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Biomedical subjects

C Verhoef

Publications and source records attributed to C Verhoef.

At least 19 recordsLinked to original sources

Randomized clinical trial comparing feeding jejunostomy with nasoduodenal tube placement in patients undergoing oesophagectomy.

BACKGROUND: Feeding jejunostomy is frequently performed in patients undergoing oesophageal surgery, but can lead to serious complications. This prospective randomized trial compared the efficacy and complications of feeding jejunostomy with those of nasoduodenal tube feeding in oesophageal surgery. METHODS: Over an 18-month period, 150 consecutive patients undergoing oesophageal resection were randomized to participate in the trial. Enteral access was by jejunostomy in 79 patients and by nasoduodenal tube in 71. Enteral feeding was started on the first day after surgery. RESULTS: Full enteral feeding took 3 days to be established in both groups. Minor catheter-related complications occurred in 28 patients (35 per cent) in the jejunostomy group, and in 21 (30 per cent) in the nasoduodenal group (P = 0.488). One patient had jejunostomy leakage that required reoperation. Enteral nutrition was given for a median of 11 days in the jejunostomy group and for 10 days in the nasoduodenal group. Nine patients who had a jejunostomy and five with a nasoduodenal tube did not tolerate full enteral feeding (P = 0.411). CONCLUSION: Nasoduodenal tube feeding is safe and efficient after oesophageal resection.

Adult↗

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↗

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↗

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↗

Aggressive angiomyxoma: multimodality treatments can avoid mutilating surgery.

AIMS: Aggressive angiomyxoma is a soft-tissue tumour of the pelvi-perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. In search of alternative treatment methods we present our experience in seven patients. METHODS: The medical charts of seven patients treated in the last 20years were reviewed. Follow-up data were obtained. In addition, a literature review from 1994 to 2004 regarding treatment and clinical outcome was performed. RESULTS: All patients were female, and three were pregnant at the time of diagnosis. All patients underwent primary surgical treatment. In five patients the surgical margins were involved; one patient received adjuvant radiotherapy treatment. Three patients experienced a total of four recurrences after 2-10years. These patients were treated with selective embolisation or surgery. At present all patients are disease-free, with follow-up ranging from 2 to 20years after last treatment. CONCLUSION: Radical surgery does not seem to lead to a significant lower recurrence rate of aggressive angiomyxoma when compared to incomplete resection (R1), with or without radiotherapy or arterial embolisation. This casts doubt on the necessity of extensive surgery, especially in cases where an extensive surgical procedure will lead to great morbidity.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Good outcomes after resection of large hepatocellular carcinoma in the non-cirrhotic liver.

BACKGROUND: The results of partial liver resection of hepatocellular carcinoma (HCC) in non-cirrhotic livers are not well known. Therefore a retrospective study was conducted. METHODS: The medical records of 180 patients with HCC were reviewed. In 40 patients (22%), HCC occurred in a non-cirrhotic liver. A detailed analysis of these patients was performed. The diagnosis HCC was based on imaging and/or percutaneous ultrasound-guided biopsy. A biopsy of the remaining liver and peroperative findings documented the absence of cirrhosis. RESULTS: Twenty-two patients underwent partial liver resection. There was no surgical mortality. The median tumour diameter in the operated patients was 10 cm. Survival rates for operated patients at 1 and 5 years were 96 and 68%, respectively. Significant factors reducing survival were portal vein thrombosis, positive lymph nodes, microscopic vascular invasion and tumour recurrence. Tumour size at the initial moment of diagnosis was not of predictive value. After surgery with curative intent disease-free interval at 1 and 5 years were 86 and 56%, respectively. CONCLUSION: In selected patients without cirrhosis, HCC can be treated successfully by surgical resection, independent of the tumour diameter, with a 5-year survival rate of 68%.

Adult↗

Interstitial laser coagulation with temporary hepatic artery occlusion for patients with cirrhosis and irresectable hepatoma.

