Intraoperative probe-directed immunodetection using a monoclonal antibody.

To assess monoclonal antibody (MAb) 17-1A and its F(ab')2 fragment in intraoperative radioimmunodetection and to evaluate further the clinical usefulness of a hand-held gamma-detecting probe (GDP), we injected radiolabeled monoclonal antibody 17-1A three to six days preoperatively or its F(ab')2 fragment two to three days preoperatively into 18 patients with colorectal cancer. Intraoperative GDP counts with tumor-tissue ratios of 1.5:1 or greater were obtained from 15 (75%) of 20 tumor sites, with ratios averaging 2.3:1 for fragments and 3.4:1 for whole antibody. The GDP counts contributed to intraoperative decision making in three patients, either by localization of tumor not identified by inspection or palpation or by mapping margins of resection with histologic confirmation of a local/regional recurrence. These preliminary data demonstrate that probe-directed, intraoperative radioimmunodetection can assist the surgeon in detecting subclinical tumor deposits and thus better evaluate the extent of primary or recurrent colorectal cancers intraoperatively.

Facial nerve sacrifice and tumor recurrence in primary and recurrent benign parotid tumors.

Three hundred eight patients underwent parotidectomy for a benign parotid tumor between 1948 and 1979. Two hundred seventy-four had operation for primary tumor, and 34, for recurrent tumor. Ninety-eight percent of those with primary tumors had superficial or total parotidectomy, and 2 percent had local excision with a wide margin of normal tissue. In those with recurrent tumor, 91 percent had superficial or total parotidectomy and 9 percent had local excision with a wide margin of normal tissue. There were nine recurrences in the primary group (3.2 percent) and 10 in the recurrent group (29 percent), at an average follow-up of 10 and 13 years, respectively. The time to recurrence in the primary group was between 5 and 20 years, whereas, second recurrences in the recurrent group generally took place within 5 years. Seven patients in the primary group (2.5 percent) and 9 in the recurrent group (26 percent) had sacrifice of the facial nerve. Most facial nerve sacrifices in the primary group were minor, involving a branch of the nerve only. Facial nerve sacrifice in the recurrent group, however, usually involved division of the nerve or the nerve trunk. These findings demonstrate that the major morbidity associated with managing benign parotid tumors occurs in dealing with recurrent tumors. Recurrence is uncommon if superficial or total parotidectomy is performed for a primary tumor.

Clinical and pathologic correlations in disease metastatic to the thyroid gland.

Findings in our series of patients and a review of the literature seem to suggest that metastatic cancer to the thyroid is much more common that is clinically evident. The clinical presentation of an asymptomatic mass, normal thyroid functions, and a cold nodule on thyroid scan can occur months to years after treatment of a primary cancer and thus often produces a clinical dilemma. Workup should include ruling out other metastatic cancer and fine-needle aspiration of the thyroid mass. If isolated metastatic cancer to the thyroid is found, surgical resection should be performed, usually by lobectomy and isthmusectomy. Unfortunately, the prognosis is poor, but surgery often prolongs the disease-free interval and occasionally will be curative.

Reoperation directed by carcinoembryonic antigen level: the importance of a thorough preoperative evaluation.

Many asymptomatic patients suspected to have recurrent colorectal cancer based on an elevated carcinoembryonic antigen level will be spared unnecessary operation if strict attention is paid to their preoperative evaluation. Liver and renal function should be assessed. Unresectable extraabdominal and intraabdominal recurrence or metastases should be excluded. Patients being evaluated for recurrence after curative resection of a rectosigmoid cancer should undergo a bone scan. Having satisfactorily ensured normal results for these investigations, the surgeon should then proceed to search for an intraabdominal source of tumor recurrence.

Radical neck dissection: is it enough?

This series of 307 patients who underwent radical neck dissection showed an overall recurrence rate of 19 percent. Clinical staging of disease was an accurate predictor of both recurrence and survival. Extranodal disease dramatically increased recurrence and decreased survival. Although our recurrence rate after radical neck dissection was lower than that previously reported for surgery alone, it was still significantly higher than that after adjuvant radiotherapy. We conclude that histologically proved neck disease should be treated by radical neck dissection, followed by adjuvant radiotherapy to decrease recurrence and, it is hoped, improve survival.

Needle localization of mammographically detected lesions in perspective.

