Colonic stent-induced mechanical compression may suppress cancer cell proliferation in malignant large bowel obstruction.

BACKGROUND: The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent (SEMS) followed by elective surgery, "bridge to surgery (BTS)", for malignant large bowel obstruction (MLBO) have been well described; however, the influence on long-term oncological outcomes is unclear. The aim of this study was to evaluate changes in oncological characteristics in colorectal cancer (CRC) tissues after SEMS insertion, focusing on growth factors, cell cycle and apoptosis. METHODS: From January 2013 to September 2014, a total of 25 patients with MLBO who underwent BTS at our single institution were retrospectively included. Paired CRC tissue samples before (endoscopic biopsy) and after SEMS insertion (surgically resected) were collected from each patient. EGFR, VEGF, Ki-67, p27kip1 and TUNEL expression were determined by immunohistochemistry. RESULTS: No clinical or subclinical perforations evaluated by mechanical ulceration pathologically were observed. Epithelial exfoliation, tumour necrosis, infiltration of inflammatory cells and fibrosis were observed in SEMS-inserted surgically-resected specimens. Overall, 84% (21/25) and 60% (15/25) of patients exhibited no change or a decrease in staining category, respectively, for EGFR and VEGF expression after SEMS insertion. A significant decrease in Ki-67 expression was observed in surgically-resected specimens compared with endoscopic biopsy specimens (P < 0.01). The upstream cell cycle inhibitor, p27kip1, was significantly increased after SEMS insertion (P = 0.049). CONCLUSIONS: Although the long-term safety of BTS should be determined in a future clinical trial, mechanical compression by SEMS may suppress cancer cell proliferation and this result could provide some insights into the issue.

[Long-Term Complete Response in an Unresectable Advanced Gastric Cancer Patient Treated with Low-Dose S-1].

After undergoing an upper gastrointestinal endoscopy, a 74-year-old woman with anemia was diagnosed with advanced lower gastric cancer. We performed laparotomy and identified the tumor as unresectable because of the direct invasion to the pancreas. S-1 was administered at 60mg/day for 2 weeks followed by 1-week discontinuation. After 6 weeks, we changed the schedule to the same dosage of S-1 for 1 week followed by 2-week discontinuation. CT and endoscopic findings showed complete response after 64weeks of S-1 administration. Since then, S-1 has been maintained at 60mg/day intermittently for 14 days in 7 weeks accordingto the patient's condition. The patient is currently doingwell with a complete response for more than 5 years.

Nestin phosphorylation at threonines 315 and 1299 correlates with proliferation and metastasis of human pancreatic cancer.

The neuroepithelial stem cell marker nestin is a cytoskeletal protein that regulates cell proliferation, invasion, and stemness in various tumors, including pancreatic tumors. In the present study, we examined the expression and roles of phosphorylated nestin in pancreatic cancer cells. Nestin phosphorylation at threonines 315 (Thr315) and 1299 (Thr1299) was observed during mitosis in human pancreatic cancer cells. Nestin phosphorylation was positively correlated with a cell proliferation marker, MIB-1 expression in human pancreatic cancer samples. Transfection of MIA PaCa-2 cells with nestin mutated at Thr315 and/or Thr1299 (to suppress phosphorylation) resulted in lower proliferation rates than those in control groups. Transfecting MIA PaCa-2 cells with wild-type nestin or with nestin mutated at Thr315 increased migration and invasion. In contrast, transfection with nestin mutated at both phosphorylation sites (Thr315 and Thr1299) did not enhance cell migration or invasion. In an intra-splenic xenograft experiment using MIA PaCa-2 cells, tumors expressing the nestin double mutant formed fewer liver metastases than tumors expressing wild-type nestin. Nestin phosphorylation at these two sites was decreased upon treatment with inhibitors for cyclin dependent kinases, AKT, and Aurora in PANC-1 cells, which express a high baseline level of phosphorylated nestin. These findings suggest that phosphorylation of nestin at Thr315 and/or Thr1299 affects cell proliferation, and inhibition of both phosphorylation sites suppresses invasion and metastasis of human pancreatic cancer. Inhibiting nestin phosphorylation at these two sites may represent a novel therapeutic strategy for pancreatic cancer.

[Radical resection of a locally advanced pancreatic tail adenosquamous carcinoma treated with S-1 and gemcitabine as neoadjuvant chemotherapy - a case report].

