[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the efficacy of gemcitabine-based chemoradiotherapy followed by surgery (gem-CRTS) for pancreatic ductal adenocarcinoma (PDAC) for borderline resectable (BR) and locally unresectable (UR) tumors.
One hundred patients with PDAC who underwent the gem-CRTS protocol were classified into 3 groups, namely, resectable (R; 14), BR (44), and UR (42). After chemoradiotherapy, the patients were reassessed for curative-intent resection.
At reassessment, distant metastases became apparent in 27% of R patients, in 12% of BR patients, and in 18% of UR patients. The multivariate analysis of preoperative factors indicated that the CA19-9 reduction rate was an independent prognostic factor in the BR group. Among reassessed patients, the resection rate was 63.6% in R, 83.7% in BR, and 50.0% in UR patients. In 63 patients that underwent curative-intent resection, the 3-year survival rate was 83.3% in R, 33.0% in BR, and 7.8% in UR patients. Using multivariate analysis, the independent prognostic factor was found to be the surgical margin in BR patients and human equilibrative nucleoside transporter 1 expression in UR patients.
We consider that our gem-CRTS protocol, even for locally UR PDAC, allows for the identification of candidates for aggressive resection at the time of reassessment and improved prognosis in the patients with positive human equilibrative nucleoside transporter 1 expression.
[Show abstract][Hide abstract] ABSTRACT: Background
EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for pancreatic diseases. However, although most reports have typically focused on cytology, histological tissue quality has rarely been investigated. The effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was recently indicated for tissue acquisition, but has not thus far been tested in a prospective, randomized clinical trial.
To evaluate the adequacy of EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25-gauge needles.
Prospective, single-blind, randomized, controlled crossover trial.
Seven tertiary referral centers.
Patients referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012, 90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative pressure (NNP) and HNP with 2 respective passes. The order of the passes was randomized, and the sample adequacy, quality, and histology were evaluated by a single expert pathologist.
EUS-FNA by using NNP and HNP.
Main Outcome Measurements
The adequacy of tissue acquisition and the accuracy of histological diagnoses made by using the EUS-FNA technique with HNP.
We found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar test). Pancreatitis developed in 1 patient after this procedure, which subsided with conservative therapy.
This was a single-blinded, crossover study.
Biopsy procedures that combine the EUS-FNA with HNP techniques are superior to EUS-FNA with NNP procedures for tissue acquisition. (Clinical trial registration number: UMIN000005939.)
[Show abstract][Hide abstract] ABSTRACT: Pancreatic tumor metastasis from colorectal cancer is very rare. This study evaluated the significance of an endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and surgical treatment. Case 1 was a 67-year-old male with a history of rectal cancer (6 years ago) and lung metastases (5 years ago) who had two masses in the pancreatic head and body. Case 2 was a 58-year-old male with the history of rectal cancer and simultaneous lung metastasis (7 years ago) who had a mass in the pancreatic body. Imaging studies showed stenosis of the pancreatic duct with distal dilatation in both cases, mimicking primary pancreatic cancer. An EUS-FNAB with immunohistochemical staining made a definitive diagnosis of pancreatic metastasis from rectal cancer. Both patients received margin-negative limited resection, middle-segment-preserving pancreatectomy and distal pancreatectomy, respectively, and were alive 16 and 6 months after pancreatectomy, respectively. An EUS-FNAB is helpful to make a definitive diagnosis of pancreatic metastasis and in determining the subsequent therapeutic approach.
[Show abstract][Hide abstract] ABSTRACT: The 13-year-old boy underwent tumor enucleation for pancreatic head insulinoma close to the pancreatic main duct after a preoperative endoscopic pancreatic stent placed by endoscopic retrograde cholangiopancreatography. The tumor was safely excised by identifying the indwelled pancreatic stent during the surgical procedure without pancreatic duct injury or postoperative complications.
Pediatric Surgery International 05/2012; 28(7):707-9. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Incomplete resection of gastric neoplasms by endoscopic treatment could lead to residual/local recurrence, which may be difficult to identify. This study aimed to evaluate the usefulness of magnifying endoscopy for identifying and demarcating residual/local recurrent gastric neoplasms after endoscopic treatment.
