Philippe Van Trappen - Academia.edu (original) (raw)

Papers by Philippe Van Trappen

Journal of Surgical Case Reports

The application of indocyanine green (ICG) has recently been reported to aid in the resection of ... more The application of indocyanine green (ICG) has recently been reported to aid in the resection of endometriosis in the bladder wall and/or involving the ureters. A symptomatic 41-year-old patient with dysmenorrhea and pollakisuria was referred to our tertiary center. Imaging revealed a 1.5–2 cm intramural endometriotic nodule in the posterior bladder wall. She was planned for robotic resection of the endometriotic nodule, under ICG guidance, together with a hysterectomy. After placement of double-J ureteral stents and clamping the bladder, perforation of the bladder mucosa could be avoided whilst performing a circumferential resection of the nodule. By clamping the bladder catheter after instillation of ICG, both the bladder wall thickness and ureters could be visualized with near-infrared imaging during robotic resection of the endometriotic nodule and hysterectomy. With the surgical approach described here, endometriotic nodules/tissue can be removed precisely with enlarged vision ...

Best Practice & Research in Clinical Obstetrics & Gynaecology, Aug 1, 2023

Surgical technology international, Jun 10, 2020

Introduction: Robotic hysterectomy using standard diathermy instruments has been reported in beni... more Introduction: Robotic hysterectomy using standard diathermy instruments has been reported in benign gynaecology over the past decade, however, perioperative outcomes, such as pain scores, for this procedure between small and large uteri using a sealing device are not well reported in large series. Hence, we aimed to investigate, in a large retrospective cohort study of 156 consecutive patients, the rate of complications between small and large uteri in robotic benign hysterectomy using a sealing device which enables simultaneous dissection, sealing, and cutting of tissues. As secondary outcomes, we investigated the differences in pain scores, operative times, and lengths of hospitalisation between the two groups. To differentiate between small and large uteri, the commonly used threshold of 250 grams was used. Eighty-two cases were included in the small uteri group and 70 in the large uteri group. For four cases, no weight was reported. Results: There was a statistically significant longer operative time for the large uteri group-105 minutes versus 85 minutes for the small uteri group. This difference was due to the longer duration of vaginal removal. The postoperative pain scores were comparable between small and large uteri. The overall complication rate in our series was very low, with 3.2% intraoperative complications and 4.4% postoperative complications. There was no significant difference in peri- and postoperative complication rate, as well as length of hospitalisation between the small and large uteri group. Conclusion: In this retrospective cohort study of robotic hysterectomy using a sealing device, there was no difference in perioperative outcome between small and large uteri, but we could demonstrate shorter operative times compared to previous reports on large uteri, most likely due to the versatility of the application of the EndoWrist® Vessel Sealer (Intuitive Surgical, Inc., Sunnyvale, California). Given the known difference in complication rate and length of hospitalization between small and large uteri in laparoscopic hysterectomy, this study shows that robotic hysterectomy is a recommended procedure for benign indications in small, and especially large uteri.

Gynecologic Oncology, Mar 1, 2005

We report a case of central pelvic recurrence 7 years after radical vaginal trachelectomy for ade... more We report a case of central pelvic recurrence 7 years after radical vaginal trachelectomy for adenocarcinoma of the cervix. A 30-year-old woman was treated by radical vaginal trachelectomy and bilateral pelvic lymph node dissection (a fertility sparing procedure) in 1996 for cervical cancer. Pathology demonstrated a well differentiated, stage 1B1 adenocarcinoma. She presented 7 years later with a central pelvic recurrence measuring 30 mm in width. She subsequently underwent radical hysterectomy for central clearance and did not require post-operative radiotherapy. Should selected patients who were initially treated by radical trachelectomy for early stage cervical cancer, in particular those with adenocarcinoma (as 50% of recurrences have been reported in this group of patients), be offered hysterectomy once child bearing is complete?

