Long-term study of ropinirole patch in Parkinson's disease patients with/without basal l-dopa.

INTRODUCTION: A dopamine agonist patch could be an important treatment option for Parkinson's disease. This study evaluated the long-term efficacy and safety of the ropinirole hydrochloride patch. The steady state plasma ropinirole concentration was also assessed. METHODS: In a multicenter, open-label, uncontrolled study, Parkinson's disease patients with/without basal levodopa and with/without prior dopamine agonist therapy (any of these four regimens) received application of a ropinirole patch once daily for up to 52 weeks with unforced titration from 8 to 64 mg. For patients with prior dopamine agonist therapy, the initial dose of ropinirole patch was determined from the prior dopamine agonist dose by using a conversion table. RESULTS: Most adverse events were mild or moderate. All application site adverse events were mild, except for moderate application site erythema in one patient. In patients with prior dopamine agonist therapy, switching to ropinirole patch did not lead to a significant early increase of adverse events. A change from baseline in the UPDRS Part III total score, the primary efficacy endpoint, showed improvement until Week 16 compared with baseline, followed by little subsequent change until Week 52, indicating maintenance of efficacy. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase. CONCLUSION: Once-daily application of ropinirole patch showed long-term efficacy and safety (52 weeks) for Parkinson's disease. Switching from other dopamine agonists to ropinirole patch was effective and safe. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.

Forestomach developmental failure in an 11-month-old Japanese Black steer with severely retarded growth and chronic ruminal tympany.

This study reports findings from the pathological examination of the forestomach of an 11-month-old Japanese Black steer with severely retarded growth (41% of expected weight) and chronic ruminal tympany. The ruminal papillae were weakly formed (0.3-0.5 cm long) and unevenly distributed. The cellulae and cristae reticuli were underdeveloped; the cristae were 0.4-0.7 cm in height and milky white. The keratinized layer in the stratified squamous epithelium was thickened. Ruminal pH was 5.25, and ruminal volatile fatty acid concentration was 11.7 mM. The steer's severely retarded growth was considered to be caused by malnutrition due to developmental and functional failure of the forestomach.

Efficacy and Safety of Fentanyl Citrate Patch, Including a Low-Dose 0.5 mg Formulation, in Opioid-Naïve Patients with Cancer Pain.

BACKGROUND AND OBJECTIVE: The use of transdermal fentanyl for opioid-naïve patients is restricted, however, transdermal fentanyl is a useful opioid analgesic for patients in whom oral administration is difficult or for those with renal failure. In this study, the efficacy and safety of fentanyl citrate patches was evaluated in opioid-naïve patients suffering from cancer pain. METHODS: An open-label uncontrolled study was conducted in opioid-naïve patients with cancer pain unable to be controlled by non-opioid analgesics. Fentanyl citrate patches starting at a low dose (0.5 mg/patch, corresponding to 6.25 µg/h fentanyl delivered) were applied once/day for up to 14 days. The analgesic effect was assessed every day from the visual analogue scale pain score and the number of doses of rescue medication. When improvement of the analgesic effect was "significant" or "moderate" at a certain dose for three consecutive days, the patient was classified as a "responder" and was considered to have "completed" the study. RESULTS: A fentanyl citrate patch was administered to 208 of 209 enrolled patients. In the full-analysis set, 87.0% of the patients were "responders" (95% confidence interval 81.7-91.3%). In 148 patients, the optimum dose was low (0.5 mg in 99, and 1 mg in 49), with patients finishing the study on days 4-8. Following dose escalation to 4 mg, respiratory depression occurred in one patient; however, this was considered a mild adverse event. CONCLUSION: A low-dose fentanyl citrate patch was effective in the management of cancer pain in opioid-naïve patients and was well tolerated. STUDY REGISTRATION: JPRN-JapicCTI-173717.

Ropinirole Patch Versus Placebo, Ropinirole Extended-Release Tablet in Advanced Parkinson's Disease.

