Endoscopic submucosal dissection for esophageal granular cell tumor using the clutch cutter

Endoscopic submucosal dissection (ESD) with a knife is a technically demanding procedure associated with a high complication rate.The shortcomings of this method are the deficiencies of fixing the knife to the target lesion,and of compressing it.These shortcomings can lead to major complications such as perforation and bleeding.To reduce the risk of complications related to ESD,we developed a new grasping type scissors forceps (Clutch Cutter,Fujifilm,Japan) which can grasp and incise the targeted tissue using an electrosurgical current.Esophagogastroduodenoscopy on a 59-year-old Japanese man revealed a 16mm esophageal submucosal nodule with central depression.Endoscopic ultrasonography demonstrated a hypoechoic solid tumor limited to the submucosa without lymph node involvement.The histologic diagnosis of the specimen obtained by biopsy was granular cell tumor.It was safely and accurately resected without unexpected incision by ESD using the CC.No delayed hemorrhage or perforation occurred.Histological examination confirmed that the granular cell tumor was completely excised with negative resection margin.We report herein a case of esophageal granular cell tumor successfully treated by an ESD technique using the CC.

Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

Improved techniques for double-balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography

AIM: To investigate the clinical outcome of double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) in patients with altered gastrointestinal anatomy. METHODS: Between September 2006 and April 2011, 47 procedures of DB-ERCP were performed in 28 patients with a Roux-en-Y total gastrectomy (n = 11), Billroth Ⅱ gastrectomy (n = 15), or Roux-en-Y anastomosis with hepaticojejunostomy (n = 2). DB-ERCP was performed using a short-type DBE combined with several technical innovations such as using an endoscope attachment, marking by submucosal tattooing,selectively applying contrast medium, and CO2 insufflations. RESULTS: The papilla of Vater or hepaticojejunostomy site was reached in its entirety with a 96% success rate (45/47 procedures). There were no significant differences in the success rate of reaching the blind end with a DBE among Roux-en-Y total gastrectomy (96%), Billroth Ⅱ reconstruction (94%), or pancreatoduodenectomy (100%), respectively (P = 0.91). The total successful rate of cannulation and contrast enhancement of the target bile duct in patients whom the blind end was reached with a DBE was 40/45 procedures (89%). Again, there were no significant differences in the success rate of cannulation and contrast enhancement of the target bile duct with a DBE among Roux-en-Y total gastrectomy (88 %), Billroth Ⅱ reconstruction (89%), or pancreatoduodenectomy (100%), respectively (P = 0.67). Treatment was achieved in all 40 procedures (100%) in patients whom the contrast enhancement of the bile duct was successful. Common endoscopic treatments were endoscopic biliary drainage (24 procedures) and extraction of stones (14 procedures). Biliary drainage was done by placement of plastic stents. Stones extraction was done by lithotomy with the mechanical lithotripter followed by extraction with a basket or by the balloon pull-through method. Endoscopic sphincterotomy was performed in 14 procedures with a needle precutting knife using a guidewire. The mean total duration of the procedure was 93.6 ± 6.8 min and the mean time required to reach the papilla was 30.5 ± 3.7 min. The mean time required to reach the papilla tended to be shorter in Billroth Ⅱ reconstruction (20.9 ± 5.8 min) than that in Roux-en-Y total gastrectomy (37.1 ± 4.9 min) but there was no significant difference (P = 0.09). A major complication occurred in one patient (3.5%); perforation of the long limb in a patient with Billroth Ⅱ anastomosis.CONCLUSION: Short-type DBE combined with several technical innovations enabled us to perform ERCP in most patients with altered gastrointestinal anatomy.

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.