Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia.

It is well known that cytokines play an important role in oral diseases. Furthermore, increased levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been reported in patients with cancer and premalignant lesions such as oral lichen planus and oral submucous fibrosis. The aim of this study was to assess salivary IL-6 and TNF-alpha levels in 30 patients with histopathologically confirmed leukoplakia (age range 24-78, mean 52.3 years) in comparison to 34 controls (age range 27-79, mean 52 years). Salivary IL-6 and TNF-alpha were determined by enzyme linked immunoadsorbent assay. Statistical analysis was performed by use of Mann-Whitney test for independent samples and values lower than 0.05 were considered as significant (p<0.05). Significantly higher levels of salivary IL-6 and TNF-alpha in patients with oral leukoplakia when compared to healthy controls were found. The levels of salivary IL-6 and TNF-alpha did not correlate with the size of leukoplakia (lesions) nor with its localization regarding high and low risk sites for malignant transformation. Levels of salivary IL-6 and TNF-alpha were not influenced by smoking habits. We can conclude that increased salivary IL-6 and TNF-alpha might play a certain role in oral leukoplakia.

Pregnancy outcomes and deliveries following laparoscopic transsection of uterine vessels: a pilot study.

OBJECTIVE: To assess pregnancy outcomes and deliveries after laparoscopic uterine artery transsection (LTUV) in symptomatic women with fibroids. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital, Kladno, Czech Republic. DESIGN: One hundred and fifty three patients underwent laparoscopic transsection of uterine vessels during a 4-year period. RESULTS: Nine of the 21 women desiring pregnancy conceived spontaneously and one after anovulation treatment. The average age of the women was 32.4 years, and the range was 26-39 years. Two women had vaginal delivery at term and one delivered vaginally at 31 weeks secondary to premature preterm rupture of membrane (PROM). Four others delivered at term by cesarean section. One woman with placenta previa was delivered by cesarean section 3 weeks before term. Mean birth weight was 3199 g (range 1710-3910 g). One spontaneous abortion was reported in the first trimester of pregnancy. One case of undesired pregnancy occurred. An extrauterine pregnancy was reported in this woman. CONCLUSION: LTUV is a minimally invasive operative procedure, that preserves the uterus and ovarian blood supply and allows for the achievement of pregnancy in women with symptomatic fibroids. Fetal growth and umbilical Doppler findings remained normal in all cases. An increased risk for preterm delivery and cesarean section was found in this small series.

[Systemic lupus erythematodes]. / Systémový lupus erythematosus.

Systemic lupus erythematodes (SLE) is chronic autoimmune disease, characteristic by production of autoantibodies against different autoantigens. Etiopathogenesis in not precise determinated, but genetic, immunologic, hormonal factors or influence of environment are assumed. It manifests by various symptoms and it can affect whichever organ or system in the body. Clinical manifestation are due chronic inflammation in the tissues, which is caused first of all by deposit of immunocomplex and by cytotoxic damage. At the last decades the mortality of patients with SLE is markly lower and their live is prolong. In spite of this diagnostic, to follow up and therapy of this disease is complicated and it requires the colaboration of more branches of medicine.

Loss of heterozygosity of APC and DCC tumor suppressor genes in human sporadic colon cancer.

We examined 36 cases of human sporadic colon carcinoma and corresponding normal tissue samples to evaluate loss of heterozygosity at the APC and DCC tumor suppressor genes loci using restriction fragment length polymorphism polymerase chain reaction and variable nucleotide tandem repeat analysis. Observed informativity was 83% for APC and 75% for DCC. DNA from 6 (20%) of 30 informative tumors exhibited loss of heterozygosity at the APC locus. Loss of heterozygosity at the DCC locus was observed in 7 (26%) of 27 informative tumor DNAs. Our results support the view that malignant progression is a consequence of more than one genetic change and suggest that inactivation of APC and DCC genes plays a role in a multistep process of colon tumor progression.

The expression and role of insulin-like growth factor II in malignant hemangiopericytomas.

