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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 73 records · Page 4Linked to original sources
PubMed2000

Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy.

BACKGROUND: Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. METHODS: In the present study liver regeneration was studied after KC-depletion by intravenous administration of liposome-encapsulated dichloromethylene-diphosphonate (C12MDP), a method known to physically eliminate KCs. Furthermore, splenectomy was performed one week prior to PH to exclude the effect of C12MDP-liposomes on macrophage populations in the spleen. RESULTS: KC-depletion was confirmed in cryostat liver sections stained with the monoclonal antibody ED2, a marker for resident tissue macrophages. Forty-eight hours after PH, the cumulative hepatocyte DNA synthesis, as determined in liver sections by the hepatocyte bromodeoxyuridine labeling index, was significantly decreased in KC-depleted rats when compared to control-rats. The weight of the remnant liver, expressed as a percentage of the initial liver weight, was significantly less at 96 h after PH in KC-depleted rats. KC-depletion abolished the hepatic interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA synthesis and decreased hepatic expression of tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF) and transforming growth factor-beta1(TGF-beta1) mRNA after PH, as was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Moreover, at 4 h after PH the systemic release of IL-6 was significantly decreased in KC-depleted rats. CONCLUSION: We conclude that KCs are important for hepatocyte regeneration after PH. Delayed liver regeneration in KC-depleted rats can be explained, at least in part, by an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating cytokines.

Animals↗
PubMed2000

The implementation of the sentinel node biopsy as a routine procedure for patients with breast cancer.

BACKGROUND: The sentinel node procedure for breast cancer allows for accurate staging of the axilla while the axillary node dissection can be avoided in patients with no sentinel node metastasis. This study describes those patients in whom an axillary dissection is performed, depending on the outcome of the sentinel node procedure, with particular emphasis on the use of strict criteria for the procedure and its practical limitations. METHODS: Preoperative lymphoscintigraphy was performed in 115 consecutive patients. The sentinel nodes were located with the use of a gamma probe and blue dye. Axillary dissection was performed at the same time when the sentinel node procedure was positive by frozen section or not successful by the criteria used. RESULTS: The sentinel node procedure was successful in 106 patients, with the sentinel node being both radioactive and blue in 94% of these patients. The frozen section was positive in 21 of 37 patients with sentinel node metastases. Axillary dissection could be avoided in 69 patients. CONCLUSIONS: The triple technique (with the use of lymphoscintigraphy, the gamma probe, and the blue dye) gives a high success rate of the sentinel node procedure, even when strict criteria for a successful sentinel node procedure are used. Palpation of the open axilla for metastatic nonsentinel nodes is advocated.

Biopsy↗
PubMed2000

Functional lymphatic anatomy for sentinel node biopsy in breast cancer: echoes from the past and the periareolar blue method.

OBJECTIVE: To simplify and improve the technique of axillary sentinel node biopsy, based on a concept of functional lymphatic anatomy of the breast. SUMMARY BACKGROUND DATA: Because of their common origin, the mammary gland and its skin envelope share the same lymph drainage pathways. The breast is essentially a single unit and has a specialized lymphatic system with preferential drainage, through select channels, to designated (sentinel) lymph nodes in the lower axilla. METHODS: These hypotheses were studied by comparing axillary lymph node targeting after intraparenchymal peritumoral radiocolloid (detected by a gamma probe) with the visible staining after an intradermal blue dye injection, either over the primary tumor site (90 procedures) or in the periareolar area (130 procedures). The radioactive content, blue coloring, and histopathology of the individual lymph nodes harvested during each procedure were analyzed. RESULTS: Radiolabeled axillary nodes were identified in 210 procedures, and these were colored blue in 200 cases (94%). The targeting concordance between peritumoral radiocolloid and intradermal blue dye was unrelated to the breast tumor location or the site of dye injection. Radioactive sentinel nodes were not stained blue in 10 procedures (5%), but this mismatching could be explained by technical problems in all cases. In two cases (1%), the (pathologic) sentinel node was blue but had no detectable radiocolloid uptake. CONCLUSIONS: The lessons learned from this study provide a functional concept of the breast lymphatic system and its role in metastasis. Anatomical and clinical investigations from the past strongly support these views, as do recent sentinel node studies. Periareolar blue dye injection appears ideally suited to identify the principal (axillary) metastasis route in early breast cancer. Awareness of the targeting mechanism and inherent technical restrictions remain crucial to the ultimate success of sentinel node biopsy and may prevent disaster.

Adult↗
PubMed2000

Bactericidal/permeability-increasing protein preserves leukocyte functions after major liver resection.

