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Biomedical subjects

I H M Borel Rinkes

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

At least 19 recordsLinked to original sources

First experience with robot-assisted thoracoscopic esophagolymphadenectomy for esophageal cancer.

BACKGROUND: Transthoracic esophagectomy with extended lymph node dissection is associated with higher morbidity rates than transhiatal esophagectomy. This morbidity rate could be reduced by the use of minimally invasive techniques. The feasibility of robot-assisted thoracoscopic esophagectomy (RTE) with mediastinal lymphadenectomy was assessed prospectively. METHODS: This study investigated 21 consecutive patients with esophageal cancer who underwent RTE using the Da Vinci robotic system. Continuity was restored with a gastric conduit and a cervical anastomosis. RESULTS: A total of 18 (86%) procedures were completed thoracoscopically. The operating time for the thoracoscopic phase was 180 min (range, 120-240 min), and the median blood loss was 400 ml (range, 150-700 ml). A median of 20 (range, 9-30) lymph nodes were retrieved. The median intensive care unit stay was 4 days (range, 1-129 days), and the hospital stay was 18 days (range, 11-182 days). Pulmonary complications occurred in 10 patients (48%), and one patient (5%) died of a tracheoneoesophageal fistula. CONCLUSIONS: In this initial experience, robot-assisted thoracoscopic esophagectomy was found to be feasible, providing an effective lymphadenectomy with low blood loss. Standardization of the technique and increased experience should reduce the complication rate, which is in the range of the rate for open transthoracic dissection.

Adenocarcinoma↗

Immunosuppression promotes reovirus therapy of colorectal liver metastases.

Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of virus-based therapies may be positively or negatively modulated by the host immune system. This study was designed to assess the effect of immunosuppression on Reovirus T3D oncolysis of established colorectal micrometastases in the liver. Mouse C26 CRC cells harbor a mutant Kras gene and are susceptible to Kras-dependent oncolysis by Reovirus T3D in vitro. Isolated C26 liver tumors were established in syngenic immunocompetent BALB/c mice by intrahepatic injection. Reovirus T3D therapy was given as a single intratumoral injection in control mice and in cyclosporin A-treated immunosuppressed mice. Tumor growth was analyzed over time by non-invasive bioluminescence imaging. The outgrowth of established CRC liver metastases in immunocompetent mice was efficiently but temporarily inhibited with a single injection of Reovirus T3D. Immunosuppression with cyclosporin A markedly increased and prolonged the therapeutic effect and allowed complete Reovirus T3D-induced tumor eradication in a subpopulation of the mice. We conclude that Reovirus T3D is an effective therapeutic agent against established C26 colorectal liver metastases and that immunosuppression enhances treatment efficacy. Cancer Gene Therapy (2006) 13, 815-818. doi:10.1038/sj.cgt.7700949; published online 10 March 2006.

Animals↗

[Better treatment for patients with colorectal liver metastases].

Three patients, 61, 58 and 63 years old, presented with non-resectable liver metastases from colorectal cancer. The first patient, a man, who had a solitary lesion in the liver and severe cardiovascular morbidity, was successfully treated with laser-induced interstitial thermotherapy. The second patient, a woman, had large multiple liver metastases and two concomitant isolated pulmonary metastases. Following chemotherapy with fluorouracil, leucovorin and oxaliplatin, all lesions were downsized and a hemihepatectomy and pulmonary wedge resections were able to be performed in two stages. At the last follow-up, both patients were disease-free after 12 and 24 months respectively. The third patient, a man, presenting with multiple synchronous liver metastases, showed a significant decrease of hepatic tumour involvement after six courses of capecitabine. At present he is in a good condition and his disease is stable. Surgical resection ofcolorectal liver metastases leads to a 5-year survival rate of up to 45% in selected patients. Unfortunately, only 10 to 20% of patients are amenable to surgical resection. In the remaining group, a combination of new treatment options using local tumour ablative therapies and novel chemotherapeutic regimens provide alternative strategies with the potential of long-term survival.