International Journal of Gynecological Cancer, 2007

The Journal of Pathology, 2003

Cervical carcinogenesis has well‐defined stages of disease progression including three grades of ... more Cervical carcinogenesis has well‐defined stages of disease progression including three grades of pre‐invasive lesions—cervical intraepithelial neoplasia grades 1–3 (CIN 1–3)—and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF‐C and VEGF‐D) involved in new lymphatic vessel formation may play a crucial role in this process. The present study has assessed the expression of VEGF‐C and VEGF‐D, and their receptor VEGFR‐3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49 squamous cell carcinomas) to determine whether expression of lymphangiogenic factors occurs prior to invasion. The presence of lymphatic vessels was determined using LYVE‐1 and podoplanin staining, as well as double immunostaining for LYVE‐1/CD34 and podoplanin/CD34. In situ hybridization was performed to determine VEGFR‐3 mRNA expression. A significant positive correlation was found between VEGF‐C, VEGF‐D, and VEGFR‐3 expression through the different stages of cervical carcinogenesis. Significant differences in protein expression for VEGF‐C, VEGF‐D, and VEGFR‐3 were found between CIN 1–2 and CIN 3 (p < 0.001 for all), but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions showed moderate to strong staining for VEGF‐C and VEGF‐D, whereas most of the early pre‐cancerous lesions (CIN 1 and 2) were negative. In cervical cancer, similar observations to those in CIN 3 were found. VEGFR‐3 mRNA expression was found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein expression was found in more than 50% of CIN 3 lesions and cervical cancers, compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth stimulation pattern via VEGFR‐3. Adjacent CIN 3 was present in nine cervical cancers and displayed strong expression for VEGF‐C, VEGF‐D, and VEGFR‐3. These results suggest that in cervical carcinogenesis a switch to the lymphangiogenic phenotype may occur at the stage of CIN 3. Copyright © 2003 John Wiley & Sons, Ltd.

Introduction/Background The LACC trial (Ramirez P, NEJM 2018; 379:1895–1904) and the Melamed repo... more Introduction/Background The LACC trial (Ramirez P, NEJM 2018; 379:1895–1904) and the Melamed report (Melamed A, NEJM 2018; 379:1905–1914) raise the question whether minimally invasive surgery (conventional and robot-assisted laparoscopy) is inferior to open abdominal surgery in early stage cervical cancer. Notable was the low rate of recurrence and death in the laparotomy group of the LACC trial. The current study investigates the results of patients with FIGO stage I cervical cancer treated with robot-assisted radical hysterectomy in hospitals of the Belgium and Luxembourg Gynaecological Oncology Group (BGOG). Methodology In this prospective follow up study combined data of different BGOG hospitals were analysed of patients with stage IA1, IA2 and IB1 cervical cancer with a histologic subtype of squamous-cell carcinoma, adenocarcinoma or adenosquamous carcinoma treated with robot-assisted laparoscopy. Inclusion criteria were the same as in the LACC trial. Outcomes were disease free and overall survival at 3 years. Results A total of 177 patients were eligible for analysis. Mean age was 46 years. Most patients had FIGO stage IB1 (84.2%) and squamous cell carcinoma as histological subtype (71,2%). Mean follow up time was 3,5 years, with a range from 0 to 131 months. 22 recurrences and 12 deaths were noted, of which 8 deaths were related to cervical cancer. Disease free survival at 3 years was 85%. Overall survival at 3 years was 96%. Conclusion Current results in Belgium show disease free and overall survival rates of patients with early stage cervical cancer after robot-assisted laparoscopy that are consistent with those mentioned by the American and Canadian Cancer Society and earlier reports, except for the LACC trial and the Melamed report. New randomized trials are needed to investigate whether minimally invasive surgery remains an equal option in the treatment of early stage cervical cancer in comparison to laparotomy. Disclosure Nothing to disclose. Abstract EP281 Table 1 Patient characteristics Characteristic Age at diagnosis (mean) 46 years BMI (mean) 24.6 kg/m2 FIGO stadium: IA1 - IA2 - IB1 8.5% - 6.2% - 84.2% Histologic type: Squamous cell carcinoma - Adenocarcinoma - Adenosquamous carcinoma 71.2% - 24.9% - 4.1% Positive lymph nodes 7.3%

European Journal of Surgical Oncology, 2020

Objective: To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surg... more Objective: To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surgery for endometrial cancer within the Belgium Gynaecological Oncology Group (BGOG). Study design: We performed a retrospective analysis of women with clinically Stage I endometrial cancer who underwent surgical treatment from 2007 to 2018 in five institutions of the BGOG group. Results: A total of 598 consecutive women were identified. The rate of conversion to laparotomy was low (0.8%). The mean postoperative Complication Common Comprehensive Index (CCI) score was 3.4. The rate of perioperative complications did not differ between age groups, however the disease-free survival was significantly lower in patients over 75 years compared to patients under 65 years of age (p¼0.008). Per-operative complications, conversion to laparotomy rate, post-operative hospital stay, CCI score and disease-free survival were not impacted by increasing BMI. Conclusion: Robot-assisted surgery for the surgical treatment of patients suffering from early-stage endometrial cancer is associated with favourable surgical and oncologic outcomes, particularly for unfavourable groups such as elderly and obese women, thus permitting a low morbidity minimallyinvasive surgical approach for the majority of patients in expert centres.

