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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 55 records · Page 3Linked to original sources

Outcome of thoracoscopic pulmonary metastasectomy evaluated by confirmatory thoracotomy.

BACKGROUND: The aim of this study was to determine the feasibility, accuracy, and outcome of thoracoscopic resection of peripherally located pulmonary metastases. METHODS: The 28 patients had three or fewer solitary metastases, located in the periphery of the lung, with a diameter 3 cm or less on computed tomography scan. A thoracoscopic resection was performed to remove all identified lesions evaluated by confirmatory thoracotomy. RESULTS: A thoracoscopic resection was technically impossible in 10 patients. In 1 patient a confirmatory thoracotomy was not performed because the lesion was diagnosed as carcinoid. Among the 17 patients who underwent confirmatory thoracotomy, 12 patients had a complete thoracoscopic resection and 5 patients had residual disease. The success rate appeared to be higher (p = 0.01) in patients with one lesion (11 of 12 patients), than in patients with more than one lesion (1 of 5 patients) found by preoperative computed tomography scan. CONCLUSIONS: Thoracoscopic resection can be considered a viable treatment option for patients who present with a solitary pulmonary metastasis with a diameter of 3 cm or less, when the lesion is located in the periphery of the lung.

Adult↗

Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.

BACKGROUND/AIMS: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). PATIENTS AND METHODS: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day. RESULTS: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure. CONCLUSIONS: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Adult↗

Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma.

BACKGROUND: Surgery induces a postoperative immunosuppression, thereby possibly facilitating the outgrowth of pre-existing occult metastases or the seeding of disseminated tumour cells in patients with primary colorectal carcinoma operated on with curative intent. The hypothesis that adjuvant therapy with perioperative recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) would minimize postoperative immunosuppression was investigated in this pilot study. METHODS: Patients were allocated randomly to receive daily subcutaneous injections with either saline (n = 8) or rhGM-CSF 2.8 microg per kg body-weight (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR expression and the extent of the acute-phase response, by determination of white blood cell count and differentiation, plasma interleukin (IL) 6 levels and body temperature in the perioperative period, were examined. RESULTS: rhGM-CSF treatment minimized postoperative suppression in PHA skin test reactivity and increased the numbers of neutrophils and monocytes while enhancing the expression of HLA-DR in the postoperative period. Additionally, both postoperative plasma IL-6 levels and the incidence of fever tended to be higher in the rhGM-CSF group. CONCLUSION: In this pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain immune functions that are normally depressed after operation. The implications for the antitumour responses directly after operation and the formation of liver metastases are currently under investigation.

Adjuvants, Immunologic↗

Metastatic pattern of CC531 colon carcinoma cells in the abdominal cavity: an experimental model of peritoneal carcinomatosis in rats.

BACKGROUND: Peritoneal spread of tumour cells is a major source of morbidity and mortality in patients with colorectal cancer. In order to develop strategies to prevent intraperitoneal dissemination and to treat peritoneal carcinomatosis, the spread of tumour cells in the peritoneal cavity was studied. METHODS: Two million CC531 colon carcinoma cells were administered intraperitoneally in five groups of eight rats. The rats were killed after 1, 2, 4 and 8 hours and 3, 7, 14 and 21 days. After inspection of the abdominal cavity, samples of blood and ascites were taken. Liver, spleen, omentum, mesentery, diaphragm, parathymic lymph nodes and lungs were removed for histology and immunohistochemistry. RESULTS: No abnormalities were seen in the abdominal cavity until day 3. Subsequently the peritoneum and omentum became thickened and after 21 days all rats had haemorrhagic ascites and peritoneal carcinomatosis. The abdominal fluid contained tumour cells at all stages. The number of tumour cells decreased in the first 8 hours, and increased thereafter. At microscopy the peritoneum was completely covered by tumour cells after 3 days. Tumour cells concentrated in the milky spots (MS) of the omentum within 4 hours. The size of the MS increased as a result of an increase in number of tumour cells and macrophages. After 7--21 days the MS were completely replaced by tumour cells and new MS were formed. In the diaphragm tumour cells invaded the lymphatic lacunae after 8 h, and obliterated these after 3--7 days. Also invasion of the muscle fibres was seen after 3 days. Microscopically no tumour cells were found in blood, liver, spleen, parathymic nodes and lung. CONCLUSION: After intraperitoneal administration of CC531 colon carcinoma cells, tumour cells spread throughout the abdominal cavity, and concentrate in the milky spots of the greater omentum, the paracolic gutters, the subhepatic and subphrenic spaces and in the lymphatic lacunae of the diaphragm.

Animals↗

Glutamine alimentation in catabolic state.

