Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Effects of Mesenchymal Stem Cells Treatment on Radiation-Induced Proctitis in Rats.

PURPOSE: There are no effective treatment methods with which to control complications of radiation proctitis with fistula or recurrent bleeding following radiation treatment for prostate, cervical, or rectal cancer. Mesenchymal stem cells (MSCs) can induce immune modification, resulting in tissue repair and regeneration. Therefore, we used a rat model of radiation-induced proctitis and observed the effects of using human placenta-derived (PD) and adipose tissue-derived (AD) MSCs. MATERIALS AND METHODS: Female Sprague Dawley rats were irradiated at the pelvic area with 25 Gy. We injected 1×106 cells of human PD-MSCs, human AD-MSCs, human foreskin fibroblasts, and control media into the rectal submucosa following irradiation. We sacrificed rats for pathologic evaluation. RESULTS: Fibrosis on the rectum was reduced in both MSC groups, compared to the control group. Mucosal Ki-67 indices of both MSC injected groups were higher than those in the control group. Although caspase-3 positive cells in the mucosa gradually increased and decreased in the control group, those in both MSC injected groups increased rapidly and decreased thereafter. CONCLUSION: We demonstrated the effects of regional MSC injection treatment for radiation-induced proctitis in rats. MSC injection reduced fibrosis and increased proliferation in rat mucosa. Human AD-MSCs and PD-MSCs had similar effectiveness.

Clinical feasibility of curative surgery after nab-paclitaxel plus gemcitabine-cisplatin chemotherapy in patients with locally advanced cholangiocarcinoma.

BACKGROUND: This study was conducted to evaluate the clinical feasibility of nab-paclitaxel plus gemcitabine-cisplatin triplet chemotherapy in patients with locally advanced cholangiocarcinoma in real-world practice. METHODS: We retrospectively reviewed patients with locally advanced cholangiocarcinoma who were treated with nab-paclitaxel plus gemcitabine-cisplatin between October 2019 and August 2021 at a single institution. The initial diagnosis of cholangiocarcinoma was histologically confirmed. RESULTS: One hundred twenty-nine patients were included in this study. Among the patients with a measurable lesion (57.4%), the objective response rate and disease control were 60.8% and 91.9%, respectively. Seventy-seven patients (59.7%) were determined as resectable after triplet chemotherapy, but 73 (56.6%) underwent subsequent curative surgery. The major postoperative complication rate was 15.1%, and there were 2 postoperative mortalities (2.7%). There were 6 complete remission cases (8.2%) in the final pathology. The R0 resection was achieved in 67 patients (91.8%). Despite the initial locally advanced cholangiocarcinoma, a pathologic T stage of less than T2 was reported in 67 patients (91.8%). Fifty-two patients (71.2%) had no lymph node metastasis. Patients who underwent surgery after triplet chemotherapy had significantly higher 12-month overall survival (95.9% vs 76.8%; P < .001) than those treated with chemotherapy alone. CONCLUSION: Nab-paclitaxel plus gemcitabine-cisplatin chemotherapy demonstrated a down-staging effect through a high response rate, indicating that this triplet chemotherapy is feasible as induction therapy in patients with locally advanced cholangiocarcinoma.

Bullous Variant of Pyoderma Gangrenosum in a Patient with Acute Myeloid Leukemia.

Unlike classic pyoderma gangrenosum (PG), the bullous variant of PG is typically represented by a painful erythematous papule, plaque, and superficial bulla that progress into the ulceration with bullous margin. Generally, bullous PG is most commonly associated with myeloproliferative disorders, such as acute myeloid leukemia (AML). Bullous PG in AML patients rarely occurs, but once it does, it suggests a poor clinical prognosis. Although many cases of classic PG in AML patients have been reported, bullous PG is relatively rare. Therefore, we present a case of bullous PG that developed in a patient with AML and was successfully treated with high-dose systemic steroids.

