Comparison between disease onset patterns of Egyptian juvenile and adult systemic lupus erythematosus (single centre experience).

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that occurs worldwide in both children and adults, with different disease manifestations, activity and severity between them. Objectives To analyse the difference in disease onset patterns and activity in Egyptian children and adults with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (≤18 years). Disease onset, clinical manifestations and laboratory investigations were recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was used to assess disease onset activity; renal biopsy was performed for all cases affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean age 29.65 ± 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis 12.63 ± 3.112 years. The most frequent initial a-SLE symptoms were constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central nervous system (11.6%). There were no significant differences between a-SLE and j-SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but the j-SLE haematological (88%) and central nervous system (30.1%) manifestations were significantly higher than a-SLE and articular manifestations were significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7% a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23 ± 4.966 in a-SLE and was significantly higher in j-SLE (27.13 ± 19.968). International Society of Nephrology lupus nephritis classes III and IV (42.4%) were the commonest findings in a-SLE; however, classes I and III (57.9%) were the commonest in j-SLE. Conclusions SLE had a wide variety of clinical and immunological manifestations, with some similarity and differences between a-SLE and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial manifestations than a-SLE.

Results of immunoscintigraphy using a cocktail of radiolabeled monoclonal antibodies in the detection of colorectal cancer.

BACKGROUND: External immunoscintigraphy using a single monoclonal antibody has been employed successfully to localize primary, recurrent, and occult colorectal carcinoma. This prospective study investigated the accuracy and sensitivity of external immunoscintigraphy when the combination or "cocktail" of radiolabeled monoclonal antibodies, CYT-103 (an IgG1a) and CYT-372 (an IgG2b) directed against TAG-72 and CEA, respectively, is given to patients with known or suspected colorectal cancer. METHODS: Eleven patients enrolled in this open label phase I/II study underwent preoperative external immunoscintigraphy after intravenous cocktail administration of two indium 111-labeled monoclonal antibodies (MoAb), CYT103 and CYT372. Antibody dose ranged from 0.2 mg (five patients) to 1.0 mg (six patients), each antibody radiolabeled with 2.5 mCi of indium 111, delivering a total dose of 5 mCi per patient. Planar and SPECT images were performed 2 to 5 days postinjection. Suspected lesions were surgically resected within 2 weeks of injection. RESULTS: A total of 23 lesions (sites) were identified in the eleven patients, 19 of which were confirmed by pathology (hematoxylin and eosin [H&E]). Cocktail immunoscintigrams identified 16 of the 19 confirmed lesions. Computed tomography (CT) scan detected 9 of the 19 lesions. The sensitivities of cocktail immunoscintigraphy and CT scan for the detection of colorectal cancer were 84% and 64%, respectively. The positive predictive value for immunoscintigraphy was 94%. The antibody scans detected six occult, previously unsuspected lesions. Cocktail immunoscintigraphy changed the surgical management in four of the 11 (36%) patients. CONCLUSIONS: The combination of In 111 CYT-103 and CYT-372 improved the sensitivity of external immunoscintigraphy for the detection of colorectal cancer compared to that obtained with a single MoAb imaging. Cocktail antibody imaging may enhance the staging and management of patients with cancers of colon and rectum.

Safety and role of repeated administrations of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE 025 in the postoperative follow-up of colorectal carcinoma patients.

The safety and clinical utility of repeated administrations of 111In-ZCE 025 were evaluated in 25 patients who have undergone colorectal carcinoma resection. Fifteen patients were clinically and radiologically free of recurrences and asymptomatic while 10 had rising CEA and/or symptoms. We repeatedly imaged the patients following intravenous administrations of 40 mg ZCE 025, every 4 to 6 mo. Side effects occurred in 16% of patients who received two or more infusions. Sixteen lesions were detected by immunoscintigraphy in 11 patients who were free of disease by CT scans or other imaging modalities. Ten recurrences were surgically confirmed in seven patients. Radiographic and clinical follow-up confirmed the remaining 6 Mab-positive lesions. Elevated human anti-mouse antibody (HAMA) titers were detectable in the sera of 30% and 64% of patients following the 1st and 2nd Mab injection respectively, but did not interfere with successful immunoscintigraphy nor correlated with the occurrence of side effects. This study suggests that a negative Mab scan indicates that a patient will remain free of recurrence; conversely, a positive scan was associated with recurrences of disease.

Multicenter clinical trials of monoclonal antibody B72.3-GYK-DTPA 111In (111In-CYT-103; OncoScint CR103) in patients with colorectal carcinoma.