BACKGROUND: A dopamine agonist patch is an important treatment option for PD. OBJECTIVES: A randomized, double-blind, parallel-group, placebo-controlled trial was conducted to evaluate superiority of ropinirole hydrochloride patch over placebo and noninferiority to ropinirole hydrochloride extended-release tablet. METHODS: PD patients using levodopa received ropinirole patch (up to 64 mg/d), ropinirole tablets (up to 16 mg/d), or placebo once-daily (double-dummy technique). The primary endpoint was the change from baseline in the total score for the UPDRS Part III (on state) at week 16. RESULTS: The change of the least squares mean (95% confidence interval) in the UPDRS Part III total score was -9.8 (-10.8 to -8.7) with ropinirole patch, -4.3 (-5.8 to -2.8) with placebo, and -10.1 (-11.2 to -9.1) with ropinirole tablet. The difference between the ropinirole patch and placebo groups was -5.4 (-7.3 to -3.6), demonstrating superiority of the patch over placebo. The difference between the ropinirole patch and tablet groups was 0.3 (-1.2 to 1.8). The upper limit of the 95% confidence interval was smaller than the noninferiority limit of 2.5, demonstrating noninferiority of ropinirole patch to ropinirole tablet. In all three groups, most adverse events were mild or moderate and there were no serious safety concerns. CONCLUSIONS: Once-daily ropinirole patch was effective in advanced PD patients, having demonstrated superiority over placebo and noninferiority to ropinirole tablet, without causing serious safety problems. Ropinirole patch can be an alternative option for PD patients. © 2020 International Parkinson and Movement Disorder Society.

Eicosapentaenoic Acid Improves Cisplatin-Induced Muscle Atrophy Without Accompanying Body Weight Gain.

INTRODUCTION: Cisplatin (CDDP) induces loss of muscle mass by activating the nuclear factor (NF)-κB signaling pathway. In this study, we investigated the effects of eicosapentaenoic acid (EPA), which inhibits NF-κB activation, on CDDP-induced loss of muscle mass in mice. METHODS: Male C57BL/6J mice received a single dose of CDDP and olive oil, linseed oil, or EPA daily for 4 days. Body weight and food intake were recorded daily for 5 days. Forelimb grip strength was determined using a strain gauge on the fourth day. The mice were killed 24 h after the final dose of fatty acid and the wet weight of their gastrocnemius, soleus, and tibialis anterior muscles measured. RESULTS: Olive oil, linseed oil, and EPA all failed to prevent decrease in food intake and loss of body weight. However, only EPA prevented loss of muscle mass and strength. CONCLUSION: EPA prevents CDDP-related loss of muscle mass and muscle but not CDDP-related loss of body weight.

Expression of protein disulfide isomerase A3 and its clinicopathological association in gastric cancer.

Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method. According to the score, GC samples were classified into PDIA3­High and PDIA3­Low GC. PDIA3­High GC samples were predominantly of the intestinal type. Multivariate survival analysis indicated that PDIA3 expression and cancer stage were independent factors. The overall survival of PDIA3­High GC cases was significantly favorable compared with that of PDIA3­Low GC cases, and this was more evident in cases at an advanced stage. In GC cell cultures, the PDIA3 and major histocompatibility complex (MHC) class I proteins were expressed in three out of the four assessed cell lines according to western blot analysis. Notably, the expression of MHC class I was increased by the stimulation of interferon γ. Co­immunoprecipitation assays suggested the formation of a PDIA3 and MHC class I complex. The findings suggested that PDIA3 may be involved in the immune response of carcinoma cells. The improved prognosis in PDIA3­High GC may be accounted for, in part, by sufficient antigen processing and expression of MHC class I, which can be mediated by PDIA3. It was suggested that PDIA3 serves an important role in the pathobiology of GC, and that PDIA3 is a useful marker for the prediction of prognosis.

Absorbable barbed suture device for laparoscopic peritoneal closure after hernia repair via the transabdominal preperitoneal approach: A single-center experience with 257 cases.