Needle localization of mammographically detected lesions has been shown to detect early breast cancer. One hundred seven patients who underwent needle localized biopsy from June 1977 to September 1985 were reviewed. Eighty percent of the biopsies were benign and 20 percent were cancers (22 patients). In patients undergoing modified radical mastectomy, 80 percent of the axillary specimens were node-negative. During the same 8 year period, 570 breast cancers were diagnosed. Needle localization was responsible for only 4 percent of all cancers found. Though needle localization represents an advance in the detection of early breast cancer, the majority of cancers are found by physical examination. The importance of routine examination by a physician and self-breast examination remains paramount.

Treatment of carotid body tumors.

Twenty patients presenting with 23 carotid body tumors compose this study group. Eleven patients underwent resection of 14 tumors, while nine patients either refused resection or were unresectable. There was one tumor recurrence following resection. Of the patients not having resection, none have experienced morbidity or death. While surgical excision remains the mainstay of treatment for carotid body tumors, those patients not undergoing resection can survive for long periods.

Does the body image exist in three dimensions? The study of visual mental representation of a body and a nonbody object.

Do the mental images of 3-dimensional objects recreate the depth characteristics of the original objects? This investigation of the characteristics of mental images utilized a novel boundary-detection task that required participants to relate a pair of crosses to the boundary of an image mentally projected onto a computer screen. 48 female participants with body attitudes within expected normal range were asked to image their own body and a familiar object from the front and the side. When the visual mental image was derived purely from long-term memory, accuracy was better than chance for the front (64%) and side (63%) of the body and also for the front (55%) and side (68%) of the familiar nonbody object. This suggests that mental images containing depth and spatial information may be generated from information held in long-term memory. Pictorial exposure to views of the front or side of the objects was used to investigate the representations from which this 3-dimensional shape and size information is derived. The results are discussed in terms of three possible representational formats and argue that a front-view 2 1/2-dimensional representation mediates the transfer of information from long-term memory when depth information about the body is required.

Deposition of low dose benzo(a)pyrene into fetal tissue: influence of protein binding.

The influence of maternal binding of benzo(a)pyrene (BaP) on its disposition into fetal tissue was investigated in pregnant Swiss-Webster mice. Low doses (10 ng/mouse) of radiolabeled BaP were administered by intravenous injection on day 15 of gestation. BaP was administered along with normal rabbit serum (NRS) (low binding paradigm) or anti-BaP antiserum (high binding paradigm) and animals killed at various time points. Total radioactivity in the fetus increased with time to peak concentrations in whole fetal homogenates at 12 hours. In contrast, maternal serum, liver, and lung showed a decrease in total radioactivity over the same time period. Total radioactivity/gram of fetal tissue was significantly higher in NRS-treated animals compared to anti-BaP-antiserum-treated animals. Since the levels of the parent compound, BaP, in fetal tissue fell over time similar to maternal liver and lung, the increase in total radioactivity in the fetus was due to an increased concentration of a BaP metabolite fraction in both the low binding and high binding groups. Significantly, a lower level of this metabolite fraction was found in fetal tissue from the anti-BaP-antiserum-treated animals. The present study shows that maternal exposure to this environmental pollutant, even at low doses, results in an accumulation of a metabolite-rich fraction in the fetal compartment, which may contribute to the teratogenic potential of BaP. The data also demonstrate that the amount of this accumulation can be diminished by increasing maternal binding proteins, such as by treatment with anti-BaP antiserum.

Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer.

The effect of 13-cis-retinoic acid (13-cis-RA) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male, random bred, Sprague-Dawley (S-D) and inbred Wister/Furth (W/Fu) rats and on isograft tumor growth and metastases in a Brown Norwegian (BN) X W/Fu F1 rat was studied. 13-cis-RA (300 mg/kg diet) was administered to S-D rats 1 week before commencing DMH injections and for the duration of the experiment. W/Fu rats received 13-cis-RA (10 mg/kg weight X 5 days) 6 weeks after DMH injection had begun and monthly thereafter. Primary tumors were detected by serial laparotomy under ether anesthesia in both strains. The time to tumor onset was significantly delayed in treated groups, S-D and W/Fu, P = 0.0339 and 0.0322, respectively (Mantel-Haenszel test), compared with placebo-treated controls. 13-cis-RA (15 mg/kg weight) administered 2 days before and for the duration of isograft tumor growth (DMH 2054, a well-differentiated mucin-producing colon adenocarcinoma that spontaneously metastasized to lung) had no effect on tumor growth or metastasis in the BN X W/Fu F1 rat. The findings suggest that the role of 13-cis-RA is in colon cancer prevention and not in its treatment either in an adjuvant or established setting.

