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Theo Wobbes

Publications and source records attributed to Theo Wobbes.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for non-sentinel lymph node metastases in patients with breast cancer. The outcome of a multi-institutional study.

BACKGROUND: In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive sentinel lymph node (SN). METHODS: In this multi-institutional study, 541 eligible breast cancer patients were included prospectively. RESULTS: The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .02), primary tumor size (P = .001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro-metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared with </=3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were no positive non-SNs when the primary tumor size was </=1.0 cm (n = 24) [95% confidence interval (95% CI) 0%-14.0%]. The proportion of positive non-SNs ranged in a prognostic logistic regression model from 9.7% (95% CI 4.0%-23.0%) for patients with SN isolated tumor cells, tumor size of 1.1-3.0 cm, and without vessel invasion, to 72.6% (95% CI 47.0%-89.0%) for patients with SN macro-metastasis, tumor size >3.0 cm, and with vessel invasion. CONCLUSION: We identified three predictive factors for non-SN metastases in breast cancer patients with a positive SN: size of the SN metastasis; primary tumor size; and vessel invasion. We were not able to identify a specific group of patients with a positive SN in whom the risk for non-SN metastases was less than 5%.

Adult↗
PubMed2006

Differences in sentinel lymph node pathology protocols lead to differences in surgical strategy in breast cancer patients.

BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN). At present, therefore, various hospitals use different SN pathology protocols of which the effect has not been fully elucidated. We hypothesized that differences between hospitals in SN pathology protocols affect subsequent surgical treatment strategies. METHODS: Patients from four hospitals (A-D) were prospectively registered when they underwent an SN biopsy. In hospitals A, B, and C, three levels of the SN were examined pathologically, whereas in hospital D, at least seven additional levels were examined. In the absence of apparent metastases with hematoxylin and eosin examination, immunohistochemical examination was performed in all four hospitals. RESULTS: In total, 541 eligible patients were included. In hospital D, more patients were diagnosed with a positive SN (P < .001) as compared with hospitals A, B, and C, mainly because of increased detection of isolated tumor cells. This led to more completion axillary lymph node dissections in hospital D (66.3% of patients (P < .0001), compared with 29.0% in hospitals A, B, and C combined). Positive non-SNs were detected in 13.9% of patients in hospital D, compared with 9.7% in hospitals A, B, and C (P = .70). That is, in 52.4% of patients in hospital D, a negative completion axillary lymph node dissection was performed, compared with 19.3% of patients in hospitals A, B, and C combined. CONCLUSIONS: Differences in SN pathology protocols between hospitals do have a substantial effect on SN findings and subsequent surgical treatment strategies. Whether ultrastaging and, thus, additional surgery can offer better survival remains to be determined.

Adult↗
PubMed2006

Outgrowth of human liver metastases after resection of the primary colorectal tumor: a shift in the balance between apoptosis and proliferation.

Rapid outgrowth of metastases after removal of the primary tumor has been described in several mouse models. Loss of primary tumor-induced inhibition of angiogenesis in the metastases has been suggested as the underlying cause. Accordingly, we recently demonstrated that vascular density in human colorectal liver metastases increases after primary tumor resection. Here, we investigate whether this increase in vascular density has, in its turn, effects on the tumor growth of the liver metastases. We analyzed tumor growth in synchronous liver metastases from patients with the primary tumor in place, in synchronous metastases from patients with the primary tumor resected and in metachronous metastases. Tumor growth was studied by assessing the percentage of cells undergoing apoptosis by activated caspase-3 staining, and the percentage of proliferating cells by Ki-67 staining. While the percentage of proliferating cells within the metastases showed a modest increase after primary tumor resection, a significant decrease in the percentage of apoptotic cells was observed. Taken together, an increased net tumor growth of the metastases occurred after primary tumor resection. This acceleration of tumor growth could be confirmed by studying biopsies taken from the same patient before and after tumor resection. Our data show that in human cancer patients, a primary tumor may inhibit the growth of its liver metastases.

Adult↗
PubMed2006

Epithelioid sarcoma: Still an only surgically curable disease.

