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R J Doerr

Publications and source records attributed to R J Doerr.

At least 55 records · Page 3Linked to original sources
PubMed1992

Augmentation of the immune response of the murine liver by levamisole.

Murine hepatic nonparenchymal cells (NPC) were studied following in vivo treatment with levamisole. This agent was found to increase the cytolytic action of these cells against YAC-1 and P815 target cells. An increase in the cytostatic activity against liver-derived murine colon adenocarcinoma 38 tumor cells was also observed. Treatment with levamisole also augmented the proliferation of the hepatic NPC. Supernatants generated by these cells contained an agent capable of stimulating the proliferation of bone marrow cells from the same mice. The effect of levamisole on different subsets of NPC derived from the liver in this model is discussed.

Animals↗
PubMed1992

Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT.

Immunoscintigraphy performed after intravenous administration of indium-111-labeled CYT-103, an immunoconjugate of monoclonal antibody B72.3, was evaluated in patients with suspected primary or recurrent colorectal cancer at 25 centers in the United States. Gamma camera imaging, computed tomography (CT), and confirmatory surgical exploration were completed in 169 of 227 patients who received single infusions of In-111 CYT-103. Eight patients (3.5%) had reversible, nonserious adverse reactions, and 39% developed antimurine antibodies. Surgery revealed that 155 of 169 patients had colorectal carcinoma. In these 155 patients, immunoscintigraphy and CT demonstrated similar sensitivity (69% and 68%, respectively) and specificity (77%). However, immunoscintigraphy had greater sensitivity in detection of pelvic tumors (74% vs 57%, P = .035) and extrahepatic abdominal tumors (66% vs 34%, P less than .001); CT enabled detection of a greater proportion of liver metastases (84% vs 41%, P less than .001). These results indicate that In-111 CYT-103 can be administered safely and that immunoscintigraphy performed with this agent frequently enables identification of extrahepatic abdominal sites of disease not visualized with CT.

Adult↗
PubMed1992

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)

Antibodies, Monoclonal↗
PubMed1992

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.

Adult↗
PubMed1991

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.

Adenocarcinoma↗
PubMed1990

Role of asialo-GM1 positive liver cells from athymic nude or polyinosinic-polycytidylic acid-treated mice in suppressing colon-derived experimental hepatic metastasis.

Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells injected into the ileocolic vein (ICV) of C57BL/6 mice developed distinct hepatic foci within 14-21 days and survived for an average of 19-35 days. In contrast, C57BL/6-nu/nu mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within 1 h and 73% of the radioactivity remained after 24 h. However, about 60% of the 111In-labeled LD-MCA-38 tumor cells were cleared from the liver of nude mice after 24 h. Nonparenchymal liver cells isolated from untreated conventional mice displayed little cytotoxicity against freshly excised 51Cr-labeled LD-MCA-38 cells but did lyse the standard natural killer target, YAC-1 tumor cells, in 4 h chromium release assays. On the other hand, nonparenchymal liver cells but not spleen cells from nude mice were cytotoxic to 51CR-labeled LD-MCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GM1 (AsGM1) positive. C57BL/6 mice treated with polyinosinic-polycytidylic acid [poly(IC)] also displayed cytotoxic activity against LD-MCA-38 tumor cells in vitro. Furthermore, poly(IC) treatment of mice 1-8 days after tumor inoculation suppressed the number of hepatic foci and also significantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM1 induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsGM1-positive cells in the liver of these mice may inhibit tumor growth in vivo. In conclusion, the host defense system of the liver from athymic nude or poly(IC)-treated mice possess AsGM1-positive cells that can suppress tumor implantation or tumor growth in the early stages of metastasis in liver.

Adenocarcinoma↗
PubMed1990

Indium 111 ZCE-025 immunoscintigraphy in occult recurrent colorectal cancer with elevated carcinoembryonic antigen level.

We investigated the utility of scanning with indium 111 labeled to monoclonal antibody in 13 patients after curative resection of colorectal cancer who had elevated carcinoembryonic antigen levels and negative results of clinical workup. Each patient received 1 mg of anti-carcinoembryonic antigen monoclonal antibody type ZCE 025 labeled with 5.5 mCi of 111In, plus 9 to 39 mg of the same antibody unlabeled. Patients underwent scanning 3 to 7 days after infusion by planar and emission computed tomography. ZCE-025 monoclonal antibody imaging detected tumor recurrence or metastasis in 11 of 13 patients. In one patient the monoclonal antibody scan gave a true-negative result, and in one patient the monoclonal antibody scan failed to disclose a metachronous cecal primary. Tumor sites identified were the pelvis (2 patients), abdominal wall (2), retroperitoneum (1), lymph nodes (3); liver (2), bone (2), and lung (1). The accurate localization of colorectal carcinoma recurrences by means of 111In ZCE-025 monoclonal antibody demonstrates the usefulness of this diagnostic agent in the setting of elevated carcinoembryonic antigen level and negative results of clinical and radiologic workup.

Adenocarcinoma↗
PubMed1990

Pancreaticoduodenectomy. University experience and resident education.