Between December 2004 and November 2010, magnifying endoscopy was performed in 15 patients with residual/local recurrent gastric neoplasms. All patients underwent conventional magnifying endoscopy (CME) and enhanced-magnification endoscopy with acetic acid instillation (EME) after conventional endoscopy (CE). Eleven patients additionally underwent magnifying endoscopy using narrow-band imaging (NBI-ME) and a combination of narrow-band imaging and acetic acid instillation (NBI-EME). For each procedure, it was recorded whether the location and circumferential demarcation of the lesions were identified. All lesions were resected by endoscopic submucosal dissection.
Eleven lesions were identified using CE. However, two and four additional lesions were identified using CME and EME, respectively. In 11 cases, NBI-ME and NBI-EME were performed and all lesions were identified. Three lesions, which were identified by CME, were not demarcated circumferentially. All 15 lesions were well demarcated by EME and 11 by NBI-ME and NBI-EME. Of the resected specimens, histopathology indicated that ten lesions were differentiated tubular adenocarcinomas and five lesions were adenomas. The histopathological diagnosis of the location and demarcation of all neoplasms corresponded to endoscopic findings.
Magnifying endoscopy techniques (CME, EME, NBI-ME, and NBI-EME) may be useful for identifying and demarcating residual/local recurrent gastric neoplasms after previous endoscopic treatment.
[Show abstract][Hide abstract] ABSTRACT: We aimed to determine the relationship between the intratumoral expression of human equilibrative nucleoside transporter (hENT1), the main gemcitabine transporter into cells, and the outcome of gemcitabine-based chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer (UICC) T3-T4 pancreatic adenocarcinoma.
The expressions of hENT1, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were immunohistochemically analyzed using the resected specimens from 55 patients (T3, 38 and T4, 17) who had received curative-intent resection after Gem-CRT.
The status of hENT1 expression (positive in 39 and negative in 16) was significantly associated with "clinical efficacy" (defined as more than 50% reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease [SD] or partial response [PR] according to the Response Evaluation Criteria in Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates were significantly higher in the positive hENT1 expression group (82.9, 39.5%) than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were significantly higher in the positive-low combination (89.1, 51.0%) group than in the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed that positive hENT1 expression and R0 resection were significant prognostic factors for OS.
The hENT1 expression in pancreatic adenocarcinoma strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker could become a useful predictor of therapeutic effect for gemcitabine-based therapy in pancreatic cancer patients.
Journal of hepato-biliary-pancreatic sciences. 09/2011; 19(4):413-25.
[Show abstract][Hide abstract] ABSTRACT: Although the prognostic benefit of neoadjuvant chemoradiotherapy (NCRT) against pancreatic cancer has been indicated by several reports, it is controversial whether histological response is associated with prognosis. The objective was to explore the relationship between histological response and prognosis in T3 and T4 pancreatic adenocarcinoma.
We histologically examined the resected specimens obtained from 58 patients (T3, n = 40; and T4, n = 18) for whom we performed curative-intent resection after NCRT. Histological response was evaluated according to Evans's criteria to determine whether it influenced survival.
In T3 tumors, 13 (32.5%) belonged to high responders (tumor destruction of >50%) (R0, n = 13) and 27 (67.5%) belonged to low responders (tumor destruction of ≤50%) (R0, n = 22, R1, n = 3, R2, n = 2). Recurrence-free survival rate was significantly higher in high responders than in low responders (3-year recurrence-free survival rates: 71.3% vs 13.1%, P = 0.0095). In T4 tumors, however, only 1 (5.6%) was a high responder, and R0 resection was obtained only in 5 patients (27.8%).
In T3 tumors, histological response is considered a significant prognostic indicator, securing the surgical margin, whereas in T4 tumors, NCRT did not provide beneficial histological response, not securing the surgical margin.
[Show abstract][Hide abstract] ABSTRACT: We report an extremely rare case of IgG4-related sclerosing cholangitis with pancreas divisum. A 62-year-old man presented to our hospital with obstructive jaundice and hilar bile duct stenosis. An inflammatory tumor was suspected due to elevated of blood IgG4 levels. Endoscopic retrograde cholangiopancreatography revealed hilar bile duct stenosis and pancreas divisum. The biopsy specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) revealed inflammatory findings. Steroid hormone therapy at an initial dose of 30mg/day resulted in dramatic improvement of the bile duct stenosis and blood chemistry data.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 07/2010; 107(7):1184-91.
[Show abstract][Hide abstract] ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori. 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells.
Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori-positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system.
In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa (p = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG (p = .004 and .007, respectively).
Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori-induced DNA damage in gastric mucosa.
[Show abstract][Hide abstract] ABSTRACT: Various techniques using magnifying endoscopy (ME) have been developed to enhance images of early gastric cancer (EGC) demarcations, which are often obscure. We investigated four ME methods to determine which is most effective in enhancing the recognition of EGC demarcations: conventional ME (CME), ME with narrow band imaging (NBI-ME), enhanced-magnification endoscopy with acetic acid (EME), and ME with NBI and acetic acid (NBI-EME).
Thirty-seven successive patients having a total of 40 EGCs participated in the investigation. The endoscope was fixed and magnification images of EGC demarcations in each patient were recorded using four different ME methods (CME, NBI-ME, EME and NBI-EME). Eight experts and eight non-experts scored each of the four images of each lesion for ease of recognition of demarcation (1 to 4, with 4 being easiest).
The mean scores of expert and non-expert judges, respectively, for images acquired using each technique were: CME 1.23, 1.24; NBI-ME 2.61, 2.95; EME 2.62, 2.32 and NBI-EME 3.54, 3.50. There were significant differences between the mean scores for the four techniques (P < 0.0001) using one-way repeated-measures anova. In a Bonferroni's multiple comparison, the average scores (expert and non-expert) of images acquired using NBI-EME were significantly higher than those acquired using other methods; images acquired by NBI-ME or EME also scored significantly higher than those by CME. Non-experts also scored NBI-ME images significantly higher than CME and EME images.
Early gastric cancer demarcations were recognized most easily using NBI-EME, and more easily using EME or NBI-ME than CME.
Journal of Gastroenterology and Hepatology 10/2009; 24(10):1625-30. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Demarcation of early gastric cancers is sometimes unclear. Enhanced-magnification endoscopy with acetic acid instillation and magnifying endoscopy with a narrow band imaging (NBI) system have been useful for recognition of demarcation of early gastric cancers. We report a patient with early gastric cancer who underwent a successful endoscopic submucosal dissection (ESD) by magnifying endoscopy with the combined use of NBI and acetic acid instillation. A 72-year-old man with early gastric cancer underwent ESD. Demarcation of the lesion was not clear, but magnifying endoscopy using the combination of NBI and acetic acid clearly revealed the demarcation. ESD was carried out after spots were marked circumferentially. We identified the positional relation between the demarcation and all markings. Resection of the lesion was on the outside of the markings. Histopathologically, the lesion was diagnosed as a well-differentiated adenocarcinoma limited to the mucosa. The margins were carcinoma free. Magnifying endoscopy combining the use of NBI with acetic acid instillation is simple and helpful for identifying the demarcation of early gastric cancer. This method may be useful in increasing the rate of complete resection by ESD for early gastric cancer.
[Show abstract][Hide abstract] ABSTRACT: Activation of the coagulation system is a critical response for both the repair of tissue injury and the host defense against microbial pathogens. Activation of the coagulation cascade culminates with the generation of thrombin. In vitro studies have shown that thrombin protects gastric epithelial cells from injury. The present study was undertaken to assess in vivo the relationship between gastric intramucosal generation of thrombin and Helicobacter pylori infection.
This study comprised 59 patients with gastroduodenal disorders. There were 27 patients with H. pylori infection (Hp+), 14 without it (Hp-), and 18 patients with cured H. pylori infection (Hp c). The gastric intramucosal concentrations of thrombin-antithrombin complex (TAT), epidermal growth factor (EGF), prostaglandin E2 (PGE2), and vacuolating cytotoxin A (VacA) were measured by specific immunoassays.
The level of TAT was significantly increased in patients with Hp+ compared to Hp- and Hp c. The levels of TAT, EGF and PGE2 were higher in VacA (+) patients than in those with VacA (-). VacA induced significant expression of tissue factor in gastric epithelial cells in vitro. The gastric intramucosal level of VacA antigen was proportionally and significantly correlated with TAT, EGF and PGE2 in Hp+ patients. The level of TAT was proportionally and significantly correlated with EGF in Hp+ patients but not in Hp- and HP c patients.
These results showed that VacA produced by H. pylori is associated with increased thrombin generation, and that thrombin may play a protective role in H. pylori-associated gastroduodenal disorders.