BACKGROUND: Epithelioid sarcoma is a rare soft tissue sarcoma with a known high propensity for locoregional recurrence and distant metastases. The clinical behavior and prognostic factors that influence the survival of patients with epithelioid sarcoma were studied. METHODS: Twenty-three patients, including 16 men (70%) and 7 women (30%), who were treated for epithelioid sarcoma between 1979-2003 at the University Medical Center Groningen and Radboud University Nijmegen Medical Center, were reviewed retrospectively. The median age at diagnosis was 22 years (range, 1-54 years). At the time of diagnosis, 11 patients (48%) had metastases. Six patients with distant metastasis and 1 patient with an unresectable tumor received palliative treatment (30%). The remaining 16 patients underwent surgical treatment of local disease (11 patients) or locoregional disease (5 patients). Five patients in that group received isolated limb perfusion with tumor necrosis factor and melphalan. RESULTS: The 5-year and 10-year disease-free survival rates for all patients were 34% and 17%, respectively; for the 16 patients who received curative treatment, both rates were 56%. In the latter group, 8 patients developed local recurrence (50%) after a median follow-up of 4 months (range, 1-14 months). Nine patients were disease free after a median follow-up of 50 months (range, 6-290 months). Tumor size >5 cm (P < .0026) at diagnosis and local recurrence (P < .0008) were significant predictors of survival. CONCLUSIONS: The prognosis for patients with epithelioid sarcoma is poor, because a substantial number of patients present with extensive disease, lymph node metastases, and/or distant metastases. Treatment consists of radical surgical excision of the tumor and, if indicated, therapeutic lymph node dissection. In patients who have large tumors, isolated limb perfusion may be useful.

Adolescent↗
PubMed2006

Level of fluorodeoxyglucose uptake predicts risk for recurrence in melanoma patients presenting with lymph node metastases.

BACKGROUND: The incidence of malignant melanoma has increased. Identification of additional prognostic factors may allow the development of individualized strategies. This multivariate analysis was undertaken to evaluate the potential role of the standard uptake value (SUV) in predicting disease-free and overall survival in melanoma patients with lymph node metastases. METHODS: All melanoma patients with palpable lymph node metastases who where referred for a fluorodeoxyglucose positron emission tomography scan were eligible. The SUV in the lymph node metastasis was calculated. Data were analyzed (Kaplan-Meier), and differences in cumulative survival and the disease-free rate were assessed (log-rank test). Univariate and multivariate analyses (Cox proportional hazard model) were performed to determine independent prognostic factors. RESULTS: There was no statistical difference in survival for the 38 patients with a high or low SUVmean (P = .11). However, a significant difference was found in disease-free survival (P = .03). Ulceration of the primary melanoma (P = .023) was an independent predictor of survival. For the disease-free survival, multivariate Cox regression showed adjuvant radiation (P = .001), localization of the primary melanoma (P = .017), and a high SUVmean (P = .009) as independent prognostic factors. CONCLUSIONS: Disease-free survival of melanoma patients was prolonged in those with a low SUVmean value (P = .03) in their lymph node metastasis, as compared with those with a high SUVmean. However, this difference was not found for overall survival. In multivariate analysis, high SUVmean was an independent prognostic factor (P = .009) for disease-free survival. Prospective research should determine whether patients with a high FDG uptake in melanoma lymph node metastases could benefit from adjuvant radiation treatment or chemotherapy.

Adult↗
PubMed2006

The value of magnetic resonance imaging in diagnosis and size assessment of in situ and small invasive breast carcinoma.

BACKGROUND: The value of magnetic resonance imaging (MRI) in diagnosis and size assessment of ductal carcinoma-in-situ (DCIS) and DCIS with small (<10 mm) invasive carcinoma was evaluated. METHODS: Fifty-four patients with DCIS and 12 patients with DCIS and small invasive carcinoma were included. Mammographic (N = 64) and MRI (N = 22) images were retrospectively reviewed. Correlation coefficients were calculated to assess differences in size between imaging and histopathologic examination. RESULTS: Mammographic rate of detection for DCIS was 48/52 (92%) and for DCIS with small invasive carcinoma, 10/12 (83%). MRI revealed 1 false negative case and the rate of detection for DCIS was 16/17 (94%). Correlation of mammographic size with histopathologic size was r = .44 (P < .01) and r = 0.49 (P = .03) for MRI. Mammography underestimated lesion size by 5 mm or more in 47%, whereas with MRI size was adequately assessed in 43% and overestimated in 38%. CONCLUSIONS: DCIS can be visualised on MRI with high sensitivity, although tumor size can be overestimated.