INTRODUCTION: The laparoscopic transabdominal preperitoneal approach requires peritoneal closure and technically skilled knotting. We have started to use a barbed running suturing device (V-Loc 180) without knotting for transabdominal preperitoneal repair of hernias. This study aimed to determine whether using V-Loc 180 was safe and shortened the time for laparoscopic peritoneal closure. METHODS: Between December 2010 and February 2017, 3-0 V-Loc 180 and a multifilament absorbable running suture (3-0 Vicryl) were used for three-port transabdominal preperitoneal repair of inguinal hernia in 363 cases. Data including peritoneal closure time and the complications were retrospectively recorded. RESULTS: Factors identified as significantly prolonging the peritoneal closure time were the hernia side (P = 0.0269), the type of hernia (P = 0.001), the suture device used (P < 0.0001), and the surgeon's experience (P < 0.0001). Use of the barbed suture was associated with a significantly shorter peritoneal closure time than the multifilament suture (mean closure time: 10.2 and 12.7 min, respectively). While there were no postoperative complications in the barbed suture group, there were two cases (1.9%) of postoperative complications in the multifilament suture group (P = 0.0272). CONCLUSION: We demonstrated that the use of the barbed suturing device for laparoscopic peritoneal closure was safe and feasible.

Evaluation of positive ductal margins of biliary tract cancer in intraoperative histological examination.

At present the only method available to confirm microscopic infiltration of cancer into ductal margins during surgery, is intraoperative histological examination. In the present study, the status of the surgical margins and postoperative course were evaluated to determine any correlation between remnant carcinoma and postoperative survival. All consecutive patients who underwent resection for biliary tract cancer between January 2004 and May 2012 were identified from a database. Positive margin cases were divided into two groups, invasive carcinoma and carcinoma in situ (CIS). Immunohistochemical staining targeting Ki67 and p53 for positive margins was performed. Cases of major vessel invasion were significantly increased in the positive group compared with the negative group. The recurrence rate was significantly lower in the CIS group compared with the invasive group. The survival rate was significantly increased in the CIS group compared with the invasive group. The expression levels of p53 and Ki67 were significantly increased in the invasive group compared with the CIS group. No statistical correlations were observed between the expression of p53 or Ki67 and the survival or recurrence of disease. In the positive group, resected margin status was the principal factor associated with recurrence-free survival according to Cox-regression analysis. In conclusion, the status of the resected margins in the positive group was the most important factor for postoperative survival and recurrence in cholangiocarcinoma, not immunohistochemical staining targeting Ki67 and p53.

Metastasis of Hepatocellular Carcinoma to the Esophagus: Case Report and Review.

A follow-up endoscopy in a 71-year-old Japanese man who had undergone a left lateral segmentectomy for HCC two years ago revealed an approximately 2 cm in diameter pedunculated polypoid mass in the middle part of the thoracic esophagus. Immunohistochemical staining of the endoscopic biopsy revealed a metastatic HCC esophageal tumor. As the patient's disease could be radically removed by preoperative examinations, we resected the metastatic esophageal tumor via right thoracotomy and esophagogastrostomy reconstruction. Histological examination of the resected specimen revealed that the esophageal tumor was compatible with a HCC metastasis. This is an extremely rare case of a solitary metastasis to the esophagus from HCC in the literature.

Evaluation of the Impact of Preoperative Values of Hyaluronic Acid and Type IV Collagen on the Outcome of Patients with Hepatocellular Carcinoma After Hepatectomy.

BACKGROUND: Recently, some reports have revealed a relationship between post-hepatectomy prognosis in hepatocellular carcinoma (HCC) and hepatic fibrosis markers. We evaluated the relationship between these markers of hepatic fibrosis, clinicopathological findings, and prognosis. METHODS: Three hundred and sixty patients underwent hepatectomy for HCC in the Nippon Medical School Hospital between 1993 and 2013. We divided these patients into two groups: normal serum hyaluronic acid (HA) levels and abnormal levels. We also divided patients into groups with normal serum type IV collagen levels and abnormal levels. RESULTS: The overall survival rate and recurrence-free survival rate of the normal group were significantly higher than those of the abnormal group. In the normal hyaluronic acid group, serum albumin and prothrombin time were significantly higher than in the abnormal group, and age, hepatitis C virus antibody (HCV)-Ab positivity, Child-Pugh grade B, liver cirrhosis, indocyanine green retention rate at 15 min (ICGR15), type IV collagen level, and type IV collagen 7s level were significantly lower than those in the abnormal group. In the normal type IV collagen group, HCV-Ab positivity, liver cirrhosis, ICGR15, HA level, and type IV collagen 7s level were significantly lower than those in the abnormal group, and the serum albumin level was significantly higher than that in the abnormal group. Multivariate analysis independently revealed the significant effect of serum type IV collagen on the overall survival rate as well as the significant effect of serum HA on the recurrence-free survival rate in patients who underwent hepatectomy for HCC. CONCLUSIONS: Preoperative examinations of serum hyaluronic acid levels and type IV collagen levels are imperative for hepatic resection for HCC because these markers are significantly associated with liver function and prognosis.