Efficacy of Chenodeoxycholic Acid and Ursodeoxycholic Acid Treatments for Refractory Functional Dyspepsia.

Refractory functional dyspepsia (RFD) is diagnosed when symptoms persist for at least 6 months despite at least two medical treatments. No consensus treatment guidelines exist. The implicated causes of functional biliary dyspepsia are a narrowed cystic duct, Sphincter of Oddi dysfunction, microlithiasis, and gallbladder dyskinesia. We investigated the treatment effects of litholytic agents. RFD patients were prospectively enrolled in six tertiary medical centers. All subjects took chenodeoxycholic and ursodeoxycholic acids (CNU) twice daily for 12 weeks. We monitored their medication adherence, laboratory results, and complications. The 7-point global symptom scale test scores were determined before and after treatment. Of the 52 patients who were prospectively screened, 37 were included in the final analysis. The mean age was 51.3 years: 14 were males, and 23 were females. Before treatment, the mean number and duration of symptoms were 2.4 and 48.2 months, and a mean of 3.3 FD-related drugs were taken. The mean CNU adherence was 95.3%. The mean global symptom scale score decreased from 5.6 pretreatment to 2.6 posttreatment. The symptom improvement rate was 94.6% (35 out of 37 patients). The only adverse event was mild diarrhea (10.8%) that was resolved after conservative management. Conclusions: CNU improved the symptoms of RFD patients who did not respond to conventional medications. Litholytic agents are good treatment options for patients with RFD and biliary dyspepsia secondary to biliary microlithiasis. Further prospective, large-scale mechanistic studies are warranted.

Comparison of the Malignant Predictors in Intrahepatic and Extrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. Methods: A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Results: Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p = 0.043) in I-IPNB and enhancement of mural nodule (p = 0.044) in E-IPNB were predictive factors for malignancy. For pathologic discrepancy before and after surgery, IPNB has a 71.2% sensitivity and 82.3% specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB patients, 43.7% progressed to IPNB with invasive carcinoma within 876 days. Conclusions: E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

Real-world efficacy and safety of nab-paclitaxel plus gemcitabine-cisplatin in patients with advanced biliary tract cancers: a multicenter retrospective analysis.

BACKGROUND: A recent phase II trial reported prolonged survival in patients with advanced biliary tract cancer (BTC) following treatment with nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P). We aimed to evaluate the clinical outcomes of Gem/Cis/nab-P in Asian patients with advanced BTC in a real-world setting. METHODS: We reviewed the data of patients who received Gem/Cis/nab-P for the management of advanced BTC between September 2019 and April 2021 at four institutes in Korea. Patients were classified into the Gem/Cis/nab-P and nab-P addition groups depending on the starting point of nab-P administration. RESULTS: A total of 178 patients treated with Gem/Cis/nab-P were included in the study. Of these, 43.8% had intrahepatic cholangiocarcinoma (CCA), 34.8% had extrahepatic CCA, and 21.3% had gall bladder cancer. A total of 117 (65.7%) patients received Gem/Cis/nab-P as the first-line treatment, while 61 (34.3%) were treated with gemcitabine-cisplatin-based chemotherapy followed by nab-P addition. The objective response rate (ORR) and disease control rate in all patients were 42.1% and 84.8%, respectively. The ORR in the Gem/Cis/nab-P group was 47.9%, while that in the nab-P addition group was 31.1%. The median progression-free survival and overall survival were 8.5 months [95% confidence interval (CI), 6.9-10.1] and 14.6 months (95% CI, 10.2-19.0), respectively. In patients who received Gem/Cis/nab-P as initial treatment, the median PFS was 9.4 months (95% CI, 7.9-10.9) and the median OS was not-reached (95% CI, not available). Anemia (n = 42, 23.6%), neutropenia (n = 40, 22.5%), and thrombocytopenia (n = 16, 9.0%) were the most common grade 3-4 toxicities. A total of 20 patients (11.2%) had conversions from unresectable to resectable disease and underwent surgery with curative intent. CONCLUSION: Gem/Cis/nab-P showed favorable real-life efficacy and safety outcomes in Korean patients with advanced BTC, which was consistent with the phase II trial outcomes.

Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study.

BACKGROUND AND AIMS: Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS: During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS: In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).

What is the better surgical treatment option for recurrent common bile duct stones?

PURPOSE: Repeating endoscopic retrograde cholangiopancreatography (ERCP) in patients with recurrent common bile duct (CBD) stones is problematic in many ways. Choledochoduodenostomy (CDS) and choledochojejunostomy (CJS) are 2 surgical treatment options for recurrent CBD stones, and each has different advantages and disadvantages. The aim of this study was to compare the 2 surgical options in terms of the recurrence rate of CBD stones after surgical treatment. METHODS: This retrospective multicenter study included all patients who underwent surgical treatment due to recurrent CBD stones that were not effectively controlled by medical treatment and repeated ERCP between January 2006 and March 2015. We collected data from chart reviews and medical records. A recurrent CBD stone was defined as a stone found 6 months after the complete removal of a CBD stone by ERCP. Patients who underwent surgery for other reasons were excluded. RESULTS: A total of 27 patients were enrolled in this study. Six patients underwent CDS, and 21 patients underwent CJS for the rescue treatment of recurrent CBD stones. The median follow-up duration was 290 (180-1,975) days in the CDS group and 1,474 (180-6,560) days in the CJS group (P = 0.065). The postoperative complications were similar and tolerable in both groups (intestinal obstruction; 2 of 27, 7.4%; 1 in each group). CBD stones recurred in 4 patients after CDS (4 of 6, 66.7%), and 3 patients after CJS (3 of 21, 14.3%) (P = 0.010). CONCLUSION: CJS may be a better surgical option than CDS for preventing further stone recurrence in patients with recurrent CBD stones.

Utility of EUS elastography in the diagnosis of gastric subepithelial tumors: a pilot study (with video).

BACKGROUND AND AIMS: EUS elastography is a real-time imaging technique that analyzes tissue elasticity. The aim of this study was to investigate the applicability of quantitative EUS elastography in the differential diagnosis of gastric subepithelial tumors (SETs). METHODS: We prospectively registered 41 consecutive patients with gastric SETs and measured their strain ratios with EUS elastography. The strain ratios of gastric SETs were compared with the histopathologic diagnosis. RESULTS: Thirty-one patients (mean age, 51.4 ± 12.6 years) were included in the analysis. The mean size of the SETs was 2.3 ± 0.7 cm. Lipomas had the lowest strain ratio of 1.6 (1.1-2.0), followed by leiomyomas 6.0 (2.0-29.0), ectopic pancreas 11.8 (1.7-29.3), gastrointestinal stromal tumors (GISTs) 51.1 (29.0-67.0), and schwannomas 62.0. With a cut-off value of 22.7, EUS elastography could differentiate GISTs from leiomyomas with sensitivity and specificity of 100% and 94.1%, respectively (P = .001; 95% confidence interval, 0.979-1.000). CONCLUSIONS: EUS elastography could be a promising diagnostic adjunct for the assessment of gastric SETs, especially in differentiating GISTs from leiomyomas.

[Relief of Obstruction in the Management of Pancreatic Cancer].

