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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 37 records · Page 2Linked to original sources
PubMed2003

Clinical outcome of stage I/II melanoma patients after selective sentinel lymph node dissection: long-term follow-up results.

PURPOSE: Although sentinel lymph node (SLN) status is part of the new American Joint Committee on Cancer staging system, there is no final proof that the SLN procedure in melanoma patients influences outcome of disease. This study investigated the accuracy of the SLN procedure and clinical outcome in melanoma patients after at least 60 months of follow-up. PATIENTS AND METHODS: Between 1993 and 1996, 209 patients with stage I/II cutaneous melanoma underwent selective SLN dissection by the triple technique. If the SLN contained metastatic disease, a completion lymphadenectomy was performed. Survival analyses were performed using the Kaplan-Meier approach. Factors associated with survival were analyzed using the Cox proportional hazards regression model. RESULTS: The success rate was 99.5%. Median follow-up was 72 months. Forty patients (19%) had a positive SLN. The false-negative rate was 9%. Five-year overall survival was 87% for the entire group and 92% and 67% for SLN-negative and SLN-positive patients (P <.0001), respectively. All patients with a positive SLN and a Breslow thickness < or = 1.00 mm survived, and SLN-positive patients with a Breslow thickness less than 2.00 mm tend to have a better prognosis compared with SLN-negative patients with a Breslow thickness greater than 2.00 mm. SLN status (P =.002), Breslow thickness (P =.002), and lymphatic invasion (P =.0009) were all found to be independent prognostic factors for overall survival. CONCLUSION: With a success rate of 99.5% and a false-negative rate of 9% after long-term follow-up, the triple-technique SLN procedure is a reliable and accurate method. Survival data seem promising, although a therapeutic effect is still questionable. As shown in this study, not all SLN-positive patients have a poor prognosis.

Female↗
PubMed2003

Systemic and peritoneal inflammatory response after laparoscopic or conventional colon resection in cancer patients: a prospective, randomized trial.

PURPOSE: This study was designed to evaluate differences in both the peritoneal and systemic immune response after laparoscopic and conventional surgical approaches. METHODS: Patients with a primary carcinoma were prospectively randomized to curative laparoscopic (n = 12) or conventional (n = 14) colon resection. The proinflammatory cytokines interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured in the peritoneal drain fluid and in the serum. C-reactive protein and leukocyte counts and the differences in leukocyte subpopulations and expression of human leukocyte antigen-DR on monocytes were measured perioperatively. RESULTS: Significantly higher levels of proinflammatory cytokine were found in the peritoneal drain fluid than in the circulation after both procedures. Serum interleukin-6 and interleukin-8 levels were significantly lower 2 hours after laparoscopic surgery than with the conventional procedure. Postoperative cellular immune counts and human leukocyte antigen-DR expression normalized earlier after the laparoscopic approach. CONCLUSIONS: The systemic proinflammatory concentrations after both surgical approaches represent only a small fragment of what is generated in the peritoneal drain fluid. Even if the immediate levels of proinflammatory cytokines in the serum are significantly lower in the laparoscopic group, the same cytokines locally produced showed no differences, which suggests that the two intra-abdominal approaches are equally traumatic. No differences in cellular response were observed between the groups.

Aged↗
PubMed2003

VEGF and endostatin levels in wound fluid and plasma after breast surgery.

Angiogenesis is essential for wound repair after surgical trauma. Vascular endothelial growth factor (VEGF) and endostatin are endogenous angiogenic factors involved in the initiation and completion of angiogenesis. The aim of this study was to examine the local and systemic VEGF and endostatin profiles in patients undergoing surgery for benign and malignant breast processes. A total of 16 patients with or without cancer underwent breast surgery. Group I: eight patients with primary breast cancer underwent a simple or radical mastectomy according to Madden including dissection of axillary lymph nodes. Group II: eight healthy female-to-male transsexuals underwent subcutaneous mastectomy. VEGF and endostatin levels in plasma and wound fluid were determined. In both groups VEGF levels in wound fluid were significantly higher compared to postoperative plasma levels, whereas wound fluid endostatin levels were lower than plasma levels and decreased progressively after surgery. In both groups plasma VEGF and endostatin levels did not change significantly before and after surgery. The local VEGF increase and endostatin decrease observed immediately after surgery appears to be a physiological response to operative trauma, which can be studied more profoundly in locally generated fluid than in blood. This process did not seem to be influenced by the type of process (cancerous or non-cancerous) involved in the surgical intervention.

Breast Neoplasms↗
PubMed2003

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Adolescent↗
PubMed2002

Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism.

