Jan G. Aalders

CA-125 - A USEFUL MARKER IN ENDOMETRIAL CARCINOMA

In a retrospective study 121 patients with endometrial cancer were examined. In addition, 20 primary endometrial adenocarcinomas were tested immunohistochemically for CA 125. All tumor tissues were demonstrated to contain CA 125. However, only 25% of 110 patients had elevated CA 125 levels in serum before treatment. The incidence of elevated CA 125 serum levels increased with higher tumor staging up to 55% and 86% in surgical Stages III and IV, respectively. In Stage I and II disease (International Federation of Gynecology and Obstetrics) elevated serum levels before treatment correlated with the presence of tumor tissues outside the uterine body or outside the uterus, respectively, as was determined histopathologically after operation. In addition a close correlation between elevated levels and vessel invasion of tumor cells was revealed. Serum levels of CA 125 paralleled the clinical course of disease. Tumor recurrence in the abdomen can be preceded by an increase of serum CA 125 levels.

Squamous cell carcinoma of the vulva: A review of 424 patients, 1956–1974

Abstract A total of 424 patients with squamous cell carcinoma of the vulva have been followed 3–21 years. The cases were reviewed according to the FIGO, TNM, and the Friedrich staging systems. The FIGO system seemed to be the most useful in predicting prognosis. There was also a good correlation between the FIGO stages and the occurrence of metastases. In stage I 10.5% lymph node metastases were found as compared to 29.8% in stage II, 66.0% in stage III, and 100% in stage IV. The 5-year actuarial survival rate for the total series was 67.0%, 93.0% in stage I, 75.0% in stage II, and 50.0% in stage III. Radical vulvectomy with bilateral inguinal lymphadenectomy was the standard primary treatment during the study period. In stage I lesions less radical procedures are recommended. If metastases to the lacunar and/or Cloquet glands are found, the patient may benefit from high-voltage irradiation against the inguinal region and the pelvic lymph nodes.

Cancer of the uterine cervix: Sensitivity and specificity of serum squamous cell carcinoma antigen determinations

Between 1978 and 1989, 451 patients with cervical squamous cell carcinoma were referred to our department, of whom 143 experienced persistent or recurrent disease. Serial serum samples of the patients were analyzed for the presence of squamous cell carcinoma antigen (SCC). The incidence of elevated pretreatment serum SCC levels ranged from 37% in stage IB (N = 173) to 90% in stage IV (N = 19). Multivariate analysis showed that deep stromal infiltration and lymph node metastases were associated with significantly higher serum SCC levels. Serum SCC trends correlated with the course of disease: after treatment the sensitivity (percentage positive results in patients with persistent disease) was 79% and the specificity (percentage negative results in patients with no evidence of disease) was 91%. During follow-up, the sensitivity of the assay was 85.5% in patients with recurrent disease. However, the positive predictive value of a single serum SCC value greater than 2.5 ng/ml for tumor recurrence was only 49%. This figure rose to 76% when two consecutive elevations were determined. Stage and pretreatment serum SCC level were the only factors found to influence survival, using Coxs regression analysis with five pretreatment variables.

Malignant struma ovarii treated by ovariectomy, thyroidectomy, and 131I administration

A 36‐year‐old woman presented with an intraperitoneally disseminated malignant struma ovarii, diagnosed by histopathology and 131I scintigraphy. The serum thyroglobulin level was elevated, and immunoperoxidase staining for thyroglobulin was positive for disease both in the tumor cells lining the follicles and in the colloid. The patient was treated successfully by a bilateral ovariectomy followed by a total thyroidectomy and administration of radioactive iodine. The clinical behavior and the presence of thyroglobulin in both serum and tumor tissue demonstrate the similarity between neoplastic thyroid tissue in the ovary and in the thyroid gland.

Clinical Value of Routine Serum Squamous Cell Carcinoma Antigen in Follow-Up of Patients With Early-Stage Cervical Cancer

PURPOSEnTo investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients.nnnPATIENTS AND METHODSnFollow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit.nnnRESULTSnRecurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found.nnnCONCLUSIONnSerum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

Serum CA 125 levels in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence.

Summary. Pre‐operative serum CA 125 levels were elevated (>35U/ ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second‐look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (< 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second‐look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1–17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of < 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.

PROGNOSTIC-SIGNIFICANCE OF SINGLE VERSUS MULTIPLE LYMPH-NODE METASTASES IN CERVICAL-CARCINOMA STAGE IB

From January 1, 1970, to December 31, 1985, 51 patients with stage IB (FIGO) carcinoma of the cervix with lymph node metastases were treated at the University Hospital, Groningen, The Netherlands. The survival rate was 54% and the average duration of follow-up was 78 months (range 47-132). Important clinical variables for survival were investigated retrospectively: the survival rate in patients with a single lymph node metastasis (with tumor confined to the node itself) (n = 23) appeared to be much better than that of patients with multiple node involvement and/or single nodes with extranodular tumor infiltration (n = 28); survival was 85 and 24%, respectively (P less than 0.001). The same applied to patients with only occult lymph node involvement: the survival rate in patients with occult involvement of the hypogastric, external iliac, or obturator nodes was 87% in 19 patients with a single metastasis and 53% in 15 patients with multiple node involvement (P less than 0.02). The survival rate in 8 patients with adenomatous histological components was 42%. In 42 patients with squamous cell carcinoma, the survival rate was 56%. This difference was not statistically significant. Treatment complications and the effect of treatment on the site of recurrence were investigated.

Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment

PURPOSEnTo analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery.nnnMETHODS AND MATERIALSnOf 114 patients with cervical cancer Stage IB-IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome.nnnRESULTSnBefore treatment, SCC antigen was elevated (>1.9 microg/L) in 60% and CYFRA 21-1 (>2.2 microg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p < 0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p = 0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p = 0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS (p = 0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty-seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%.nnnCONCLUSIONSnIn patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional salvage surgery. SCC antigen proved to be superior to CYFRA 21-1 in predicting DFS and disease recurrence.

High-dose chemotherapy with autologous bone marrow transplantation in patients with refractory ovarian cancer

Eleven patients with persistent ovarian cancer after remission-induction chemotherapy were treated with high-dose cyclophosphamide and etoposide followed by autologous bone marrow transplantation (ABMT). Six complete responses (CR), of which five were pathologically confirmed, were achieved in eight patients who had microscopic or residual disease less than or equal to 2 cm at the start of high-dose chemotherapy. The median duration of response was 15 months with two sustained CRs after respectively 43 and 75 months. None of the three patients with residual disease greater than 2 cm responded. The median survival measured from the start of the ABMT regimen was for all patients 23 months. These results suggest that high-dose systemic chemotherapy followed by ABMT is a therapeutic option in patients with refractory ovarian cancer deserving further investigation.

Vulvar melanoma - Is there a role for sentinel lymph node biopsy?

The objective of this study was to evaluate the authors recent, preliminary experience with the sentinel lymph node procedure in patients with vulvar melanoma and to compare this experience with treatment and follow‐up of patients with vulvar melanomas who were treated previously at their institution.