We report a case of locally advanced pancreatic tail adenosquamous carcinoma that was treated by performing R0 resection after neoadjuvant chemotherapy with S-1 and gemcitabine. A 75-year-old man visited our hospital because of left lateral abdominal pain. On the basis of computed tomography and endoscopic biopsy findings, an 80-mm locally advanced pancreatic tail carcinoma with direct invasion to the gastric upper body, splenic flexure of the colon, and left kidney was diagnosed. Combined chemotherapy with S-1 and gemcitabine was initiated for reduction in the tumor size. After 11 courses of treatment, computed tomography revealed a partial response in tumor size reduction. Grade 3 neutropenia was observed as an adverse event. Distal pancreatectomy, proximal gastrectomy, partial resection of the descending colon, resection of the left kidney and left adrenal gland, and D2 lymph node dissection were performed. The pathological diagnosis was adenosquamous carcinoma in the pancreatic tail, and an R0 resection was achieved. However, a month after surgery, multiple distant liver metastases were observed. Neoadjuvant chemotherapy with S-1 and gemcitabine may reduce the tumor size in locally advanced pancreatic tail adenosquamous carcinoma and increase the R0 resection rate. However, treatment for distant metastasis is warranted in cases of pancreatic adenosquamous carcinoma.

Gallbladder strangulation caused by a fibrotic band due to chlamydia infection: A case report.

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.

Prosthetic repair of an incarcerated groin hernia with small intestinal resection.

PURPOSE: No consensus has been reached on the use of prostheses in a potentially infected operating field. In this study, we evaluated the validity of a mesh prosthesis for the repair of incarcerated groin hernias with intestinal resection. METHODS: Twenty-seven patients underwent operations for correction of incarcerated groin hernias with small intestinal resection at our hospital between January 2000 and March 2010. The patients were divided into two groups: those who underwent repair with a prosthetic mesh and those who underwent primary hernia repair. Patients with intestinal perforations, abscess formations, panperitonitis, and those who required colon resections were excluded. The length of the operation, blood loss, and incidences of surgical site infection, postoperative ileus, and recurrence were evaluated in each group. RESULTS: Of the 27 patients studied, 10 (37%) underwent tension-free repair with a mesh, and 17 (63%) underwent primary hernia repair. Although the patients who underwent primary hernia repair were significantly older than the patients who underwent mesh repair (P = 0.015), no statistically significant differences in morbidity, including surgical site infection, or mortality, were identified. CONCLUSION: Strangulated inguinal hernias cannot be considered a contraindication to the use of a prosthetic mesh even in cases requiring small-intestinal resection.

Laparoscopic distal pancreatectomy preserving spleen and splenic vessels for pancreatic insulinoma.

We describe a 43-year-old woman who underwent laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for the treatment of insulinoma in the pancreatic body. The patient experienced cold sweats on fasting, received diagnosis of insulinoma, and was referred to our hospital for laparoscopic surgery. Blood biochemistry studies showed low fasting blood glucose of 42 mg/dL, serial immunoreactive insulin of 15.2 microU/mL, and a Fajans index (immunoreactive insulin/blood glucose) of 0.36 (normal <0.30). Contrast-enhanced early-phase computed tomography of the abdomen showed a circular, intensely stained, 1.6-cm-diameter tumor in the pancreatic body close to the main pancreatic duct. A solitary insulinoma of the pancreatic body was diagnosed on the basis of the result of hematologic studies, and diagnostic imaging results. Because of the location of the tumor, we elected to perform distal pancreatectomy preserving the spleen and splenic vessels, rather than enucleation. Insulin and blood glucose levels were monitored during surgery. Before removal of the tumor, insulin levels remained consistently high, never decreasing to less than 10 microU/mL. After surgery, insulin levels decreased rapidly, to less than 5 microU/mL within 30 minutes and subsequently remained at the new low level, leading us to conclude that the entire tumor had been removed. There were no postoperative complications, and the patient was discharged from the hospital on day 7. There was no major intraoperative bleeding other than at the resected surface. The patient was ambulatory soon after the procedure, and had a brief hospital stay therefore, the surgery was judged to have been highly useful in this case.

[Pancreaticoduodenal lymph node metastasis of neuroendocrine carcinoma of unknown primary associated with duodenal carcinoma].