Hemangiopericytoma is a rare soft tissue tumor originating from contractile pericapillary pericytes. To address the issue of molecular genetic events that participate in genesis and progression of hemangiopericytoma we analyzed insulin-like growth factor (IGF) II and IGF I receptor in 29 tumors collected from a human tumor bank network. Seven of these tumors were associated with severe hypoglycemia; six were retroperitoneal and one was located in the leg. Of 22 tumors tested 12 (54.5%) exhibited IGF II mRNA, while almost 90% (17 of 19) of hemangiopericytomas exhibited IGF I receptor mRNA. Sera from some patients whose tumors expressed IGF II mRNA contained elevated levels of IGF II. Removal of the tumor eliminated most of the IGF II immunoreactivity from the sera. The potential role of IGF II as a growth-promoting factor was examined on three malignant primary hemangiopericytoma cell cultures. Extracellular addition of IGF II significantly enhanced cell proliferation in a dose-dependent manner. Antisense oligodeoxynucleotides that specifically inhibit IGF II mRNA, at a concentration of 40 or 80 micrograms/ml, inhibited the growth of hemangiopericytoma cells significantly, by 40%. Simultaneous administration of antisense deoxyoligonucleotides to both IGF II and IGF I receptor inhibited tumor cell proliferation by even 80%. Our data suggest that tumor cells produce IGF II, and that this in turn stimulates their proliferation by autocrine mechanisms.

Salivary and serum interleukin 6 and basic fibroblast growth factor levels in patients with oral squamous cell carcinoma.

AIM: A role of various cytokines has been implicated in the pathogenesis of many carcinomas, and albeit the role of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) in sera has been studied in patients with oral carcinomas, data upon salivary IL-6 and bFGF are lacking. The aim of this study was to evaluate levels of IL-6 and bFGF in the saliva and serum of patients with oral squamous cell carcinoma. METHODS: Salivary and serum IL-6 and bFGF were evaluated in a group of 33 patients (28 men, 5 women) with oral squamous cell carcinoma (OSCC), age range 40-73 years , mean 54.05 years. Control group consisted of 23 healhy participants, mean age 25 years. RESULTS: Serum IL-6 and bFGF levels were not significantly different between patients with OSCC and healthy controls. Elevated levels of salivary IL-6 and bFGF in patients with OSCC when compared to the healthy controls were found (p<0.001). CONCLUSIONS: The conclusion is drawn that higher levels of salivary IL-6 and bFGF in patients with OSCC might originate from the local production, probably from carcinoma cells.

Intravenous immunoglobulin treatment of lupus nephritis.

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.

Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells.

PURPOSE: Nonsteroidal anti-inflammatory drugs lower the incidence of and mortality from colon cancer. In this paper, we present the effect of indomethacin on growth inhibition and alterations in the expression of several genes involved in cell cycle and apoptosis in CaCo-2 colon adenocarcinoma cells. METHODS: We used the MTT test to evaluate the effect of indomethacin on the proliferation rate of colon cancer and normal fibroblast cells in vitro. The expression of c-myc oncoprotein and p53 and p27 suppressor proteins was examined using the immunocytochemical method. RESULTS: We have shown that indomethacin reduces the proliferation rate of CaCo-2 colon cancer cells (up to 60% at the concentration of 4 x 10(-4) M), alters their morphology, and induces cell death by apoptosis. The most pronounced inhibitory effect was observed at the concentration of 6 x 10(-4) M where the growth was completely suppressed. However, the growth of normal fibroblasts (Hef 522) was much less inhibited (about 30% of inhibition at the concentration of 6 x 10(-4) M). Indomethacin reduces the proliferation rate and induces apoptosis in CaCo-2 colon cancer cells through enhanced expression of c-myc, p53, and p27 proteins. CONCLUSIONS: This is the first report about p27-increased expression in colon carcinoma cells induced by indomethacin treatment. Increased expression of p27 represents a new mechanism of apoptosis in cells treated with NSAIDs (indomethacin). This effect probably contributes to the anti-proliferative effect on colon cancer cells in vitro.

Dipeptidyl peptidase IV in patients with systemic lupus erythematosus.

The activity of dipeptidyl peptidase IV (DPP IV) was measured in the serum and peripheral blood mononuclear cells (MNC) of patients with systemic lupus erythematosus (SLE). The number of DPP IV positive (DPP IV+) lymphocytes in blood smears was determined cytochemically in groups of patients with active, moderate and inactive disease. Compared with healthy subjects, serum DPP IV activity was significantly decreased regardless of the level of disease activity. DPP IV activity in MNC was markedly decreased only in the patients with the active disease. Moreover, marked differences in the number of DPP IV+ lymphocytes could be detected between the groups of patients with the inactive and/or moderately active forms of the disease and those with active disease. The percentages of DPP IV+ lymphocytes, as well as DPP IV activity in MNC, showed significant correlations with the percentages of E-rosetting cells. Evaluation of DPP IV in SLE patients represents a new approach in the study of the pathological process of this disease.

