Roy E. Ritts

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses. Discrimination of benign from malignant disease

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.

A 20-year old women and her infant daughter had recurrent bacterial infections and chronic mucocutaneous candidiasis and were found to have extreme hyperimmunoglobulinemia E, defective neutrophil chemotaxis, and diminished lymphocyte responses to Candida antigen. Studies of members of the mothers family showed mild increases of IgE and mildly depressed chemotactic activity of neutrophils in a brother, the father, and the paternal grandfather. The recurrent bacterial infections in these two patients can be explained by the defective neutrophil chemotaxis. It is not known whether the mucocutaneous candidiasis is related to the neutrophil chemotaxis with the lymphocyte defect being secondary to the Candida infection or, alternatively, the Candida infection being secondary to the lymphocyte defect. Furthermore, the family data suggest a familial pattern of hyperimmunoglobulinemia E and defective neutrophil motility.

An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma

Preoperative serum CA 125 levels were determined for 36 patients with Stage I and II ovarian carcinoma. Levels ranged from 9 to 1962 U/ml with a mean of 216 U/ml. In Stage I patients, CA 125 levels averaged 133 U/ml and in Stage II patients 382 U/ml. Nine of 24 Stage I (38%) and 9 of 12 Stage II patients (75%) had CA 125 levels in excess of 65 U/ml in a population somewhat overrepresented in mucinous tumors. Patients with non-mucinous neoplasms had CA 125 elevations more often--in 75% of the cases--than those with mucinous tumors. A larger study will be required to more precisely estimate the fraction of early stage patients with elevated preoperative serum CA 125 levels; however, this investigation demonstrates an assay sensitivity minimally adequate to initiate a pilot evaluation of serum CA 125 levels in a population at risk for ovarian carcinoma.

A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma

Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression. Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.

CA 125 in gynecologic practice

Serum CA 125 levels were determined in 64 women with benign ovarian lesions, 92 women with uterine fundal lesions, and six patients who had negative second-look laparotomy for epithelial ovarian carcinoma. Of those with benign lesions, 13 of 31 patients with endometriosis had levels greater than 35 U/ml. Six of 34 patients with endometrial carcinoma had elevated levels before the primary operation, and six of 15 patients with recurrent endometrial carcinoma had elevated levels. The six ovarian cancer patients had had negative findings at second look 7 to 40 months before recurrence. Where close serial levels were available, the level became elevated 2 to 5 months before clinically apparent recurrent disease was noted.

Effect of surgery on the quantity of lymphocyte subpopulations

Abstract Surgical procedures cause an equal decrease in the number of peripheral blood T and B lymphocytes. This decrease attained its lowest value in 2 to 7 days with recovery or approaching recovery by 10 days. The percentages of T and B lymphocytes obtained postoperatively do not vary from preoperative values; this indicates an equal depression of lymphocytes rather than selective depression of one of the two lymphocyte subpopulations. Neutrophils increased and eosinophils decreased, attaining average maximum and minimum values, respectively, at 2 days postoperatively with subsequent recovery by 10 days.

A prospective study of immune responsiveness in human melanoma. I. Assessment of initial pretreatment status with stage of disease

The clinical findings in 262 patients with melanoma were correlated with an assessment of their cellular‐mediated immunity by delayed‐type hypersensitivity (DTH) skin tests, by lymphocyte blastogenesis, and by leukocyte enumerations. Patients with systemic metastases (stage IV) and those with evidence of tumor burden had fewer positive DTH reactions for recall antigens than did patients with localized disease (stage I), patients with no evidence of tumor burden, and 227 normal controls. However, no differences were found in the magnitude of response among patients with melanoma or when compared with controls. Patients with melanoma had fewer responses to dinitrochlorobenzene (40%) than did controls (98%), but there were no differences by stage or tumor burden. Similarly, blastogenesis in the presence of PHA, Con A, and PWM was depressed when compared with controls, but there was no meaningful correlation with the clinical status. Leukocyte, T cell, or B cell counts revealed no alteration from normal for the patients with melanoma. The usefulness of these studies for routine clinical monitoring is questioned.