Poster exhibition Day 1, 2019

Introduction/Background The aim of this prospective study was to report perioperative outcomes, d... more Introduction/Background The aim of this prospective study was to report perioperative outcomes, disease-free and overall survival of robot-assisted management of patients with endometrial cancer, treated in 5 centers in Belgium. Methodology Patients undergoing surgery between August 2007 and December 2018 (n=615) were prospectively collected. Results Median age was 68 years (range, 31–92), median BMI 28 kg/m2 (range, 17–61). Five-hundred-ninety-nine patients underwent robot-assisted hysterectomy and bilateral salpingo-oophorectomy. In addition, full pelvic lymphadenectomy was performed in 151 (25%), and pelvic sentinel nodes biopsies only in 181 patients (29%). Sixteen patients were referred for robotic node staging after hysterectomy performed elsewhere. Histological types were endometrioid (n=512, 84%), serous (n=43, 7%), clear cell (n=8, 1%), mucinous (n=3, 0.5%), squamous (n=2, 0.3%) and carcinosarcoma (n=20, 3%). FIGO stage was: IA (61%), IB (24%), II (4%), IIIA (2%), IIIB (0,3%), IIIC (8%), IV (1%). Metastatic pelvic nodes were found in 43 (7%), positive para-aortic nodes in 3 (0,4%), pelvic and para-aortic nodal metastases in 7 patients (1,2%). Median number of removed pelvic and para-aortic nodes was 15 (range, 0–64) and 10 (range 1–47), respectively. Median estimated blood loss was 50 mL (range 0– 1000), median skin-to-skin time 150 minutes (range 55–480) and conversion rate 0.8% (n=5). Intra-operative complications occurred in 5% (n=30). At least one postoperative complication occurred in 15% (n=89). Median follow-up was 27 months (range, 1–131). Recurrence occurred in 63 patients (11%) and 38 patients (6%) died of endometrial cancer. The 2- and 5-year recurrence-free survival rates were 89% and 84%, respectively. The 2- and 5-year overall survival rates were 92% and 83%, respectively. Conclusion This study confirms the feasibility and safety of robot-assisted management of endometrial cancer with a low complication, conversion and recurrence rate. Disclosure Nothing to disclose.

Annals of Oncology, 1998

Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases ... more Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. The real incidence of gastrointestinal metastases in breast cancer patients is probably underestimated owing to the non-specific presenting symptoms and death of patients caused by other more obvious metastases. The predominant histological subtype of gastrointestinal metastases of breast cancer is invasive lobular carcinoma and the median interval from diagnosis of primary breast cancer to gastrointestinal metastases is five years. We report two cases of disseminated breast cancer with gastrointestinal involvement with a rather long survival.

Open Access Surgery, 2013

Chronic wounds are common and their incidence has been on the increase. They place an enormous bu... more Chronic wounds are common and their incidence has been on the increase. They place an enormous burden on health care services and have a major impact on several aspects of patients' wellbeing. It is vital for clinicians to recognize the complexity of the underlying processes leading to the development of a chronic wound. With this knowledge, the key factors that led to their development in each patient can be identified and appropriate steps taken to address modifiable factors. There is currently a wide range of treatments available for treatment of chronic wounds, with a range of exciting new treatments being developed. This paper aims to give an overview of the common etiology and pathophysiology of chronic wounds followed by a discussion of a range of current and future developments in their treatment.