Serum adenosine deaminase activity and its isoenzyme pattern in patients with systemic lupus erythematosus.

OBJECTIVE: To study the correlation between serum adenosine deaminase (ADA) activity and clinical activity in patients with systemic lupus erythematosus (SLE). The patterns of two ADA isoenzymes, ADA1 and ADA2, were also analysed in healthy controls and patients to determine the source of increased ADA activity in patients. METHODS: Total serum ADA activity (tADA) was measured spectrophotometrically. The isoenzyme pattern of ADA was analysed by the HPLC method using a specific inhibitor of ADA1, erytro-9-(2-hydroxy-3-nonyl)adenine (EHNA). Disease activity was assessed using the European Consensus Lupus Activity Measurement index (ECLAM). RESULTS: Serum tADA activity was significantly increased in patients compared to healthy controls (mean +/- SD; 476.9 +/- 145.3 vs 254.0 +/- 98.9 ncat/L, p < 0.001). The isoenzyme analyses showed that the increased total ADA activity in the patients was mainly due to increased ADA2 activity (371.3 +/- 154.8 vs 214.2 +/- 47.9 ncat/L in healthy controls, p < 0.001). The mean values for ADA1 activity in the patients (64.6 +/- 37.9 ncat/L) and healthy controls (69.2 +/- 26.9 ncat/L) were similar. A strong correlation was found between serum ADA activity and disease activity as measured by ECLAM (Spearman's rank correlation coefficient 0.74, p < 0.0001, linear regression coefficient 0.68, p < 0.01). CONCLUSION: Serum ADA activity is closely associated with SLE activity and appears to be useful as a new disease activity parameter of SLE.

Association between systemic lupus erythematosus and insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene.

OBJECTIVE: ACE takes part in the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin-II and inactivating bradykinin. ACE gene insertion/deletion polymorphism is associated with the level of circulating enzymes--subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards impaired vascular function and structure. Patients with systemic lupus erythematosus (SLE) suffer from differentially expressed vascular pathology. We attempted to determine whether the type of ACE polymorphism could contribute to this pathology. METHODS: 101 SLE patients fulfilling the ACR criteria were investigated. The I/D polymorphism was ascertained by PCR, followed by electrophoresis of the amplified fragments and UV visualization. RESULTS: The frequency of the D allele was higher in the SLE group (0.623) than in the controls (0.520) (chi 2 test, p < 0.025). The distribution of the ACE genotype in SLE group was different from that in the control group (p < 0.05). An association between the DD genotype and visceral damage (p < 0.006) was observed. CONCLUSION: Our results suggest that in the multifactorially determined vascular pathology of SLE, changes associated with I/D polymorphism could influence vessel wall inflammation (monocyte adhesion and activation with cytokine release, T-lymphocyte metabolism), a tendency towards vascular impairment (neointimal proliferation, vasospasm, platelet activation, myocyte proliferation) and lead to the subsequent ischemia. The ACE gene could serve as the visceral damage indicator in SLE.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus.

OBJECTIVE: Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred not only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively signalling molecule CTLA-4 is involved in establishing and maintaining of peripheral T cell tolerance, which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses. We tested if there was an association between CTLA-4 and SLE, a disease with B and T cell hyperreactivity and impaired peripheral T cell tolerance. METHODS: Using the polymerase chain reaction--restriction fragment length polymorphism method with Bbv I digestion, we assessed an exon 1 transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls. RESULTS: The distribution of CTLA-4 exon 1 genotypes in the SLE group was significantly different from that in the controls (chi 2 = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homozygotes vs 53.9% of the controls. The frequency of the G allele was significantly higher in SLE patients (35.8%) than in controls (25.7%; chi 2 = 4.142, p = 0.042). CONCLUSION: Our results indicate that the non-MHC linked CTLA-4 gene could confer susceptibility in SLE, as it does in various other autoimmune diseases (Hashimoto thyroiditis, Graves' disease, IDDM).

Neutrophil and monocyte phagocytic functions in patients with colorectal adenocarcinoma during fluorouracil therapy.

