Bcl-xL inhibition by molecular-targeting drugs sensitizes human pancreatic cancer cells to TRAIL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various types of cancer cells without damaging normal cells. However, in terms of pancreatic cancer, not all cancer cells are sensitive to TRAIL. In this study, we examined a panel of human pancreatic cancer cell lines for TRAIL sensitivity and investigated the effects of Bcl-2 family inhibitors on their response to TRAIL. Both ABT-263 and ABT-737 inhibited the function of Bcl-2, Bcl-xL, and Bcl-w. Of the nine pancreatic cancer cell lines tested, six showed no or low sensitivity to TRAIL, which correlated with protein expression of Bcl-xL. ABT-263 significantly sensitized four cell lines (AsPC-1, Panc-1, CFPAC-1, and Panc10.05) to TRAIL, with reduced cell viability and increased apoptosis. Knockdown of Bcl-xL, but not Bcl-2, by siRNA transfection increased the sensitivity of AsPC-1 and Panc-1 cells to TRAIL. ABT-263 treatment had no effect on protein expression of Bcl-2, Bcl-xL, or c-FLIPs. In Panc-1 cells, ABT-263 increased the surface expression of death receptor (DR) 5; the NF-κB pathway, but not endoplasmic reticulum stress, participated in the increase. In xenograft mouse models, the combination of TRAIL and ATB-737 suppressed the in vivo tumor growth of AsPC-1 and Panc-1 cells. These results indicate that Bcl-xL is responsible for TRAIL resistance in human pancreatic cancer cells, and that Bcl-2 family inhibitors could represent promising reagents to sensitize human pancreatic cancers in DR-targeting therapy.

Laparoscopic stomach-partitioning gastrojejunostomy with reduced-port techniques for unresectable distal gastric cancer.

BACKGROUND: The improvement of quality of life is of great importance in managing patients with far-advanced gastric cancer. We report a new cure and less invasive method of creating a stomach-partitioning gastrojejunostomy in reduced-port laparoscopic surgery for unresectable gastric cancers with gastric outlet obstruction. MATERIALS AND METHODS: A 2.5-cm vertical intraumbilical incision was made, and EZ Access (Hakko Co., Ltd., Tokyo, Japan) was placed. After pneumoperitoneum was created, an additional 5-mm trocar was inserted in the right upper abdomen. A gastrojejunostomy was performed in the form of an antiperistaltic side-to-side anastomosis, in which the jejunal loop was elevated in the antecolic route and anastomosed to the greater curvature of the stomach using an endoscopic linear stapler. The jejunal loop together with the stomach was dissected with additional linear staplers just proximal to the common entry hole so that a functional end-to-end gastrojejunostomy was completed. At the same time, the stomach was partitioned using a linear stapler to leave a 2-cm-wide lumen in the lesser curvature. Subsequently, jejunojejunostomy was performed 30 cm distal to the gastrojejunostomy, and the stomach-partitioning gastrojejunostomy resembling Roux-en Y anastomosis was completed. RESULTS: All patients resumed oral intake on the day of operation. Neither anastomotic leakage nor anastomotic stricture was observed. CONCLUSIONS: Our less invasive palliative operation offers the utmost priority to improve quality of life for patients with unresectable gastric cancer.

Secure hemostasis in transhiatal esophagectomy for esophageal cancer with gauze packing.

BACKGROUND: Transhiatal esophagectomy for esophageal cancer implies blind manipulation of the intrathoracic esophagus. We report a secure hemostatic method with gauze packing in transhiatal esophagectomy. METHODS: The gauze-packing technique is utilized for hemostasis just after removal of the thoracic esophagus during transhiatal esophagectomy. After confirming cancer-free margins, the abdominal esophagus and cervical esophagus are transected. A vein stripper is inserted into the oral-side stump of the esophagus and led to exit from the abdominal-side stump of the esophagus. The vein stripper and the oral stump of the esophagus are affixed by silk thread. A polyester tape is then affixed to the vein stripper, as the polyester tape is left in the posterior mediastinum after removal of the esophagus toward the abdominal side. The polyester tape on the cervical side is ligated with gauze and the polyester tape is removed toward the abdominal side. The oral stump of gauze and new additional gauze are affixed. As the first gauze is pulled out from the abdominal side, the second gauze gets drawn from the cervical wound into the mediastinum. The posterior mediastinum is finally packed with gauze and possible bleeding at this site undergoes a complete astriction. The status of hemostasis with the gauze packing is checked by an observation of color and bloodstain on the gauze. RESULTS: Between January 2005 and February 2012, 13 consecutive patients with esophageal cancer underwent a transhiatal esophagectomy with the gauze-packing hemostatic technique. Hemostasis at the posterior mediastinum was performed successfully and quickly in all cases with this method, requiring up to four pieces of gauze for a complete hemostasis. Median required time for hemostasis was 1219 (range 1896 to 1293) seconds and estimated blood loss was 20.4 (range 15 to 25) ml during gauze packing. CONCLUSIONS: Our technique could minimize bleeding after the removal of the thoracic esophagus. The gauze-packing method is a simple and easy technique for secure hemostasis when performing a transhiatal esophagectomy.

Mesenteric artery fenestration for type B dissection with visceral ischemia.

We describe a successful case of direct superior mesenteric artery fenestration for an acute type B dissection complicated by bowel necrosis in a 68-year-old man. At 11 days after the onset, computed tomography showed superior mesenteric artery obstruction. We fenestrated and connected the true lumen to the false lumen of the superior mesenteric artery, and performed thrombectomy in both lumens. A bowel resection was carried out immediately. The patient was discharged uneventfully after recovery.

Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos syndrome: report of a case.

The vascular type of Ehlers-Danlos syndrome (vEDS) is a rare inherited disease of the connective tissues, and is caused by abnormal type III collagen resulting from heterogeneous mutations of the type III collagen COL3A1 gene. We herein report the case of a vEDS patient who developed a sigmoid colon perforation and was given a definitive diagnosis by a genetic and biomolecular assay. The patient demonstrated clinical manifestations caused by tissue weakness such as frequent pneumothorax events and a detached retina. During the operation, we noticed easy bruising and thin skin with visible veins on the patient's abdominal wall. Finally, a diagnosis was confirmed by the reduction of type III collagen synthesis and by the identification of a mutation in the gene for type III collagen. We conclude that it is difficult to diagnose a vEDS patient without clinical experiences and specialized genetic methods. Furthermore, all organs must be treated gently during therapy, because the tissues of vEDS patients are extremely fragile.