Nuclear Medicine Communications, 1999

Gynecologic Oncology, 2003

AACR Meeting …, 2006

Proc Amer Assoc Cancer Res, Volume 47, 2006 2810 Chemokines and their receptors play important ro... more Proc Amer Assoc Cancer Res, Volume 47, 2006 2810 Chemokines and their receptors play important roles in cancer biology influencing the movement of both stromal and malignant cells and modulating the expression of other cytokines, chemokines and proteases. In order to further understand the role of chemokines in cervical cancer the expression of twenty-three chemokines and fifteen chemokine receptors was investigated in normal and malignant cervix using a Rnase Protection Assay. The relative contribution of epithelial and stromal compartments in the chemokine network were assessed using low density gene-array and laser capture microdissection. Immunohistochemical staining was employed to validate and locate a tumour associated chemokine receptor in normal, pre-invasive and invasive cervical tissue and also on infiltrating cells. We found two key differences in chemokine receptor expression between normal and malignant tissue. First, mRNA for CX3CR1 was detected in normal cervical tissue, but was absent in malignant tissue. Second, higher expression of mRNA for CCR4 was detected in malignant cervical tissue compared to normal cervix. Both the stromal and epithelial compartments contributed to the high mRNA CCR4 expression. In normal cervical tissue, CCR4 protein expression was detected only on macrophages. However, in pre-malignant stages of cervical cancer (CIN) and invasive cervical tissues, CCR4 protein was not only detected on infiltrating macrophages and regulatory T cells but also, surprisingly, on tumour cells. The macrophage and regulatory T cell infiltration in samples of normal cervical tissue, pre-malignant lesions, and stages I, II and III of invasive epithelial cervical cancer were further characterized. Normal cervical tissue contained few, if any, macrophages and regulatory T cells. These numbers were increased in pre-malignant lesions and invasive cervical cancers. This data, to our knowledge, is the first description of CCR4 expression by malignant epithelial cells. Increased CCR4 expression in cervical cancer is also due to increased number of CCR4 expressing macrophages and regulatory T cells. The observation that CCR4 is expressed by the pre-malignant stages (CIN1, CINII and CINIII) of cervical cancer, may indicate that CCR4 expression may play an important, yet-undefined, role in early events of cervical carcinogenesis.

British Journal of Clinical Pharmacology, 1995

The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of m... more The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of maternal and foetal serum obtained at delivery. The binding of the enantiomers of both drugs was lower in foetal than in maternal serum. In maternal serum the mean (+/‐ s.d.) unbound percentages were 22.4 +/‐ 6.2 and 20.7 +/‐ 6.6 for R‐ and S‐ propranolol, and 16.8 +/‐ 5.5 and 22.5 +/‐ 6.2 for R‐ and S‐verapamil; in foetal serum the values were 38.8 +/‐ 8.6 and 40.4 +/‐ 10.6 for R‐ and S‐propranolol, and 34.7 +/‐ 10.5 and 44.8 +/‐ 10.7 for R‐ and S‐ verapamil. For propranolol, in maternal, but not in foetal serum, the difference between the binding of the R‐ and S‐enantiomers was significant; the R/S ratio was significantly (P < 0.01) larger in the mother (1.099 +/‐ 0.072) than in the foetus (0.973 +/‐ 0.068). For verapamil, the difference in binding between the R‐ and S‐enantiomers was significant in both maternal and foetal serum, but the R/S ratio was similar in mother (0.735 +/‐ 0....

British Journal of Cancer, 2007

Most cancer patients die of metastatic or recurrent disease, hence the importance to identify tar... more Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up-and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-b) were upregulated at least twofold. Some of these genes (AKT and MMP3) are key regulators of epithelial-mesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer.

Journal of Surgical Case Reports

Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnos... more Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnosis is based on pathology and immunohistochemistry. Surgery with a total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the standard. A female patient in her 60s presented with heavy postmenopausal bleeding. Vaginal ultrasound scan and magnetic resonance imaging showed a large strongly vascularized cervical mass with features suspicious of sarcomatous degeneration. Positron Emission Tomography-Computed Tomography (PET-CT) did not reveal any evidence of metastases nor lymphadenopathy, but presence of right hydronephrosis. An abdominal hysterectomy with bilateral salpingo-oophorectomy, and end-to-end anastomosis of the right ureter, was performed. Pathology showed an International Federation of Gynecology and Obstetrics (FIGO)-stage 1B leiomyosarcoma of the uterine cervix. No adjuvant treatment was given. Adjuvant radiotherapy reduces the risk of recurrence but no surviv...

Frontiers in Surgery

IntroductionPrimary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly i... more IntroductionPrimary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly in elderly women. The diagnosis is based on histology and immunohistochemistry of a biopsy. Given the rarity of vaginal melanoma, no standardized treatment guidelines are established; however, surgery is the primary treatment modality in the absence of metastatic disease. Most reports in the literature are retrospective single cases, case series, and population-based studies. The open surgical approach is the main modality reported. Here, we report for the first time a 10-step combined robotic-vaginal technique, with en bloc resection of the uterus and total vagina, for treating clinically early-stage primary vaginal melanoma. In addition, the patient in our case underwent a robotic pelvic bilateral sentinel lymph node dissection. The literature on the surgical approach for vaginal melanoma is reviewed.Case presentationA 73-year-old woman was referred to our tertiary cancer center and was...