Antineoplastic Agents↗

Selective portal clamping to minimize hepatic ischaemia-reperfusion damage and avoid accelerated outgrowth of experimental colorectal liver metastases.

BACKGROUND: Temporary vascular clamping during local ablation for colorectal liver metastases increases destruction volumes. However, it also causes ischaemia-reperfusion (IR) injury to the liver parenchyma and accelerates the outgrowth of microscopic tumour deposits. The aim of this study was to investigate the effects of selective portal clamping on hepatocellular damage and tumour growth. METHODS: Mice carrying pre-established hepatic colorectal micrometastases underwent either simultaneous clamping of both the portal vein and the hepatic artery or selective clamping of the portal vein to the median and left liver lobes for 45 min. Sham-operated mice served as controls. Hepatic injury and tumour growth were assessed over time. RESULTS: Standard inflow occlusion resulted in a rise in liver enzymes, a local inflammatory response and hepatocellular necrosis. The outgrowth of pre-established micrometastases was accelerated three- to fourfold in clamped compared with non-clamped liver lobes (27.4 versus 7.8 per cent, P < 0.010). Conversely, selective portal clamping induced minimal liver injury, tissue inflammation or hepatocellular necrosis, and completely stopped the accelerated outgrowth of micrometastases. CONCLUSION: Selective portal clamping does not induce liver tissue damage or accelerate micrometastasis outgrowth and may therefore be the preferable clamping method during local ablative treatment of hepatic metastases.

Animals↗

Mouse models of colorectal cancer and liver metastases.

Colorectal cancer (CRC) is one of the most common malignancies in the western world. Its high mortality rates are particularly related to the occurrence of liver metastases. Many mouse models have been developed to evaluate the various features of CRC in human. Since none of the existing mouse models mimics all the characteristics of human CRC, it is of crucial importance that the optimal model is chosen for each experiment to resolve a specific experimental question. Currently used mouse models for CRC include chemically induced CRC models, genetically engineered mouse models and models in which colon tumors are implanted in recipient mice. Recently, conditional mouse models have been created in which a gene of interest can be (in)activated in a time- and tissue-specific manner. All models have their advantages and limitations. This review highlights the most commonly used mouse models for CRC and its liver metastases, their usefulness and shortcomings, as well as recent improvements, particularly regarding intravital (tumor) imaging.

Animals↗

Early endostatin treatment inhibits metastatic seeding of murine colorectal cancer cells in the liver and their adhesion to endothelial cells.

Endostatin, a carboxy-terminal fragment of collagen XVIII, potently inhibits angiogenesis and tumour growth, presumably through induction of apoptosis in endothelial cells and/or inhibition of their migration. Here we have tested how the timing of recombinant human endostatin (rh-E) administration affects its antitumour activity in a liver metastasis model of mouse C26 colorectal carcinoma cells. The effects of rh-E treatment on hepatic tumour load and on early tumour cell seeding were evaluated. Recombinant human endostatin was most effective in reducing intrahepatic tumour growth when administered prior to tumour cell inoculation. Analysis of early tumour cell seeding by using [(125)I]iododeoxyuridine-labelled C26 cells or by in vivo microscopy showed that rh-E reduced tumour cell seeding in the liver sinusoids. Recombinant human endostatin did not inhibit tumour growth when administered later than 4 days after tumour injection. Pretreatment of human umbilical vein endothelial cells with rh-E in vitro reduced C26 tumour cell adhesion under flow conditions two-fold as assessed by video microscopy and multiphoton laser scanning microscopy. Our results show that rh-E, in addition to antiangiogenic effects, reduces tumour cell adhesion in the liver sinusoids during the very early phases of metastasis formation. These data point towards a previously unknown mode of action of endostatin, that is, its ability to interfere with tumour cell seeding. Such insights may be helpful in the design of trials to improve (surgical) treatment of colorectal carcinoma and liver metastases.

Animals↗

Precoagulation minimizes blood loss during standardized hepatic resection in an experimental model.

