector computed tomography for detecting protruding lesions in intraductal papillary mucinous neoplasm of the pancreas in comparison with single-detector computed tomography and endoscopic ultrasonography.

Objectives: To retrospectively evaluate the usefulness of multidetector computed tomography (MDCT) with multiplanar reformations (MPRs) and curved planar reformations (CPRs) for detecting protruding lesions in intraductal papillary mucinous neoplasms of the pancreas (IPMNs) as compared with single-detector CT (SDCT) and endoscopic ultrasonography (EUS). Methods: Eighty-six patients with IPMNs were imaged either with SDCT (n = 52) or MDCT with MPRs/CPRs and EUS (n = 34). The diagnostic accuracy of each imaging modality for identifying protruding lesions was compared with histological samples. Results: Among the patients in whom protruding lesions were histopathologically identified, the lesions were detected in 9 of the 33 patients subjected to SDCT (51.9% accuracy), in 17 of the 25 patients subjected to MDCT with MPRs and CPRs (76.5% accuracy), and in 21 of the 25 patients subjected to EUS (70.6% accuracy). Thus, significant difference was observed between MDCT and SDCT regarding accuracy (P < 0.05); however, no significant difference was seen between MDCT and EUS. Protruding lesions of less than 10 mm in height were better visualized with MDCT (53.3%) than with SDCT (13.0%; P < 0.05). Conclusions: Multidetector computed tomography proved more useful than SDCT and equivalent to EUS in detecting protruding lesions in IPMNs.

S-1 in the treatment of pancreatic cancer

S-1 is an oral 5-fluorouracil (5-FU) prodrug, which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase, the key enzyme of 5-FU catabolism. Recently, two important studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study (GEST study), S-1 demonstrated non-inferiority to gemcitabine (GEM) in overall survival (OS) for metastatic or locally advanced pancreatic cancer, but combination chemotherapy with GEM and S-1 did not show superiority to GEM in OS. In the second study (JASPAC-01 study), S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic cancer. In addition to GEM, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. To date, many studies have investigated the effectiveness of S-1 in various settings, such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer, second-line chemotherapy after GEM failure, and chemoradiotherapy for locally advanced disease. In this review, we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.

Usefulness of brush cytology combined with pancreatic juice cytology in the diagnosis of pancreatic cancer: significance of pancreatic juice cytology after brushing.

Objectives Pancreatic juice cytology (PJC) and brush cytology (BC) performed during endoscopic retrograde cholangiopancreatography could make a definite diagnosis of pancreatic cancer. The aim of this study was to improve the diagnostic value of cytology performed during endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic cancer. Methods The subjects comprised 127 patients with pancreatic ductal adenocarcinoma (PDAC) and 74 with benign pancreatic duct stricture mimicking PDAC. Final diagnosis was confirmed based on histopathology by resection or on more than 1 year of follow up. Pancreatic juice cytology was examined before and after BC. And the sensitivity of PJC combined with BC was examined. Results No malignancy was detected by PJC or by BC in patients with benign pancreatic duct strictures (specificity, 100%). In those with PDAC, the sensitivity of PJC before and after brushing was 21.3% and 40.9%, respectively; that of BC was 48.8%. Of 65 patients with PDAC, in whom neither PJC before brushing nor BC indicated malignancy, 16 were diagnosed with pancreatic cancer using PJC after brushing. Brush cytology combined with PJC after brushing significantly raised the diagnostic sensitivity for PDAC to 61.4%. Conclusions Diagnosis of pancreatic cancer based on BC combined with PJC after brushing was more reliable than PJC before brushing or BC.

Assessment of Portal Vein Invasion in Pancreatic Cancer by Fusion 3-Dimensional Ultrasonography

The purpose of this study was to assess the usefulness of a newly developed imaging technique, fusion 3‐dimensional ultrasonography (3DUS) in the diagnosis of portal vein (PV) invasion in patients with pancreatic cancer (PC).

