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J H W de Wilt

Publications and source records attributed to J H W de Wilt.

18 recordsLinked to original sources
PubMed2006

Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma.

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.

Adolescent↗
PubMed2006

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer.

AIMS: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. METHODS: In the period 1994-2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. RESULTS: Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p=0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. CONCLUSION: TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Adult↗
PubMed2006

Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative?

As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.

Adolescent↗
PubMed2006

Sentinel node biopsy for clear cell sarcoma.

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.

Adult↗
PubMed2006

Isolated limb perfusion for melanoma patients--a review of its indications and the role of tumour necrosis factor-alpha.

AIMS: The treatment of melanoma in-transit metastases (IT-mets) can vary widely and is dependant on the size and the number of the lesions. When multiple, large lesions exist, isolated limb perfusion (ILP) has established itself as an attractive treatment option with high response rates. METHODS: Review on the various methods of treatment of melanoma in-transit metastases, with a focus on isolated limb perfusion. A Medline based literature search was performed for articles relating to this topic. Additional original papers were obtained from citations in those identified by the initial search. Indications and results are discussed and the extra value of tumour necrosis factor (TNF) is evaluated. RESULTS: ILP with Melphalan results in complete response rates of 40-82% and showed to be 54% in a large retrospective meta-analysis. The addition of TNF can improve these completes response rates (59-85%) and although no data from randomized controlled trials are available, it seems of particular value in large, bulky lesions or in patients with recurrent disease after previous ILP. CONCLUSIONS: TNF-based ILP has earned a permanent place in the treatment of patients with melanoma IT-mets. In patients with a high tumour burden, TNF-based ILP is the most efficacious procedure to obtain local control and achieve limb salvage.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed2006

High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma.

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Adolescent↗
PubMed2006

Angiogenesis inhibitors: perspectives for medical, surgical and radiation oncology.

In the past decade, many angiogenesis inhibitors have been developed for clinical use in oncology. Surgeons, radiotherapists as well as medical oncologists have been investigating with much effort and enthusiasm the translation of these agents from the preclinical setting into treatment strategies of patients. Recently, for the first time in history, the angiogenesis inhibitor bevacizumab (avastin), a humanized anti-vascular endothelial growth factor (VEGF) antibody, showed a survival benefit of 4.7 months in a phase III clinical trial in patients with advanced colorectal cancer when this agent was given in combination with chemotherapy. At the annual meeting of the American Association of Clinical Oncology 2005, similar results of bevacizumab in lung, breast and ovarian cancer clinical trials have been shown. These landmark studies proofed for the first time in the clinical setting that Dr. Folkman back in 1971 was right by proposing: "in order to stop tumor growth, one should attack its blood supply". Nowadays it seems trivial to propose such a hypothesis, at that time it was a very provocative hypothesis and it took more than 30 years to proof this hypothesis in the clinic. Although one may be excited about this major finding, there is no time to relax. The survival benefit of bevacizumab is only about 4 months. Therefore more potent antiangiogenic agents and more active treatment strategies are urgently warranted. Newer angiogenesis inhibitors that are currently in preclinical or early clinical development have shown in preclinical experiments improved antitumor activities. In addition, combinations of biological agents that interfere in multiple biological pathways in cancer growth including chemotherapy, are of major clinical interest as well. The multimodality approach in which surgeons, radiotherapists and medical oncologists collaborate needs to be explored as well. In a variety of cancer types, like breast colon and lung cancer, these specialists should design multimodality strategies based on current standard treatment in which they incorporate angiogenesis inhibitors in the right time frame of surgery and radiotherapy. In this review we will bring you up to date on the clinical development of angiogenesis inhibitors and we will summarize the multimodality strategies that are under development.

Angiogenesis Inhibitors↗
PubMed2005

TNF dose reduction in isolated limb perfusion.

AIMS: Isolated limb perfusion with TNF and melphalan (TM-ILP) is highly effective in the local treatment of advanced sarcoma and melanoma of the limb. The optimal dose of TNF for this procedure is not well established. The aim of this study was to assess the efficacy and toxicity of TM-ILPs with reduced TNF dose. METHOD: Largest single institution prospective database on TNF-based ILP. Out of 339 TM-ILPs performed between 1991 and 2003, 64 procedures were performed with reduced TNF dose (<3 mg in arm perfusions, <4 mg in leg perfusions). Response rates and toxicity of the procedure and outcome of the patients are evaluated. RESULTS: Complete response in melanoma patients after reduced-dose ILP was 75 vs 69% after standard-dose ILPs (overall response 94 vs 95%, respectively); overall response in non-melanoma patients was 69 (reduced) vs 74% (standard). Response rates and outcome were comparable with the procedures performed with standard-dose TNF (p=NS for response, local/systemic progression and survival after multivariate analysis, both in melanoma and in non-melanoma patients). Systemic and local toxicity did not differ statistically between reduced- and standard dose TM-ILPs. CONCLUSION: Provided doses at 1mg or higher are used, TM-ILP with TNF dose reduction for both melanoma and non-melanoma patients seems to be as effective as the standard dose procedure in terms of response rate and patient outcome. Numbers to formally confirm or reject this hypothesis are too large for such a non-inferiority trial to be conducted in patients with these rare conditions.