Single-port laparoscopic-assisted resection for a large abdominal cystic lymphangioma: a case report.

BACKGROUND: We report the case of a young woman with a large abdominal cystic lymphangioma that was successfully resected using single-port laparoscopic-assisted cystectomy. This avoided the need for a large surgical incision, as would result during conventional laparotomy. CASE PRESENTATION: A 17-year-old young woman was admitted to our hospital complaining of abdominal pain that had persisted for 3 days. Computed tomography revealed a 10 × 10 × 10-cm low-density area in the mid-abdomen, and magnetic resonance imaging showed a large abdominal cystic lesion. A mesenteric cyst was suspected, and single-port laparoscopic-assisted resection was performed. The cyst fluid was aspirated using a tissue adhesive, a suction tube with negative pressure, and a 16-gage over-the-needle catheter and syringe. The tumor size was reduced without any spillage of cyst fluid into the abdominal cavity. Then, the shrunken cystic tumor was successfully removed via the small wound and resected outside the abdomen. Pathological findings revealed an abdominal cystic lymphangioma derived from the greater omentum. CONCLUSIONS: Our procedure was easy to perform and required no special materials. Therefore, it could be applied to various cases, such as for abdominal cystic diseases.

Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage after laparoscopic anterior resection in patients with rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer. METHODS: This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL. RESULTS: The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p <  0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL. CONCLUSIONS: Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery.

Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer.

BACKGROUND/AIM: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). PATIENTS AND METHODS: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. RESULTS: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). CONCLUSION: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.

Optimal Interval From Placement of a Self-expandable Metallic Stent to Surgery in Patients With Malignant Large Bowel Obstruction: A Preliminary Study.

OBJECTIVES: The aim of this study was to investigate the risk factors for postoperative complications (POCs) and optimal interval between a self-expandable metallic stent (SEMS) placement and elective surgery, "bridge to surgery (BTS)" in patients with malignant large bowel obstruction. MATERIALS AND METHODS: BTS strategy was attempted in 49 patients with malignant large bowel obstruction from January 2013 to March 2017 in our institution. Two of these patients were excluded because they had undergone emergency surgery for SEMS migration. RESULTS: Of these 47 patients, 8 had developed POC (Clavien-Dindo grading ≥II), whereas 39 patients had no such complications. Multivariate analysis identified only the interval between SEMS and surgery as an independent risk factor for POC. Furthermore, a cutoff value of 15 days for interval between SEMS and surgery was identified by receiver operating characteristic curve analysis. CONCLUSIONS: An interval of over 15 days is recommended for minimizing POC in patients undergoing elective surgery in a BTS setting.

Lysophosphatidylcholine as a predictor of postoperative complications after colorectal cancer surgery.

PURPOSE: Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC). METHODS: The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7. Patients were divided into a No-POC group (n = 33) and a POC group (n = 10). Blood LPC, IL-6, PC, and ATX levels were measured by specific enzymatic assays or ELISA. RESULTS: The postoperative to preoperative LPC ratios were lowest on POD 1 in both groups. The POC group had significantly lower LPC ratios throughout the perioperative period than the No-POC group. The LPC ratios were inversely correlated with IL-6. The predictive impact of LPC ratios on POCs was demonstrated by ROC analysis (cut-off 51.2%, AUC 0.798) and multivariate analysis (OR 15.1, P = 0.01). The postoperative PC ratios decreased more after surgery in the POC group. ATX levels did not change significantly in either group. CONCLUSIONS: Decreased postoperative LPC is associated with increased postoperative inflammatory response and POCs. The decreased PC supply to the circulation is a mechanism of the postoperative LPC decrease.

Phlegmonous gastritis associated with advanced esophageal cancer.

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient's condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.