OBJECTIVE: To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy, and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). SUMMARY BACKGROUND DATA: Extensive liver resection is associated with a high incidence of infectious complications. Because elimination of pathogenic microorganisms occurs mainly by leukocytes, this increased rate of infections is most likely due to an impaired function of these cells. Endotoxin, translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection, may play an important role in the impairment of posthepatectomy leukocyte function. METHODS: To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process, leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients: patients undergoing a hemihepatectomy and receiving rBPI21 treatment, patients undergoing hemihepatectomy and receiving placebo, and as an extra control group patients undergoing other major abdominal surgeries. Blood samples were collected before surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine, and leukocyte surface expression of the antigens CD11b, CD16, and CD14 was investigated by indirect immunofluorescence. Both oxidative burst and membrane surface expression were quantified by flow cytometry. An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein (LBP) levels by enzyme-linked immunosorbent assay. RESULTS: The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery, whereas it decreased in the rBPI21-treated patients, resulting in significant differences between the groups. On day 1, neutrophil CD11b expression and monocyte CD14 expression in the rBPI21-treated patients and controls were significantly lower than in the placebo group. At 2 hours, CD16 expression in the placebo-treated patients was significantly higher than in the rBPI21-treated patients and controls. On day 5 and day 7, plasma LBP levels were significantly higher in the placebo-treated patients compared with the rBPI21-treated patients. CONCLUSIONS: The results of this study show that patients undergoing major liver resection have an increased activation of leukocytes compared with those undergoing other major abdominal surgery. This enhanced activation may contribute to the increased risk of infection in these patients. Administration of the endotoxin-neutralizing agent rBPI21 to hemihepatectomy patients was shown to reduce plasma LBP levels, to preserve leukocyte functions partially, and to reduce leukocyte activation to the level of other, nonhepatic abdominal surgery.

Acute-Phase Proteins↗
PubMed2000

Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Adolescent↗
PubMed1999

[Follow-up after melanoma resection is more extensive than recommended in the practice guidelines, primarily for reassurance of the patient].

OBJECTIVE: To determine to what extent the follow-up after resection of melanoma in practice corresponds to the relevant guidelines in the first revised version of the consensus 'Melanoma of the skin'. DESIGN: Descriptive, retrospective. METHOD: For 67 patients, who had a melanoma resected in September 1993-April 1995 in the Academic Hospital, Vrije Universiteit, Amsterdam, the Netherlands, data were collected in May-August 1997 on the first two years of follow-up from the medical records (n = 42) and through communication in writing with the referring physicians and the physicians involved in the follow-up in other hospitals in the Netherlands (n = 25). The frequency of physical examination and routine diagnostics by the doctor was evaluated. To gain insight into the reasons why in some cases the guidelines were not followed, we set up an inquiry among the 20 doctors involved in the follow-up in August 1998. RESULTS: The mean frequency of outpatient visits and physical examinations was 3-4 times per year, practically consistent with the guideline. Routine blood testing was performed in 17 patients (25%) and diagnostic imaging (X-ray or CT scan of the chest, ultrasonography of the liver) in 51 patients (76%) in deviation from the guideline. Non-compliance with the guideline could not be explained by unfamiliarity with the consensus, disagreement with the contents or existence of local protocols. Extra diagnostics were mostly meant to reassure patients. No metastases or recurrences were encountered during routine follow-up examinations, but some were found (in 8 patients) at interim visits to the outpatient clinic. CONCLUSION: The national guidelines regarding diagnostic tests in the follow-up of melanoma patients are insufficiently followed. Because redundant routine diagnostics probably have more disadvantages than benefits, a more active implementation of (future) guidelines appears necessary.

Biopsy↗
PubMed1999

Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial.

BACKGROUND: Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer. METHODS: In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat. FINDINGS: The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival. INTERPRETATION: ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.

Adjuvants, Immunologic↗
PubMed1999

Ultrasound-guided lumpectomy of nonpalpable breast cancers: A feasibility study looking at the accuracy of obtained margins.

BACKGROUND AND OBJECTIVES: Complete excision of a nonpalpable breast cancer after wire localization is a difficult procedure. Often, adequate margins are not obtained, and a second procedure is then required. Prospectively, we studied the feasibility of ultrasound-guided excisions of nonpalpable breast cancers, with particular attention to the accuracy of the procedure in obtaining adequate margins. METHODS: Prospectively, 19 patients with 20 mammographically detected nonpalpable, highly suspect, breast tumors were entered in this feasibility study. In 15 of these, the diagnosis of invasive malignancy was established preoperatively. All patients underwent ultrasound-guided excision with the intent to obtain adequate margins. We also reviewed our own experience with the excision of nonpalpable breast cancers after wire localization. RESULTS: Of the 20 excisions with ultrasound guidance, there were 19 carcinomas and 1 ductal carcinoma in situ. Of the 19 carcinomas, 17 (89%) were excised with adequate margins. Of the 43 carcinomas that were excised after wire localization, only 17 (40%) had been resected with adequate margins. CONCLUSIONS: Ultrasound-guided excision appears to be a reliable procedure for obtaining adequate margins in the resection of nonpalpable breast cancers. Other advantages of this procedure are increased patient comfort and decrease in operating room time.

Adult↗
PubMed1999

Impaired leukocyte phagocytosis in patients undergoing hemihepatectomy for liver metastases.