Adult↗
PubMed2005

Sister Joseph's Nodule and pneumatosis: a rare presentation of ovarian cancer.

BACKGROUND: The condition of pneumatosis intestinalis is characterized by gas in the intestinal wall, with a variety of causes. CASE: A septic patient with intestinal pneumatosis, locally advanced ovarian cancer, and Sister Joseph's Nodule. CONCLUSION: The clinical significance of this rare combination of symptoms and signs is discussed.

Aged↗
PubMed2005

Role of epoxide hydrolase, NAD(P)H:quinone oxidoreductase, cytochrome P450 2E1 or alcohol dehydrogenase genotypes in susceptibility to colorectal cancer.

Colorectal cancer (CRC) is one of the most common forms of cancer in Western countries. CRC has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. Therefore, we determined whether polymorphisms in the genes coding for microsomal epoxide hydrolase (EPHX1), NAD(P)H:quinone oxidoreductase (NQO1), cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase (ADH3) predispose to the development of CRC. DNA samples were obtained from 371 patients with sporadic CRC and 415 healthy controls. Patients and controls were all of Caucasian origin. All genetic polymorphisms were determined by polymerase chain reaction, eventually followed by restriction-fragment-length-polymorphism analyses, except for the EPHX1 codon 113 polymorphism, which was genotyped by an allele-specific discrimination assay. Calculation of crude Odds Ratios (ORs) revealed an increased risk for CRC associated with variant NQO1 (OR 1.5, 95% CI 1.1-2.0) and CYP2E1 intron 6 genotypes (OR 2.2, 95% CI 1.3-3.8). However, after adjustment for age and gender, logistic regression analyses only showed a statistically significant risk for CRC associated with variant NQO1 genotypes (OR 1.6, 95% CI 1.03-2.4). No associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, these data suggest that the presence of variant NQO1 genotypes, with expected reduced enzyme activities might enhance susceptibility to CRC.

Adult↗
PubMed2005

Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer.

mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8, P<0.001). For active MMP-2, but not for MMP-9, a significant negative partial correlation (R(p)=-0.440, P<0.001) for RECK was found in tumor tissue, which was confirmed by linear regression analysis. In exploratory survival analyses we found that in patients with localized disease the RECK level in normal or tumor tissue had a significant (P=0.017) association with overall survival.

Basigin↗
PubMed2005

High oxygen radical production in patients with sporadic colorectal cancer.

It is hypothesized that excessive generation of reactive oxygen species (ROS) by phagocytes or leakage from mitochondria may harm key genes or proteins responsible for intestinal cell homeostasis. This may initiate the multistage process of colon cancer development. The present study investigates whether ROS production by whole blood may contribute to the etiology of colorectal cancer (CRC). Whole-blood oxygen radical production was measured by luminol-enhanced chemiluminescence and performed in fourfold with and without the stimuli phorbol 12-myristate 13-acetate (PMA) and serum-treated zymosan (STZ). We evaluated patients (i) with a history of sporadic CRC at least 3 months after surgery, (ii) who were hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers, and (iii) with familial adenomatous polyposis (FAP). For each patient group (n = 20) an age- and gender-matched healthy control group was measured. Unstimulated and PMA-stimulated values for maximal oxygen radical production were significantly higher in patients with sporadic CRC in comparison to controls (p = 0.01, p = 0.04, respectively). Furthermore, trends toward higher unstimulated and PMA-stimulated area under the curve chemiluminescence were seen in CRC patients compared with controls (p = 0.08, p = 0.09, respectively). In patients with HNPCC or FAP, unstimulated or PMA- or STZ-stimulated chemiluminescence did not differ compared to their control groups. In conclusion, whole-blood oxygen radical production was higher in patients with a history of sporadic CRC, in comparison with age- and gender-matched controls, which indicates that ROS may play a role in the etiology of sporadic CRC.