BACKGROUND: Precoagulation of liver tissue before transection is a novel concept in hepatic surgery. Comparative data with conventional techniques are lacking. This study tested the hypothesis that precoagulation results in reduced blood loss during hepatic transection. METHODS: Precoagulation was performed with two different devices, the TissueLink floating ball (group 1) and a dissecting sealer (group 2), and compared with ultrasonic dissection (group 3). For each technique 12 partial liver resections were performed in six pigs. Blood loss per dissection surface area was the main outcome parameter. RESULTS: The transected surface area was similar in all groups. Animals in groups 1 and 2 had significantly less blood loss than those in group 3 (3.6 and 1.3 versus 11.9 ml/cm2 respectively; P = 0.009 and P = 0.002). One pig in group 1 died as a result of wound dehiscence. In one animal in group 2 a gastric perforation was observed after death. In group 3 bile leakage occurred in two animals, and a large haematoma was observed on the transection surface in one animal after death. CONCLUSION: Precoagulation of liver tissue before transection is associated with less blood loss compared with ultrasonic dissection.

Animals↗

[The adrenocortical carcinoma, a tumour of wide clinical diversity].

Over the course of a few years, an obese 52-year-old woman with a 23-year history of hypertension developed a number of abdominal complaints including gall stones. Her blood pressure became increasingly difficult to control and she developed diabetes mellitus and suffered palpitations and headaches. It became noticeable that she had a moon face. Laboratory tests revealed hypercortisolism. CT-scan showed a large inhomogeneous mass of nine centimetres in her left adrenal gland, which was subsequently removed surgically. The histopathological diagnosis was consistent with an adenoma. After a number of months the patient developed bone and liver metastases and the diagnosis was amended to carcinoma of the adrenal cortex. She then underwent radiotherapy and chemotherapy treatment. One year after surgery she developed a pancytopenia and died. Adrenocortical carcinomas are rare tumours with an incidence of about 1-2 cases per million of the population. Symptoms are heterogeneous since both functional (hormonal overproduction) and non-functional (mass effect) tumours exist. Surgical resection is the only curative therapy. It may be difficult to distinguish between benign and malignant cortical tumours.

Adrenal Cortex Neoplasms↗

[The surgical treatment of nonpalpable breast carcinoma in a university teaching hospital and a general teaching hospital by residents-in-training and surgeons; comparable results].

OBJECTIVE: To compare the results of the surgical treatment of nonpalpable breast cancer between two teaching hospitals in The Netherlands; the University Medical Centre Utrecht (UMCU) and the Rijnstate Hospital, Arnhem (RHA). DESIGN: Retrospective. METHOD: A total of 240 patients from the UMCU (n = 126) and the RHA (n = 114) diagnosed with a malignancy at stereotactic histological needle biopsy from 1 February 1997-31 May 2002 were included. The average age of the patients at the RHA was 61.3 and at the UMCU 58.0 years. The total number of procedures was recorded, as well as the type of operation and whether the first surgeon was a resident-in-training or registered as a surgeon. RESULTS: Of the 240 patients, biopsy results showed that 163 had invasive carcinoma (IC) and 77 had a ductal carcinoma in situ (DCIS). In 74% of cases one operation was sufficient (79% in the RHA versus 69% in the UMCU; p = 0.08). In the RHA fewer operations per patient were carried out before radical resection was attained (1.25 versus 1.4; p = 0.02). IC was more often treated by breast conserving surgery in the RHA than in the UMCU (74% versus 55%; p = 0.01). The intention to treat DCIS by breast conserving surgery was more often seen in the UMCU than in the RHA (90% versus 69%; p = 0.02). Of all operations analysed in the RHA 48% were performed by a resident-in-training as first surgeon versus 87% in the UMCU (p < 0.001). In those patients whose first operation was carried out by a resident-in-training, the percentages of 'radical resections' were equal: 78% in the RHA and 77% in the UMCU. CONCLUSION: Outcomes of surgical treatment were comparable in both types of teaching hospital. Good results were achieved in nonpalpable breast cancer surgery that was carried out by residents-in-training.

Biopsy, Needle↗

Tumour cell displacement after 14G breast biopsy.