Patients undergoing partial hepatectomy have an increased susceptibility to infection. To investigate whether this increased risk is related to impaired leukocyte function, we studied polymorphonuclear leukocyte (PMN) phagocytosis in patients undergoing a hemihepatectomy because of liver metastasis (LM, n = 11) and in patients undergoing major abdominal surgery because of abdominal malignancy (AM, n = 8). Eight healthy volunteers (HVs) served as controls. Leukocyte suspensions were incubated with fluorescein isothiocyanate-labeled Staphylococcus aureus, and phagocytosis was measured by flow cytometry. Preoperative PMN phagocytosis, in the presence of autologous plasma, was significantly less in patients with LM compared with patients with AM or HVs. This impaired phagocytosis was potentially restored in the presence of normal plasma. The decreased phagocytic capacity of PMNs from patients with LM was not related to levels of known plasma opsonins or phenotypic changes of PMNs. Rather, it was related to a deficiency of unidentified plasma factors. After surgery, the phagocytic capacity of PMNs of patients with AM decreased by approximately 30%, which correlated with decreasing levels of immunoglobulin G and C3. In conclusion, patients with LM had a decreased PMN phagocytic capacity before surgery. This impairment in phagocytosis disappeared 1 week after surgery. We propose that the presence of LM leads to a deficiency of factor(s) in the blood that impairs PMN phagocytic capacity.

Case-Control Studies↗
PubMed1999

Palliative cryosurgery for rectal carcinoma.

Cryosurgery is one of the palliative treatment options to decrease local symptoms due to rectal carcinoma. A total of 106 patients (aged 45-92 years) underwent palliative cryosurgery for primary rectal cancer. Inclusion criteria were prohibitive surgical risk, unresectability, distant metastases, patient refusal of surgical intervention, and old age. The palliative effect of cryosurgery on local symptoms was classified as good, moderate, or none. The duration of palliation was calculated in relation to survival as a palliative index: the number of months of (moderate or good) palliation divided by the number of months of survival from the start of the treatment, multiplied by 100. In 66 patients (62%) there was complete relief of local symptoms, with a palliative index of 88%. In 17 patients (16%) palliation was moderate, and in 23 patients (22%) no palliation was achieved. The 50% survival duration in the 66 patients was 33 months. Especially symptoms of blood and/or mucous discharge were easily alleviated. Good alleviation of local symptoms was associated with the extent of the primary tumor process. Palliative effect was be assessed after a few treatments. Patients with circular rectal tumors seldom had long-term palliative effects of cryosurgery. Our findings show that Cryosurgery is a simple and safe treatment for rectal cancer. It should be considered for alleviation of local symptoms in patients with rectal cancer who are unsuitable for radical surgery.

Aged↗
PubMed1999

Immunological consequences of laparoscopic surgery, speculations on the cause and clinical implications.

BACKGROUND: Immune suppression is an established consequence of surgical stress and trauma. Postoperative changes in the systemic immune system are proportional to the degree of surgical trauma and subsequent immune suppression may be implicated in the development of infectious complications and tumor metastasis formation. Laparoscopic surgery reduces the magnitude of the operative trauma and is thought to preserve postoperative immunological defenses. METHODS: Relevant literature concerning postoperative immune functions and laparoscopic surgery was reviewed and clinical implications are discussed. RESULTS: The influence of laparoscopic surgery on the postoperative systemic immune response is significantly less after laparoscopic cholecystectomy than with the conventional approach. Few immunological data are available concerning more advanced laparoscopic procedures. Various animal model studies of postoperative septic complications and tumor growth show that the postoperative preservation of the systemic immune response after laparoscopic surgery can have enormous clinical advantages. CONCLUSION: Laparoscopic surgery preserves the postoperative immunological defenses. In the future, this may imply a lower number of infections, less local recurrence and even fewer distant metastases. Prospective randomized studies are necessary to see whether these suspected advantages can be demonstrated in clinical practice.

Cholecystectomy, Laparoscopic↗
PubMed1999

Membrane sidedness of biosynthetic pathways involved in the production of lysophosphatidic acid.

Lysophosphatidic acid (LPA) is a novel phospholipid mediator with diverse biological activities such as smooth muscle contraction, and proliferative effects or modifications of cytoskeleton. Activated blood platelets are the best identified source, explaining accumulation of LPA in serum upon blood coagulation. However, the metabolic pathways responsible for LPA synthesis are still poorly known. Using a model of human erythrocytes treated with the calcium ionophore A23187, we have shown that type II secretory phospholipase A2 (sPLA2) is able to produce LPA by hydrolyzing phosphatidic acid exposed on the cell surface after phospholipid scrambling. A similar mechanism does not appear to occur in platelets, where inhibitors of sPLA2 or genetic lack of the enzyme do not modify LPA production. However, this does not definitely eliminate the possibility that LPA is also produced in platelets in the external leaflet of the membrane by other phospholipases, which have to be better characterized.

Animals↗