A radical pancreaticoduodenectomy offers the best chance for survival in patients with periampullary and pancreatic malignant neoplasms. A pancreaticoduodenectomy has educational value since complex pancreatic operations are demanding and important to the training of surgical residents. Increased pancreaticoduodenectomy experience (per surgeon) has been associated with improved outcomes. We examined the hypothesis that residents who are supervised by faculty surgeons can perform pancreaticoduodenectomies with acceptable outcomes. From 1976 to 1987, 127 pancreatic resections were performed by 81 residents who were supervised by 15 faculty surgeons in four teaching hospitals. A pancreaticoduodenectomy was performed on 61 patients. All residents served as an operating surgeon on a pancreatic resection, and 58 (82%) performed pancreaticoduodenectomies. The mortality for the pancreaticoduodenectomies was 8%, with a 36% major complication rate. A pancreaticoduodenectomy can be performed safely by residents under supervision. A review of the results identifies the means of improving outcomes. These results justify the preservation of a pancreaticoduodenectomy as an important experience for residents.

Adult↗
PubMed1990

Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3.

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

Adenocarcinoma↗
PubMed1990

Surgical management of complications of endoscopic sphincterotomy with precut papillotomy.

We reviewed 574 endoscopic sphincterotomy procedures. Fifty-six precut papillotomies were performed. Presenting conditions included choledocholithiasis, cholangitis, benign and malignant papillary strictures, and stenosing papillitis. Complications were identified in 16 percent: perforation in 9 percent, pancreatitis in 5 percent, bleeding in 2 percent, and pancreatic abscess in 2 percent. One patient died. Six patients required operation for complications. Perforation of the duodenum or common bile duct seen within 8 hours was managed with drainage and closure of the perforation with minimal complications. Duodenal perforations operated on later than 8 hours required more extensive procedures. All these patients had significant post-operative complications. Three patients were managed nonoperatively. Precut papillotomy carries a significantly higher complication rate than conventional sphincterotomy. Our experience suggests that there is no place for conservative management of duodenal perforation.

Aged↗
PubMed1990

In-111-labeled monoclonal antibody immunoscintigraphy in colorectal carcinoma: safety, sensitivity, and preliminary clinical results.

A phase I/II prospective clinical trial was performed with indium-111-labeled monoclonal antibody (MoAb) conjugate B72.3-glycyl-tyrosyl N-epsilon-diethylenetriaminepentaacetic acid (CYT-103) in 28 preoperative patients with biopsy-proved or suspected colorectal carcinomas. Immunoscintigraphy was performed 2-7 days after infusion of 4.1 mCi (152 MBq) of In-111 labeled to CYT-103 at doses of 0.5, 1.0, 2.0, and 20.0 mg. Surgical and histologic confirmation was available in all cases. Use of In-111 CYT-103 made possible detection of 75% of colorectal carcinomas at doses of 1.0 mg and higher, compared with only 20% detection at the 0.5-mg MoAb dose. Immunohistochemical staining for tumor-associated glycoprotein (TAG)-72 in resected carcinoma tissues demonstrated a positive correlation between MoAb imaging and the percentage of cells that expressed TAG-72. One patient suffered an adverse reaction after MoAb infusion. Human antimouse response to CYT-103 developed in 16% of patients.

Adenocarcinoma↗
PubMed1990

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.

Adult↗
PubMed1990

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.

Antibodies, Monoclonal↗
PubMed1989

Hepatectomy prolongs survival of mice with induced liver metastases.

Resection of hepatic metastases from colorectal cancer has been shown to prolong survival in some patients. Whether this results from a reduction of tumor burden or is an indirect effect mediated by hepatectomy is questionable. Male C57BL/6Ros 8-week-old mice underwent ileocolic vein injection of a suspension of 0.3 mL of 2 x 10(5) viable liver-derived murine (MCA-38) colonic adenocarcinoma cells. This model produces hepatic metastases in all lobes of the liver. At 7, 14, or 21 days after tumor injection, mice were randomized to receive either 42% resection of the liver or laparotomy alone. Survival in the animals with hepatectomy was significantly prolonged when the hepatectomy was performed 14 or 21 days after tumor injection.

Animals↗
PubMed1989

The role of pediatric surgery in the medical school curriculum.

In most medical schools, exposure to pediatric surgery is presented as a subspecialty elective. We have offered it as an integral part of the surgical clerkship for 10 years in the belief that it provides an excellent educational environment. To confirm this concept, the quizzes (Q), final examinations (FE), and grades of students assigned to the pediatric surgical service were prospectively studied. All students (N = 139) in the surgical clerkship entered the study. Thirty-two students were randomly selected and assigned to the surgical service of a major pediatric hospital (P-Surg) for 50% of their clerkship. The other students (N = 107) were assigned to a variety of adult surgical services (G-Surg) and served as the control group. All students attended the same seminars, used the same educational materials, were examined with the same test items, and were evaluated by the same oral examiners. Test items were electronically scored and the database was analyzed on an IBM computer. The statistical analysis was performed using a Student's t test and chi 2 analysis. There was no significant difference in the demonstrated cognitive performance and grades awarded to the two groups of students. We conclude that a pediatric surgical service provides an atmosphere that is educationally comparable to the adult general surgical service.

Curriculum↗
PubMed1989

Duodenal lipoma causing intussusception.

Duodenal intussusception and duodenal lipomas are both rare clinical entities. A case of duodenal intussusception caused by a lipoma is presented. The diagnosis of lipoma may be made endoscopically and radiographically using both upper gastrointestinal series and computed tomographic scan. Intussusception in the duodenum may be partial and cause minimal symptoms, but it has distinctive roentgenographic findings. The treatment of symptomatic lipomas may be endoscopic removal, using snare and cautery, or local excision via duodenotomy. Intussusceptions must be reduced operatively.

Aged↗