BACKGROUND: The aim was to determine the degree of local control of hepatocellular carcinoma (HCC) in patients with cirrhotic liver disease when treated with ultrasonographically guided interstitial laser coagulation (ILC) with temporary hepatic artery occlusion. METHODS: Sixteen patients with 24 HCC tumours were treated. Follow-up was by computed tomography or magnetic resonance imaging every 3 months. RESULTS: Nineteen of 24 tumours showed complete necrosis immediately after treatment, and there was no tumour recurrence during follow-up (mean 14 months, median 12 months). No effect on liver function was observed after 1 week and there was no death. In 13 of the 16 patients, new HCC foci developed at other sites. CONCLUSION: Percutaneous ILC combined with temporary hepatic artery occlusion during a single session is an effective local treatment for HCC nodules smaller than 5 cm. However, new HCC lesions develop in the majority of patients, which underscores the need for adjuvant therapy or repeated treatment in these patients.

Aged↗

Fluorine-18 FDG imaging in hepatocellular carcinoma using positron coincidence detection and single photon emission computed tomography.

BACKGROUND/AIMS: We prospectively evaluated whether fluorine-18 deoxyglucose (FDG) positron coincidence detection (PCD) or FDG single-photon emission computed tomography (SPECT) provides additional benefits to our conventional preoperative evaluation of lesion detection in patients suspected to have hepatocellular carcinoma (HCC). METHODS: Thirteen consecutive patients with a suspected HCC underwent conventional preoperative evaluation with ultrasonography (US), triple-phase helical computed tomography (CT), superparamagnetic iron oxides (SPIO) enhanced magnetic resonance imaging (MRI) and serum alpha-fetoprotein (AFP) level. All 13 patients had an FDG-PCD and SPECT. These results were evaluated to assess the value of FDG-PCD and SPECT in addition to US, SPIO-enhanced MRI and triple-phase helical CT. RESULTS: Ten of the 13 (77%) patients had at least one histologically confirmed HCC without extrahepatic abdominal spread. The tumors ranged in size from 1 to 8 cm and the serum AFP ranged from 3 to 30 000 microg/l. Of these 10 patients, two patients had an increased tumor F-FDG uptake (sensitivity of 20%); one patient with an AFP of 5 microg/l and a tumor size of maximum 4.5 cm and one patient with an AFP of 249 microg/l and a tumor size of maximum 2 cm. In three patients with a benign liver mass, FDG imaging with either PCD or SPECT was negative. There was no false positive finding. CONCLUSIONS: We found poor sensitivity of FDG-PCD and FDG-SPECT for the detection of HCC. There were no clear relations between AFP or tumor size and FDG uptake. Therefore, we conclude that FDG imaging with PCD or SPECT has no value in the preoperative work-up for HCC in patients with cirrhosis.

Adult↗

New pore protein produced in cells lysogenic for Escherichia coli phage HK253hrk.

Outer membrane pore protein OmpC was identified as the receptor for the temperate Escherichia coli phage HK253hrk. The part of OmpC protein recognized by the phage was identified by using hybrid proteins in which parts of OmpC protein are replaced by the corresponding parts of the related PhoE protein. In contrast to other OmpC-specific phages, HK253hrk recognizes a part of OmpC within the C-terminal 50 amino acids of the protein. E. coli strains lysogenic for HK253hrk produce reduced amounts of OmpC protein, and produce a new pore protein instead. Expression of this new protein was temperature-dependent, i.e. low at 30 degrees C. The functioning of this new pore protein was characterized both in vivo by studying the uptake of beta-lactam antibodies and in vitro after reconstitution of the protein in black lipid films. Its effective pore size was larger than that of the OmpF pores of E. coli B. The new porin appears to be cation-selective. A comparison with the selectivity of the known OmpC and OmpF pores of E. coli showed that the new pore has a higher selectivity than OmpF but is less selective than OmpC. The new pore protein appears to function in E. coli K12 lysogens as the receptor for the phages HK187, HK189 and HK332.

Bacterial Outer Membrane Proteins↗