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Biomedical subjects

Inne H M Borel Rinkes

Publications and source records attributed to Inne H M Borel Rinkes.

At least 19 recordsLinked to original sources
PubMed2007

Sentinel lymph node mapping in colon cancer: current status.

BACKGROUND: The primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer. METHODS: A systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated. RESULTS: The literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye. CONCLUSIONS: Sentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients.

Colonic Neoplasms↗
PubMed2006

Liver metastases of neuroendocrine tumours; early reduction of tumour load to improve life expectancy.

BACKGROUND: Neuroendocrine tumours frequently metastasize to the liver. Although generally slowly progressing, hepatic metastases are the major cause of carcinoid syndrome and ultimately lead to liver dysfunction, cardiac insufficiency and finally death. METHODS: A literature review was performed to define the optimal treatment strategy and work-up in patients with neuroendocrine hepatic metastases. Based on this, an algorithm for the management of these patients was established. RESULTS: Platelet serotonin and chromogranin A are useful biomarkers for detection and follow-up of neuroendocrine tumour. Helical computed tomography and somatostatin receptor scintigraphy are the most sensitive diagnostic modalities. Surgical debulking is an accepted approach for reducing hormonal symptoms and to establish better conditions for medical treatment, but is frequently impossible due to the extent of disease. A novel approach is the local ablation of tumour by thermal coagulation using therapies such as radiofrequency ablation (RFA) or laser induced thermotherapy (LITT). These techniques preserve normal liver tissue. There is a tendency to destroy metastases early in the course of disease, thereby postponing or eliminating the surgically untreatable stage. This can be combined with postoperative radioactive octreotide to eliminate small multiple metastases. In patients with extensive metastases who are not suitable for local destruction, systemic therapy by octreotide, 131I-MIBG treatment or targeted chemo- and radiotherapy should be attempted. A final option for selective patients is orthotopic liver transplantation. CONCLUSION: Treatment for patients with neuroendocrine hepatic metastases must be tailored for each individual patient. When local ablative therapies are used early in the course of the disease, the occurrence of carcinoid syndrome with end stage hepatic disease can be postponed or prevented.

Journal Article↗
PubMed2006

KRAS(D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosis-inducing ligand.

Colorectal tumors frequently contain activating mutations in KRAS. ReovirusT3D is an oncolytic virus that preferentially kills tumor cells with an activated Ras pathway. Here we have assessed the contribution of endogenous mutant KRAS in human colorectal cancer cell lines to ReovirusT3D replication and to tumor cell oncolysis. In addition, treatment combinations involving ReovirusT3D, oxaliplatin, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were tested for their efficacy in tumor cell killing. The mutation status of KRAS did not predict the sensitivity of a panel of human colorectal cancer cell lines to ReovirusT3D. Virus replication was observed in all cell lines tested regardless of KRAS status and was not affected by deletion of endogenous mutant KRAS(D13). However, deletion of KRAS(D13) or p53 did reduce apoptosis induction by ReovirusT3D whereas deletion of beta-catenin(DeltaS45) had no effect. Likewise, KRAS(D13)- or p53-deficient cells display reduced sensitivity to oxaliplatin but not to death receptor activation by TRAIL. Finally, the treatment of colorectal cancer cells with ReovirusT3D combined with either oxaliplatin or TRAIL resulted in a nonsynergistic increase in tumor cell killing. We conclude that oncolysis of human tumor cells by ReovirusT3D is not determined by the extent of virus replication but by their sensitivity to apoptosis induction. Oncogenic KRAS(D13) increases tumor cell sensitivity to activation of the cell-intrinsic apoptosis pathway without affecting ReovirusT3D replication.

Apoptosis↗
PubMed2006

Synergistic effect of interstitial laser coagulation and doxorubicin in a murine tumor recurrence model of solitary colorectal liver metastasis.

BACKGROUND: Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model. METHODS: Single C26 colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium-yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging. RESULTS: Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load. CONCLUSIONS: A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.

Animals↗
PubMed2006

Aortoesophageal fistula successfully treated by endovascular stent-graft.

The case of a patient with an aortoesophageal fistula is presented, which was caused by ingestion of a chicken bone and was treated by endovascular stent-graft placement and esophagectomy with early reconstruction. The diagnostic and therapeutic options and challenges encountered in treating an aortoesophageal fistula are discussed.

Adult↗
PubMed2006

Multiple fiber laser-induced thermotherapy for ablation of large intrahepatic tumors.

