The aim of this study was to examine the effects of fibroblast growth factor-2 (FGF-2) on cancer cell invasion and on fibroblast proliferation in an in vitro model of invasion. Three kinds of human oral squamous cell carcinoma cell lines with different invasive activity were used: OSC-20, OSC-19 (lower invasive type), and HOC313 (higher invasive type). FGF-2 and its high-affinity receptors FGFR-1 and FGFR-2 were detected by western blotting. The expression of FGF-2 and FGFRs mRNA was examined in cultured human oral squamous cell carcinoma cells by reverse transcriptase polymerase chain reaction (RT-PCR). Furthermore, recombinant human FGF-2 (rhFGF-2) was reacted with each cell line, and the invasion rate was determined by invasion assay. We also observed the behavior of cancer cell invasion in the collagen gel invasion model in the presence or absence of FGF-2-neutralizing antibody (anti-FGF-2). HOC313 cells showed higher expression of FGF-2 than OSC-20 and OSC-19 cells. The addition of rhFGF-2 promoted not only the proliferation of fibroblasts, but also the invasion of all cancer cell lines. In contrast, the addition of anti-FGF-2 completely inhibited the invasion of OSC-20 and OSC-19 cells. These results suggest that a higher invasiveness of squamous carcinoma cells is associated with higher production of FGF-2, which acts in an autocrine fashion to promote cancer cell invasion, and in a paracrine fashion to promote fibroblast proliferation.

Endoscopic ultrasound-guided biliary drainage (EUS-BD), EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS) can effectively palliate obstructive jaundice, but have not been well established yet. The incidence of complications is about 30% in EUSBD and higher for EUS-HGS. Several complications have been reported such as bleeding, perforation and peritonitis. Bleeding occurs due to puncture of portal vein, hepatic vein and artery, and we should use color Doppler. When a cautery dilator is used for fistula dilation, burn effects may cause delayed bleeding. Endoscopic hemostasis is only effective for anastomotic bleeding and embolization with interventional radiology technique is required for pseudo aneurysm. There are some types of perforation: failed stent placement after puncture or fistula dilation, double puncture during CDS procedure, and stent migration. Peritonitis with perforation requires surgery and can be fatal. Stent migration before mature fistula formation causes severe peritonitis because EUS-BD makes fistula between two unattached organs. Stents with flaps or long covered self-expandable metallic stents (cSEMSs) are effective to prevent migration. Recent development of lumen apposing stents may reduce early migration in EUS-CDS. Peritonitis without migration can be due to 1) leakage of bile juice or gastric/duodenal contents during EUS-BD or 2) leakage along the placed stent. We should make procedure time as short as possible, and cSEMSs reduce bile leak along the stent by occluding the dilated fistula. In summary, we should understand the mechanism of complications and the technique to prevent and manage complications. Development of dedicated devices to increase the success rate and reduce complications is required.
Aneurysm ; Arteries ; Bile ; Burns ; Cautery ; Choledochostomy ; Drainage* ; Fistula ; Hemorrhage ; Hemostasis, Endoscopic ; Hepatic Veins ; Incidence ; Jaundice, Obstructive ; Peritonitis ; Portal Vein ; Punctures ; Radiology, Interventional ; Stents

BACKGROUND/AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) has emerged as a palliative treatment for malignant gastric outlet obstruction (GOO). Although covered SEMSs can prevent tumor ingrowth, frequent migration of covered SEMSs may offset their advantages in preventing tumor ingrowth. METHODS: We conducted this multicenter, single-arm, retrospective study at six tertiary referral centers to evaluate the safety and efficacy of a partially covered SEMS with an uncovered large-bore flare at the proximal end as an antimigration system in 41 patients with symptomatic malignant GOO. The primary outcome was clinical success, and the secondary outcomes were technical success, stent dysfunction, adverse events, and survival after stent placement. RESULTS: The technical and clinical success rates were 100% and 95%, respectively. Stent dysfunctions occurred in 17 patients (41%), including stent migration in nine (23%), tumor ingrowth in one (2%), and tumor overgrowth in four (10%). Two patients (5%) developed adverse events: one pancreatitis and one perforation. No procedure-related death was observed. CONCLUSIONS: A novel partially covered SEMS with a large-bore flare proximal end was safe and effective for malignant GOO but failed to prevent stent migration. Further research is warranted to develop a covered SEMS with an optimal antimigration system.
Gastric Outlet Obstruction* ; Humans ; Palliative Care ; Pancreatitis ; Retrospective Studies ; Self Expandable Metallic Stents ; Stents* ; Tertiary Care Centers