Successful abdominal wound closure for treatment of severe peritonitis using negative pressure wound therapy with continuous mesh fascial traction: a case report.

BACKGROUND: Surgery for severe peritonitis often entails difficult wound closure and may require open abdominal management due to gut edema and/or concern of abdominal compartment syndrome. Negative pressure wound therapy (NPWT) is known to have good outcomes for wound closure after surgery for severe peritonitis. NPWT with continuous mesh fascial traction may result in even better outcomes, especially for fascial closure. CASE PRESENTATION: An 81-year-old man was hospitalized for abdominal pain. At admission, computed tomography (CT) demonstrated multiple liver metastases and a tumor perforating the sigmoid colon. Acute peritonitis due to perforated sigmoid colon cancer was diagnosed, and emergency peritonitis surgery and Hartmann's operation were performed. However, at the end of the operation, the surgical abdominal wound could not be closed due to gut edema and concern of abdominal compartment syndrome. Thus, the abdominal wound was left open and NPWT was performed in the primary operation. In the second and subsequent operations, NPWT with mesh fascial traction was performed. The wound was ultimately closed in the fifth operation, which took place 9 days after the primary operation. CONCLUSIONS: Treatment of severe peritonitis requires that gastroenterological surgeons learn some form of open abdominal management. This case suggests that NPWT with fascial mesh traction is a suitable solution. Furthermore, it does not require any special materials, and surgeons will find it easy to perform. In sum, NPWT with fascial mesh traction may be the preferred method of open abdominal management over other techniques currently available.

Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection.

BACKGROUND: Relatively high mortality and morbidity rates are reported after liver resection (LR). However, the early predictors of complications after LR are not clear. This study was performed to clarify the usefulness of procalcitonin (PCT) for the early prediction of complications after elective LR. METHODS: This observational study included 72 consecutive patients who underwent elective LR from December 2015 to March 2017. Patients were categorized into two groups: those with and without postoperative complications (Clavien-Dindo grade ≥II). The values of postoperative inflammatory markers (white blood cell [WBC] count, C-reactive protein [CRP] and PCT) were compared between the two groups. RESULTS: CRP and PCT were significantly higher in patients with than without complications; however, the WBC count showed no difference within 5 days postoperatively. The maximum area under the receiver operating characteristic curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697 and 0.860, respectively, PCT had the best predictive ability in the early postoperative period. The PCT level peaked within 2 days postoperatively in 61 patients (85%). The maximum PCT level within 2 days postoperatively (PCT1-2) was significantly higher in patients with than without complications (0.52 vs. 0.19 ng/mL, p<0.001). A cutoff PCT1-2 level of 0.35 ng/mL achieved 80% sensitivity and 83% specificity. In patients without complications, there was no difference in PCT1-2 even when the surgical procedure differed (p=0.935). CONCLUSIONS: PCT1-2 is an early predictive marker after LR and can be similarly used regardless of the LR procedure.

Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth.

Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies. N-Methyl-N-nitrosourea (MNU) was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only 1 tumor from a p53 knockout mouse could be cultured and the cells s.c. transplanted into a C57BL/6 mouse. We cultured this s.c. tumor, and subcloned it. mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and fibroblast growth factor receptor 4 (FGFR4) in YTN16 cells was knocked out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931. These transplanted cell lines formed s.c. tumors in C57BL/6 mice. Four cell lines (YTN2, YTN3, YTN5, YTN16) were subcloned and established. Their in vitro growth rates were similar. However, s.c. tumor establishment rates, metastatic rates, and peritoneal dissemination rates of YTN2 and YTN3 were lower than for YTN5 and YTN16. YTN16 established 8/8 s.c. tumors, 7/8 with lung metastases, 3/8 with lymph node metastases and 5/5 with peritoneal dissemination. FGFR4 expression by YTN16 was 121-fold higher than YTN2. FGFR4-deleted YTN16 cells failed to form s.c. tumors and showed lower rates of peritoneal dissemination. BLU9931 significantly inhibited the growth of peritoneal dissemination of YTN16. These studies present the first transplantable mouse gastric cancer lines. Our results further indicate that FGFR4 is an important growth signal receptor in gastric cancer cells with high FGFR4 expression.