Stool antigen test is a reliable method to detect Helicobacter pylori in the gastric remnant after distal gastrectomy for gastric cancer.

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A case of needle tract seeding after EUS-guided FNA in pancreatic cancer, detected by serial positron emission tomography/CT.

A 68-year-old woman suspected of having pancreatic body/tail cancer underwent EUS-guided FNA for pathologic confirmation. EUS-guided FNA with 2 passes using a 22G needle was conducted through the body of the stomach, and the diagnosis of pancreatic cancer was confirmed. The patient was treated using intensity-modulated radiation therapy and remained stable for 4 months. At that time, positron emission spectroscopy (PET)/CT showed indeterminate weak accumulation at the gastric wall with a maximum standardized uptake value of less than 3.5 (A). PET/CT performed after 7 months showed strong accumulation at the same lesion (B). Upper GI endoscopy was performed and a submucosal-like tumor was detected

Changes in Plasma Ghrelin and Serum Leptin Levels after Cisplatin-Based Transcatheter Arterial Infusion Chemotherapy for Hepatocellular Carcinoma

Background and Objective. Cisplatin-based chemotherapy is widely recognized to cause severe gastrointestinal disorders like nausea, vomiting, and appetite loss. The aim of this study was to assess whether cisplatin-based transcatheter arterial infusion (TAI) chemotherapy reduces plasma ghrelin levels and food intake in hepatocellular carcinoma (HCC) patients. Methods. Seventeen patients with HCC who underwent cisplatin-based TAI chemotherapy (80–100 mg/body) were enrolled in this study. Changes in peptide hormones, including ghrelin and leptin, as well as cytokines, were measured before and after chemotherapy. Appetite was evaluated by visual analog scale (VAS) and food intake was scored by eleven stages (0–10). Results. Appetite and food intake were significantly decreased after chemotherapy (P < 0.05). Plasma acylated ghrelin levels before therapy and at day 1, day 7, and day 14 after chemotherapy were 10.4 ± 7.2, 4.7 ± 4.7, 11.7 ± 8.9, and 9.3 ± 6.6 fmol/mL, respectively. The level on day 1 was decreased significantly (P < 0.05). In contrast, the levels of leptin, granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) on day 1 were increased significantly (P < 0.05). Conclusions. TAI for HCC reduced plasma acylated ghrelin levels, appetite, and food intake significantly. In addition, it increased serum leptin levels.

Signet ring cell carcinoma of the extrahepatic bile duct diagnosed by preoperative biopsy: a case report.

A 73-year-old woman was admitted because of obstructive jaundice. Computed tomography revealed a stricture in the lower bile duct with enhanced bile duct wall. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a tapering stenosis at the lower bile duct. Transpapillary histological biopsy using biopsy forceps through ERCP was performed; the diagnosis of signet ring cell carcinoma (SRCC) of the bile duct was established. Regional lymph node enlargement and distant metastases were not detected on diagnostic imaging. Pancreaticoduodenectomy with pylorus preservation was performed. Histological examination of the resected specimen confirmed SRCC of the extrahepatic bile duct coexisting with adenocarcinoma (ADC) of the extrahepatic bile duct with negative resection margins. However, tumor cells directly invaded the pancreatic parenchyma and the muscle layer of the duodenum, prompting us to administer adjuvant chemotherapy to the patient, with no sign of tumor recurrence at 1-year follow-up. Almost all tumors originating from the extrahepatic bile duct are ADC and other histological variants are rare. Of these, SRCC is extremely rare and only four cases have been reported. Furthermore, to the best of our knowledge, this is the first case report regarding the preoperative diagnosis of SRCC of the bile duct. Current reports indicate that younger age and Asian ethnicity are the clinical features of SRCC of the extrahepatic bile duct. Immunohistochemical staining of CK7, CK20 and MUC2 may be useful for predicting prognosis. Chemotherapy has not resulted in increased survival rates and only surgical resection currently serves as a curative treatment.