Nonspecific immune determinants in the patient with unresectable gastrointestinal carcinoma.

Assays of immune function (recall skin tests to microbial antigens; total circulating lymphocytes, T‐cells, B‐cells; lymphocyte blastogenesis with PHA, Con A, and pokeweed mitogens; and serum immunoglobulins IgA, IgM, IgG) were obtained in 408 patients with unresectable gastrointestinal carcinoma. The overall patient population, in comparison to normal controls, was characterized by reduced response to recall skin tests, reduced total lymphocyte and T‐cell counts, reduced lymphocyte blastogenesis assays, increased B‐cell counts and increased IgA and IgM. Significant immunosuppression was associated with prior radiation or chemotherapy, and with impaired patient performance status. There was no apparent correlation between extent of clinically evident malignant disease and immune function within this patient population. No assay of immune function matched the prognostic value of the more readily available and less expensive determinations of performance status, serum alkaline phosphatase, or SGOT. Only reactivity to recall skin tests had a significant correlation to patient survival independent of performance status. Among patients with little or no disability, only intensity of skin test reactivity correlated significantly with survival; and among those with greater disability, there was correlation only with proportion of skin tests positive. The combination of candida and streptokinase antigens provided the best recall skin test survival correlation. Adding a third, fourth, or fifth antigen did not add to prognostic value. From an overall standpoint, the immune determinants which we studied do not appear to provide useful additions to the evaluation of the patient with unresectable gastrointestinal cancer.

TRANSFER FACTOR VERSUS COMBINATION CHEMOTHERAPY: A PRELIMINARY REPORT OF A RANDOMIZED POSTSURGICAL ADJUVANT TREATMENT STUDY IN OSTEOGENIC SARCOMA*

Twenty-six patients with classic osteosarcoma were randomized to receive either transfer factor or combination chemotherapy. Eight of 14 patients who received transfer factor converted their skin test markers, evidence of activity of the transfer factor. Of these eight patients, all are alive; four are free of disease. Of the 18 patients who received combination chemotherapy, 14 are alive, 12 of whom are free of disease. The immunologic test procedures performed sequentially reveal that transfer factor appears to enhance cell-mediated immunity, but it is evident that in this study, a control (saline) arm in the protocol could not be included. It is of interest that the chemotherapy regimen used does not appear to suppress such activity permanently. The individual test results, however, are not very helpful for predicting response to treatment. The small numbers of patients and the short duration of this study, combined with the exclusion of parosteal osteogenic sarcomas and jaw tumors, do not permit a meaningful comparison with other published studies.

T-lymphocyte subsets in patients with idiopathic dilated cardiomyopathy

T-cell subsets were measured in the peripheral blood of 33 patients with heart failure from idiopathic dilated cardiomyopathy, 22 patients with heart failure from other causes, and 33 normal controls. Mean T-suppressor cell percentage was 30% in normals, 21% in patients with idiopathic dilated cardiomyopathy whose duration of symptoms was less than 1 year (P = 0.0005), and 26% in those with symptoms for greater than 1 year (P = 0.05). Similarly, percentage of T-suppressor cells in the group with heart failure from causes other than idiopathic dilated cardiomyopathy was significantly lower (23%; P = 0.005) in those with short duration of symptoms. When both heart failure groups were combined those with symptoms for less than 1 year had significantly lower T-suppressor frequencies (22%) than those with symptoms for more than 1 year (P = 0.015). Multivariate analysis identified duration of symptoms and age as the only independent predictors of T-suppressor cell frequencies. Decreased percentage of T-suppressor cells in patients with idiopathic dilated cardiomyopathy may be an epiphenomenon related to duration of heart failure. This should be taken into account in assigning an etiologic mechanism for T-suppressor cells in idiopathic dilated cardiomyopathy.