European Journal of Obstetrics & Gynecology and Reproductive Biology

Journal of Surgical Case Reports

The application of indocyanine green (ICG) has recently been reported to aid in the resection of ... more The application of indocyanine green (ICG) has recently been reported to aid in the resection of endometriosis in the bladder wall and/or involving the ureters. A symptomatic 41-year-old patient with dysmenorrhea and pollakisuria was referred to our tertiary center. Imaging revealed a 1.5–2 cm intramural endometriotic nodule in the posterior bladder wall. She was planned for robotic resection of the endometriotic nodule, under ICG guidance, together with a hysterectomy. After placement of double-J ureteral stents and clamping the bladder, perforation of the bladder mucosa could be avoided whilst performing a circumferential resection of the nodule. By clamping the bladder catheter after instillation of ICG, both the bladder wall thickness and ureters could be visualized with near-infrared imaging during robotic resection of the endometriotic nodule and hysterectomy. With the surgical approach described here, endometriotic nodules/tissue can be removed precisely with enlarged vision ...

Best Practice & Research in Clinical Obstetrics & Gynaecology, Aug 1, 2023

Surgical technology international, Jun 10, 2020

Introduction: Robotic hysterectomy using standard diathermy instruments has been reported in beni... more Introduction: Robotic hysterectomy using standard diathermy instruments has been reported in benign gynaecology over the past decade, however, perioperative outcomes, such as pain scores, for this procedure between small and large uteri using a sealing device are not well reported in large series. Hence, we aimed to investigate, in a large retrospective cohort study of 156 consecutive patients, the rate of complications between small and large uteri in robotic benign hysterectomy using a sealing device which enables simultaneous dissection, sealing, and cutting of tissues. As secondary outcomes, we investigated the differences in pain scores, operative times, and lengths of hospitalisation between the two groups. To differentiate between small and large uteri, the commonly used threshold of 250 grams was used. Eighty-two cases were included in the small uteri group and 70 in the large uteri group. For four cases, no weight was reported. Results: There was a statistically significant longer operative time for the large uteri group-105 minutes versus 85 minutes for the small uteri group. This difference was due to the longer duration of vaginal removal. The postoperative pain scores were comparable between small and large uteri. The overall complication rate in our series was very low, with 3.2% intraoperative complications and 4.4% postoperative complications. There was no significant difference in peri- and postoperative complication rate, as well as length of hospitalisation between the small and large uteri group. Conclusion: In this retrospective cohort study of robotic hysterectomy using a sealing device, there was no difference in perioperative outcome between small and large uteri, but we could demonstrate shorter operative times compared to previous reports on large uteri, most likely due to the versatility of the application of the EndoWrist® Vessel Sealer (Intuitive Surgical, Inc., Sunnyvale, California). Given the known difference in complication rate and length of hospitalization between small and large uteri in laparoscopic hysterectomy, this study shows that robotic hysterectomy is a recommended procedure for benign indications in small, and especially large uteri.

Gynecologic Oncology, Mar 1, 2005

We report a case of central pelvic recurrence 7 years after radical vaginal trachelectomy for ade... more We report a case of central pelvic recurrence 7 years after radical vaginal trachelectomy for adenocarcinoma of the cervix. A 30-year-old woman was treated by radical vaginal trachelectomy and bilateral pelvic lymph node dissection (a fertility sparing procedure) in 1996 for cervical cancer. Pathology demonstrated a well differentiated, stage 1B1 adenocarcinoma. She presented 7 years later with a central pelvic recurrence measuring 30 mm in width. She subsequently underwent radical hysterectomy for central clearance and did not require post-operative radiotherapy. Should selected patients who were initially treated by radical trachelectomy for early stage cervical cancer, in particular those with adenocarcinoma (as 50% of recurrences have been reported in this group of patients), be offered hysterectomy once child bearing is complete?

