J. Hendriks

Distinct angiogenic and non-angiogenic growth patterns of lung metastases from renal cell carcinoma

Aims:  We have recently evaluated a classification of non‐small‐cell lung cancer based upon the presence of an angiogenic or a non‐angiogenic growth pattern. The aim of the present study was to test the hypothesis that lung metastases of clear cell renal cell carcinoma (RCC) can grow without eliciting angiogenesis and give rise to the same set of growth patterns.

Early Endothelial Dysfunction in Young Type 1 Diabetics

OBJECTIVES Endothelial dysfunction is a known precursor of atherosclerosis and can be assessed by measuring the brachial artery flow-mediated dilatation (FMD) via ultrasonography. This study investigated endothelial function in young type 1 diabetics without cardiovascular morbidity or diabetes-related pathology. METHODS Young diabetics and healthy controls were recruited, both meeting strict inclusion and exclusion criteria. To prove absence of subclinical atherosclerosis, intima-media thickness (IMT) measurements at the carotid bifurcation were done in all of them. FMD was measured at the brachial artery. The results were compared using the t-test and the influences of different variables on FMD were assessed using multiple linear regression. RESULTS Twenty-six diabetics (23.4+/-5.8 years) and 36 healthy volunteers (23.1+/-2.8 years) were recruited. The duration of diabetes was 9.2+/-5.3 years; metabolic control was moderate (HbA1c 7.6+/-1.0%) and IMT was normal in both groups. FMD was significantly impaired in type 1 diabetics (7.13+/-0.43 vs. 8.77+/-0.43%; p=0.002). The FMD grade was associated with diabetes and age. Patients with a good metabolic control (HbA1c</=7.0%) had a better FMD. CONCLUSIONS In type 1 diabetics, even without preclinical or clinical atherosclerosis, endothelial function is already disturbed and can be detected using ultrasonography.

Primary chondrocytes enhance cartilage tissue formation upon co-culture with a range of cell types

Co-culture models have been increasingly used in tissue engineering applications to understand cell–cell interactions and consequently improve regenerative medicine strategies. Aiming at further elucidating cartilage tissue formation, we co-cultured bovine primary chondrocytes (BPCs) with human expanded chondrocytes (HECs), human dermal fibroblasts (HDFs), mouse embryonic stem cells (MESCs), or mouse-3T3 feeder cells (M3T3s) in micromasses. BPCs were either co-cultured (1:5 ratio) with all cell types allowing direct cell–cell contacts or as separate micromasses in the same well with HECs. In co-culture groups with direct cell–cell contacts cartilaginous tissue was formed in all experimental groups. In situ hybridization showed that only 16–27% of the cells expressed type II collagen mRNA. Corresponding with the fact that micromasses consisted for approximately 20% only of BPCs, the amount of GAG was similar between 100% BPC micromass and the co-culture groups with HECs and HDFs. Therefore, co-culture micromasses support cartilage tissue formation predominantly originating from primary chondrocytes in direct contact with a variety of cell types. These findings potentially could be applied to optimize cell-therapy treatments for cartilage regeneration.

Long-Term Results after Video-Assisted Thoracic Surgery for Spontaneous Pneumothorax

Abstract Objective: Analysis of the long-term results of video-assisted thoracic surgery (VATS) for spontaneous pneumothorax in patients treated in two surgical centres from May 1994 until December 2000. Methods: A cohort of 86 patients was studied retrospectively. For final analysis, 74 patients undergoing 76 VATS procedures were included. Results: Sixty-three procedures for primary spontaneous pneumothorax (PSP) and 13 procedures for secondary spontaneous pneumothorax (SSP) were performed. In 78.9% (n = 60) blebs or bullae were resected with an endostapler device. In 2.6% (n = 2) an apical fibrotic zone was resected. In 71.1% (n = 54) a subtotal pleurectomy was performed combined with an abrasion in 41 cases. In 21.1% (n = 16) a total pleurectomy and in 7.8% (n = 6) an abrasion was performed. Operative mortality was 1.3% (n = 1) and total operative morbidity 25.4% in the PSP group and 76.9% in the SSP group. Mean follow-up was 36 months. The global recurrence rate was 5.3% (n = 4), being 4.8% (n = 3) in the PSP group and 7.7% (n = 1) in the SSP group. Recurrences occurred at 1 (n = 2), 2 (n = 1) and 16 (n = 1) months after the initial operation. The incidence of postoperative neuralgia was 17.1% (n = 13). One patient needed analgesics for the neuralgia. Conclusion: VATS treatment of spontaneous pneumothorax proves to be effective. In cases of SSP, VATS treatment is feasible but a higher morbidity rate should be anticipated.

Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer.

An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P<0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117–2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169–3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage.

Paravertebral schwannoma with high uptake of fluorodeoxyglucose on positron emission tomography.

Abstract A paravertebral mass was discovered in a 27-year-old woman, while investigating a painful shoulder and arm. CT, MRI and fine needle aspiration cytology (FNAC) pointed in the direction of a benign mass, but positron emission tomography (PET) showed a high uptake of [18F]fluorodeoxyglucose (FDG), which was indicative of a malignant lesion. Pathological analysis of the thoracoscopically resected tumour gave us the final diagnosis of a benign schwannoma. This report demonstrates that a high uptake of FDG in a non-malignant mediastinal tumour is possible.

Urinothorax: a rare pleural effusion.

Abstract A 68-year old man suffered severe respiratory distress, secondary to massive pleural effusion on the right side several hours after removing the nephrostomy tube from both right and left kidneys. A chest tube was placed and a yellowish fluid was evacuated. This was found to be urine from a fistula between the right pelvis and the chest cavity. Diagnosis and management of urinothorax are discussed.

Restaging the Mediastinum in Non-Small Cell Lung Cancer after Induction Therapy: Non-Invasive Versus Invasive Procedures

Abstract Objective : Nodal status after induction therapy in patients with stage III non-small cell lung cancer (NSCLC) is an independent prognostic factor for survival. Prognosis is poor in patients with persisting mediastinal lymph node involvement. Methods : From February 2000 to September 2007, restaging for NSCLC was performed in 25 patients (23 men, 2 women) by computed tomography (CT), positron emission tomography (PET) as well as repeat mediastinoscopy. Initial proof of N2 or N3 disease was obtained by mediastinoscopy. Results : The non-invasive restaging modalities CT and PET had a rather low accuracy of 64% and 72%, respectively. Repeat mediastinoscopy performed better with an accuracy of 84%. Conclusion : Histological proof of mediastinal involvement after induction therapy in NSCLC is necessary to select those patients who will benefit from surgical resection. When a first mediastinoscopy has been performed to obtain pathological proof of N2 or N3 disease, repeat mediastinoscopy proves to be more accurate than CT or PET scanning for mediastinal restaging.

Decision Making about Operability in Non-small Cell Lung Cancer

Abstract With the introduction of combined modality therapy and better staging techniques, the role of surgical resection for non-small cell lung cancer is continuously redefined. The final aim of surgical treatment for lung cancer is complete resection, also after neoadjuvant or induction therapy. Precise criteria for complete resection have recently been defined. Definite indications for surgery include clinical stages I, II and resectable IIIA. The precise role for surgical resection in stage IIIA-N2 lung cancer remains controversial but only downstaged patients should be considered. Stage IIIB is mostly treated by chemoradiotherapy. Accurate peroperative or surgical staging is necessary, as well regarding the tumour as nodal factor, to determine the extent of resection. A systematic nodal dissection should be performed including at least three hilar and three mediastinal lymph node stations. Post-induction surgical therapy often represents a greater technical challenge due to a pronounced hilar and mediastinal fibrosis. Downstaging is an important prognostic factor and persisting mediastinal lymph node involvement carries a poor prognosis. The optimal restaging method has not been established yet, but a pathological proof should be obtained. Remediastinoscopy is feasible with an acceptable accuracy but less invasive techniques are currently evaluated.

Effects of suramin on anastomotic colon tumors in a rat model

Background: The development of antiangiogenic drugs offers new promise in the treatment of malignancy. Suramin has been reported to inhibit tumor growth by blocking angiogenesis and has been used in clinical trials. The aim of the present study was to examine the effects of suramin on colonic anastomotic tumors in the rat. Methods: (a) Colonic anastomotic tumor was induced in 120 WAG/RIJ rats. Half of the animals were given 100 mg/kg of suramin intraperitoneally at the time of tumor induction. Rats were sacrified after 2, 4 and 8 weeks; tumor take and tumor weight were evaluated. (b) The number of red blood cell clusters per ×400 field was counted in each tumor. (c) A lymphocyte transformation test was performed in four groups of animals, 2 weeks before and 2 weeks after tumor implantation and/or suramin administration. Results: (a) A significant enhancement of tumor growth was observed in the suramin-treated animals. (b) This was accompanied by a significant increase in functional blood vessels. (c) Suramin-treated rats had markedly decreased lymphocyte stimulation, pointing to a possible immunosuppressive effect. Conclusions: The growth of an anastomotic colon tumor is rather enhanced by a single intraperitoneal administration of 100 mg/kg suramin in the rat, possibly by an unexpected immunosuppressive effect.