Adolescent↗
PubMed2005

Primary and secondary reconstruction after surgery of the irradiated pelvis using a gracilis muscle flap transposition.

INTRODUCTION: The aim of this study is to describe our experience with reconstruction of pelvic defects after surgery for previously irradiated malignancies using a gracilis muscle flap transposition. PATIENTS AND METHODS: Between 1993 and 2002, 25 patients were treated by primary (n=7) or secondary reconstruction (n=18) using a gracilis muscle transfer. All patients were previously irradiated with a median dosage of 50 Gy. RESULTS: Direct reconstruction following resection of the tumour was accompanied with minor complications in three patients and without major complications. Median time to complete healing of the donor site and perineal defect was 11 and 46 days, respectively. Reconstruction of persistent perineal infections resulted in minor complications at the donor site (n=3) and at the perineal wound (n=11). Three patients experienced a major complication. Median time to complete healing of the donor site and perineal defect was, respectively, 17 and 190 days. Necrosis of the gracilis muscle flaps was not observed. CONCLUSION: Direct reconstruction with a gracilis transfer resulted in primary wound healing with low morbidity, hereby preventing potentially disabling persistent defects. After debridement of persistent wounds, indirect reconstruction with gracilis muscle resulted in the majority of patients in healing of the defects with acceptable morbidity.

Adult↗
PubMed2005

Isolated limb perfusions with tumor necrosis factor and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs.

BACKGROUND: Recurrent extremity soft tissue sarcoma (STS) in a previously operated and irradiated area can usually be managed only by amputation. Tumor necrosis factor (TNF)-alpha-based isolated limb perfusion (ILP) is an established alternative to achieve limb salvage but is assumed to require sufficient vasculature. Because radiotherapy is known to destroy vasculature, we wanted to evaluate retrospectively whether the outcome of ILP in patients with radiotherapy for their primary tumor nonetheless showed a benefit from TNF treatment. METHODS: We consulted a prospective database of TNF-based ILPs at the Erasmus MC-Daniel den Hoed Cancer Center in Rotterdam. Out of 342 TNF-based ILPs between 1991 and 2003, 30 ILPs were performed in 26 patients with recurrent STS in the irradiated field after prior surgery and radiotherapy. Eleven patients (42%) had multiple tumors (n = 2-20). All patients were candidates for amputation. RESULTS: We observed 6 complete responses (20%), 15 partial responses (50%), no change in 8 patients (27%), and progressive disease in 1 patient (3%). The median duration of response was 16 months (range, 3-56 months) at a median follow-up of 22 months (range, 3-67 months). The local recurrence rate was 45% in patients with multiple tumors and 27% in patients with single tumors. Ten patients (35%) died of systemic metastases. Limb salvage was achieved in 17 patients (65%). Regional toxicity was limited and systemic toxicity minimal. CONCLUSIONS: TNF-based ILP can avoid amputations in most patients with recurrent extremity STS in a prior operated and irradiated field.

Adult↗
PubMed2005

Bio-chemotherapeutic strategies and the (dis) utility of hypoxic perfusion of liver, abdomen and pelvis using balloon catheter techniques.

AIMS: To review the development and current status of balloon catheter mediated hypoxic perfusion of abdomen, pelvis and liver for treatment of locally advanced malignancies. Within this context we focus on the addition of tumour necrosis factor-alpha (TNF) to these minimal invasive perfusion procedures. METHODS: A literature search on these topics was carried out in PubMed for indexed articles and in all issues of Regional Cancer Treatment. The findings were related to our own experiences. RESULTS: Hypoxic abdominal (HAP) and hypoxic pelvic perfusion (HPP) using balloon catheters, are currently applied modalities for treatment of a wide variety of abdominal and pelvic tumours, yet scientific validation of these procedures is poor. Following the results of several Phase I-II trials, both treatments are associated with severe systemic toxicity, significant morbidity and even mortality. The degree of systemic leakage associated with these procedures prohibits addition of TNF. For leakage free liver perfusion surgery is still required, as with current balloon catheter techniques it is not possible to perform leakage free isolated hypoxic hepatic perfusion (IHHP), using either orthograde or retrograde hepatic flow. Experimental and clinical observations suggest that within any perfusion setting, the utilization of TNF is only indicated for treatment of highly vascularised tumours and not for treatment of colorectal tumours. CONCLUSION: Balloon catheter technology in its present form does not provide adequate leakage control in any of these settings and is therefore associated with considerable toxicity. It is associated with poor response rates and cannot be considered in any setting as a standard of care.

Abdominal Neoplasms↗
PubMed2005

TNF-based isolated limb perfusion in unresectable extremity desmoid tumours.