INTRODUCTION: Seeding of biopsy needle tracks with viable malignant cells was an initial concern with all diagnostic breast needle procedures, including 14G automated needle biopsy. In an attempt to further evaluate this phenomenon, we have addressed the following questions: (1) are the tracks left by the needle biopsy procedure detectable in the surgical excision specimen? (2) Are displaced tumour cells visible along the needle tracks? (3) Is it possible to identify and excise the entire needle track for thorough histopathologic evaluation? METHODS: Surgical biopsy specimens of patients previously diagnosed with cancer on stereotactic 14G-needle biopsy were studied to find needle tracks. These are characterised by hemosiderin, scar tissue, foreign body giant cell reaction, fat necrosis, or organizing haemorrhage. Occurrence of displaced tumour cells or groups of cells along the tracks was registered. RESULTS: Needle tracks were found in 22/64 excision specimens of patients who underwent 14G-needle biopsy and surgery on the same day. Tumour-cell displacement along the needle track was seen in 11/22 cases (50%). In a prospective study, an attempt was made to excise the entire needle track in 13 consecutive cancer cases after 14G biopsy. Median time interval between core biopsy and first surgical excision was 21 days (range 7-35). Needle tracks could be visualised in 11/13 cases; displaced cells were seen in seven. CONCLUSION: Needle tracks can be found in the excision specimens of patients who previously underwent 14G biopsy, and displaced tumour cells can be recognised. Excision of the entire needle track is neither feasible, nor advisable as a routine measure, since radiotherapy is advised for both in situ and invasive carcinoma after conservative surgery.

Biopsy, Needle↗

Robot-assisted laparoscopic choledochojejunostomy.

BACKGROUND: Endoscopic stenting is the treatment of choice for palliative relief of biliary obstruction by a periampullary tumor. If treated surgically, a choledochojejunostomy and Roux-en-Y diversion is still performed by laparotomy in a large number of cases due to technical challenges of the biliodigestive anastomosis in the laparoscopic approach. Robotic systems may enhance dexterity and vision and might therefore support surgeons in delicate laparoscopic interventions. The purpose of this study is to assess the efficacy and safety of performing a laparoscopic choledochojejunostomy and Roux-en-Y reconstruction with the aid of a robotic system. METHODS: Ten laparoscopic procedures were performed in pigs with the da Vinci robotic system and compared to 10 procedures performed by laparotomy (controls). Operation room time, anastomoses time, blood loss, and complications were recorded. The effectiveness of the anastomoses was evaluated by postoperative observation for 14 days and by measuring passage, circumference, and number of stitches. RESULTS: Operating room time was significantly longer for the robot-assisted group than for controls (140 vs 82 min, p < 0.05). The anastomoses times were longer in the robot-assisted cases but not statistically significant (biliodigestive anastomosis, 29 vs 20 min; intestinal anastomosis, 30 vs 15 min), Blood loss was less than 10 cc in all robot-assisted cases and 30 cc (10-50 cc) in the controls. In both groups, there were no intraoperative complications. In the control group, one pig died of gastroparesis on postoperative day 6. In the robot-assisted group, one pig died on postoperative day 7 due to a volvulus of the jejunum. At autopsy, a bilioma was found in one pig in the robot-assisted group. In all pigs, the biliodigestive and intestinal anastomoses were macroscopically patent with an adequate passage. Circumference and number of stitches were similar. CONCLUSION: The safety and efficacy of robot-assisted laparoscopic choledochojejunostomy was proven in this study. The procedure can be performed within an acceptable time frame.

Anastomosis, Roux-en-Y↗

[Stereotactic large core needle biopsy for the diagnosis of nonpalpable breast lesions: reliable without additional excision biopsy].