Neutrophil and monocyte phagocytic functions, i.e % of phagocytic cells, ingestion and intracellular microbe killing were determined in 51 patients with colorectal adenocarcinoma, 43 with localized disease and 8 with distant metastases. Phagocytic functions were determined at the time of diagnosis, following surgery are before each of 6 cycles of fluorouracil chemotherapy. Four of six phagocytic parameters determined were decreased at diagnosis while all 6 decreased following surgery. During chemotherapy, neutrophil phagocytic activity recovered to normal value while all other neutrophil and monocyte functions remained decreased. Even so, neutrophil ingestion and monocyte phagocytic and bactericidal activities increased reaching from time to time values significantly higher than that found before the start of chemotherapy. The results showed significant alterations of neutrophil and monocyte phagocytosis in colorectal adenocarcinoma patients at the time of diagnosis, with further decrease following surgery. Fluorouracil chemotherapy did not exert suppressive effects on these functions; on the contrary, it seemed to support, or at least not to prevent, their partial recovery.

Evaluation of genital human papillomavirus infections by polymerase chain reaction among Croatian women.

Infection with specific human papillomavirus (HPV) types is the strongest risk factor in cervical carcinogenesis. In this study we analysed, by means of polymerase chain reaction (PCR), cervical specimens obtained from consenting women with abnormal Pap smears collected from 1996 to 1998. Consensus- and type-specific-primers directed PCR were used in order to detect the presence and to determine the most common HPV types: 6, 11, 16, 18, 31 and 33. Out of 1874 specimens, 1207 (64%) contained one or more HPV types. Approximately half HPVs were typed (621 out of 1207) and the others remained untyped (586 out of 1207), 51% and 49%, respectively. Beside low-risk HPV 6/11 (5%), the most frequently observed HPVs were high-risk HPV types, especially type 16 (12%), while HPV types 18 (2%), 31 (5%) and 33 (3%) were less frequent. The HPV positivity rate declined with age, although all HPV types were equally distributed in different age groups. The presence of HPV DNA significantly increased from 55% to 78% along with the severity of the cervical lesions, i.e. low- and high-grade squamous intraepithelial lesions (LSIL, HSIL). Undetermined HPV types, other than 6/11, 16, 18, 31 and 33 were equally distributed in LSIL and HSIL which indicates that they represent low- as well as high-risk HPV types. Our results indicated that HPV infections, especially those with HPV 16, represent a significant public health concern in Croatia.

Midterm follow-up study of laparoscopic dissection of uterine vessels for surgical treatment of symptomatic fibroids.

BACKGROUND: This study aimed to assess laparoscopic dissection of uterine vessels (LDUV) for symptomatic fibroids in women. METHODS: A total of 69 women entered the study between March 2000 and June 2003. In this case series, 68 consecutive women underwent LDUV using ultrasonically activated sheers or electrosurgery for the treatment of fibroids over 3 years (median follow-up period, 14.5 months). Ultrasound or magnetic resonance imaging was carried out 3, 6, 12, 24, and 36 months after treatment. The tissue markers, gonadotropin, and estrogen levels were studied postoperatively. RESULTS: Almost all the patients (98.5%) had a successful LDUV with a low rate (7.3%) of postoperative complications. The time of surgery ranged from 15 to 50 min (mean, 30.8 min). The blood loss was minimal (mean, 14.7 ml), and the hospital stay was 2.4 days. Symptom improvement (menorrhagia or dysmenorrhoea) was 93.2%, and the average reduction in the dominant myoma was 57.8% during a follow-up period longer than 12 months. All the patients with anemia had normal red cell counts after 3 months. CONCLUSIONS: Uterine volume and the dominant fibroid were significantly reduced and symptoms were improved by LDUV. The laparoscopic procedure is associated with insignificant tissue damage and normal gonadotropin and estrogen levels.

Allogeneic peripheral blood stem cell transplantations in children--a single center experience.