Pancreatic cancer is a major cause of cancer-related mortality and morbidity, and its incidence is increasing as the population is aging. On the other hand, significant improvement in the prognosis has not occurred. The absence of early diagnosis means that many patients are diagnosed only when they develop symptoms, such as jaundice, due to a biliary obstruction. The role of endoscopy in multidisciplinary care for patients with pancreatic cancer continues to evolve. Controversy remains regarding the best preoperative biliary drainage in patients with surgically resectable pancreatic head cancer. In general, patients undergoing a surgical resection usually do not require preoperative biliary drainage unless they have cholangitis or receive neoadjuvant chemotherapy. If biliary drainage is performed prior to surgery, the patient's condition and a multidisciplinary approach should be considered. With the increasing life expectancy of patients with pancreatic cancer, the need for more long-time biliary drainage or pre-operative biliary drainage is also increasing. Strong evidence of endoscopic retrograde cholangiopancreatography (ERCP) as a first-line and essential treatment for biliary decompression has been provided. On the other hand, the use of endoscopic ultrasound-guided biliary drainage as well as percutaneous biliary drainage has been also recommended. During ERCP, self-expandable metal stent could be recommended instead of a plastic stent for the purpose of long stent patency and minimizing stent-induced complications. In this review, several points of view regarding the relief of obstruction in patients with pancreatic cancer, and optimal techniques are being discussed.

Endoscopic Submucosal Dissection Followed by Concurrent Chemoradiotherapy in Patients with Early Esophageal Cancer with a High Risk of Lymph Node Metastasis.

Endoscopic submucosal dissection is recommended as an alternative therapy for early esophageal cancer. However, achieving curative resection in this procedure remains controversial since precise prediction of lymph node metastasis can be difficult. Here, we present the preliminary results of endoscopic submucosal dissection followed by concurrent chemoradiotherapy for early esophageal cancer with a high risk of lymph node metastasis. From May 2006 to January 2014, six patients underwent concurrent chemoradiotherapy after endoscopic submucosal dissection with a median follow-up period of 63 months. No complications were encountered during concurrent chemoradiotherapy. Although local recurrence did not occur in all patients, two patients were diagnosed with metachronous cancer. Overall, the survival rate was 100%. Thus, endoscopic submucosal dissection followed by concurrent chemoradiotherapy may be a feasible treatment for early esophageal cancer in patients with a high risk of lymph node metastasis. Future prospective large-scale studies are warranted to confirm our results.

Performance of disposable endoscopic forceps according to the manufacturing techniques.

BACKGROUND/AIMS: Recently, to lower the production costs and risk of infection, new disposable biopsy forceps made using simple manufacturing techniques have been introduced. However, the effects of the manufacturing techniques are unclear. The aim of this study was to evaluate which types of biopsy forceps could obtain good-quality specimens according to the manufacturing techniques. METHODS: By using an in vitro nitrile glove popping model, we compared the popping ability among eight different disposable biopsy forceps (one pair of biopsy forceps with cups made by a cutting method [cutting forceps], four pairs of biopsy forceps with cups made by a pressing method [pressing forceps], and three pairs of biopsy forceps with cups made using a injection molding method [molding forceps]). Using an in vivo swine model, we compared the penetration depth and quality of specimen among the biopsy forceps. RESULTS: In the in vitro model, the molding forceps provided a significantly higher popping rate than the other forceps (cutting forceps, 25.0%; pressing forceps, 17.5%; and molding forceps, 41.7%; p = 0.006). In the in vivo model, the cutting and pressing forceps did not provide larger specimens, deeper biopsy specimen, and higher specimen adequacy than those obtained using the molding forceps (p = 0.2631, p = 0.5875, and p = 0.2147, respectively). However, the molding forceps showed significantly more common crush artifact than the others (cutting forceps, 0%; pressing forceps, 5.0%; and molding forceps, 43.3%; p = 0.0007). CONCLUSION: The molding forceps provided lower performance than the cutting and pressing forceps in terms of crush artifact.

Robotic transduodenal ampullectomy: A novel minimally invasive approach for ampullary neoplasms.

