[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Pancreas divisum, the most common congenital anomaly of the pancreas, is caused by failure of the fusion of the ventral and dorsal pancreatic duct systems during embryological development. Although various pancreatic tumors can occur in patients with pancreas divisum, intraductal papillary mucinous neoplasm is rare.
A 77-year-old woman was referred to our hospital because she was incidentally found to have a cystic tumor in her pancreas at a regular health checkup. Contrast-enhanced abdominal computed tomography images demonstrated a cystic tumor in the head of the pancreas measuring 40 mm in diameter with slightly enhancing mural nodules within the cyst. Endoscopic retrograde pancreatography via the major duodenal papilla revealed a cystic tumor and a slightly dilated main pancreatic duct with an abrupt interruption at the head of the pancreas. The orifice of the major duodenal papilla was remarkably dilated and filled with an abundant extrusion of mucin, and the diagnosis based on pancreatic juice cytology was "highly suspicious for adenocarcinoma". Magnetic resonance cholangiopancreatography depicted a normal, non-dilated dorsal pancreatic duct throughout the pancreas. The patient underwent a pylorus-preserving pancreaticoduodenectomy under the diagnosis of intraductal papillary mucinous neoplasm with suspicion of malignancy arising in the ventral part of the pancreas divisum. A pancreatography via the major and minor duodenal papillae on the surgical specimen revealed that the ventral and dorsal pancreatic ducts were not connected, and the tumor originated in the ventral duct, i.e., the Wirsung's duct. Microscopically, the tumor was diagnosed as intraductal papillary mucinous carcinoma with microinvasion. In addition, marked fibrosis with acinar cell depletion was evident in the ventral pancreas, whereas no fibrotic change was noted in the dorsal pancreas.
Invasive ductal carcinomas of the pancreas associated with pancreas divisum usually arise from the dorsal pancreas, in which the occurrence of pancreatic cancer may link to underlying longstanding chronic pancreatitis in the dorsal pancreas; however, the histopathogenesis of intraductal papillary mucinous neoplasm in this anomaly is a critical issue that warrants further investigation in future.
[Show abstract][Hide abstract] ABSTRACT: Background:
Unnecessary intra-abdominal drain insertion must be avoided, but little is known about the value of prophylactic drainage following laparoscopic distal gastrectomy (LDG). In this study, we investigated the significance of prophylactic drain placement after LDG for gastric cancer.
Seventy-eight consecutive patients with gastric cancer who underwent LDG in our department were retrospectively analyzed. The patients were divided into two groups according to the insertion of a prophylactic intra-abdominal drain following LDG. The 'drain group' comprised 45 patients with routine use of a prophylactic intra-abdominal drain, and the 'no-drain group' comprised 33 patients who did not undergo placement of an intra-abdominal drain.
There were no significant differences in terms of the mean age of the patients, male/female ratio, body mass index, and concurrent diseases between the drain group and the no-drain group. In addition, there were no significant differences in the tumor location, tumor diameter, depth of the tumor, nodal metastasis, and tumor stage between the two groups. All patients in each group were successfully treated with R0 surgery, and no patient required conversion to open surgery. Surgery-related factors, including lymph node dissection and operative time, were similar in the drain group and the no-drain group. A comparison of the amount of intraoperative blood loss between patients with and without postoperative complications revealed that patients who experienced postoperative complications had a significantly larger amount of blood loss than those without postoperative complications. A comparison of operative times between patients with and without surgery-related postoperative local complications revealed that patients who experienced surgery-related postoperative local complications had a significantly longer operative time than those without surgery-related postoperative local complications. Analysis of operative times in each group revealed that patients with surgery-related postoperative local complications had a significantly longer operative time than those without surgery-related postoperative local complications in the no-drain group.
Intraoperative factors such as the operative time and the amount of intraoperative blood loss affected the occurrence of postoperative complications following LDG. A prophylactic drain may thus be useful in patients at higher risk and in those with a longer operative time or massive intraoperative bleeding.