OBJECTIVE: The aim of this study was to test three techniques used simultaneously to increase lesion size. BACKGROUND DATA: Laser-induced thermotherapy (LITT) is a method of local tumor ablation, which may prolong survival in patients with unresectable liver metastases. The main limitation has been the production of lesions with sufficient tumor-free margin. METHODS: LITT treatment was performed with water-cooled, multiple fiber application and hepatic blood flow occlusion in six patients with unresectable intrahepatic metastases. Response was measured by computed tomography scan. RESULTS: In all patients, tumors were effectively ablated. In two patients with colorectal metastases, lesions up to 8.6 cm could be created. CONCLUSION: The use of watercooled multiple fiber application and hepatic inflow occlusion makes LITT an effective ablative method, expanding the treatment options for patients with large intrahepatic masses.

Aged↗
PubMed2006

Multipolar radiofrequency ablation of large hepatic metastases of endocrine tumours.

Radiofrequency ablation (RFA) is a reliable method of creating thermally induced coagulation necrosis. Local recurrence after RFA of hepatic metastases is directly dependent on tumour size related to the free margin of ablation. To produce larger coagulation volumes a bipolar radiofrequency device was developed that allows the simultaneous activation of three active needles. This technique was used at laparotomy in a patient with liver metastases of an endocrine tumour. Coagulation size up to 12 cm in diameter could be created. The postoperative recovery of the patient was uncomplicated. No local recurrence was seen after 13 months of follow-up with computed tomography scan. The use of simultaneously operated multiple radiofrequency electrodes in a multipolar mode expands the treatment options for patients with large and unresectable intrahepatic metastases.

Catheter Ablation↗
PubMed2006

Robot-assisted laparoscopic resection of a large paraganglioma: a case report.

A 19-year-old female patient presented with headache, nausea, hypertension, visual impairment of the left eye and exertion-related complaints of palpitations since 1 year. Fundoscopy showed severe hypertensive retinopathy grade IV. A paraganglioma in the left para-aortic region was diagnosed by urinary screening and magnetic resonance imaging scanning. The tumor was resected by a robot-assisted laparoscopic procedure. The surgical operating time was 250 minutes and the blood loss was 150 mL. After surgery the blood pressure normalized and antihypertensive drugs were no longer required. Oral intake was resumed on the first postoperative day and the hospital stay was 3 days. Final pathology examination revealed a paraganglioma with pheochromocytomal features of 7x5.1x3.5 cm. Reports on laparoscopic resection of large paragangliomas are scarce. This case has demonstrated that the procedure is feasible and associated with rapid recovery from surgery. The surgical team experienced explicit support by the robot in the dissection of this highly vascularized tumor.

Abdominal Neoplasms↗
PubMed2005

Dual effect of Kras(D12) knockdown on tumorigenesis: increased immune-mediated tumor clearance and abrogation of tumor malignancy.

Activating mutations in the human KRAS proto-oncogene are acquired during the earliest stages of colorectal cancer development. If mutant KRAS is to be used as a target for therapy in colorectal cancer, tumor growth should depend on its continued presence. Here, we report that stable knockdown of Kras(D12) in murine C26 colorectal cancer cells by RNA interference resulted in loss of transformed properties in vitro. The incidence of subcutaneous tumor formation was reduced by 60% and the lag time was increased sevenfold. Kras(D12)-knockdown tumors grew noninvasively and did not cause morbidity. Remarkably, some of the Kras(D12)-knockdown tumors regressed spontaneously, which rendered these mice resistant to parental C26 tumor growth. In immune-deficient hosts, the incidence of tumor formation by Kras(D12)-knockdown cells was 100%. None of these tumors regressed spontaneously. We conclude that the reduced incidence of tumor formation by Kras(D12)-knockdown cells is due to tumor cell clearance by the host immune system, but not to an intrinsic inability of these cells to grow out as tumors. Interestingly, Kras(D12) knockdown resulted in increased production of interleukin 18 (Il-18), an immune-stimulatory cytokine that has been implicated in limiting colorectal tumor formation. Thus, mutant Kras(D12) suppresses Il-18 production in colorectal tumor cells, which may contribute to evasion of the local immune system during tumor development.

Animals↗
PubMed2005

Robot-assisted endoscopic surgery: a four-year single-center experience.