International Journal of Gynecological Cancer, 2007

The Journal of Pathology, 2003

Cervical carcinogenesis has well‐defined stages of disease progression including three grades of ... more Cervical carcinogenesis has well‐defined stages of disease progression including three grades of pre‐invasive lesions—cervical intraepithelial neoplasia grades 1–3 (CIN 1–3)—and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF‐C and VEGF‐D) involved in new lymphatic vessel formation may play a crucial role in this process. The present study has assessed the expression of VEGF‐C and VEGF‐D, and their receptor VEGFR‐3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49 squamous cell carcinomas) to determine whether expression of lymphangiogenic factors occurs prior to invasion. The presence of lymphatic vessels was determined using LYVE‐1 and podoplanin staining, as well as double immunostaining for LYVE‐1/CD34 and podoplanin/CD34. In situ hybridization was performed to determine VEGFR‐3 mRNA expression. A significant positive correlation was found between VEGF‐C, VEGF‐D, and VEGFR‐3 expression through the different stages of cervical carcinogenesis. Significant differences in protein expression for VEGF‐C, VEGF‐D, and VEGFR‐3 were found between CIN 1–2 and CIN 3 (p &lt; 0.001 for all), but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions showed moderate to strong staining for VEGF‐C and VEGF‐D, whereas most of the early pre‐cancerous lesions (CIN 1 and 2) were negative. In cervical cancer, similar observations to those in CIN 3 were found. VEGFR‐3 mRNA expression was found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein expression was found in more than 50% of CIN 3 lesions and cervical cancers, compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth stimulation pattern via VEGFR‐3. Adjacent CIN 3 was present in nine cervical cancers and displayed strong expression for VEGF‐C, VEGF‐D, and VEGFR‐3. These results suggest that in cervical carcinogenesis a switch to the lymphangiogenic phenotype may occur at the stage of CIN 3. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Introduction/Background The LACC trial (Ramirez P, NEJM 2018; 379:1895–1904) and the Melamed repo... more Introduction/Background The LACC trial (Ramirez P, NEJM 2018; 379:1895–1904) and the Melamed report (Melamed A, NEJM 2018; 379:1905–1914) raise the question whether minimally invasive surgery (conventional and robot-assisted laparoscopy) is inferior to open abdominal surgery in early stage cervical cancer. Notable was the low rate of recurrence and death in the laparotomy group of the LACC trial. The current study investigates the results of patients with FIGO stage I cervical cancer treated with robot-assisted radical hysterectomy in hospitals of the Belgium and Luxembourg Gynaecological Oncology Group (BGOG). Methodology In this prospective follow up study combined data of different BGOG hospitals were analysed of patients with stage IA1, IA2 and IB1 cervical cancer with a histologic subtype of squamous-cell carcinoma, adenocarcinoma or adenosquamous carcinoma treated with robot-assisted laparoscopy. Inclusion criteria were the same as in the LACC trial. Outcomes were disease free and overall survival at 3 years. Results A total of 177 patients were eligible for analysis. Mean age was 46 years. Most patients had FIGO stage IB1 (84.2%) and squamous cell carcinoma as histological subtype (71,2%). Mean follow up time was 3,5 years, with a range from 0 to 131 months. 22 recurrences and 12 deaths were noted, of which 8 deaths were related to cervical cancer. Disease free survival at 3 years was 85%. Overall survival at 3 years was 96%. Conclusion Current results in Belgium show disease free and overall survival rates of patients with early stage cervical cancer after robot-assisted laparoscopy that are consistent with those mentioned by the American and Canadian Cancer Society and earlier reports, except for the LACC trial and the Melamed report. New randomized trials are needed to investigate whether minimally invasive surgery remains an equal option in the treatment of early stage cervical cancer in comparison to laparotomy. Disclosure Nothing to disclose. Abstract EP281 Table 1 Patient characteristics Characteristic Age at diagnosis (mean) 46 years BMI (mean) 24.6 kg/m2 FIGO stadium: IA1 - IA2 - IB1 8.5% - 6.2% - 84.2% Histologic type: Squamous cell carcinoma - Adenocarcinoma - Adenosquamous carcinoma 71.2% - 24.9% - 4.1% Positive lymph nodes 7.3%

European Journal of Surgical Oncology, 2020

Objective: To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surg... more Objective: To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surgery for endometrial cancer within the Belgium Gynaecological Oncology Group (BGOG). Study design: We performed a retrospective analysis of women with clinically Stage I endometrial cancer who underwent surgical treatment from 2007 to 2018 in five institutions of the BGOG group. Results: A total of 598 consecutive women were identified. The rate of conversion to laparotomy was low (0.8%). The mean postoperative Complication Common Comprehensive Index (CCI) score was 3.4. The rate of perioperative complications did not differ between age groups, however the disease-free survival was significantly lower in patients over 75 years compared to patients under 65 years of age (p¼0.008). Per-operative complications, conversion to laparotomy rate, post-operative hospital stay, CCI score and disease-free survival were not impacted by increasing BMI. Conclusion: Robot-assisted surgery for the surgical treatment of patients suffering from early-stage endometrial cancer is associated with favourable surgical and oncologic outcomes, particularly for unfavourable groups such as elderly and obese women, thus permitting a low morbidity minimallyinvasive surgical approach for the majority of patients in expert centres.

