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Biomedical subjects

Richard van Hillegersberg

Publications and source records attributed to Richard van Hillegersberg.

At least 19 recordsLinked to original sources

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↗

Combining partial liver resection and local ablation of liver tumours: a preliminary Dutch experience.

BACKGROUND: The combination of partial liver resection and radiofrequency ablation (RFA) is a novel concept in the treatment of unresectable liver malignancies. The aim of this study is to evaluate the results of this combined strategy in the Netherlands. METHODS: Thirty-five patients treated with a combination of partial liver resection and RFA were identified from a prospectively registered pooled multicentre database. All patients were operated between June 1999 and November 2003 in 8 medical centres in The Netherlands. Main outcome parameters were morbidity, mortality, local success rate, and survival. RESULTS: Thirty-seven operations were performed in 35 patients. The group consisted of 20 male and 15 female patients with a median age of 59 years (range 41-76). Seventy-six lesions were resected and RFA was performed to ablate 82 unresectable liver tumours. Twelve patients developed a total of 24 complications, resulting in an overall perioperative morbidity rate of 32%. In two patients major complications resulted in postoperative death (postoperative mortality rate 5.4%). Local success rate after RFA was 88% and the estimated 1-, 2- and 3-year overall survival rates were 84%, 70% and 43%, respectively. CONCLUSION: This strategy should only be performed following strict patient selection and within the context of prospective clinical trials.

Journal Article↗

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↗

Factors influencing the local failure rate of radiofrequency ablation of colorectal liver metastases.

BACKGROUND: The prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases. METHODS: A total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature. RESULTS: The local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location. CONCLUSIONS: Because accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.

Adult↗

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↗

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↗

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↗

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↗

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↗

Local treatment in unresectable hepatic metastases of carcinoid tumors: Experiences with hepatic artery embolization and radiofrequency ablation.

BACKGROUND: Hepatic metastases of carcinoid tumors cause incapacitating symptoms, but are usually diffuse and therefore unresectable. In this article we evaluate our experiences with local treatment techniques in the management of carcinoid patients with hepatic metastases and failing systemic treatment. METHODS: Fifteen consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45-71 years) were treated with either hepatic artery embolization (HAE) with Ivalon particles or radiofrequency ablation (RFA) (percutaneously or intra-operatively). Follow-up evaluation was performed by CT scan and 24-hours urinary 5-HIAA excretions. RESULTS: A total of 18 HAE's was performed in 13 patients, while 10 lesions in 3 patients were treated with RFA. Median follow-up was 12.5 months (2 - 25 months). Median duration of symptoms was 22 months (8 - 193 months). Median overall decrease of 5-HIAA excretion 2 months after HAE was 32% with tumor regression on CT-scan in 4 patients (30%) and improvement of symptoms with a median duration of 15 months in 3 of them (23%). Embolization led to fatal hepatic failure in one patient. The 3 patients treated with RFA showed a decrease of urinary 5-HIAA values of 34, 81 and 93% respectively, with tumor regression in all of them. Improvement of symptoms was reported in 2 patients up to 25 months. CONCLUSION: Liver embolization performed late in the clinical course had limited effect on symptoms and biochemical and radiological parameters. First experiences with RFA are favorable and might encourage to apply RFA more widely in metastatic carcinoid.

Journal Article↗

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↗

Adequate symptom relief justifies hepatic resection for benign disease.

BACKGROUND: The purpose of this study was to evaluate the long-term results of partial liver resection for benign liver lesions. METHODS: All patients operated on for benign liver lesions from 1991 to 2002 were included. Information was retrieved from medical records, the hospital registration system and by a telephonic questionnaire. RESULTS: Twenty-eight patients with a median age of 41 years (17-71) were operated on (M/F ratio 5/23). The diagnosis was haemangioma in 8 patients, FNH in 6, HCA in 13 and angiomyolipoma in 1. Eight patients were known to have relevant co-morbidity. Median operating time was 207 minutes (45-360). The morbidity rate was 25% and no postoperative mortality was observed. Twenty-two patients (79%) had symptoms (mainly abdominal pain) prior to surgery. Twenty-five patients were reached for a questionnaire. The median follow up was 55 months (4-150). In 89% of patients preoperative symptoms had decreased or disappeared after surgery. Four patients developed late complications. CONCLUSION: Long-term follow up after liver surgery for benign liver lesions shows considerable symptom relief and patient satisfaction. In addition to a correct indication these results justify major surgery with associated morbidity and mortality.

Adolescent↗

Invasive carcinoma after endoscopic ablative therapy for high-grade dysplasia in Barrett's oesophagus.