Needle aspiration biopsy of major salivary gland tumors. Its value.

Three hundred forty-one needle aspiration biopsies (NAB) of major salivary gland tumors were performed over a 32-year period. Eighty percent of tumors were benign, and 20% were malignant. Preoperative NAB findings were compared with pathologic diagnosis of the surgically resected specimen in all cases. Forty-six of 63 aspirates from malignant tumors were correctly diagnosed by NAB, establishing a sensitivity at 73%. Two hundred forty-nine of 265 aspirates from benign tumors were correctly diagnosed by NAB, establishing a specificity at 94%. Overall accuracy was 90%. Diagnostic error or difficulty in clinically localizing the tumor to the salivary gland was encountered in 64 patients with parotid tumors and 12 patients with submandibular tumors. NAB correctly localized over 85% of these tumors to the salivary gland, thus enabling both immediate and correct decision-making concerning subsequent management to be undertaken.

Intestinal anastomosis after preoperative radiation therapy for carcinoma of the rectum.

A retrospective review was conducted on 133 patients who underwent anterior resection and primary intestinal anastomosis for adenocarcinoma of the rectum from 1973 to 1983 at the Baystate Medical Center. Forty patients received a moderate dose, 4,500 rads, of radiation therapy preoperatively. Twenty-six of these patients (65 per cent) underwent protective colostomy at operation. An additional 93 patients underwent an operation without radiation and 38 of these (42 per cent) had a colostomy. We found no significant difference between patients who did or did not undergo radiation therapy in the over-all rate of complications (25 per cent for those who underwent radiation and 29 per cent for those who did not). Furthermore, there was no significant difference in anastomotic leak rates between the two groups (10 and 7 per cent respectively), even after controlling for the presence of a protective colostomy. We did find that leak rates for both groups were markedly higher for patients with a colostomy (14 per cent) than for patients without (1 per cent) (p less than 0.005). We conclude that a moderate dose of radiation therapy preoperatively does not increase the risk of anastomotic leakage or other operative complications with anterior resection. Colorectal intestinal anastomosis may be safely performed without routine colostomy after planned preoperative adjuvant radiation therapy if the anastomosis is technically satisfactory.

Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer.

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.

Variation in recognition of recurrent colonic cancer by different CEA assays.

Forty-six patients were followed with serial CEA determinations by two CEA assays after curative resection of a primary or recurrent colonic cancer. Thirteen have had a histologically proven recurrence, of which only six (46 percent) were predicted by both assays, while seven (54 percent) were predicted by one assay only. The assays appear complementary in indicating tumor recurrence, and preliminary findings suggest that it may be beneficial to follow patients with more than one CEA assay after resection of a primary or recurrent colonic cancer.

Phase I/II trial of recombinant methionyl human tumor necrosis factor binding protein PEGylated dimer in patients with active refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the safety, immunogenicity, pharmacokinetics, and efficacy of intravenous administration of tumor necrosis factor binding protein (TNFbp) dimer in patients with rheumatoid arthritis (RA). METHODS: This phase I/II study was a multicenter, randomized, double blind, placebo controlled, ascending dose study evaluating TNFbp dimer administered by i.v. infusion. Thirty-three patients with RA divided into 3 cohorts received TNFbp dimer (30, 100, 300 microg/kg) or placebo during a 5 min infusion at baseline and at 3 and 6 weeks; patients were followed at routine intervals after each infusion through 77 days postinfusion. Pharmacokinetics were analyzed using a log-linear regimen and comparisons were made between half-life after first, 2nd, and 3rd doses. Plasma TNFbp dimer concentrations and serum antibody levels were used in the measurement of pharmacokinetics. RESULTS: Administration of 30 microg/kg of TNFbp dimer was generally well tolerated; the maximum tolerated dose was 100 microg/kg. No serious adverse events were reported. A significant antibody response affected the half-life and clearance of TNFbp dimer at each dose group. Anti-TNFbp antibodies were noncytotoxic and nonagonistic. Clinical evaluations provided evidence of in vivo activity of TNFbp dimer in these patients. CONCLUSION: TNFbp dimer administered to patients with long standing RA resulted in significant antibody production to the study drug. This effect reduced the half-life and clearance of the TNFbp. This TNFbp will not be a viable option for treating patients with RA secondary to immunogenicity.