We analyzed 30 peripheral blood stem cell transplantations (PBSCT) from 25 human leukocyte antigen (HLA) matched sibling donors (MSD) and 4 HLA-matched unrelated donors (MUD) in 29 patients, done between November 1996 and March 2003. Patients aged 3 to 17 years underwent allogeneic PBSCT for malignant (16 patients) and non-malignant (13 patients) diseases. Sibling donors aged 3 to 23 years were given granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/day for 4 to 5 days. All but one of the 29 donors underwent one single leukapheresis for stem cell collection. The patients received a median of 4.2 x 10(6) CD34+ cells/kg of body weight, they all engrafted after a median of 13.5 days (range 10-25 days). Acute graft-versus-host disease (GVHD) grade II to IV developed in 11 of 26 MSD transplants and in all 4 patients after MUD PBSCT. Eleven of 27 evaluable patients experienced chronic GVHD. After a median follow-up of 662 days, 20 out of 29 patients (69%) are alive, three of them need systemic immunosuppression for chronic GVHD. Six patients experienced relapse of their underlying malignant disease, one of them still alive in complete remission. Two patients died of grade IV acute GVHD and two others due to an opportunistic infection. Based upon our experience, PBSCT is a feasible and safe method for both pediatric donors and patients. It is associated with rapid engraftment, no greater incidence of acute but a higher incidence of chronic GVHD as compared to bone marrow transplantation (BMT) and therefore suitable mainly for children suffering from malignant diseases.

Immunoscintigraphy with 99Tcm-labelled monoclonal anti-CEA BW 431/26 antibodies in patients with suspected recurrent and metastatic colorectal carcinoma: two-year follow-up.

The aim of this study was to evaluate immunoscintigraphy with BW 431/26 anti-CEA antibody in the follow-up of 15 patients with colorectal carcinoma. A whole-body scan followed by SPET imaging of the abdomen and pelvis was performed 4-6 and 20-24 h after the intravenous infusion of 0.6-1.0 mg of intact anti-CEA monoclonal BW 431/26 antibody labelled with 814-1110 MBq of 99Tcm. The HAMA response and serum CEA levels were determined. Immunoscintigraphic findings were verified by biopsy, radiologically and/or by 2 year follow-up. On an individual patient basis, immunoscintigraphy demonstrated an overall sensitivity of 83%, specificity of 100%, accuracy of 87%, positive predictive value of 100% and negative predictive value of 60%. Better results were achieved in the pelvic region than in the liver or in the extra-hepatic abdominal region. We evaluated 40 lesions; on an individual lesion basis, immuno-scintigraphy gave a sensitivity of 80% and an accuracy of 80%. SPET images detected significantly more lesions than whole-body planar images (P < 0.05). SPET at 20-24 h detected significantly more 'hot' lesions than at 4-6 h (P < 0.01). No correlation between CEA serum levels and immunoscintigraphy was observed (r = 0.376, P > 0.05). One of nine patients (11%) developed HAMA after immunoscintigraphy. We conclude that immunoscintigraphy with BW 431/26 antibody appears able to differentiate between tumour recurrence and scar tissue, and to evaluate liver metastases of colorectal carcinoma. Serum CEA levels appear not to influence the result of immunoscintigraphy and the HAMA response is minimal. A delayed SPET scan should be part of an immunoscintigraphic imaging protocol when 99Tcm-labelled BW 431/26 monoclonal antibody is used.

Bone marrow immunoscintigraphy for the detection of skeletal metastases in patients with breast cancer.

In this study, we evaluated the efficacy of bone marrow immunoscintigraphy (BMIS) for the detection of skeletal metastases in 23 patients with histologically confirmed breast cancer. All patients underwent whole-body BMIS 3-6 h after the intravenous injection of 0.20-0.33 mg of the intact anti-NCA 95 MAb BW 250/183 labelled with 259-555 MBq 99Tcm and a whole-body 99Tcm-MDP bone scan. In four patients, BMIS SPET of the lumbar spine was also performed. Serum alkaline phosphatase was determined in all patients and the level of human anti-mouse antibody (HAMA) in 16. Final diagnosis was confirmed by radiology and 2 years follow-up. Compared with the 99Tcm-MDP bone scan, BMIS demonstrated better specificity (88% vs 75%) and a better positive predictive value (92% vs 85%). There were no significant differences between BMIS and the bone scan in the detection of skeletal metastases (P > 0.05). In one patient with normal planar BMIS of the lumbar spine, SPET disclosed a metastatic lesion in the bone marrow. The correlation coefficient between BMIS and bone scan and between BMIS and serum alkaline phosphatase was r = 0.688 and r = 0.483 respectively. One patient developed a minor HAMA response after BMIS. Patients with diffuse increased activity of the skull on the bone scan had a significantly higher skull to whole body ratio on BMIS (P < 0.01). Thus BMIS can improve the specificity and positive predictive value of bone scanning in the detection of skeletal metastases, with a low HAMA response. Diffuse increased activity of the skull on bone scans could be explained by bone marrow extension. SPET scanning of the spine may improve the sensitivity of BMIS.