The results of this clinical trial involving 23 sites indicated that 111In-CYT-103 immunoscintigraphy identified 70% of all patients with surgically confirmed disease when interpreted by the on-site physician. The sensitivity of 111In-CYT-103 imaging was slightly lower when interpreted retrospectively by the blinded readers in the absence of any patient-specific information. 111In-CYT-103 imaging sensitivity was similar in patients with primary and recurrent disease, but lower for liver metastases than for extrahepatic disease. Thirty-three previously unknown lesions were visualized by immunoscintigraphy; tissue confirmation was available for only five lesions, and all were found to be free of tumor. Only one of the lesions evaluated was TAG-72 positive. Twenty-eight lesions were outside the surgical field or not biopsied. Although no tissue confirmation was available, seven (25%) of these lesions were identified as consistent with metastatic disease by other conventional modalities. Importantly, antibody scans detected occult tumor lesions in 11 of the 92 patients with surgically confirmed adenocarcinoma, and accurately diagnosed 7 of 10 patients with elevated serum CEA levels and negative conventional workup. Surgery confirmed the presence of tumor identified only by 111In-CYT-103 in three patients, while four patients with negative scans had no evidence of recurrent disease at surgery. Antibody scans confirmed the absence of additional disease in 18 of 22 patients with isolated hepatic or pelvic recurrences in whom curative surgery was contemplated. The results of this multicenter trial suggest that CYT-103 immunoscintigraphy can provide information that is complementary to that derived from standard diagnostic techniques. During the workup of patients with primary colorectal carcinoma, this modality assesses the entire body and allows for the identification of multiple lesions at various locations simultaneously. It can then redirect attention and further workup to those areas not originally surveyed. Of special interest in this regard is the identification of occult lesions in five patients with primary colorectal cancer. 111In-CYT-103 imaging was found superior to CT in the localization of primary colorectal cancer, but neither modality could adequately assess the extent of tumor penetration through the bowel wall (the T stage in the TNM system) or the N status. The limitations of CT in evaluating T and N are well documented, and the limitations of 111In-based immunoscintigraphy for these same lesions have recently been described. Another limitation of 111In-CYT-103 immunoscintigraphy is in the identification of liver metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Scintigraphic detection of gastric and pancreatic carcinomas with In-111 ZCE 025 monoclonal antibody.

We have evaluated the role of In-111 anti-CEA (carcinoembryonic antigen) monoclonal antibody ZCE 025 in 8 patients. Three patients had a confirmed diagnosis of gastric carcinoma. Three had a confirmed diagnosis of pancreatic carcinoma. Two patients had elevated serum levels of CEA with no known primary. Each patient received 5.5 mCi In-111 ZCE 025 infused at doses of 10-80 mg. Planar and single photon emission computed tomography (SPECT) imaging at 3 and 7 days after infusion detected 9 of 12 known tumor sites and all 5 of the previously identified sites of metastasis. In-111 ZCE 025 MoAb imaging also found 6 previously unsuspected tumor sites and changed the preoperative evaluation in 50% of the patients studied. It changed the clinical management in 2 patients and established the site of primary involvement in 2 others. There were no clinical or biochemical reactions. In-111 ZCE 025 monoclonal antibody scintigraphy is a useful adjunct in the evaluation of patients with either gastric or pancreatic carcinoma. It may have a beneficial impact on the surgical decision making in these patients.

Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma.

Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation.

Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

Clinical experience with intra lymphatic administration of 111In-labelled monoclonal antibody PAY 276 for the detection of pelvic nodal metastases in prostatic carcinoma.

The ability of 111In-PAY 276 (anti prostatic acid phosphatase antibody) in detecting pelvic lymph node metastasis following bipedal intra lymphatic administration was studied in five patients with carcinoma of the prostate. The labeled antibody was injected directly into the lymphatics of each foot. Planar and tomographic images radioactivity content of lymph nodes resected during staging pelvic lymphadenectomy were compared to the histologic and immunoperoxidase findings. Radioactivity in pelvic lymph nodes was prominently seen within 20 min of injection and was present 16 days later. Persistent accumulation of tracer in the lymphatics of the lower extremities was also observed in all patients 16 days post injection. Radioactivity counts in tumor-free lymph nodes were higher than in tumored lymph nodes resected. Our results demonstrate that intra lymphatic administration of 111In-labeled PAY 276 monoclonal antibody has major technical limitations, and that further research directed at the causes of tracer accumulation in the lymphatics and tumor-free lymph nodes is required.

Colorectal tumors: scintigraphy with In-111 anti-CEA monoclonal antibody and correlation with surgical, histopathologic, and immunohistochemical findings.

A prospective clinical study of 17 patients with a histologic diagnosis of colorectal carcinoma proved at colonoscopy and surgery was performed with indium-111 anticarcinoembryonic-antigen (CEA) monoclonal antibody (MoAb), ZCE-025. MoAb scanning depicted nine of 16 primary colorectal carcinomas on planar scintigrams (true-positive findings = 56%) and ten of 16 lesions on single-photon emission computed tomography (SPECT) scans (true-positive findings = 62%). Liver metastases were detected in three of three patients, and lymph node metastases were detected in one of four patients. Immunohistochemical examination for CEA in resected colorectal cancer tissues demonstrated a positive correlation between MoAb imaging of primary lesions and cytoplasmic-stromal intracellular CEA distribution. There was no correlation between CEA serum levels and lesion detectability with MoAb scanning.

Colorectal carcinoma: detection with indium-111 anticarcinoembryonic-antigen monoclonal antibody ZCE-025.

A phase I and II clinical trial with indium-111-labeled anticarcinoembryonic-antigen monoclonal antibody ZCE-025 (In-111 ZCE-025) was initiated. Fifteen patients with colorectal tumors underwent external scintigraphy following the administration of 5.5 mCi (203.5 MBq) In-111 ZCE-025 at doses of 2.5-80.0 mg. Eighteen of 20 documented tumor sites, excluding those in the liver, were detected with In-111 ZCE-025. Lesions less than 1.5 cm could not be detected. Twenty-five percent of liver metastases exhibited positive accumulation of In-111 ZCE-025 at doses of 40-80 mg. No side effects were encountered. Because of the high detection rate of lymph node metastases from colorectal carcinoma with In-111 ZCE-025, this technique may be helpful in preoperative staging of patients with colorectal tumors, as well as in distinguishing recurrent tumors from postoperative or postradiation changes seen on computed tomography scans or other radiologic images.