Glutamine should be reclassified as a conditionally essential amino acid in the catabolic state because the body's glutamine expenditures exceed synthesis and low glutamine levels in plasma are associated with poor clinical outcome. After severe stress, several amino acids are mobilized from muscle tissue to supply energy and substrate to the host. Glutamine is one of the most important amino acids that provide this function. Glutamine acts as the preferred respiratory fuel for lymphocytes, hepatocytes and intestinal mucosal cells and is metabolized in the gut to citrulline, ammonium and other amino acids. Low concentrations of glutamine in plasma reflect reduced stores in muscle and this reduced availability of glutamine in the catabolic state seems to correlate with increased morbidity and mortality. Adding glutamine to the nutrition of clinical patients, enterally or parenterally, may reduce morbidity. Several excellent clinical trials have been performed to prove efficacy and feasibility of the use of glutamine supplementation in parenteral and enteral nutrition. The increased intake of glutamine has resulted in lower septic morbidity in certain critically ill patient populations. This review will focus on the efficacy and the importance of glutamine supplementation in diverse catabolic states.

Acquired Immunodeficiency Syndrome↗

No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm.

In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it is relevant to perform the SN procedure - seems to depend on the Breslow thickness of the primary tumour. However, a Breslow thickness cut-off point has not yet been established. We evaluated a melanoma population that had undergone an SN procedure to determine this point, so that the procedure can be restricted to a smaller group of patients in future. In a total of 348 patients with proven American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of preoperative visualization of the lymph channels from the initial site of the melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval 0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31 months. Our data suggest that this procedure need no longer be indicated for almost a quarter of the patient population, because the cut-off point for nodal involvement appears to be a Breslow thickness of 0.90 mm.

Adolescent↗

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Abdomen↗

Sentinel node investigation in breast cancer: detailed analysis of the yield from step sectioning and immunohistochemistry.

AIMS: To evaluate in detail the extent to which step sectioning and immunohistochemical examination of sentinel lymph nodes (SNs) in patients with breast cancer reveal additional node positive patients, to arrive at a sensitive yet workable protocol for histopathological SN examination. METHODS: This study comprised 86 women with one or more positive SN after a successful SN procedure for clinical stage T1-T2 invasive breast cancer. SNs were lamellated into pieces of approximately 0.5 cm in size. One initial haematoxylin and eosin (H&E) stained central cross section was made for each block. When negative, four step ribbons were cut at intervals of 250 microm. One section from each ribbon was stained with H&E, and one was used for immunohistochemistry (IHC). RESULTS: When taking the cumulative total of detected metastases at level 5 as 100%, the percentage of SN positive patients increased from 80%, 83%, 85%, 87% to 88% in the H&E sections through levels 1 to 5, and with IHC these values were 86%, 90%, 94%, 98%, and 100%. Three of nine patients in whom metastases were detected at levels 3-5 only had metastases in the subsequent axillary lymph node dissection. CONCLUSIONS: Multiple level sectioning of SNs (five levels at 250 microm intervals) and the use of IHC detects additional metastases up to the last level. Although more levels of sectioning might increase the yield even further, this protocol ensures a reasonable workload for the pathologist with an acceptable sensitivity when compared with the published literature.

Adult↗

Perioperative treatment with bactericidal/permeability-increasing protein (rBPI21) in major liver surgery: a concise summary.

INTRODUCTION: Major hepatic resections are still associated with considerable morbidity. Gut-derived bacteria and bacterial endotoxin are considered to play a central role in the pathophysiology of complications. Experimental studies suggest that bactericidal/permeability-increasing protein (BPI), which has both antibacterial and endotoxin-neutralising properties, can reduce postoperative complications. MATERIAL AND METHODS: A phase II, double-blind, placebo-controlled, multicentre, dose escalation trial was conducted in patients undergoing major liver resection, and clinical outcome, infectious complications, plasma amino acid patterns, coagulation and fibrinolytic cascade systems and neutrophil functions were compared between the two treatment groups and an extra group of patients undergoing major abdominal non-hepatic surgery. RESULTS: Drug administration in this patient group was safe, and resulted in a significant reduction of infectious complications. Furthermore, beneficial effects were found in the postoperative amino acid ratio and fibrinolytic cascades, and rBPI21 preserved leukocyte functions. CONCLUSION: Administration of rBPI21 in patients undergoing major liver resection is well tolerated and results in improvement of both clinical and biochemical parameters.

Adult↗

Vital dye and radiolabelled colloids--complement or alternative?