BACKGROUND: Patients with high-grade dysplasia (HGD) in Barrett's oesophagus carry a significant risk of developing adenocarcinoma. Endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) aim at the radical ablation of the dysplastic area. METHODS: We used EMR to resect the macroscopic area of dysplastic mucosa followed by PDT to eliminate residual disease. PDT was performed after oral administration of 5-aminolevulinic acid (ALA, 40 mg/kg), using fractionated illumination 3 and 6 h later with 630 nm light at 100 J/cm(2) through an endoscopic balloon diffuser. RESULTS: We report 2 patients who developed adenocarcinoma shortly after incomplete endoscopic ablation of Barrett's epithelium. In a 61-year-old man with HGD in 8-cm Barrett's segment, HGD persisted 3 months after treatment. The oesophagectomy specimen showed a 2.3-cm pT2N0M0 adenocarcinoma in Barrett's. In a 69-year-old woman with extensive HGD in 5-cm Barrett's, HGD persisted after 3 PDT sessions in 1 year. Adenocarcinoma occurred 6 months after treatment. The oesophagectomy showed a pT1bN0M0 adenocarcinoma and extensive multifocal HGD in Barrett's. CONCLUSIONS: The combination of EMR and PDT may be a promising option for local treatment of patients with HGD in Barrett's oesophagus, provided all dysplastic tissue can be removed. Currently it should be offered only to patients who are willing to participate in a clinical trial with an intensive endoscopic follow-up programme.

Adenocarcinoma↗

Arterial wall strength after endovascular photodynamic therapy.

BACKGROUND AND OBJECTIVES: Vascular photodynamic therapy (PDT) inhibits intimal hyperplasia (IH) induced by angioplasty in rat iliac arteries by eradicating the proliferating smooth muscle cells. This process may jeopardise the structure and strength of the arterial wall, reflected by a decreased bursting pressure. STUDY DESIGN/MATERIALS AND METHODS: Thirty male Wistar rats of 250-300 g were subdivided into 3 groups (n = 10). In all groups, IH was induced by balloon injury (BI). One experimental group received PDT at 50 J/cm diffuser length, the other group at 100 J/cm diffuser length. The third group served as control group and received no PDT. In half of each group the bursting pressure was analyzed after 2 hours (n = 5), in the other half after 1 year. RESULTS: Two hours after the procedure the bursting pressure was 3.37 +/- 0.58 (+/-SEM) bar in the BI + PDT 50 and 3.96 +/- 0.43 bar in the BI + PDT 100 group, compared to 2.20 +/- 0.27 bar in the BI group (P < 0.05). After 1 year these values were 3.18 +/- 0.87 bar in the BI + PDT 50 (P < 0.05) and 2.02 +/- 0.31 bar in the BI + PDT 100 group, compared to 2.10 +/- 0.30 bar in the BI group (NS). In the BI + PDT 100 group, 3 out of 5 rats appeared to have aneurysmal dilatation after 1 year. CONCLUSIONS: Endovascular PDT increases the arterial wall strength as measured by the bursting pressure at short-term. After 1 year, wall strength is not diminished as measured by bursting pressure, but aneurysmal dilatation nevertheless developed with 100 J/cm. dl. This may limit the use of high energy PDT.

Aminolevulinic Acid↗

Aminolaevulinic acid-induced protoporphyrin IX pharmacokinetics in central and peripheral arteries of the rat.

Photodynamic therapy (PDT) based on the photosensitive protoporphyrin IX (PpIX) may prevent restenosis after transluminal angioplasty. PpIX is synthesized in mitochondria, which differ in number and activity among various tissues. Therefore, we questioned whether the course of PpIX concentration after systemic aminolaevulinic acid (ALA) administration differed among various arteries. ALA was administered intravenously (200 mg/kg) to male Wistar rats (n = 21). At varying time intervals (0, 1, 2, 3, 6, 12 and 24 h) both central and peripheral arteries were isolated and homogenized, and the concentration of the various heme intermediates was determined by a fluorometric extraction method. The maximal PpIX concentration was more than two-fold higher in peripheral arteries (20.49 +/- 3.0 to 24.0 +/- 7.5 pmol/mg protein) than in central arteries (0-9.46 +/- 0.01 pmol/mg protein) (P < 0.004). However, the amount of citrate synthase, reflecting the mitochondrial mass, was lower (0.14-0.61 and 1.87-2.32 U/mg protein, respectively). Apparently, the level of PpIX cannot simply be explained by the mitochondrial content of the arteries. The time interval of maximal PpIX accumulation was similar in peripheral and central arteries (2 h and 27 min vs. 2 h and 8 min) (P = 0.13). Thus, if the efficacy of PDT in vivo is directly related to the tissue concentration of PpIX, more effect can be expected in peripheral arteries than in central arteries.

Aminolevulinic Acid↗