A 73-year-old man was admitted with bloody stool. Duodenoscopy showed a hemorrhagic ulceration in the duodenum on the side opposite to the papilla of Vater. Abdominal CT demonstrated a well-defined hypervascular mass, adjacent to the lesion of the duodenum. Although as duodenal GIST was diagnosed, histologic examination for frozen sections during the procedure revealed tubular adenocarcinoma of the duodenum and pancreaticoduodenal lymph node metastasis of neuroendocrine carcinoma. He underwent a subtotal stomach-preserving pancreaticoduodenectomy. Clinicopathologically, the neuroendocrine carcinoma of the pancreaticoduodenal lymph node was considered to be metastasis from an unknown primary lesion.

Surgical treatment for isolated multiple pancreatic metastases from renal cell carcinoma: report of a case.

A 70-year-old man was admitted to our hospital for evaluation of multiple pancreatic tumors. Twelve years earlier he had undergone left radical nephrectomy for renal cell carcinoma (RCC). Computed tomography revealed two well-defined mass lesions in the head and tail of the pancreas, with strong contrast enhancement in the arterial phase. Fluorine-18 fluorodeoxyglucose positron emission tomography detected an elevated uptake within the lesions but no extrapancreatic uptake. The preoperative diagnosis was isolated multifocal metastatic pancreatic tumors from RCC. The patient underwent total pancreatectomy with splenectomy. Both of the tumors were well-demarcated, gray-white, and firm on gross observation. Microscopic examination, meanwhile, revealed solid tumors consisting of clear oval cells with severe nuclear atypia. These pathologic findings were consistent with the preoperative diagnosis of pancreatic metastasis from RCC. Radical resection improves the long-term survival of patients, and total pancreatectomy may be an appropriate procedure.

Clinical outcomes for 14 consecutive patients with solid pseudopapillary neoplasms who underwent laparoscopic distal pancreatectomy.

INTRODUCTION: The postoperative results of laparoscopic distal pancreatectomy for solid pseudopapillary neoplasm of the pancreas (SPN), including the effects of spleen-preserving resection, are still to be elucidated. METHODS: Of the 139 patients who underwent laparoscopic pancreatectomy for non-cancerous tumors, 14 consecutive patients (average age, 29.6 years; 1 man, 13 women) with solitary SPN who underwent laparoscopic distal pancreatectomy between March 2004 and June 2015 were enrolled. The tumors had a mean diameter of 4.8 cm. Laparoscopic spleen-preserving distal pancreatectomy was performed in eight patients (spleen-preserving group), including two cases involving pancreatic tail preservation, and laparoscopic spleno-distal pancreatectomy was performed in six patients (standard resection group). RESULTS: The median operating time was 317 min, and the median blood loss was 50 mL. Postoperatively, grade B pancreatic fistulas appeared in two patients (14.3%) but resolved with conservative treatment. No patients had postoperative complications, other than pancreatic fistulas, or required reoperation. The median postoperative hospital stay was 11 days, and the postoperative mortality was zero.None of the patients had positive surgical margins or lymph nodes with metastasis. The median follow-up period did not significantly differ between the two groups (20 vs 39 months, P = 0.1368). All of the patients are alive and free from recurrent tumors without major late-phase complications. CONCLUSION: Laparoscopic distal pancreatectomy might be a suitable treatment for patients with SPN. A spleen-preserving operation is preferable for younger patients with SPN, and this study demonstrated the non-inferiority of the procedure compared to spleno-distal pancreatectomy.

Clinical outcomes of 15 consecutive patients who underwent laparoscopic insulinoma resection: The usefulness of monitoring intraoperative blood insulin during laparoscopic pancreatectomy.

BACKGROUND: Insulinoma is a very serious functional tumor. Surgeons should confirm complete resection of insulinomas before completing the operation, even in laparoscopic surgery. METHODS: Between August 2007 and September 2014, 15 consecutive patients with biochemical evidence of an insulinoma underwent laparoscopic pancreatectomy. Intraoperatively, a peripheral arterial blood sample was taken, and insulin was measured by quick insulin assay. Insulin levels were determined before anesthesia induction, every 30 min thereafter, and every 30 min for at least 1 h after tumor resection to confirm insulin levels did not increase before surgery was completed. RESULTS: All 15 patients (3 men and 12 women, average age 57.2 years) successfully underwent laparoscopic resection. One patient had two tumors, and the remaining 14 patients had one tumor each (three in the head, five in the body, and eight in the tail of the pancreas). Preoperative localization and regionalization studies identified the tumor correctly through CT (12/15 [80.0%]), MRI (9/12 [75.0%]), angiography (11/13 [84.6%]), endoscopic ultrasonography (7/10 [70.0%]), and selective arterial calcium injection (14/14 [100%]). Intraoperative ultrasonography detected 13 of 15 tumors (86.7%), and intraoperative blood insulin monitoring confirmed the complete resection of 16 of 16 tumors (100%). All patients were discharged with normal insulin levels and have been followed up for 3-88 months. There has been no recurrence of symptoms in any patients and none has died. CONCLUSION: Complete removal of an insulinoma can be reliably predicted by intraoperative blood insulin monitoring even in laparoscopic pancreatectomies.

Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis.

The class VI intermediate filament protein, nestin is reported to be a progenitor cell marker in various tissues. In the present study, we analyzed the expression and roles of nestin in angiogenesis of pancreatic ductal adenocarcinomas, and determined whether nestin is a potential target for inhibiting tumor angiogenesis using a gene silencing strategy. Nestin expression was detected only in small vessels, whereas CD34, CD31 and factor VIII were also expressed in large-sized blood vessels in PDAC. The number of nestin-positive vessels was approximately 20% the number of CD34-positive vessels, and the average dimension of nestin-positive vessels was approximately 75% that of CD34-positive vessels. The PCNA labeling indices of nestin-positive vessels were higher than those of CD34-positive vessels and nestin-negative vessels. Reducing nestin expression by use of siRNA targeting nestin transcripts inhibited growth of the vascular endothelial cell lines, but there was no difference in cell motility. In xenograft models, administration of siRNA targeting mouse-nestin suppressed subcutaneous human pancreatic cancer cell growth in nude mice. In conclusion, nestin was expressed in small proliferating blood vessels in pancreatic cancer tissues and may be a useful marker of angiogenesis in pancreatic ductal adenocarcinoma tissues. Furthermore, nestin is a potential novel therapeutic target in pancreatic cancers to inhibit tumor angiogenesis.

Pancreaticojejunostomy with closure of the pancreatic stump by endoscopic linear stapler in laparoscopic pancreaticoduodenectomy: a reliable technique and benefits for pancreatic resection.

INTRODUCTION: We introduce a technique for pancreaticojejunostomy with closure of the pancreatic stump by endoscopic linear stapler as a reliable intervention with benefits for pancreatic resection in laparoscopic pancreaticoduodenectomy (Lap-PD). MATERIALS AND SURGICAL TECHNIQUE: Following laparoscopic resection, we perform pancreaticojejunostomy under direct visualization. We employ the same method as in open surgery and enter via a 4-5-cm incision, the minimum size feasible for easy removal of resected material from the body, positioned directly above the stump of the distal pancreas. In January 2011, we began using endoscopic linear stapler when cutting the pancreas during Lap-PD in order to reduce the leakage of pancreatic juice, which may contain tumor cells from the neoplastic lesion. Since then, we have used this procedure in 12 subjects undergoing Lap-PD and 5 subjects undergoing laparoscopic central pancreatectomy. We have observed postoperative complication in only one of the laparoscopic central pancreatectomy cases, involving grade B/C pancreatic fistula, and in none of the Lap-PD cases. DISCUSSION: Our pancreaticojejunostomy with closure of the pancreatic stump by endoscopic linear stapler is a feasible procedure in Lap-PD and has produced positive results over a short time frame.

Successful laparoscopic pancreaticoduodenectomy for intraductal papillary mucinous neoplasm: a case report and a reliable technique for pancreaticojejunostomy.

Like other forms of laparoscopic surgery, laparoscopic pancreaticoduodenectomy (Lap-PD) is a minimally invasive procedure that can greatly reduce bleeding during surgery. We performed Lap-PD for a case of intraductal papillary mucinous neoplasm. To remove the resected tissue from the body, we made a small incision directly above the line of transection of the distal pancreas (the cut stump). This procedure requires complex reconstructive procedures, which we performed through the same small incision. All reconstructive procedures, except for hepaticojejunostomy, were performed under direct visualization; hepaticojejunostomy was performed laparoscopically. The reconstructive surgery was effective and was as safe as open abdominal surgery. We also discuss the value of using an endoscopic linear stapler for Lap-PD pancreatic transection, to reduce extravasation of pancreatic fluid into the abdominal cavity during the resection of tumors involving the pancreatic ducts, such as intraductal papillary mucinous neoplasm.