OBJECTIVE: To determine the reliability of stereotactic large core needle biopsy (SLCNB) in the diagnostic work-up of suspected carcinomatous non-palpable breast lesions. DESIGN: Prospective. PATIENTS AND METHODS: Between 1 February 2000 and 6 June 2002, data were collected on all patients with a non-palpable breast lesion who were scheduled to undergo a SLCNB. SLCNB procedures were performed in 4 centres and patients were referred from 40 hospitals in the Netherlands. Histological diagnosis at SLCNB and subsequent therapy were recorded. Results were compared with results of the preceding 'Core biopsy after radiological localisation' (COBRA) study, where each large core needle biopsy was followed by an excision biopsy. Follow-up data were also obtained from the Dutch National Automated Pathology Archive (PALGA). The adherence to the COBRA guidelines was also evaluated. RESULTS: Nine hundred and fifty-five patients were included with 995 lesions, and 905 biopsy procedures were completed in 874 patients (mean age: 59 years; range: 23-86). Of the high-risk lesions, 27% were found to be carcinomas upon excision biopsy, which is comparable to the results of the COBRA study (23%). Twenty-eight percent of the ductal in-situ carcinomas were found to be invasive, which is higher than in the COBRA study (17%). No malignancies were found during the limited follow-up period (mean: 20.0 months; range: 5.8-34.0). Ninenty-six percent of the patients were treated according to the COBRA guidelines. CONCLUSION: No malignancies were missed during the limited follow-up period, and therefore, to date, the sensitivity of SLCNB seems to be comparable to that estimated in the study setting.

Adult↗

Plasminogen mediates liver regeneration and angiogenesis after experimental partial hepatectomy.

BACKGROUND: Plasmin system components are upregulated after partial hepatectomy, but their contribution to surgery-induced hepatic angiogenesis and regeneration is unclear. Liver regeneration and angiogenesis after partial hepatectomy were examined in mice lacking plasminogen or urokinase plasminogen activator (uPA). METHODS: Mice with a single-gene deletion of plasminogen or uPA were subjected to 70 per cent partial hepatectomy. Liver regeneration was measured as relative liver weight and cell proliferation index. Angiogenesis was quantified by determining hepatic microvessel density after staining for sinusoidal endothelial cells. RESULTS: The liver remnant weight was significantly reduced in mice lacking plasminogen or uPA compared with that in wild-type mice on days 2 and 7 after partial hepatectomy. This correlated with impaired cell proliferation. In wild-type mice, regeneration was accompanied by a significant increase in microvessel density after hepatectomy; this increase was impaired in plasminogen-deficient mice. CONCLUSION: Plasminogen and uPA are essential for optimal liver regeneration. In addition, plasminogen appears to be a major determinant in regeneration-associated hepatic angiogenesis.

Animals↗

Initial experience with radiofrequency ablation for hepatic tumours in the Netherlands.

AIMS: The aim of this study is to report initial experience with radiofrequency thermoablation (RFA) of malignant hepatic tumours. METHODS: From June 1999 to November 2001, a seven centre study of 50 patients who had undergone RFA, included 102 primary or metastatic tumours. Multimodality therapy, complications, disease free survival and location of recurrence were recorded. Histopathologic examination was performed in a number of tumours treated with RFA and subsequently resected to determine the effect of RFA on the tissue level. RESULTS: 11 tumours (seven patients) were resected after prior treatment with RFA; NADH-diaphorase staining in all these tumours demonstrated non-viable tumour. Postoperative morbidity and mortality occurred in 14 patients and one patient, respectively, in three cases related to the RFA procedure. Median follow-up of 41 patients with non-resected RF ablated tumours was 11 months (range 1-24 months). 26 patients developed a recurrence of which three at the RFA site after 6-12 months. CONCLUSIONS: RFA provides a simple method for local treatment of liver tumours. The introduction of this technique nevertheless involves morbidity and mortality.

Adult↗

Vacuum-assisted breast biopsy: a critical review.