BACKGROUND: The adoption of minimally invasive surgery for transduodenal ampullectomy has been slow because of special characteristics and complexity of this procedure. METHODS: Six patients underwent robotic transduodenal ampullectomy. We employed novel methods to facilitate exposure of the ampulla. RESULTS: All patients completed robotic transduodenal ampullectomy, but one patient was immediately converted to robotic pancreaticoduodenectomy because of presence of invasive carcinoma on frozen biopsy. The final pathologic report revealed high-grade dysplasia in four patients, low-grade dyplasia in one, and T2N0 in one patient who converted to pancreaticoduodenectomy. There was no immediate postoperative complication or mortality. One patient was readmitted after 3 months because of stricture of the bile duct outlet. There was no recurrence over a median follow-up period of 20 months. CONCLUSION: An appropriate combination of patient positioning and retraction method helps the robot surgical system to provide competent performance for sophisticated and precise manipulation of ampullary lesions.

Experimental study on the friction effect of plastic stents for biliary stone fragmentation (with video).

BACKGROUND AND AIM: In patients with irretrievable or intractable bile duct stone, temporary insertion of a plastic stent (PS) followed by further endoscopic retrograde cholangiopancreatography (ERCP) or surgery has been recommended as a 'bridge' therapy. However, the exact mechanism of stone fragmentation has not been discovered. The aim of the present study was to evaluate whether PS shape can facilitate stone fragmentation. METHODS: Using a new in vitro bile flow phantom model, we compared the friction effect among three different PS groups (straight PS group, double pigtail-shaped PS group, and screw-shaped PS group) and a control group. Each group had 10 silicon tube blocks that separately contained one stone and two PS. The control group had 10 blocks each with only a stone and no PS. We carried out analysis of the friction effect by stone weight and volume changes among the groups, excluding fragmented stones. RESULTS: After 8 weeks, complete fragmentation was noted in one out of 34 cholesterol stones (2.9%) and in four out of six pigmented stones (66.7%). Fragmentation tended to be more prominent in the screw-shaped PS group than in the straight PS group, double pigtail-shaped group, and control group (volume change: -11.33%, 7.94%, 4.43%, and 2.05%, respectively, P = 0.1390; weight change: -9.30%, 0.71%, -0.10%, and -1.23%, respectively, P = 0.3553). CONCLUSION: Stone fragmentation may be induced by PS friction effect. Also, screw-shaped plastic stents may improve friction effect. These results may help guide future PS development and clinical decisions.

Synthetic 8-hydroxydeoxyguanosine inhibited metastasis of pancreatic cancer through concerted inhibitions of ERM and Rho-GTPase.

8-hydroxydeoxyguanosine (8-OHdG) is generated consequent to oxidative stress, but its paradoxical anti-oxidative, anti-inflammatory, and anti-mutagenic effects via Rho-GTPase inhibition were noted in various models of inflammation and cancer. Metastasis occurs through cell detachment, epithelial-mesenchymal transition (EMT), and cell migration; during these processes, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. In this study, we explored the anti-metastatic mechanisms of 8-OHdG in Panc-1 pancreatic cancer cells. 8-OHdG inhibits cell migration by inactivating ERM and Rho-GTPase proteins, and inhibiting focal adhesion kinase (FAK) and matrix metalloproteinases (MMPs). At 15min, 8-OHdG significantly inactivated ERM (p < 0.05) and led to a significant retardation of wound healing; siERM and H1152 (ROCK inhibitor) had similar effects (p < 0.05). However, FAK inhibitor 14, DPI (NOX inhibitor), and NAC (antioxidant) significantly delayed wound healing without inhibiting ERM or CD44 (p < 0.05). In the experiments on cell migration, siERM, siCD44, DPI, and 8-OHdG significantly inhibited MMPs. 8-OHdG significantly decreased DCF-DA activation in Panc-1 pancreatic cancer cells and down-regulated NOXs (nox-1, nox-2, and nox-3). Finally, all of these anti-migration actions of 8-OHdG resulted in significant inhibition of EMT, as evidenced by the up-regulation of ZO-1 and claudin-1 and down-regulation of vimentin. We found significant inhibition of lung metastasis of Panc-1 cells by 8-OHdG. In conclusion, exogenous 8-OHdG had potent anti-metastasis effects mediated by either ERM or Rho GTPase inhibition in metastasis-prone pancreatic cancer cells.