Poster exhibition Day 1, 2019

Introduction/Background The aim of this prospective study was to report perioperative outcomes, d... more Introduction/Background The aim of this prospective study was to report perioperative outcomes, disease-free and overall survival of robot-assisted management of patients with endometrial cancer, treated in 5 centers in Belgium. Methodology Patients undergoing surgery between August 2007 and December 2018 (n=615) were prospectively collected. Results Median age was 68 years (range, 31–92), median BMI 28 kg/m2 (range, 17–61). Five-hundred-ninety-nine patients underwent robot-assisted hysterectomy and bilateral salpingo-oophorectomy. In addition, full pelvic lymphadenectomy was performed in 151 (25%), and pelvic sentinel nodes biopsies only in 181 patients (29%). Sixteen patients were referred for robotic node staging after hysterectomy performed elsewhere. Histological types were endometrioid (n=512, 84%), serous (n=43, 7%), clear cell (n=8, 1%), mucinous (n=3, 0.5%), squamous (n=2, 0.3%) and carcinosarcoma (n=20, 3%). FIGO stage was: IA (61%), IB (24%), II (4%), IIIA (2%), IIIB (0,3%), IIIC (8%), IV (1%). Metastatic pelvic nodes were found in 43 (7%), positive para-aortic nodes in 3 (0,4%), pelvic and para-aortic nodal metastases in 7 patients (1,2%). Median number of removed pelvic and para-aortic nodes was 15 (range, 0–64) and 10 (range 1–47), respectively. Median estimated blood loss was 50 mL (range 0– 1000), median skin-to-skin time 150 minutes (range 55–480) and conversion rate 0.8% (n=5). Intra-operative complications occurred in 5% (n=30). At least one postoperative complication occurred in 15% (n=89). Median follow-up was 27 months (range, 1–131). Recurrence occurred in 63 patients (11%) and 38 patients (6%) died of endometrial cancer. The 2- and 5-year recurrence-free survival rates were 89% and 84%, respectively. The 2- and 5-year overall survival rates were 92% and 83%, respectively. Conclusion This study confirms the feasibility and safety of robot-assisted management of endometrial cancer with a low complication, conversion and recurrence rate. Disclosure Nothing to disclose.

Annals of Oncology, 1998

Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases ... more Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. The real incidence of gastrointestinal metastases in breast cancer patients is probably underestimated owing to the non-specific presenting symptoms and death of patients caused by other more obvious metastases. The predominant histological subtype of gastrointestinal metastases of breast cancer is invasive lobular carcinoma and the median interval from diagnosis of primary breast cancer to gastrointestinal metastases is five years. We report two cases of disseminated breast cancer with gastrointestinal involvement with a rather long survival.

Open Access Surgery, 2013

Chronic wounds are common and their incidence has been on the increase. They place an enormous bu... more Chronic wounds are common and their incidence has been on the increase. They place an enormous burden on health care services and have a major impact on several aspects of patients' wellbeing. It is vital for clinicians to recognize the complexity of the underlying processes leading to the development of a chronic wound. With this knowledge, the key factors that led to their development in each patient can be identified and appropriate steps taken to address modifiable factors. There is currently a wide range of treatments available for treatment of chronic wounds, with a range of exciting new treatments being developed. This paper aims to give an overview of the common etiology and pathophysiology of chronic wounds followed by a discussion of a range of current and future developments in their treatment.