BACKGROUND/AIMS: Groove pancreatitis (GP) is an uncommon disease involving the pancreaticoduodenal area. Possible pathogenesis includes obstructive pancreatitis in the duct of Santorini and impaired communication with the duct of Wirsung, minor papilla stenosis, and leakage causing inflammation. Limited data regarding endoscopic treatment have been published. METHODS: Seven patients with GP receiving endoscopic treatment were reviewed. The morphology of the pancreatic duct was evaluated by a pancreatogram. Endoscopic dilation of the minor papilla and drainage of the duct of Santorini were performed. RESULTS: There were two pancreatic divisum cases, one ansa pancreatica case and four impaired connections between the duct of Santorini and the main pancreatic duct. Three to 31 sessions of endoscopy, with 2 to 24 sessions of transpapillary stenting and dilation, were performed. Interventions through the minor papilla were successfully performed in six of seven cases. The pancreatic stenting duration ranged from 2 to 87 months. Five patients with evidence of chronic pancreatitis (CP) tended to receive more endoscopic interventions than did the two patients without CP (2–24 vs 2, respectively) for GP and other complications associated with CP. CONCLUSIONS: Disconnection or impairment of communication between the ducts of Santorini and Wirsung was observed in all cases of GP. No surgery was required, and endoscopic minor papilla dilation and drainage of the duct of Santorini were feasible for the treatment of GP.
Constriction, Pathologic ; Drainage ; Endoscopy ; Humans ; Inflammation ; Pancreatic Ducts* ; Pancreatitis* ; Pancreatitis, Chronic ; Stents

BACKGROUND/AIMS: Stent migration occurs frequently, but the prevention of complications resulting from covered self-expandable metal stents (C-SEMSs) remains unresolved. We prospectively assessed a newly developed C-SEMS, a modified covered Zeo stent (m-CZS), in terms of its antimigration effect. METHODS: Between February 2010 and January 2011, an m-CZS was inserted into 42 patients (31 initial drainage cases and 11 reintervention cases) at a tertiary referral center and three affiliated hospitals. The laser-cut stent was flared for 1.5 cm at both ends, with a 1 cm raised bank located 1 cm in from each flared end. The main outcome of this study was the rate of stent migration, and secondary outcomes were the rate of recurrent biliary obstruction (RBO), the time to RBO, the frequencies of complications, and overall survival. RESULTS: Of the 31 patients with initial drainage, stent migration occurred in four (12.9%, 95% confidence interval, 5.1% to 29.0%), with a mean time of 131 days. RBO occurred in 18 (58%), with a median time to RBO of 107 days. Following previous C-SEMS migration, seven of 10 patients (70%) did not experience m-CZS migration until death. CONCLUSIONS: m-CZSs with antimigration properties effectively, although not completely, prevented stent migration after stent insertion.
Aged ; Aged, 80 and over ; Alloys ; Carcinoma/*complications ; Cholestasis/etiology/*therapy ; Digestive System Neoplasms/*complications ; Drainage ; Equipment Design ; Feasibility Studies ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; *Prosthesis Failure ; Recurrence ; Reoperation ; *Stents/adverse effects ; Time Factors

BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.
Adult ; Aged ; Aged, 80 and over ; Cholesterol/*blood ; Cholinesterases/blood ; Diabetes Mellitus, Type 2/complications ; Exocrine Pancreatic Insufficiency/*blood/etiology ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis, Alcoholic/blood ; Male ; Middle Aged ; Nutritional Status ; Pancreas/enzymology ; Pancreatitis, Alcoholic/blood/complications ; Pancreatitis, Chronic/blood/*complications ; Serum Albumin/analysis

BACKGROUND/AIMS: In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. METHODS: Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. RESULTS: In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced non-occlusion cholangitis. CONCLUSIONS: The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted.
Arm ; Asian Continental Ancestry Group ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis ; Cholecystitis ; Drainage ; Humans ; Liver Abscess ; Pancreatic Neoplasms ; Pancreatitis ; Pilot Projects* ; Retrospective Studies ; Sewage ; Stents*