Thymidylate synthase (TS) is a key enzyme in the de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) from 2'-deoxyuridine-5'-monophosphate (dUMP), for which 5,10-methylene-tetrahydrofolate (CH(2)-THF) is the methyl donor. TS is an important target for chemotherapy; it is inhibited by folate and nucleotide analogs, such as by 5-fluoro-dUMP (FdUMP), the active metabolite of 5-fluorouracil (5FU). FdUMP forms a relatively stable ternary complex with TS and CH(2)THF, which is further stabilized by leucovorin (LV). 5FU treatment can induce TS expression, which might bypass dTMP depletion. An improved efficacy of 5FU might be achieved by increasing and prolonging TS inhibition, a prevention of dissociation of the ternary complex, and prevention of TS induction. In a panel of 17 colon cancer cells, including several variants with acquired resistance to 5FU, sensitivity was related to TS levels, but exclusion of the resistant variants abolished this relation. For antifolates, polyglutamylation was more important than the intrinsic TS level. Cells with low p53 levels were more sensitive to 5FU and the antifolate raltitrexed (RTX) than cells with high, mutated p53. Free TS protein down-regulates its own translation, but its transcription is regulated by E2F, a cell cycle checkpoint regulator. Together, this results in low TS levels in stationary phase cells. Although cells with a low TS might theoretically be more sensitive to 5FU, the low proliferation rate prevents induction of DNA damage and 5FU toxicity. TS levels were not related to polymorphisms of the TS promoter. Treatment with 5FU or RTX rapidly induced TS levels two- to five-fold. In animal models, 5FU treatment resulted in TS inhibition followed by a two- to three-fold TS induction. Both LV and a high dose of 5FU not only enhanced TS inhibition, but also prevented TS induction and increased the antitumor effect. In patients, TS levels as determined by enzyme activity assays, immunohistochemistry and mRNA expression, were related to a response to 5FU. 5FU treatment initially decreased TS levels, but this was followed by an induction, as seen with an increased ratio of TS protein over TS-mRNA. The clear retrospective relation between TS levels and response now forms the basis for a prospective study, in which TS levels are measured before treatment in order to determine the treatment protocol.

Animals↗
PubMed2002

[Negative sentinel node in breast cancer patients a good indicator for continued absence of axillary metastases].

OBJECTIVE: To determine the prevalence of axillary recurrences in sentinel-node-negative patients with breast cancer who had no axillary dissection. DESIGN: Follow-up study. METHOD: The first one hundred consecutive sentinel-node-negative patients with a minimal follow-up of 36 months (median 47) were included in this study. All patients underwent sentinel-node biopsy using the triple technique. During the first year after the operation patients were seen on a 3-monthly basis and thereafter every 6 months. RESULTS: Intensive pathological examination of the harvested sentinel nodes revealed no (micro)metastases in any patient. One patient developed an axillary recurrence after 24 months. Three out of the 100 patients developed distant metastases during follow-up; 2 of them died as a result of these metastases. One patient was treated for a local mammary recurrence. In terms of survival the sentinel-node procedure did not appear to be disadvantageous: the 3-year survival rate in our study was 98% for node-negative patients, compared to 88-94% quoted in the literature for node-negative patients after axillary dissection. This apparent improvement may be due to better staging of breast-cancer patients through the use of the sentinel-node procedure (stage migration). CONCLUSION: The triple technique was a reliable method for identifying the sentinel node in breast-cancer patients. Compared to the historical data on node-negative breast cancer, the sentinel-node procedure improved the prognosis of node-negative breast-cancer patients. This effect was probably due to the more accurate staging of breast-cancer patients using the sentinel-node procedure.

Adult↗
PubMed2002

A phase II study of active specific immunotherapy and 5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma.

Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40-50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity.

Adult↗
PubMed2002

Ultrasound-guided lumpectomy of nonpalpable breast cancer versus wire-guided resection: a randomized clinical trial.

BACKGROUND: The wire-guided excision of nonpalpable breast cancer often results in tumor resections with inadequate margins. This prospective, randomized trial was undertaken to investigate whether intraoperative ultrasound (US) guidance enables a better margin clearance than the wire-guided technique in the breast-conserving treatment of nonpalpable breast cancers. METHODS: Patients with a preoperative histological diagnosis of nonpalpable breast cancer that could be visualized both with US and mammography were included. Patients were randomized to undergo either a wire-guided or a US-guided excision. Adequate margins were defined as >or=1 mm. RESULTS: Of 49 included patients, 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision. One patient crossed over to US-guided excision after inadvertent wire displacement. Mean tumor diameter, specimen weight, and operating time were similar in both groups. The excision was adequate in 24 (89%) of 27 US-guided excisions and 12 (55%) of 22 wire-guide excisions (P =.007). CONCLUSIONS: US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected and US-visible nonpalpable breast cancers. Patients do not have to undergo the unpleasant wire placement before surgery.

Breast Neoplasms↗
PubMed2002

Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer.

A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.

Adult↗
PubMed2002

Long term survival of thoracoscopic metastasectomy vs metastasectomy by thoracotomy in patients with a solitary pulmonary lesion.