Nuclear Medicine Communications, 1999

Gynecologic Oncology, 2003

AACR Meeting …, 2006

Proc Amer Assoc Cancer Res, Volume 47, 2006 2810 Chemokines and their receptors play important ro... more Proc Amer Assoc Cancer Res, Volume 47, 2006 2810 Chemokines and their receptors play important roles in cancer biology influencing the movement of both stromal and malignant cells and modulating the expression of other cytokines, chemokines and proteases. In order to further understand the role of chemokines in cervical cancer the expression of twenty-three chemokines and fifteen chemokine receptors was investigated in normal and malignant cervix using a Rnase Protection Assay. The relative contribution of epithelial and stromal compartments in the chemokine network were assessed using low density gene-array and laser capture microdissection. Immunohistochemical staining was employed to validate and locate a tumour associated chemokine receptor in normal, pre-invasive and invasive cervical tissue and also on infiltrating cells. We found two key differences in chemokine receptor expression between normal and malignant tissue. First, mRNA for CX3CR1 was detected in normal cervical tissue, but was absent in malignant tissue. Second, higher expression of mRNA for CCR4 was detected in malignant cervical tissue compared to normal cervix. Both the stromal and epithelial compartments contributed to the high mRNA CCR4 expression. In normal cervical tissue, CCR4 protein expression was detected only on macrophages. However, in pre-malignant stages of cervical cancer (CIN) and invasive cervical tissues, CCR4 protein was not only detected on infiltrating macrophages and regulatory T cells but also, surprisingly, on tumour cells. The macrophage and regulatory T cell infiltration in samples of normal cervical tissue, pre-malignant lesions, and stages I, II and III of invasive epithelial cervical cancer were further characterized. Normal cervical tissue contained few, if any, macrophages and regulatory T cells. These numbers were increased in pre-malignant lesions and invasive cervical cancers. This data, to our knowledge, is the first description of CCR4 expression by malignant epithelial cells. Increased CCR4 expression in cervical cancer is also due to increased number of CCR4 expressing macrophages and regulatory T cells. The observation that CCR4 is expressed by the pre-malignant stages (CIN1, CINII and CINIII) of cervical cancer, may indicate that CCR4 expression may play an important, yet-undefined, role in early events of cervical carcinogenesis.

British Journal of Clinical Pharmacology, 1995

The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of m... more The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of maternal and foetal serum obtained at delivery. The binding of the enantiomers of both drugs was lower in foetal than in maternal serum. In maternal serum the mean (+/‐ s.d.) unbound percentages were 22.4 +/‐ 6.2 and 20.7 +/‐ 6.6 for R‐ and S‐ propranolol, and 16.8 +/‐ 5.5 and 22.5 +/‐ 6.2 for R‐ and S‐verapamil; in foetal serum the values were 38.8 +/‐ 8.6 and 40.4 +/‐ 10.6 for R‐ and S‐propranolol, and 34.7 +/‐ 10.5 and 44.8 +/‐ 10.7 for R‐ and S‐ verapamil. For propranolol, in maternal, but not in foetal serum, the difference between the binding of the R‐ and S‐enantiomers was significant; the R/S ratio was significantly (P < 0.01) larger in the mother (1.099 +/‐ 0.072) than in the foetus (0.973 +/‐ 0.068). For verapamil, the difference in binding between the R‐ and S‐enantiomers was significant in both maternal and foetal serum, but the R/S ratio was similar in mother (0.735 +/‐ 0....

British Journal of Cancer, 2007

Most cancer patients die of metastatic or recurrent disease, hence the importance to identify tar... more Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up-and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-b) were upregulated at least twofold. Some of these genes (AKT and MMP3) are key regulators of epithelial-mesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer.

Journal of Surgical Case Reports

Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnos... more Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnosis is based on pathology and immunohistochemistry. Surgery with a total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the standard. A female patient in her 60s presented with heavy postmenopausal bleeding. Vaginal ultrasound scan and magnetic resonance imaging showed a large strongly vascularized cervical mass with features suspicious of sarcomatous degeneration. Positron Emission Tomography-Computed Tomography (PET-CT) did not reveal any evidence of metastases nor lymphadenopathy, but presence of right hydronephrosis. An abdominal hysterectomy with bilateral salpingo-oophorectomy, and end-to-end anastomosis of the right ureter, was performed. Pathology showed an International Federation of Gynecology and Obstetrics (FIGO)-stage 1B leiomyosarcoma of the uterine cervix. No adjuvant treatment was given. Adjuvant radiotherapy reduces the risk of recurrence but no surviv...

Frontiers in Surgery

IntroductionPrimary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly i... more IntroductionPrimary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly in elderly women. The diagnosis is based on histology and immunohistochemistry of a biopsy. Given the rarity of vaginal melanoma, no standardized treatment guidelines are established; however, surgery is the primary treatment modality in the absence of metastatic disease. Most reports in the literature are retrospective single cases, case series, and population-based studies. The open surgical approach is the main modality reported. Here, we report for the first time a 10-step combined robotic-vaginal technique, with en bloc resection of the uterus and total vagina, for treating clinically early-stage primary vaginal melanoma. In addition, the patient in our case underwent a robotic pelvic bilateral sentinel lymph node dissection. The literature on the surgical approach for vaginal melanoma is reviewed.Case presentationA 73-year-old woman was referred to our tertiary cancer center and was...

European Journal of Obstetrics & Gynecology and Reproductive Biology