Full-text · Article · May 2015 · World Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Sarcoidosis is a multisystemic disorder that is characterized by the formation of noncaseating granulomas. Although sarcoidosis can affect any organ, gastrointestinal tract involvement in sarcoidosis is very rare, and gastric cancer associated with gastric sarcoidosis has hardly been reported. A 64-year-old female with a 10-year history of the medical treatment of gastric sarcoidosis received a routine follow-up gastrointestinal endoscopy and an irregular-shaped, elevated lesion was detected in the gastric corpus. The gastric mucosal surface was nodular and ulcerated throughout the stomach. The gastric lumen was narrow, and the gastric wall was stiff and nondistensible, resembling linitis plastica. The biopsies of the elevated lesion in the gastric corpus revealed well-differentiated adenocarcinoma. An endoscopic ultrasonography was then performed, but it failed to assess precisely the depth of cancer invasion because of sarcoidosis-related gastritis and fibrosis of the gastric wall. The patient underwent a laparoscopic total gastrectomy under the diagnosis of gastric cancer associated with gastric sarcoidosis. Histologic examination of the surgical specimen demonstrated well-differentiated adenocarcinoma in the gastric corpus, and the histologic mapping of cancer cells revealed that the tumor spread within the mucosal layer of the stomach. No lymph node metastasis was found. The patient's postoperative course was uneventful. We experienced a rare case of early gastric cancer associated with gastric sarcoidosis, which identified the troublesome issue that the assessment of depth of cancer invasion is difficult, because patients with longstanding gastric sarcoidosis may involve various degrees of fibrosis of the gastric wall.
No preview · Article · May 2015 · International surgery
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to characterize the intratumoral expression profiles of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and human equilibrative nucleotide transporter 1 (hENT1) in ampullary carcinomas (ACs) to evaluate their prognostic values and better tailor adjuvant chemotherapy for individual patients with AC after surgery.
This study included 49 patients with AC who underwent a curative pancreaticoduodenectomy. Various clinicopathological factors, including ERCC1, DPD, and hENT1, were analyzed in relation to postoperative disease recurrence and the patients' survival.
The median recurrence-free survival and overall survival were 24.5 months and 32.4 months, respectively. Multivariate Cox regression analysis of recurrence-free survival identified a DPD expression (hazard ratio [HR], 8.18; 95% confidence interval [CI], 2.00-34.8; P = 0.003) and combined ERCC1/DPD expression (HR, 134.8; 95% CI, 11.8-1920; P < 0.001) as independent predictors of disease recurrence. Multivariate Cox regression analysis of overall survival also identified a DPD expression (HR, 8.48; 95% CI, 1.71-46.3; P = 0.008) and combined ERCC1/ DPD expression (HR, 135.6; 95% CI, 11.8-1940; P < 0.001) as independent predictors of survival.
The DPD and ERCC1 expression profile could potentially serve as a useful prognostic biomarker and therapeutic target for surgically resected patients with AC.
[Show abstract][Hide abstract] ABSTRACT: Milk fat globule-epidermal growth factor 8 (MFG-E8) promotes phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis. However, its functions in intestinal inflammation and carcinogenesis are unknown.
Experimental colitis was induced in MFG-E8 knockout (KO) and wild-type (WT) mice by dextran sodium sulfate (DSS) administration. Colon tissues were used for assessments of colitis activity and epithelial proliferation. A mouse colitis-associated cancer (CAC) model was induced by intraperitoneal injection of azoxymethane (AOM) and then the animals were given a single administration of DSS. A sporadic colon cancer model was established by repeated intraperitoneal injections of AOM. The role of MFG-E8 in epithelial proliferation with or without treatment of siRNA targeting αv-integrin was examined in vitro using a WST-1 assay.
The severity of colitis in KO mice was greater than that in WT mice, while the proliferative potential of colonic epithelial cells in KO mice was lower during the regenerative phase. In both CAC and sporadic models, tumor size in KO was lower as compared to WT mice, while decreased tumor incidence was only found in the CAC model. In vitro findings showed that MFG-E8 promotes epithelial cell proliferation, and treatment with a siRNA targeting αv-integrin reduced the proliferation of Colon-26 cells stimulated with recombinant MFG-E8.
MFG-E8 promotes tumor growth regardless of the presence or absence of colonic inflammation, whereas colon tumor development is initiated by MFG-E8 under inflammatory conditions. These MFG-E8 functions may be dependent on integrin-mediated cellular signaling.
No preview · Article · Jan 2015 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: We report a rare case of acinar cell carcinoma (ACC) of the pancreas concomitant with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. An 83-year-old woman with a past history of colon cancer and breast cancer had been followed up for a branch duct type IPMN of the pancreas for 32 months. Enhanced CT and MRI studies depicted a solid tumor, 3.6 cm in diameter, in the head of the pancreas along with existing IPMN in the inferior head of the pancreas. The tumor involved the main pancreatic duct and the superior mesenteric vein. Under a diagnosis of pancreatic ductal carcinoma associated with branch duct IPMN, subtotal stomach preserving pancreaticoduodenectomy with resection of the portal vein was performed. Histopathological examination revealed an ACC and a branch duct IPMN with high-grade dysplasia. Although IPMN often coexists with pancreatic ductal carcinoma, IPMN concomitant with ACC is extremely rare. This case should alert surgeons to be aware of such rare pancreatic malignancies associated either synchronously or metachronously with IPMN of the pancreas.