Vacuum-assisted biopsy is an image-guided technique introduced in 1995 that is thought to be superior to 14G automated-needle biopsy for the evaluation of non-palpable breast lesions. However, prospective randomised studies evaluating its accuracy are unavailable. We conducted a critical review of the currently available literature on the accuracy of vacuum-assisted biopsy and compared it with published data on the accuracy of 14G automated-needle biopsy. The diagnostic performance of vacuum-assisted biopsy was evaluated by reviewing all available English-language literature published in Medline between 1995 and November 2001. Four independent reviewers used standard forms to extract the data. Twenty-two published studies were included. High-risk and DCIS underestimate rates, as well as the miss-rate of cancer, were assessed. High-risk and DCIS underestimate rates for 11G vacuum biopsy were 16% (95% Confidence Interval (CI) 12-20%) and 11% (95% CI 9-12%), respectively, and both were lower than the rates reported for 14G automated-needle biopsy (40% (95% CI 26%;56%) and 15% (95% CI 8%;26%), respectively). Due to incomplete follow-up of the benign lesions, it was impossible to calculate the miss-rates and the sensitivity rate. The results of this review indicate that vacuum-assisted biopsy can decrease the high-risk and DCIS underestimate rates, but it is unclear whether it can also decrease the miss-rates of cancer.

Biopsy↗

Interobserver variability between general and expert pathologists during the histopathological assessment of large-core needle and open biopsies of non-palpable breast lesions.

The purpose of this study was to assess whether general pathologists are able to make as accurate and reproducible a diagnosis on large-core needle biopsies as on open breast biopsy specimens. A total of 688 patients underwent a stereotactic large-core (14G) needle biopsy and subsequent surgical excision of 718 non-palpable breast lesions. Forty-two pathologists from 10 departments of pathology (generalists) made a diagnosis on both the needle and open biopsy specimens. Afterwards, three pathologists and two radiologists with extensive experience in breast pathology (experts) diagnosed all of the biopsy specimens. The general pathologists made a similar histological diagnosis as the experts in 632 (88%) of the needle biopsies and 649 (90%) of the open biopsy specimens. Accordingly, the interobserver agreement for the diagnosis of large-core needle biopsies between the general and experts pathologists was excellent (kappa 0.83) and not significantly different from the interobserver agreement for the diagnosis of open breast biopsies (kappa 0.86). However, many inconsistencies were observed in the category of borderline lesions: only 24% of the large-core needle biopsies and 43% of the open biopsies with an expert diagnosis of 'borderline' were diagnosed similarly by the general pathologists. Additionally, the risk of benign/malignant inconsistencies between general pathologists and experts was approximately 1 in 55 for both needle and open biopsies.

Adult↗

Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor.

Plasmin and other components of the plasminogen activation system play an important role in tissue repair by regulating extracellular matrix remodeling, including fibrin degradation. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, after activation, can attenuate plasmin-mediated fibrin degradation by removing the C-terminal lysine residues from fibrin, which play a role in the binding and activation of plasminogen. To test the hypothesis that TAFI is an important determinant in the control of tissue repair, we investigated the effect of TAFI deficiency on the healing of cutaneous wounds and colonic anastomoses. Histological examination revealed inappropriate organization of skin wound closure in the TAFI knockout mice, including an altered pattern of epithelial migration. The time required to completely heal the cutaneous wounds was slightly delayed in TAFI-deficient mice. Healing of colonic anastomoses was also impaired, as reflected by decreased strength of the tissue at the site of the suture, and by bleeding complications in 3 of 14 animals. Together, these abnormalities resulted in increased mortality in TAFI-deficient mice after colonic anastomoses. Although our study shows that tissue repair, including re-epithelialization and scar formation, occurs in TAFI-deficient mice, TAFI appears to be important for appropriate organization of the healing process.

Anastomosis, Surgical↗

[Chronic radiation enteritis after irradiation of the lesser pelvis: surgical (im)possibilities].

Three women aged 74, 59 and 36 years, had chronic complaints of abdominal pain, nausea, vomiting and diarrhoea, 1 to 8 years after radiotherapy for pelvic malignancies. Mechanical ileus due to fibrotic adhesions was found to be the cause; all three patients recovered after one or more operations. The prevalence of chronic radiation injury correlates with both radiation factors (volume) and patient characteristics. If possible, tumour recurrence needs to be excluded. Chronic intermittent ileus is the predominant symptom of chronic radiation injury. It often occurs within 2 years, but sometimes as long as 10 to 20 years after radiotherapy. Resection is warranted when short segments are affected. In other cases an intestinal bypass or stoma is the treatment of choice.

Adult↗