Adenomatous Polyposis Coli↗
PubMed2005

Plasma levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 correlate with disease stage and survival in colorectal cancer patients.

PURPOSE: The matrix metalloproteinases and their inhibitors are known to be involved in the process of tumor invasion and progression. Our objective was to investigate the potential diagnostic and prognostic value of plasma matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 in colorectal cancer. METHODS: Gelatinase bioactivity and immunoreactivity of pro-matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen were determined simultaneously in preoperative plasma and serum of colorectal cancer patients (n = 94) and in healthy controls (n = 51). RESULTS: Plasma pro-matrix metalloproteinase-2 levels were lower in colorectal cancer patients (P < 0.0001) than in controls, and its gelatinolytic activity revealed an inverse correlation with adverse clinicopathologic parameters, such as lymph node involvement (P = 0.017), stage (0, I, II vs. III, IV; P = 0.012), and the carcinoembryonic antigen level (P = 0.016). Pro-matrix metalloproteinase-9 levels did not differ between patients and controls. Pro-matrix metalloproteinase-2 gelatinolytic activity showed potential value in colorectal cancer diagnosis, identifying patients with 70 percent sensitivity at 95 percent specificity. Pro-matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen all showed lower sensitivities. Combining pro-matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 measurements increased the sensitivity significantly to 84 percent. With respect to prognosis, tissue inhibitor of metalloproteinase-1 showed value in predicting disease outcome in our patient group, whereas pro-matrix metalloproteinase-2 and -9 did not. The combination of tissue inhibitor of metalloproteinase-1 and carcinoembryonic antigen was better in predicting three-year survival than tissue inhibitor of metalloproteinase-1 alone, but it remains to be determined if the combination would be a better marker for survival than carcinoembryonic antigen alone. CONCLUSIONS: Low pro-matrix metalloproteinase-2 levels and high tissue inhibitor of metalloproteinase-1 levels correlate with parameters of colorectal cancer disease. These correlations may be used in the search for new markers in colorectal cancer diagnosis and prognosis.

Adult↗
PubMed2005

Decrease in circulating anti-angiogenic factors (angiostatin and endostatin) after surgical removal of primary colorectal carcinoma coincides with increased metabolic activity of liver metastases.

Removal of a primary colorectal tumor resulted in an increase in metabolic activity in its liver metastasis. Concomitantly, levels of angiostatin and endostatin in urine and plasma, respectively, dropped. This finding indicates that the primary tumor suppressed angiogenesis in its distant metastasis, and that removal of the primary lesion caused a flare-up in vessel neoformation and, thus, enhanced metabolic activity in its liver metastasis.

Aged↗
PubMed2005

Magnetic resonance-guided biopsies and localizations of the breast: initial experiences using an open breast coil and compatible intervention device.

OBJECTIVE: The objective of this study was to evaluate the performance of a new commercially available open breast coil and compatible intervention device (Machnet) for magnetic resonance image (MRI)-guided breast interventions. MATERIALS AND METHODS: Breast lesions detected on MRI were evaluated using MRI-guided core biopsy (n = 20) and/or preoperative wire localization (n = 23) on histologic outcome and accuracy of localization. Time needed to perform a procedure and occurring problems were recorded. RESULTS: Mean lesion size was <10 mm. Two of 20 lesions could not be biopsied because they were out of range for the device. Biopsies were conclusive in half of the cases; most lesions missed were <10 mm. The average accuracy for needle placement in the localization procedures was less than 2 mm (range, 0-5 mm). The average procedure time was 40 minutes for a biopsy procedure and 33 minutes for an MRI-guided localization. CONCLUSIONS: Preoperative MRI-guided localizations can be performed quickly and accurately. However, in MRI-guided core biopsies, especially in small lesions, the device does not guarantee conclusive histologic evaluation of the lesion targeted.

Biopsy↗
PubMed2004

Vascular density in colorectal liver metastases increases after removal of the primary tumor in human cancer patients.