BACKGROUND: Robotic systems were introduced in the late 1990s with the objective to overcome the technical limitations of endoscopic surgery. In this prospective cohort study the potential safety, feasibility, pitfalls and challenges of robotic systems in gastrointestinal endoscopic surgery are assessed and our vision on future perspectives is presented. METHODS: Between August 2000 and December 2004, 208 procedures were performed with support of the Intuitive Surgical da Vincitrade mark robotic system. We started with cholecystectomies (40) and Nissen fundoplications (41) to gain experience with robot-assisted surgery. In the following years more complex procedures were carried out, i.e. colorectal procedures (7), type III/IV paraesophageal hernia repair (32), redo Nissen fundoplications (9), Heller myotomies (24), esophageal resections (22), rectopexies (16) and aortobifemoral bypasses (3). RESULTS: The median robotic set-up time was 13 min, and 7 min in the last 50 procedures. The median operating time for the total of procedures was 120 min (45-420) and the median blood loss was 30 ml (0-800). Fourteen procedures were converted to open surgery (6.7%). Equipment-related problems, such as start-up failures and positioning difficulties of the robotic arms, were encountered in 11 cases (5.3%). Postoperative complications were seen in 11 patients (11/176, 6.3%) after robot-assisted laparoscopic procedures. Pulmonary complications occurred in 11 patients, cardiac in 3, anastomic leakage in 3, chylous leakage in 3 and vocal cord paralysis in 3 after thoracoscopic esophagolymphadenectomy for esophageal cancer. One patient died 12 days after esophageal resection (0.5%). CONCLUSION: During the implementation of this robotic system, we experienced an obvious learning curve, particularly with regard to the positioning of the robot cart and communication between the surgeon and operating team. After 4 years, we have experienced that the merits of the current generation of this technology probably is preserved to complex endoscopic procedures with delicate dissection and suturing. In the nearby future we will focus on the treatment of motility disorders and malignancies of the esophagus and stomach. The position of the robot in the endoscopic operating room will have to be clarified by the outcome of prospective research. Furthermore, priorities have to be acclaimed on technical sophistication and cost reduction of these systems.

Adolescent↗
PubMed2005

Control of colorectal metastasis formation by K-Ras.

Mutational activation of the K-Ras proto-oncogene is frequently observed during the very early stages of colorectal cancer (CRC) development. The mutant alleles are preserved during the progression from pre-malignant lesions to invasive carcinomas and distant metastases. Activated K-Ras may therefore not only promote tumor initiation, but also tumor progression and metastasis formation. Metastasis formation is a very complex and inefficient process: Tumor cells have to disseminate from the primary tumor, invade the local stroma to gain access to the vasculature (intravasation), survive in the hostile environment of the circulation and the distant microvascular beds, gain access to the distant parenchyma (extravasation) and survive and grow out in this new environment. In this review, we discuss the potential influence of mutant K-Ras on each of these phases. Furthermore, we have evaluated the clinical evidence that suggests a role for K-Ras in the formation of colorectal metastases.

Cathepsins↗
PubMed2005

Cyclooxygenase-2 is a target of KRASD12, which facilitates the outgrowth of murine C26 colorectal liver metastases.

PURPOSE: Mutational activation of the KRAS oncogene and overexpression of cyclooxygenase-2 (COX-2) contribute to colorectal carcinoma (CRC) development, but the relationship between these two events is unclear. This study was designed to clarify that relationship and to assess the contribution of KRAS-dependent COX-2 to the seeding of CRC cells in the liver and to their outgrowth as liver metastases in an experimental mouse model. EXPERIMENTAL DESIGN: The effect of RNA interference-mediated KRAS knockdown on COX-2 expression and activity was tested in murine C26 CRC cells. The contribution of KRAS-dependent COX-2 to early metastatic tumor cell seeding (by intravital microscopy) and outgrowth of metastases in the liver (by bioluminescence imaging) was studied by using parecoxib, a novel and highly selective liver-activated COX-2 inhibitor. Intratumoral cell proliferation, apoptosis, and tumor-associated angiogenesis were assessed by immunohistochemistry on liver tissue sections. RESULTS: Stable knockdown of mutant KRAS(D12) in murine C26 CRC cells by RNA interference lead to a dramatic reduction of COX-2 synthesis and prostaglandin E2 production. Inhibition of host or tumor cell COX-2 activity had no effect on early metastatic cell seeding in the liver but greatly reduced intrahepatic tumor cell proliferation and the rate of liver metastasis outgrowth. COX-2 inhibition had no effect on early tumor vascularization or on tumor cell apoptosis. CONCLUSIONS: The high levels of COX-2 enzyme and prostaglandin production in C26 CRC cells are primarily caused by the presence of endogenous mutant KRAS(D12). Furthermore, COX-2 inhibition affects the tumoral rather than the vascular compartment during the early stages of C26 liver metastasis outgrowth.

