Clinical Evaluation of a Newly Developed Guidewire for Pancreatobiliary Endoscopy.

BACKGROUND: The guidewire (GW) plays an important role in pancreatobiliary endoscopy. GW quality is a critical factor in the effectiveness and efficiency of pancreatobiliary endoscopy. In this study, we evaluate a new 0.025 inch multipurpose endoscopic GW: the M-Through. METHODS: Our study was a multicenter retrospective analysis. We enrolled patients who underwent endoscopic procedures using the M-Through between May 2018 and April 2020. Patients receiving the following endoscopic treatments were enrolled: common bile duct (CBD) stone extraction, endoscopic drainage for distal and hilar malignant biliary obstruction (MBO), and endoscopic drainage for acute cholecystitis. For each procedure, we examined the rate of success without GW exchange. RESULTS: A total of 170 patients (80 with CBD stones, 60 with MBO, and 30 with cholecystitis) were enrolled. The rate of completion without GW exchange was 100% for CBD stone extraction, 83.3% for endoscopic drainage for MBO, and 43.3% for endoscopic drainage for cholecystitis. In unsuccessful cholecystitis cases with the original GW manipulator, 1 of 8 cases succeeded in the manipulator exchange. Including 6 cases who changed GW after the manipulator exchange, 11 of 16 cases succeeded in changing GW. There was significant difference in the success rate between the manipulator exchange and GW exchange (p = 0.03). The insertion of devices and stent placement after biliary cannulation (regardless of type) were almost completed with M-through. We observed no intraoperative GW-related adverse events such as perforation and bleeding due to manipulation. CONCLUSION: The 0.025 inch M-Through can be used for endoscopic retrograde cholangiopancreatography-related procedures efficiently and safely. Our study found high rates of success without GW exchange in all procedures except for endoscopic drainage for cholecystitis. This GW is considered (1) excellent for supportability of device insertion to remove CBD stones; (2) good for seeking the biliary malignant stricture but sometimes need the help of a hydrophilic GW; (3) suboptimal for gallbladder drainage that require a high level of seeking ability.

Efficacy and safety of gemcitabine plus S-1 in pancreatic cancer: a pooled analysis of individual patient data.

BACKGROUND: Three randomised trials (GEST, JACCRO PC-01, and GEMSAP) were conducted to evaluate the efficacy of gemcitabine plus S-1 (GS) vs gemcitabine alone in patients with advanced pancreatic cancer (PC). In this pooled analysis, the efficacy and safety of GS vs gemcitabine were evaluated. METHODS: Additional follow-up was conducted and survival data were updated in each study. A total of 770 patients (gemcitabine 389; GS 381) were included in the pooled analysis. The efficacy and safety data were analysed according to disease extent: locally advanced PC (LAPC) or metastatic PC (MPC). RESULTS: There were 738 (95.8%) overall survival events. In patients with LAPC (n=193), the median survival was 11.83 months for gemcitabine and 16.41 months for GS (hazard ratio (HR)=0.708; 95% confidence intervals (CI), 0.527-0.951; P=0.0220). In patients with MPC (n=577), the median survival was 8.02 months for gemcitabine and 9.43 months for GS (HR=0.872; 95% CI, 0.738-1.032; P=0.1102). The rate of grade 3/4 toxicity (rash and thrombocytopenia in LAPC; rash, diarrhoea, vomiting, and neutropaenia in MPC) was significantly higher for GS than for gemcitabine. CONCLUSIONS: Gemcitabine plus S-1 is a viable treatment alternative to gemcitabine, which is one of the standard treatments in patients with LAPC.

Improved survival with combined gemcitabine and S-1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies.

BACKGROUND: The long-term prognosis for localized pancreatic cancer (PC) remains poor. Three randomized trials (GEST phase III, JACCRO PC-01 phase II and GEMSAP phase II) evaluated gemcitabine (Gem) with or without S-1 for patients with metastatic and locally advanced PC. A pooled analysis based on published data examined whether Gem with S-1 (GS) is superior to Gem alone in overall survival (OS) in patients with locally advanced PC. METHODS: Data were extracted on 193 patients: 31 (JACCRO), 28 (GEMSAP), and 134 (GEST). OS was used for primary endpoint and progression-free survival (PFS) was used for secondary endpoint. A general variance-based method was used to estimate the pooled HR and 95% CI between GS (n = 96) and Gem (n = 97). RESULTS: Meta-analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies (hazard ratio = 0.673, 95% confidence interval: 0.488-0.929, P = 0.016). The median PFSs for GS and GEM in the JACCRO, GEMSAP, and GEST studies were 12.0, 12.6, and 10.7 months, and 4.1, 8.1, and 6.2 months, respectively (P = 0.001). The random-effect pooled estimate for 165 patients showed the objective response rate (ORR) in the GS group (28.4%) was better in the Gem group (8.3%, P = 0.001). CONCLUSIONS: GS improved ORR, PFS and OS in patients with locally advanced PC over Gem alone. GS could become one of the front-line chemotherapeutic agents.

Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study).

PURPOSE: To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer. METHODS: In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival. RESULTS: We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group). CONCLUSIONS: The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.

Dlk-1, a cell surface antigen on foetal hepatic stem/progenitor cells, is expressed in hepatocellular, colon, pancreas and breast carcinomas at a high frequency.

Delta-like 1 protein (Dlk-1), also known as preadipocyte factor 1 (Pref-1), is a transmembrane and secreted protein with epidermal growth factor (EGF)-like repeats. Dlk-1 is known to be expressed in foetal liver, but absent in neonatal and adult liver in mice and rats. Dlk-1 is also expressed in a subpopulation of hepatic oval cells, which are considered as stem/progenitor cells in rat adult liver. In this study, we generated monoclonal antibodies against human Dlk-1 (hDlk-1) and investigated hDlk-1 expression in human liver and hepatocellular carcinoma (HCC). Like rodent livers, hDlk-1 was detected in foetal liver, but not in adult liver. In HCC, hDlk-1 was positive for 20.5% of the cases examined and was localized in both cytoplasm and cell membrane, whereas hDlk-1 was undetected in viral hepatitis, nodular cirrhosis. Interestingly, hDlk-1 positive HCC was found more frequently in younger patients and its expression was correlated with alpha-fetoprotein expression. Furthermore, hDlk-1 was also detected frequently in colon adenocarcinomas (58%), pancreatic islet carcinoma (50%), and small cell lung carcinoma (50%). Thus, hDlk-1 is a cell surface protein expressed in many carcinomas including HCC and may be a potential target for monoclonal antibody therapy for carcinomas.

Adjuvant treatments for resectable hepatocellular carcinoma.

Hepatocellular carcinoma often recurs even after curative resection. Although some encouraging data showing improvements in recurrence-free times have been reported with the use of intraarterial 131I-lipiodol infusion, retinoids, interferon, or immunotherapy after hepatectomy, there is no consensus regarding standard adjuvant therapy for resectable hepatocellular carcinoma. A novel target agent, sorafenib, which has recently become a standard of care for advanced disease, may also be promising in an adjuvant setting to prevent early recurrence after curative surgery. In future trials, it will be important to identify appropriate target populations for each type of adjuvant approach; that is, an agent with definitive antitumor activity for high-risk patients, and one that shows chemoprevention for low-risk patients.

[A case of splenic inflammatory pseudotumor].

A 51-year-old woman who had undergone gastrectomy for advanced gastric cancer was found to have a splenic tumor during the postoperative clinical observation. Abdominal computed tomography (CT) demonstrated solitary splenic tumor 15mm in diameter with delayed contrast enhancement. Abdominal ultrasonography (US) revealed low echoic mass with enhancement at vascular and perfusion image. We performed splenectomy to exclude the possibility of the metastatic tumor. The tumor was histopathologically diagnosed as inflammatory pseudotumor because of the presence of acidophilic fiber proliferation, hyalinized tissue and infiltration of lymphocytes and plasma cells.

[Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) for metastatic liver tumors in patients with gastric cancer].

We reviewed the effects and complications of transcatheter arterial chemoembolization (TACE), using degradable starch microspheres (DSM) in eight patients with hepatic metastases from gastric cancer. The rate of complete remission (CR) +partial remission (PR) was 62.5%, and the actual survival rates at one and two years post-treatment were 87.5%, and 52.5% respectively. The median survival time was 36.1 months. Almost all side effects were acceptable but in one case, we observed liver abscess. From this study, we suggest that DSM-TACE might be a safe and effective multimodal treatment for metastatic liver tumors in patients with gastric cancer.

[Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) (DSM-TACE) for primary and metastatic liver neuroendocrine tumors from gastrointestinal neuroendocrine tumors].

We reviewed the efficacy and complications of transcatheter arterial chemoembolization using degradable starch microspheres (DSM) for primary neuroendocrine tumors of the liver or liver metastases from gastrointestinal neuroendocrine tumors in ten patients. The rate of complete and partial response was 70.0%. The one year and two year survival rate was 77.8% respectively, with a median survival time of 852 days (28.4 months). All symptoms and laboratory data related to treatment were acceptable. It is thought that DSM-TACE is an effective treatment for inoperable liver neuroendocrine tumors or liver metastases from gastrointestinal neuroendocrine tumors.

Locally advanced intrahepatic cholangiocarcinoma successfully resected after transcatheter arterial chemoembolization with degradable starch microspheres: report of a case.