In animal models, explosive growth of metastases after removal of the primary tumor has been attributed to abolishment of angiogenesis inhibition. We investigated the influence of (removal of) the primary tumor on vascularization of liver metastases in human colorectal cancer patients. We analyzed vascular density in synchronous liver metastases from patients with the primary tumor in situ, in synchronous metastases from patients with the primary tumor resected and in metachronous metastases. In a limited number of cases, biopsies from metastases from the same patient before and within 3 months after resection were analyzed. In addition, vascular density in metastases was compared to the vascular density in the corresponding primary tumor. Peritumoral and intratumoral vascular density were determined by staining for endothelial antigens CD31 and CD34, respectively. Both peritumoral and intratumoral vascular density were elevated in synchronous metastases from patients with the primary tumor removed compared to synchronous metastases from patients with the primary tumor in situ. Comparable results were observed in patients with metachronous metastases. An increase in vascular density after resection of the colorectal malignancy was also observed in biopsies taken from the same patient before and after tumor resection. Remarkably, vascular density in the liver metastases was always lower than that in the corresponding primary tumor. Our data show for the first time in humans that the presence of a primary tumor is correlated with decreased vascularization of its distant metastases. Resection of the primary tumor results in an increased vascularization of metastatic lesions.

Adult↗
PubMed2004

Sentinel lymph node biopsy performed under local anesthesia is feasible.

BACKGROUND: A sentinel lymph node (SLN) biopsy in breast cancer patients, performed under local anesthesia (LA), could have advantages such as more efficient use of operating room time and pathologist time. It also provides a histologic diagnosis before definitive breast surgery is undertaken. The aim of this study was to assess feasibility by comparing the results of SLN procedures performed under LA versus general anesthesia (GA). METHODS: The SLN procedure was performed in 50 consecutive outpatients and 167 inpatients with clinical T1-2N0 breast cancer while they were under LA and GA, respectively. The SLN detection rate, a comparison of mapped and harvested SLNs, was compared for both groups. The duration of the SLN biopsies performed under LA was also measured. RESULTS: For both groups a median of 2 SLNs/patient were harvested. The detection rate was 1.00 for the LA group and 0.99 for the GA group. The learning curve for SLN procedures under LA showed a decrease in duration for the consecutive months (not significant). CONCLUSIONS: SLN biopsy can be safely and adequately performed with the patient under LA. It allows early diagnosis of the lymph node status, acquired on an outpatient basis, with minimal discomfort to the patient. The learning curve demonstrated that the LA procedure can quickly be mastered if the surgeon is experienced in performing SLN biopsies.

Ambulatory Surgical Procedures↗
PubMed2004

The role of MRI in invasive lobular carcinoma.

PURPOSE: To determine the value of MR imaging in the detection and measurement of tumor size in patients with invasive lobular carcinoma (ILC) compared to mammography and ultrasound. MATERIALS AND METHODS: From 36 cases of ILC in 34 patients who were surgically treated, the pre-operative imaging measurements, being mammography, ultrasound and contrast enhanced MR, were retrospectively re-evaluated for tumor detection and size. Findings were compared with pathology. Two radiologists were used for evaluation of the mammograms, the other imaging modalities were only evaluated by one radiologist. The Pearsons correlation test was used to determine the correlation between histopathological and imaging measurements for each imaging modality. RESULTS: For mammography, ultrasound and MRI the false negative scores were respectively 14%, 3% and 0%. The percentage for underestimated, correctly estimated and overestimated measurements on imaging were 56%, 33% and 11% for radiologist 1 and 50%, 33% and 17% for radiologist 2 on mammography. For ultrasound and MRI these percentages were respectively 53%, 47%, 0% and 14%, 75%, 11%. The correlation coefficients for mammography were respectively r = 0.34 (p < 0.05) and r = 0.27 (p > 0.05) for both radiologists, for Ultrasound r = 0.24 (p > 0.05) and for MRI r = 0.81 (p < 0.01). CONCLUSION: Of the three imaging modalities contrast enhanced MR has the lowest false negative rate in detecting ILC and has the highest accuracy in measuring the size of the ILC. MR could play a key role in the pre-operative work-up for accurate tumor size determination.

Adult↗