Animals↗
PubMed2005

Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model.

Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five- to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants alpha-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods. In conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon.

Animals↗
PubMed2005

NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder carcinoma and has been correlated with an increased disease stage and with reduced patient survival. METHODS: NS-398 was used to inhibit COX-2 selectively in human T24 bladder carcinoma cells. Lentiviral transduction of the firefly luciferase gene allowed us to assess the effect of NS-398 on orthotopic bladder carcinoma growth over time in a noninvasive manner. Immunohistochemistry on bladder tissue sections was performed to determine the effect of NS-398 treatment on tumor cell proliferation (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (von Willebrand factor; CD31). RESULTS: T24 cells expressed COX-2 and secreted prostaglandin E2 (PGE2). Selective COX-2 inhibition using NS-398 abrogated PGE2 secretion and inhibited cell proliferation in vitro in a dose-dependent manner, without affecting cell viability. In vivo administration of NS-398 reduced the outgrowth of experimental orthotopic T24 bladder carcinoma. This was accompanied by a significant reduction in Ki-67-positive tumor cells but not by a reduction in tumor cell viability or tumor vascularization. CONCLUSIONS: Selective COX-2 inhibition by NS-398 reduces the outgrowth of T24 human bladder carcinoma in an orthotopic mouse model. The therapeutic activity was most likely caused by inhibition of tumor cell proliferation, rather than by inhibition of angiogenesis or tumor cell survival.

Animals↗
PubMed2005

Sensitization to apoptosis underlies KrasD12-dependent oncolysis of murine C26 colorectal carcinoma cells by reovirus T3D.

Reovirus T3D is an oncolytic agent that preferentially targets tumor cells expressing an activated Ras oncogene. Ras signaling interferes with the cellular stress response that inhibits translation of reovirus RNAs. Murine C26 colorectal carcinoma cells express a mutant KrasD12 gene. Reovirus T3D efficiently kills C26 cells, but not C26 cells in which the KrasD12 mRNA is stably repressed by expression of KrasD12-directed short-hairpin RNAs. Surprisingly, neither reovirus T3D protein synthesis nor T3D virus yields were suppressed by deletion of KrasD12. Rather, reovirus-induced tumor cell apoptosis was completely abrogated as a result of Kras knockdown. We conclude that sensitization of C26 tumor cells to reovirus-induced apoptosis underlies the Ras dependency of reovirus T3D oncolysis.

3T3 Cells↗
PubMed2005

VEGF as a target of therapy in gastrointestinal oncology.

The last decade has seen enormous progress in understanding the development of cancer. It is now recognized that tumor growth is a multistep process that may take years to become clinically relevant. Angiogenesis is an absolute requirement for tumors to become clinically detectable. The importance of angiogenesis for tumor growth is supported by several clinical studies that showed a positive correlation between tumor angiogenesis and tumor stage. In animal studies, inhibition of angiogenesis caused impressive reduction of tumor growth. The aim of antivascular therapy in the treatment of cancer is to attack the tumor through its vasculature. Antivascular therapy can be divided in two different areas: (1) inhibition of angiogenesis with the aim to prevent formation of new blood vessels and (2) vascular targeting agents with the goal to destroy the existing tumor vasculature. Vascular endothelial growth factor (VEGF) has been recognized as one of the most important factors involved in tumor angiogenesis and has become an important target for anticancer treatment. This review focuses mainly on the inhibition of angiogenesis in gastrointestinal tumors by blocking the VEGF receptor/ligand signaling. We will discuss the biology of the VEGF receptor/ligand signaling system and give an overview of the current approaches for therapy in gastrointestinal cancer targeting the VEGF signaling pathway.

Gastrointestinal Neoplasms↗
PubMed2004

Surgery and angiogenesis.

Surgery may be regarded as an angiogenesis-inducing condition since it evokes the release of many angiogenic factors. Regarding the mechanistic overlap between tumor-associated neovascularisation and (physiological) angiogenesis in response to injury and hypoxia, surgery may promote the uncontrolled growth of residual dormant tumor cells. With the advent of anti-angiogenic agents, surgeons will be faced with more patients undergoing surgery for primary and secondary tumors under anti-angiogenic treatment. This could present problems with regard to angiogenesis-dependent phenomena such as wound repair, healing of intestinal anastomoses and liver regeneration. In this review we will discuss these matters from a biomedical and clinical point of view.

Angiogenesis Inducing Agents↗