AIMS: The aim of this study was to compare long term survival after resection of solitary pulmonary metastasis on CT scan performed by either thoracoscopy or through a standard thoracotomy. METHODS: Patients with a solitary, CT scan confirmed, peripherally located lesion suspected for metastasis, less than 3cm in diameter were included. End points were: postoperative complication rate, disease free and overall survival and location of recurrence in the lung. RESULTS: Thirty-five patients who underwent a thoracoscopic metastasectomy with (n=19) or without (n=16) confirmatory thoracotomy were included in this study. Patients experienced more complications following a thoracotomy (n=5) compared to those who had a thoracoscopy (n=0) (P=0.049). Two patients appeared to have further disease at thoracotomy besides the CT scan identified lesion, and some at thoracoscopy. At definitive histology, seven lesions were benign and eight appeared to be a second primary. Analysis of 20 patients with histological confirmed metastasis demonstrated a 2-year disease free and overall survival rate of 50% and 67% respectively following thoracoscopic metastasectomy (n=8) compared to 42% and 70% respectively following confirmatory thoracotomy (n=12). Recurrence occurred in three of the patients after thoracoscopic metastasectomy and in five patients after thoracotomy. CONCLUSION: Our results suggest that thoracoscopic resection of solitary peripherally located metastasis is a safe and potentially curative procedure with a long term outcome that is comparable with that after resection by thoracotomy.

Adult↗
PubMed2001

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

BACKGROUND: In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient. METHODS: In 263 consecutive patients with proven American Joint Committee on Cancer Stages I and II cutaneous melanoma, the triple technique SLN procedure was used, i.e., preoperative visualization of the lymph channels from the initial site of the melanoma toward the SLN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and lymph nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabeled lymph nodes. Median follow-up time was 48 months (range, 36-84 months). Multivariate logistic regression analysis was performed to examine the influence of the SLN status and several other prognostic factors on a minimum 3-year disease free survival. RESULTS: In 20% of patients, the SLN proved to be tumor positive. For SLN negative patients, the 5-year disease free survival rate was 91% (+/- 2.4%), and for SLN positive patients it was 49% (+/- 9%). Five variables showed a strong and statistically significant independent prognostic association with outcome, i.e., SLN status (P = 0.0007), thickness of primary melanoma (1.01-2.0 mm; P = 0.04), ulceration (P = 0.05), and lymphatic invasion (P = 0.01) of primary melanoma, and age (40-50 years; P = 0.01). CONCLUSIONS: The SLN status-along with Breslow thickness, ulceration, lymphatic invasion, and age--seems to have strong additional value in predicting a minimum 3-year disease free period after the SLN procedure. Patients with a positive SLN have a poorer prognosis than those with a negative SLN.

Adolescent↗
PubMed2001

Technical considerations in laparoscopic liver surgery.

BACKGROUND: Laparoscopic solid organ surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver. Laparoscopic liver surgery mainly comprizes diagnostic procedures and treatment of liver cysts. However, we believe there is room for a laparoscopic approach to the liver in selected cases, with the benefits that may be expected from laparoscopic solid organ surgery. METHODS: Between 1993 and 2000, 10 patients with various lesions of the liver underwent laparoscopic surgery. Indications consisted of cystic disease (n = 2), hemangioma (n = 2), focal nodular hyperplasia (n = 2), liver abcess (n = 1), and liver metastasis (n = 3). Laparoscopic treatment varied from fenestration (n = 3) to wedge resections (n = 5), and formal left lateral hepatectomy (n = 2). RESULTS: The mean patient age was 54 years (range, 34-71 years). The mean operative time, including laparoscopic ultrasonography, measured 180 min (range, 80-240 min). Peroperative blood loss ranged from 200 to 450 ml. There was no mortality. In two patients, conversion to laparotomy was necessary. There were no postoperative complications. The mean hospital stay was 6 days (range, 4-11 days). CONCLUSION: Laparoscopic treatment should be considered in selected patients with benign and malignant lesions in the left lobe or frontal segments of the liver.

Adult↗
PubMed2001

Predictive factors for metastatic involvement of nonsentinel nodes in patients with breast cancer.

BACKGROUND: The potential morbidity of an axillary lymph node dissection in patients with breast cancer can be avoided in patients with a negative sentinel node (SN). HYPOTHESIS: It may be possible to identify a subset of patients with a positive SN and without metastases in the remaining axillary lymph nodes. DESIGN: Case-control study. SETTING: Both primary and referral hospital care. PATIENTS: Data were studied for 255 consecutive patients with stage T1 or T2 breast cancer who had a successful identification of the SN. INTERVENTIONS: In patients with a positive SN, histological examination of all non-SNs that were negative by routine examination was the same as that for SNs (multiple sectioning and immunohistochemical analysis). MAIN OUTCOME MEASURES: The incidence of non-SN metastases was correlated with the surface area and number of SN metastases and primary tumor characteristics. A micrometastasis was defined as less than 1 mm(2). RESULTS: Of 255 patients, the SN appeared to be positive in 93 (36%). Subsequent axillary lymph node dissection revealed positive non-SNs in 46 patients (49%). Patients with a single positive SN and patients with metastases less than 1 mm(2) in the SN had significantly less non-SN involvement than patients with more than 1 positive SN (40% vs. 78%) and patients with macrometastases (27% vs. 49%). CONCLUSIONS: The incidence of non-SN metastases seemed to be related to the number of positive SNs and the size of SN metastases. However, in the group of patients with a positive SN, it was not possible to identify a subset of patients without non-SN metastases.

Axilla↗