Several different protocols for retrieval of the sentinel node (SN) have been described: gamma probe (GP) and/or dye guided biopsy, preceded by lymphoscintigraphy or not. Especially in American studies, predominantly executed by surgeons, dye or GP guidance only is used with good results. The disadvantages of applying dye only are: an extensive learning curve, lower retrieval rate of the SN and, especially in the learning phase, a higher rate of false negative biopsies. If only GP guidance is applied, the technique seems more simple to master. A recent multicentre study, however, revealed an unacceptably high false negative rate. It must be considered that most published studies were executed by highly experienced surgeons. In most European studies, scintigraphy is a standard part of the procedure. Lymphoscintigraphy provides the surgeon with a "road map", revealing the number and approximate location of the SNs in the lymphatic basin(s). Scintigraphy proves useful especially if an SN is situated close to the injection site (breast cancer), or if SNs are situated at unexpected locations (head-and-neck or trunk melanoma). A combination of all three available steps results in the highest number of successful procedures with the lowest false negative rate. This may prove to be especially important for general hospitals where the number of biopsy procedures is often smaller compared to specialized centres.

Axilla↗

Lack of nephrotoxicity of new oral platinum drug JM216 in lung cancer patients.

PURPOSE: The purpose of this study was to assess renal function in patients treated with the oral platinum drug JM216 [bisacetato-ammine-dichloro-cyclohexylamine-platinum(IV)], since the effects of JM216 on renal function have only partly been investigated using serum parameters or 51Cr-EDTA clearance. We used a sensitive method that assessed glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and indicators of tubular and glomerular damage. METHODS: A group of 24 patients with either non-small-cell lung cancer (NSCLC) stage IIIb/IV or small-cell lung cancer (SCLC), limited disease (LD) or extensive disease (ED), treated with JM216 were studied. All patients had no prior chemotherapy, a performance score < 2, a life expectancy of more than 3 months and normal liver, renal and bone marrow functions before treatment. All patients received oral JM216 120 mg/m2 per day for 5 consecutive days, repeated every 21 days with a maximum of six cycles. In six SCLC patients the dose was escalated to 140 mg/m2 per day after the first cycle. Prior to treatment, after the first cycle and after the end of treatment renal function was assessed by 125I-sodium thalamate and 131-hippurate clearances to determine acute and cumulative changes in GFR and ERPF, respectively. Furthermore, tubular and glomerular damage were assessed by urinary excretion of beta2-microglobulin, lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and albumin. RESULTS: In 20 evaluable patients no significant acute impairment of renal function was observed. Median (range) GFR, ERPF and filtration fraction (FF) before treatment were 101 ml/min (53-164 ml/min), 417 ml/min (227-719 ml/min), and 0.25 (0.19-0.33), respectively. After the first cycle values were 117 ml/min (71-189 ml/min), 418 ml/min (228-709 ml/ min) and 0.28 (0.21-0.33), respectively. Also, no indications of tubular or glomerular damage were found. In four patients renal function was evaluated at the end of treatment (one after three cycles, one after five cycles and two after six cycles). Median (range) GFR, ERPF and FF were 99 ml/min (74-139 ml/min), 401 ml/min (277-496 ml/min) and 0.26 (0.23-0.30), respectively, revealing no delayed nephrotoxicity. CONCLUSION: We conclude that oral JM216 shows no nephrotoxicity.

Administration, Oral↗

Laparoscopic surgery preserves monocyte-mediated tumor cell killing in contrast to the conventional approach.

BACKGROUND: Experimental animal research shows that immunologic defenses against tumor cells are disturbed by surgical trauma, resulting in an increased rate of tumor implantation and the growth of subsequent metastases. Minimally invasive surgery is associated with a preservation of postoperative immunologic functions and, in animal models, with decreased tumor growth. The objective was to study the influence of several surgical procedures, approached conventionally and laparoscopically, on interleukin-6 (IL-6) and monocyte-mediated cytotoxicity (MMC). METHODS: Five groups of five patients each were included in this prospective study: laparoscopic cholecystectomy (minor trauma) group, Nissen fundoplication (laparoscopic and conventional as moderate trauma) groups, and sigmoid colectomy (laparoscopic and conventional as major trauma) groups. Preoperatively, 1 and 4 days after surgery, IL-6 and MMC against SW948 colon cancer cell line were determined. RESULTS: The IL-6 levels differed significantly between the three laparoscopic procedures (p = 0.004) and increased according to the degree of trauma. There was no significant difference in MMC between the three laparoscopic procedures. However, MMC was suppressed after conventional procedures and preserved after laparoscopic procedures (p = 0.001). There was no correlation between IL-6 levels and changes in MMC. CONCLUSIONS: More extensive laparoscopic procedures induce increased levels of IL-6, reflecting higher levels of trauma. Conventional surgical procedures result in depressed MMC in the postoperative period. After laparoscopic procedures, MMC is preserved. These findings may be of importance in preventing implantation and growth of cancer cells spread by surgical manipulation.

Adult↗

The influence of laparoscopic surgery on postoperative polymorphonuclear leukocyte function.

