The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.
R0 resectability is thought to be one of the important prognostic factors in bile duct cancer. To achieve R0 resection, accurate preoperative diagnosis is essential. However, intraoperative frozen-section diagnosis sometimes reveals positive ductal margins. It is known that nodular infiltrative tumors tend to extend to the subserosal layer. On the other hand, papillary tumors often have extensive intramural extension, the so-called intraepithelial spread. This type of extension remains difficult to diagnose preoperatively. Some investigators query the clinical significance of positive ductal margins with carcinoma in situ or severe dysplasia. However, even in such instances, local recurrence 5 years after the initial surgery was reported in several articles. Middle bile duct cancer often extends to the upper (hilar bile duct) and lower (intrapancreatic bile duct) sections of the bile duct. To achieve R0 resection, a variety of operative procedures should be considered. For example, hepatopancreatoduodenectomy is required in patients with broad tumor extension up to the hilar bile ducts. However, hilar bile duct resection can result in R0 resection for patients with limited tumor extension. Thus, appropriate operative procedures should be selected based on patients' organ function and other possible prognostic factors, such as lymph node metastases.
A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1 combined with gemcitabine was conducted. But one year later, a recurrent tumor was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial response, and after 9 courses, a radiological complete response was achieved. We could then perform total pancreatotectomy and resection of the metastatic liver tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be considered.
We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.
Recent advances in multidetector computed tomography (MDCT) offer several benefits for management of perihilar tumors. Resection planning for perihilar cholangiocarcinoma should consider two factors: safety and curability. Recognition of individual anatomic variations is particularly important for avoiding intraoperative injury. In particular, hepatic arterial variations often restrict resection procedures. Extent of both longitudinal and vertical invasion by biliary tumors can be estimated from multiplanar reconstruction (MPR) images. Longitudinal extent of resection can be planned based on two anatomic landmarks, the U point and the P point, readily identifiable in preoperative 3-dimensional (3D) images and by intraoperative inspection. Concerning vertical invasion, when direct vascular invasion is suspected from a finding of attachment of tumor and vessels such as portal veins and/or hepatic arteries without a thin low-density plane of separation shown by MPR, these vessels should be resected en bloc with the tumor. Surgical team members can plan and simulate details of vascular resection and reconstruction using 3D images. Reduced operative morbidity and increased R0 resection rates are expected because of better planning of procedures. These techniques soon may increase long-term survival for patients with perihilar cholangiocarcinoma.
Background and Aim: Advanced hepatocellular carcinoma (HCC) with portal vein invasion or intrahepatic metastases has an unfavorable prognosis, even after curative hepatic resection. The aim of the present study was to evaluate the efficacy of adjuvant hepatic arterial infusion chemotherapy with 5-fluorouracil (5-FU) and systemic interferon (IFN).
Little is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer.
A 61-year-old female underwent right hemihepatectomy and caudate lobectomy for hilar cholangiocarcinoma in 1999. Ten years later, increasing serum carbohydrate 19-9 was detected by routine follow-up. Subsequent positron emission tomography revealed an asymptomatic lesion in the right 11th rib. As the mass steadily grew in size, the lesion was resected en bloc with the affected rib and muscle. The histopathological findings closely resembled those of the primary cholangiocarcinoma. Thus, the tumor was diagnosed as a metastatic recurrence 10 years after resection of the primary tumor. There have been a few reports of cholangiocarcinoma recurrence in long-term survivors at the surgical margins, peritoneum, or transhepatic drainage route. However, there are no reports of solitary extra-abdominal recurrence. This case highlights the need for careful follow-up of patients with cholangiocarcinoma and nodal metastasis, even in the absence of recurrence for >5 years after curative resection.
The use of immunosuppressants after liver transplantation (LT) is associated with postoperative complications, including infections. A 49-year-old male underwent living-donor (LD) LT because of primary sclerosing cholangitis. He was treated with tacrolimus, mycophenolate mofetil, and steroids as immunosuppressants, discharged on postoperative day (POD) 40, and re-admitted because of severe acute cellular rejection on POD 48. Three courses of steroid pulse therapy were performed, and continuous peripheral intravenous drip infusion therapy via the left forearm was necessary for 20 days because of appetite loss. The patient was discharged on POD 83, but re-admitted on POD 87 with pyrexia. A subcutaneous abscess was present at a puncture wound on the left forearm formed by an intravenous drip during the last hospital stay. Furthermore, computed tomography showed five pieces of cavitary or wedge-shaped nodules in the bilateral lung. Because sputum revealed the presence of Gram-positive coccus, and subcutaneous abscess and blood cultures revealed Staphylococcus aureus, the pathogenesis was septic pulmonary embolism (SPE) secondary to S. aureus septicemia originating from a subcutaneous abscess formed by an intravenous drip. The patient was treated with drainage of the subcutaneous abscess and antibiotic therapy, and recovered immediately. Although there have been few reports of SPE after LDLT, SPE is fatal in up to 13.3 % of patients. Early diagnosis, drainage of the infectious source, and appropriate use of antimicrobial therapy should be necessary to overcome SPE. Furthermore, the identical intravenous catheters should be removed whenever possible to avoid infectious complications including SPE for patients who receive steroid pulse therapy after LDLT.
Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period.
The purpose of this study was to determine the efficacy of hepatic artery infusion (HAI) plus systemic chemotherapy (SYS) as the prehepatectomy chemotherapy for liver metastases from colorectal cancer. Clinicopathologic data were available for 117 patients who were treated with chemotherapy before liver surgery. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with HAI/SYS (n=26; 65% and 96%, respectively) were higher than those treated with HAI alone (n=63; 41% and 70%) or SYS alone (n=28; 25% and 42%). Histological examination of adjacent nonneoplastic liver confirmed that severe sinusoidal dilatation was less frequent in HAI/SYS group than in SYS group, and moderate to severe steatosis was also less frequent in HAI/SYS group as compared to HAI group. The combination of regional HAI and systemic chemotherapy is an effective prehepatectomy regimen for the treatment of patients with aggressive liver metastases from colorectal cancer.
BACKGROUND: Although correlation of postoperative morbidity with long-term survival is recognized to influence long-term survival after other cancer surgery, little information exists about the impact of postoperative morbidity on patient outcomes following liver resection for colorectal metastases. METHODS: We studied the impact of postoperative morbidity on long-term survival after liver resection for colorectal cancer metastases using data from 312 patients with curative hepatectomy. RESULTS: Among all 312 patients evaluated, 98 complications occurred, affecting 80 patients (26%). The 80 patients with morbidity had a lower disease-free rate (P = 0.03), resulting in poor overall survival (P = 0.02) compared with the group with no morbidity (n = 232). Decreases in disease-free and overall survival also were associated with severity of postoperative complications. When patients were divided according to extent of metastases, little impact of morbidity on overall survival (P = 0.10) and disease-free rate (P = 0.35) was demonstrated in patients whose metastases were less advanced. However, a negative impact of morbidity compared with no morbidity on disease-free rate (P < 0.01) and overall survival (P < 0.01) was confirmed in patients with aggressive or advanced metastases. CONCLUSIONS: Postoperative morbidity had a negative impact on long-term survival, especially for aggressive or advanced metastases or severe complications.
We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy.
Although portal vein embolization (PVE) and staged hepatectomy (StHx), as well as prehepatectomy chemotherapy, have improved the resectability rate of patients with multiple bilobar colorectal liver metastases, the impact of prehepatectomy chemotherapy on liver hypertrophy following PVE and/or StHx has remained unclear.
This report presents a rare case of intrahepatic cholangiocarcinoma (IHCC) arising 28 years after excision of a type IV-A congenital choledochal cyst. The patient underwent excision of a congenital choledochal cyst (Todanis type IV-A) at 12 years of age, with Roux-en-Y hepaticojejunostomy reconstruction. She received a pancreaticoduodenectomy (PD) using the modified Child method for an infection of a residual congenital choledochal cyst in the pancreatic head at the age of 18. She was referred to this department with a liver tumor 22 years later. Left hemihepatectomy with left-side caudate lobectomy was performed and the tumor was pathologically diagnosed to be IHCC. The cause of the current carcinogenesis was presumed to be reflux of pancreatic juice into the residual intrahepatic bile duct during surgery. This case suggests that a careful long-term follow-up is important for patients with congenital choledochal cysts, even if a separation-operation was performed at a young age, and especially after PD.
As laparoscopic cholecystectomy and liver transplantation (LT) have become more common, so has biliary stricture. Fortunately, endoscopic treatment has almost simultaneously been developed. This article reviews the recent reports concerning the management of benign biliary strictures (BBS).
Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.
Effectiveness of gastric emptying after pylorus-preserving gastrectomy (PPG) remains unclear and a method for continuous assessment is needed. We assessed post-PPG gastric emptying with a continuous real-time ¹³C breath test (BreathID system, Oridion, Israel).
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.