Kimitoshi Kubo

Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction.

BACKGROUND AND STUDY AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has gained popularity as an alternative to percutaneous biliary drainage for patients in whom endoscopic retrograde cholangiopancreatography has failed. There are no previous studies comparing EUS-CDS with endoscopic transpapillary stenting (ETS) as first-line treatment for distal malignant obstruction. The aim of this study was to compare the clinical efficacy and safety of EUS-CDS and ETS as first-line treatment in patients with distal malignant biliary obstruction. PATIENTS AND METHODS A total of 82 patients with distal malignant biliary obstruction underwent initial biliary drainage using self-expandable metal stents at a tertiary care university hospital. ETS was performed between June 2009 and May 2012, and EUS-CDS was performed between May 2012 and March 2014. Clinical success rates, adverse event rates, and reintervention rates were retrospectively evaluated for EUS-CDS and ETS. RESULTS A total of 26 patients underwent EUS-CDS and 56 underwent ETS. Clinical success rates were equivalent between the groups (EUS-CDS 96.2 %, ETS 98.2 %; P = 0.54). The mean procedure time was significantly shorter with EUS-CDS than with ETS (19.7 vs. 30.2 minutes; P < 0.01). The rate of overall adverse events was not significantly different between the groups (EUS-CDS 26.9 %, ETS 35.7 %; P = 0.46). Post-procedural pancreatitis was only observed in the ETS group (0 % vs. 16.1 %; P = 0.03). The reintervention rate at 1 year was 16.6 % and 13.6 % for EUS-CDS and ETS, respectively (P = 0.50). CONCLUSIONS EUS-CDS performed by expert endoscopists was associated with a short procedure time and no risk of pancreatitis, and would therefore be feasible as a first-line treatment for patients with distal malignant biliary obstruction.

Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Liver Fibrosis in Rats

Background Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis. Methods Liver fibrosis was induced by an intraperitoneal injection of 2 mL/kg of 50% carbon tetrachloride twice a week for 6 weeks. At 3 weeks, hAMSCs (1 × 106 cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative reverse-transcription polymerase chain reaction were performed. In vitro experiments were conducted to investigate the effect of hAMSCs on the activation of Kupffer cells. Results Transplantation of hAMSCs significantly reduced the fibrotic area, deposition of type-I collagen, the number of &agr;-smooth muscle actin–positive hepatic stellate cells, and CD68-positive Kupffer cells in the livers. messenger RNA expression of &agr;-smooth muscle actin and tissue inhibitor of metalloproteinase-1 was significantly decreased and the expression of matrix metalloproteinase-9 and hepatocyte growth factor was significantly increased in the liver of hAMSC-treated rats. Transplantation of hAMSCs at 3 weeks plus 5 weeks did not have an additive effect. In vitro experiments demonstrated that Kupffer cell activation induced by lipopolysaccharide was significantly decreased by culturing with conditioned medium obtained from hAMSCs. Conclusions Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through the inhibition of Kupffer cell and hepatic stellate cell activation. hAMSCs may be a potential new treatment for liver fibrosis.

Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer

BACKGROUND Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. METHODS Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015. In the FOLFIRINOX group, patients received 85 mg/m2 oxaliplatin followed by 180 mg/m2 irinotecan and 200 mg/m2 L-leucovorin, and by 400 mg/m2 fluorouracil as a bolus and 2,400 mg/m2 fluorouracil as a 46-h continuous infusion every 14 days. In the GnP group, patients received 125 mg/m2 nab-PTX followed by 1 g/m2, and gemcitabine on days 1, 8 and 15, repeated every 28 days. RESULTS Response rate was 6.3% in the FOLFIRINOX group and 40.9% in the GnP group (P=0.025). Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 3.0-4.5] in the FOLFIRINOX group and 6.5 months (95% CI, 6.2-6.9 months) in the GnP group (P=0.031). Drug toxicity in the GnP group was less than in the FOLFIRINOX group. CONCLUSIONS Efficacy and safety of GnP compare favorably to those of FOLFIRINOX in patients with pancreatic cancer. Additional prospective trials are warranted.

Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method

Endoscopic double self‐expandable metallic stent (SEMS) placement by the partial stent‐in‐stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO).

Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction : a feasibility study

Bilateral self‐expandable metallic stent (SEMS) placement for the management of unresectable malignant hilar biliary obstruction (UMHBO) is technically challenging to perform using the existing metallic stents with thick delivery systems. The recently developed 6‐Fr delivery systems could facilitate a single‐step simultaneous side‐by‐side placement through the accessory channel of the duodenoscope. The aim of this study was to evaluate the feasibility of this procedure.

Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.

AIM To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma. METHODS In total, 118 patients with hilar cholangiocarcinoma underwent endoscopic management [endoscopic nasobiliary drainage (ENBD) or endoscopic biliary stenting] as a temporary drainage in our institution between 2009 and 2014. We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment. The risk factors for biliary reintervention, post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis, and percutaneous transhepatic biliary drainage (PTBD) were also analyzed using patient- and procedure-related characteristics. The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage. RESULTS In total, 137 complications were observed in 92 (78%) patients. Biliary reintervention was required in 83 (70%) patients. ENBD was significantly associated with a low risk of biliary reintervention [odds ratio (OR) = 0.26, 95%CI: 0.08-0.76, P = 0.012]. Post-ERCP pancreatitis was observed in 19 (16%) patients. An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis (OR = 3.46, 95%CI: 1.19-10.87, P = 0.023). PTBD was required in 16 (14%) patients, and Bismuth type III or IV cholangiocarcinoma was a significant risk factor (OR = 7.88, 95%CI: 1.33-155.0, P = 0.010). Of 102 patients with initial unilateral drainage, 49 (48%) required bilateral drainage. Endoscopic sphincterotomy (OR = 3.24, 95%CI: 1.27-8.78, P = 0.004) and Bismuth II, III, or IV cholangiocarcinoma (OR = 34.69, 95%CI: 4.88-736.7, P < 0.001) were significant risk factors for bilateral drainage. CONCLUSION The endoscopic management of hilar cholangiocarcinoma is challenging. ENBD should be selected as a temporary drainage method because of its low risk of complications.

Transpapillary selective bile duct cannulation technique: Review of Japanese randomized controlled trials since 2010 and an overview of clinical results in precut sphincterotomy since 2004.

In 1970, a Japanese group reported the first use of endoscopic retrograde cholangiopancreatography (ERCP), which is now carried out worldwide. Selective bile duct cannulation is a mandatory technique for diagnostic and therapeutic ERCP. Development of the endoscope and other devices has contributed to the extended use of ERCP, which has become a basic procedure to diagnose and treat pancreaticobiliary diseases. Various techniques related to selective bile duct cannulation have been widely applied. Although the classical contrast medium injection cannulation technique remains valuable, use of wire‐guided cannulation has expanded since the early 2000s, and the technique is now widely carried out in the USA and Europe. Endoscopists must pay particular attention to a patients condition and make an attendant choice about the most effective technique for selective bile duct cannulation. Some techniques have the potential to shorten procedure time and reduce the incidence of adverse events, particularly post‐ERCP pancreatitis. However, a great deal of experience is required and endoscopists must be skilled in a variety of techniques. Although the development of the transpapillary biliary cannulation approach is remarkable, it is important to note that, to date, there have been no reports of transpapillary cannulation preventing post‐ERCP pancreatitis. In the present article, selective bile duct cannulation techniques in the context of recent Japanese randomized controlled trials and cases of precut sphincterotomy are reviewed and discussed.

Pazopanib-Induced Severe Acute Pancreatitis

Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis.

Endoscopic ultrasonography-guided liver abscess drainage using a dedicated, wide, fully covered self-expandable metallic stent with flared-ends

Title Endoscopic ultrasonography-guided liver abscess drainage using a dedicated, wide, fully covered self-expandable metallic stent with flared-ends Author(s) Kawakami, Hiroshi; Kawakubo, Kazumichi; Kuwatani, Masaki; Kubota, Yoshimasa; Abe, Yoko; Kawahata, Shuhei; Kubo, Kimitoshi; Sakamoto, Naoya Citation Endoscopy, 46(S 01): E982-E983 Issue Date 2014-12-19 Doc URL http://hdl.handle.net/2115/60351 Rights

Endoscopic ultrasound-guided antegrade diathermic dilation followed by self-expandable metal stent placement for malignant distal biliary stricture.

Endoscopic ultrasound (EUS)-guided antegrade stenting (AGS) is established as an alternative interventional technique in patients in whom endoscopic transpapillary stenting has failed [1,2]. Here, we present a patient who underwent EUSAGS after diathermic dilation with placement of a self-expandable metal stent (SEMS) for a malignant distal biliary stricture. A 58-year-old woman with cancer of unknown origin and obstructive jaundice was referred to our hospital. She had undergone transpapillary stenting using a plastic stent at another hospital 2 months previously. Esophagogastroduodenoscopy (EGD) to reach the papilla of Vater was not feasible because of gastric outlet obstruction. Therefore, we attempted EUS-AGS via the stomach. First the intrahepatic bile