We describe a case of initially unresectable locally advanced intrahepatic cholangiocarcinoma that showed remarkable regression after transcatheter arterial chemoembolization with degradable starch microspheres, allowing for subsequent successful curative resection. A 75-year-old female was referred to our hospital with a large hepatic mass. Computerized tomography examination showed a huge mass in the right liver extended partially to the left liver. Intrahepatic cholangiocarcinoma was strongly suspected, but surgical resection was abandoned due to the local spread in the liver. Three courses of transcatheter arterial chemoembolization with degradable starch microspheres were performed. The anticancer agents, mitomycin C and epirubicin, combined with degradable starch microspheres were injected from the catheter for chemoembolization. After three courses of transcatheter arterial chemoembolization, the tumor size decreased from 10cm to 5.5cm in diameter. Then right trisegmentectomy together with extra-hepatic bile duct excision was performed. At 25 months after the first therapy and 21 months after operation, the patient remains healthy without recurrence. Transcatheter arterial chemotherapy with degradable starch microspheres may be a treatment of choice with locally advanced intrahepatic cholangiocarcinoma.

Transcatheter arterial chemoembolization with DSM for primary hepatic malignant carcinoid.

A 66-year-old male with multiple liver tumors was diagnosed as having malignant carcinoid. The case exhibited carcinoid syndrome with wheezing and high urine 5-Hydroxy-Indole Acetic Acid and serum serotonin concentrations. A search for the primary lesion failed to detect tumors except those in the liver, leading to the diagnosis of primary hepatic carcinoid. Repeated transcatheter arterial chemoembolization with degradable starch microspheres decreased the tumors in size and improved the subjective symptoms. Transcatheter arterial chemoembolization with degradable starch microspheres is a useful treatment for unresectable malignant carcinoid of liver origin.

CT and MRI findings with contrast enhancement of small pancreatic adenocarcinoma in the late phase.

A 60-year-old female was found to have high serum amylase concentrations at a medical check-up. Dynamic computed tomography and magnetic resonance imaging demonstrated a mass in the body of the pancreas, which was enhanced in the late phase of the scans by administration of a contrast medium. Endoscopic retrograde pancreatography showed a stenosis of the main pancreatic duct at the body, and brushing cytology from the region revealed adenocarcinoma. Distal pancreatectomy was performed. The tumor was a well-differentiated adenocarcinoma, measuring 15 x l0 mm. Fibrous tissues were sparsely distributed in the tumor, and there was an increase of dilated veins, in particular at the margin. Late-phase enhancement of the tumor with computed tomography or magnetic resonance imaging was considered to be correlated with this abundant vascular structure in the tumor. Marked tumor enhancement in the late phase might be a characteristic finding suggesting an early-stage pancreatic adenocarcinoma, which should be carefully checked.

Strategies for surgical treatment of gallbladder carcinoma based on information available before resection.

HYPOTHESIS: Precise preoperative staging for gallbladder carcinoma is difficult, despite recent advances in hepatobiliary imaging. However, the most accurate preoperative staging may be possible by integrating preoperative key data. OBJECTIVE: To establish useful strategies for the surgical treatment of gallbladder cancer based on information available before resection. DESIGN: Retrospective review. SETTING: University hospital and tertiary referral cancer center. PATIENTS AND METHODS: From January 1, 1978, through March 31, 2001, 152 patients with gallbladder cancer underwent surgical resection with curative intent. Preoperative diagnoses of the T factor (image-T) and N factor (image-N) in the TNM classification were determined by evaluating all findings of diagnostic imaging, including ultrasonography, enhanced computed tomography, endoscopic ultrasonography, and angiography. The distribution of lymph node metastasis and prognostic factors were also analyzed. RESULTS: The overall diagnostic accuracy for image-T was 52.6% (95% confidence interval, 44.7%-60.6%) and was lower in patients with pT1 and pT2 disease (37.2% and 33.9%, respectively). However, image-T was a significant predictor of lymph node metastasis and patient outcome. Preoperative staging for N was more difficult, with only 24.5% (95% confidence interval, 12.4%-36.5%) of the node-positive patients being correctly diagnosed. An analysis of harvested lymph nodes showed that the cystic, pericholedochal, and posterosuperior peripancreatic nodes were the most prevalent sites of metastasis, and these were considered key nodes for the lymphatic spread of gallbladder cancer. By combining data on image-T and positivity of these key nodes, more accurate TNM staging was possible. Although an extended lymph node dissection provided significantly better survival in patients with pN2 disease, there was no survival advantage to more radical operations, including bile duct resection or pancreaticoduodenectomy. CONCLUSIONS: Although precise preoperative TNM staging for gallbladder carcinoma was difficult, the most accurate staging before resection was possible by integrating image-T classification and data from the intraoperative histopathologic examination of key lymph nodes. Based on this staging, we propose algorithms for the surgical treatment of gallbladder carcinoma.