Dedifferentiated liposarcoma arising from the mesocolon ascendens: report of a case.

Dedifferentiated liposarcoma of the mesentery is an extremely rare tumor. A 71-year-old man with a 2-month history of abdominal distention was admitted to our department for evaluation and treatment of an abdominal mass. Computed tomography and magnetic resonance imaging revealed an 11 × 9 cm mass lesion with fat density in the upper right abdominal cavity, displacing the ascending and transverse colon ventrally. Abdominal angiography showed small feeding vessels of the tumor from the ileocolic artery and the middle colic artery. On basis of these findings, liposarcoma arising from the mesocolon ascendens was diagnosed, and complete removal of the tumor and central pancreatectomy (partial resection of the body of the pancreas) were performed. The histopathological diagnosis was dedifferentiated liposarcoma, and the patient is free from recurrence 6 months after surgery. The treatment strategy for abdominal dedifferentiated liposarcoma is surgical resection with a wide surgical margin.

Comparison of fixation methods for preservation of morphology, RNAs, and proteins from paraffin-embedded human cancer cell-implanted mouse models.

Xenograft transplantation of human tumor cells into immunodeficient mice is an important method to clarify the roles of specific molecules or chemicals in vivo. Recently, this method has been reported as a definitive examination to identify tumor stem cells. In this study, the authors compared the morphology and the quality and quantity of ribonucleic acid (RNA) and protein in paraffin-embedded tissues of nude mice implanted with human uterine cervical cancer cells, followed by fixation with commonly used fixatives, including 4% paraformaldehyde (PFA), 10% neutral buffered formalin (NBF), 20% NBF, and 99% ethanol (EtOH). The quality of the isolated RNA from PFA- and NBF-fixed paraffin-embedded tissues was high, while EtOH-fixed tissues showed degradation of RNA. NBF-fixed tissues showed excellent quality of morphology, but EtOH-fixed tissues showed contraction of cells. Immunohistochemical results showed differences depending on fixations. The 99% EtOH-fixed samples showed decreases of Ki-67 and VEGF-A immunoreactivities, but improved cytokeratin immunoreactivity. This study indicated that formalin fixation is better than alcohol fixation for RNA preservation in paraffin-embedded cancer cell implantation models. Immunohistochemical results differed markedly depending on fixation materials and antibodies; therefore, suitable fixations are needed to quantify and compare the results of immunohistochemical staining on cancer cell implanted nude mice tissues.

Current surgical treatment for chronic pancreatitis.

Chronic pancreatitis (CP) is a painful, yet benign inflammatory process of the pancreas. Surgical management should be individualized because the pain is multifactorial and its mechanisms vary from patient to patient. Two main pathogenetic theories for the mechanisms of pain in CP have been proposed: the neurogenic theory and the theory of increased intraductal/intraparenchymal pressures. The latter theory is strongly supported by the good results of drainage procedures in the surgical management of CP. Other possible contributing factors include pancreatic ischemia; a centrally sensitized pain state; and the development of complications, such as pseudocysts and stenosis of the duodenum or common bile duct. Common indications for surgery include intractable pain, suspicion of neoplasm, and complications that cannot be resolved with radiological or endoscopic treatments. Operative procedures have been historically classified into 4 categories: decompression procedures for diseased and obstructed pancreatic ducts; resection procedures for the proximal, distal, or total pancreas; denervation procedures of the pancreas; and hybrid procedures. Pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy, once the standard operations for patients with CP, have been replaced by hybrid procedures, such as duodenum-preserving pancreatic head resection, the Frey procedure, and their variants. These procedures are safe and effective in providing long-term pain relief and in treating CP-related complications. Hybrid procedures should be the operations of choice for patients with CP.

Overexpressed fibroblast growth factor receptor 2 in the invasive front of colorectal cancer: a potential therapeutic target in colorectal cancer.

Fibroblast growth factor receptor 2 (FGFR2) is considered a novel therapeutic target for various cancer. We used a silencing strategy to clarify the effect of reduced FGFR2 expression in human colorectal cancer (CRC) cells. The invasive front of cancer cells exhibited stronger FGFR2 expression than the surface area of the cancers. FGFR2 shRNA-transfected LoVo cells inhibited cell migration, invasion and tumor growth in vitro and in vivo. Thus, FGFR2 plays important roles in CRC progression in association with tumor cell migration, invasion and growth, and FGFR2 might be a novel therapeutic target for CRC.