BACKGROUND: Laparoscopic surgery is thought to result in a better preservation of patients' immunological defenses. Polymorphonuclear leukocytes (PMN) are the most important effector cells in the elimination of pathogenic microorganisms. Because little is known about their function after laparoscopic surgery, we studied PMN phagocytosis, antigen expression, and oxygen radical production. METHODS: In this study, 17 patients scheduled for Nissen fundoplication were randomly assigned to undergo either a laparoscopic or conventional procedure. To study phagocytic capacity, PMN were incubated with fluorescein isothiocyanate (FITC)-labeled Staphylococcus aureus. Plasma opsonic capacity was measured by comparing PMN phagocytosis in the presence of patients' own plasma with phagocytosis in the presence of control plasma. Cellular activation was measured by the expression of various cell surface markers and by assessment of PMA-stimulated oxidative burst. RESULTS: Phagocytosis by PMN in the presence of patients' plasma was significantly lower 2 h after the conventional operation. No decrease in phagocytosis was observed when control plasma was used, indicating a decreased opsonic capacity of plasma after conventional surgery. No changes were observed after laparoscopic surgery. Furthermore, CD11b expression was significantly lower after the laparoscopic approach, indicating a blunted cellular activation. A significantly lower PMA-stimulated oxidative burst further confirmed the tempered stimulation after laparoscopic surgery. CONCLUSIONS: Laparoscopic surgery results in a preservation of the plasma opsonic capacity, and thereby the ability of PMN to phagocytose bacteria. Moreover, the postoperative cellular activation is reduced. The preserved phagocytosis and the blunted activation may prevent the development of postoperative infectious complications.

Adult↗

Reliability of the sentinel node procedure in melanoma patients: analysis of failures after long-term follow-up.

BACKGROUND: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability of this procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years. METHODS: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date. RESULTS: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases. CONCLUSIONS: With a 99% success rate and a 1.5% rate of failed SN procedures (7% false-negative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.

Adolescent↗

Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: experience in 81 patients.

BACKGROUND: Currently there is no standard adjuvant treatment following surgical resection of metastatic melanoma. We investigated whether surgery followed by autologous tumor cell-BCG vaccination was beneficial for malignant melanoma patients. In this study we focus on the prognostic value of DTH response following vaccination therapy. PATIENTS AND METHODS: Eighty-one patients with AJCC stage III and IV melanoma were selected. Whenever feasible, radical metastasectomy was performed. ASI was initiated by the administration of three weekly intra-cutaneous vaccinations with 10(7) irradiated autologous tumor cells, starting four weeks after surgery. Depending on the size of DTH response to the first three injections, subsequent vaccinations were planned. The first two vaccines also contained 10(7) BCG organisms as an immune stimulatory adjuvant. RESULTS: Induration as well as erythema correlated strongly with survival (P < 0.0001 and P = 0.0004). After radical metastasectomy in stage III melanoma patients a five-year survival of 48% was observed. In stage IV disease, a five-year survival of 34% was seen, after radical surgery had been performed. When macroscopic disease was present at start of vaccination treatment, no clinical responses occurred. Apart from transient skin ulceration at the site of BCG-containing vaccinations, no serious side effects were observed. CONCLUSIONS: This study shows that large-scale preparation of autologous melanoma cell vaccines is feasible. while vaccination results in DTH responses that correlate significantly with survival. ASI seemed to be beneficial in stage III and stage IV melanoma when given in the adjuvant setting, while causing only very mild side effects.

Adjuvants, Immunologic↗

Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: single-centre experience in 145 patients.

BACKGROUND: Hepatic arterial chemotherapy for liver metastases of colorectal cancer is still under discussion. Mainly because of the technical complications of this mode of treatment and the lack of a survival benefit in randomized studies. We performed an analysis of hepatic arterial 5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at a single institution. PATIENTS AND METHODS: One hundred forty-five patients with inoperable liver metastases from colorectal cancer were included. 5-FU, 1000 mg/m2/day continuous infusion for five days every three weeks, was delivered in the hepatic artery by percutaneous catheter or arterial access device. RESULTS: The response rate was 34% for all patients, 40% in patients with extrahepatic disease, and 15% in patients with i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and 14.3 months, respectively. In patients with extrahepatic disease or i.v. 5-FU-based pretreatment, OS was significantly shorter compared to patients without extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 months and 10.1 vs. 17.4 months, respectively), forty-seven percent of patients stopped treatment because of a complication. Complications most often seen in patients with arterial ports were hepatic artery thrombosis (48%) and dislocation of the catheter (22%). CONCLUSIONS: The results of our analysis are in line with previous phase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment were prognostic for reduced OS. The complication rate of hepatic arterial delivery was worrisome. although, no negative impact on survival could be established. There is a strong need for improvement of hepatic arterial delivery methods before further evaluation of hepatic arterial

Adult↗