BACKGROUND: Desmoid tumours are soft tissue sarcomas with local aggressive behaviour and a high rate of local recurrence after treatment. Although they do not tend to metastasise systemically, the local aggressiveness can lead to situations in which limb-preserving surgery cannot be performed without severe disability. As isolated limb perfusion (ILP) with TNF and melphalan has proven to be extremely effective in the treatment of soft tissue sarcoma, we studied its potential in locally advanced extremity desmoid tumours. METHODS: Prospectively maintained database in a tertiary referral centre. Between 1991 and 2003, 12 ILP procedures were performed in 11 patients for locally advanced desmoid tumours. Local surgical therapy with preservation of limb function was impossible in all patients due to large or multifocal tumours, multiple recurrences or extensive previous treatment. Perfusions were performed with 4-3mg TNF and 10-13 mg/l limb volume melphalan form leg and arm perfusions, respectively. RESULTS: Overall response rate was 75%: Two complete responses were recorded (17%) and seven patients had a partial response (58%). Amputation could be avoided in all cases. Local control was obtained after 10/12 ILPs and in the other two patients through repeat ILP and systemic chemotherapy, thus leading to an overall local control rate of 100%. Local toxicity was mild and systemic toxicity was absent in all patients. CONCLUSION: ILP is a very effective treatment option in the multimodality treatment of limb desmoid tumours. It should be considered in patients with aggressive and disabling disease where resection without important functional sacrifice is impossible.

Adolescent↗
PubMed2004

Hepatocellular carcinoma in the Netherlands incidence, treatment and survival patterns.

To examine recent trends of hepatocellular carcinoma (HCC) in an unselected patient population in the Western world, cancer registration data of HCC in the Netherlands were analysed. Trends in incidence, mortality, treatment and survival, according to gender, age, stage of disease and period of diagnosis were studied. Age-standardised incidence of HCC in the Netherlands did not rise from 1989 to 2000. In men older than 75 years, there was a significant increase. Mortality due to primary liver cancer increased from 1989 to 2000. There was no change in the treatment pattern (1989-1998), whereas 73% of patients with HCC received no cancer-related therapy during this period of analysis. Twelve percent of the patients underwent either a partial liver resection or orthotopic liver transplantation. This low percentage suggests that patients with HCC must be analysed and discussed in specialised centres to minimise the number of patients not receiving possible curative therapy.

Adult↗
PubMed2002

Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity.

Previously we demonstrated that addition of Tumour Necrosis Factor-alpha to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan.

Animals↗
PubMed2002

Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable sSewart-Treves lymphangiosarcoma.

BACKGROUND: Cutaneous Stewart-Treves lymphangiosarcomas represent a rare group of tumors characterized by a high grade of vascularization and by localization in an extremity with lymphedema. The multifocality and the localization makes these tumors eligible for treatment with isolated limb perfusion (ILP). ILP with tumor necrosis factor (TNF) and melphalan is a safe and highly effective procedure that can achieve limb salvage in >or=80% of all patients with nonresectable extremity soft tissue sarcoma or melanoma. METHODS: In 10 patients with multifocal Stewart-Treves lymphangiosarcoma of the extremities, 16 ILPs with TNF plus melphalan were performed. All patients would have been candidates for exarticulation of the extremity. RESULTS: We observed an 87% overall response rate (complete and partial responses); one patient had a mixed response, and one patient did not respond to the therapy. In nine perfusions (56%), a complete response was achieved, and five perfusions (31%) resulted in a partial response. Limb salvage was achieved in eight patients (80%), with a mean follow-up duration of 34.8 months (range, 3 to >or=115 months). Regional toxicity was limited and systemic toxicity minimal to moderate, with no toxic deaths. CONCLUSIONS: Multifocal Stewart-Treves lymphangiosarcomas in extremities with chronic lymphedema can be successfully treated by ILP with TNF and melphalan.

Aged↗
PubMedDate not supplied

Resection of extrahepatic hepatocellular carcinoma metastasis can result in long-term survival.

Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world and the third most common cause of cancer mortality world-wide. Surgery is the gold standard in the treatment of patients with HCC. The prognosis is mainly determined by the underlying liver disease and recurrent rates. In the Western World, up to 30% of the patients with HCC have a non-cirrhotic liver. The main prognostic factor in this special group of patients are the recurrences. Most recurrences are intrahepatic; however, 30% of the recurrences are extrahepatic. The role of resection in case of intrahepatic recurrences is widely accepted, particularly in the non-cirrhotic liver. The role of resection in extrahepatic HCC recurrences is not well established and unknown among many physicians. We present two patients with HCC in a non-cirrhotic liver with extrahepatic recurrences and long-term survival after resection. The corresponding literature support an aggressive approach in case of extrahepatic HCC recurrence in selected cases: resectable metastasis, preserved liver function, absence of intracranial metastasis and control of the primary tumour. Further research is warranted because of the limited number of reports and the absence of randomized trials.

Adult↗