[Show abstract][Hide abstract] ABSTRACT: A 71-year-old woman with borderline resectable cancer of the head of the pancreas with involvement of the portal vein and splenic artery was referred to our hospital. Gastrointestinal endoscopy and contrast-enhanced CT scan demonstrated a large tumor in the head of the pancreas involving the duodenum, portal venous system, and splenic artery. ERCP showed an abrupt interruption of the main pancreatic duct in the head of the pancreas and subsequent pancreatic juice cytology demonstrated adenocarcinoma. The patient underwent pancreaticoduodenectomy with splenic artery reconstruction to avoid performing a total pancreatectomy, which resulted in the R0 resection. Histologically, the tumor was a well-differentiated invasive ductal adenocarcinoma of the pancreas with invasion to the portal vein, as well as the duodenum. The patient received adjuvant chemoradiotherapy and has been cancer-free for 91 months after surgery with favorable nutrition and quality of life. Our case suggests that a curative pancreatectomy with preservation of the pancreatic functional reserve, as much as possible, may allow the patient to receive an adequate postoperative adjuvant therapy and lead to a favorable outcome in patients with borderline resectable pancreatic head cancer.
[Show abstract][Hide abstract] ABSTRACT: Background:
Previously it has reported that the incidence of internal hernia can be decreased by closing Petersen's defect, but the perfect closure method, in fact, has not been discovered yet. In this study we have developed an easy and reliable method for closing Petersen's defect in the Roux-en-Y reconstruction after a laparoscopic distal gastrectomy.
Materials and methods:
We performed intracorporeal Roux-en-Y reconstruction after laparoscopic distal gastrectomy with antiperistaltic gastrojejunostomy. The greater omentum is placed on the cranial side of the transverse colon through the defect between the elevated jejunum and the transverse mesocolon. Anastomosis is performed of the transverse mesocolon attached to the transverse colon, the greater omentum is passed through the Petersen's defect, and the stump of the mesojejunum is attached to the elevated jejunum by an interrupted suture. Petersen's defect is spread and straightened to stabilize the visual field. The thread is inserted first at the base of the stump of the elevated mesojejunum, next to the greater omentum, which has passed through Petersen's defect, and then to the transverse mesocolon to set the starting point of continuous suture. The stitches of continuous suture are sewn toward the transverse colon. Petersen's defect is closed completely.
We performed this technique in 37 patients. All procedures were completed without intraoperative complication or conversion to laparotomy. During the follow-up period, none of the patients developed complications related to the internal hernia, such as Petersen's hernia.
We have indicated a novel, easy, and secure closure procedure of Petersen's defect following laparoscopic distal gastrectomy with Roux-en-Y reconstruction.
Full-text · Article · Dec 2014 · Journal of Laparoendoscopic & Advanced Surgical Techniques
[Show abstract][Hide abstract] ABSTRACT: We report a case of giant urachal cyst in a neonate presenting characteristic features on fetal ultrasonography.•A fetal ultrasonography demonstrating a unilocular serous cyst that separates the two umbilical arteries is an important clue to the prenatal diagnosis of a urachal cyst.•The infant underwent surgery to make a definite diagnosis and to prevent future complications. The cyst was excised without any complication and finally diagnosed as a urachal cyst based on morphological and pathological findings.
Preview · Article · Oct 2014 · Journal of Pediatric Surgery Case Reports
[Show abstract][Hide abstract] ABSTRACT: Background: Ezrin is a linker protein between actin filaments and cell adhesion molecules, which plays an important role in cancer progression. There are only a few studies available that have investigated ezrin expression in different types of tumors. However, the prognostic importance of ezrin and its correlation with clinicopathological characteristics are yet to be delineated in gastric carcinoma. Methods: Specimens from 124 gastric carcinoma patients of T2 and T3 diseases treated in a defined period with curative operation were evaluated for ezrin, CD8 and cleaved caspase-3 expression by immunohistochemical methods. Results: Ezrin expression was detected in both can-cer cells and interstitial cells (ISCs) infiltrated into the tumor. According to our criterion, 37 pa-tients (29.8%) were positive for ezrin expression and 87 (70.2%) were negative. A significant correlation between ezrin expression and any of the clinicopathological characteristics could not be found. In Spearman-rank correlation test, a significant correlation was found between the num-ber of ezrin-stained ISCs and apoptotic index (AI) of cancer cells. Also the AI of cancer cells was significantly higher in ezrin-positive group when compared with ezrin-negative group. Patients with ezrin-expressing tumors had a significantly better disease-free survival, and in multivariable analysis ezrin expression status remained significant as an independent prognostic factor. Con-clusion: Taken together, our results suggest that ezrin expression may play a vital role in tumor apoptosis and that it can be a useful tool for therapeutic intervention.
No preview · Article · Sep 2014 · Open Journal of Gastroenterology