How safe is surveillance in patients with histologically low-risk non-seminomatous testicular cancer in a geographically extended country with limited computerised tomographic resources?

In patients with clinical stage I non-seminomatous testicular cancer only limited information is available about the administrative problems with the surveillance programme, in particular if this policy is to be implemented in a geographically extended country with limited computerised tomography (CT) resources. One hundred and two patients with non-seminomatous testicular cancer clinical stage I and low-risk histology (MRC criteria, UK) were followed by the surveillance policy for at least 1 year after orchiectomy (median 47 months, range 21-81 months). Twenty-two patients (22%) relapsed after a median time of 5 months (range 2-18 months), 14 of them in the retroperitoneal space. Serum alpha-fetoprotein and/or human chorionic gonadotrophin were elevated in eight of the 22 relapsing patients. The progression-free and cancer-corrected survival rates were 78% and 99% respectively. Patient non-compliance did not represent a major problem, whereas the regular and adequate performance of necessary CT examinations yielded some administrative difficulties. One and 3 years after orchiectomy about 50% of the relapse-free patients had no psychological problems and were satisfied with the surveillance programme, whereas 46% reported minor and 4% major psychological distress. Despite non-negligible administrative difficulties in geographically extended countries, surveillance is feasible and safe in compliant patients with low-risk non-seminomatous testicular cancer stage I. The responsible cancer centre and the local hospitals should establish a high degree of cooperation and enable adequate follow-up examinations in these patients.     

Gonadal function and fertility in patients with bilateral testicular germ cell malignancy

OBJECTIVE: To evaluate gonadal function and fertility in patients with bilateral testicular cancer (TC). METHODS: In 1999, 63 patients with bilateral invasive TC or carcinoma in situ (CIS) in the contralateral testis completed a mailed questionnaire evaluating their fatherhood (Cases). Their gonadal function had also been assessed after the first orchiectomy for TC before further treatment.The results were compared with those from 174 patients with unilateral TC (Controls). RESULTS: In Cases the post-orchiectomy serum levels of FSH and LH were above those of the Controls (p<0.001). Serum testosterone was similar, whereas sperm concentrations were lower in Cases (p<0.001). In Cases with metachronous invasive TC the level of serum FSH was associated with the interval between the two diagnoses. After the first orchiectomy, 10 of 25 Cases (40%) initiated a pregnancy, in 4 Cases by assisted fertilization. In the Control group 74% of the patients who attempted fatherhood succeeded (p=0.002). CONCLUSIONS: After unilateral orchiectomy for TC elevated serum FSH and/or oligospermia represent a high-risk factor of metachronous bilateral TC or synchronous CIS. At least one-third of these patients attempting fatherhood are successful after the first orchiectomy. Assisted fertilization is often necessary and the overall paternity rate is below that of patients with unilateral TC.     

Treatment and outcome of patients with extragonadal germ cell tumours--the Norwegian Radium Hospital's experience 1979-94.

This report reviews 48 patients who from 1979 to 1994 were treated at the Norwegian Radium Hospital for newly diagnosed noncerebral extragonadal malignant germ cell tumour (EGGCT). Based on histology and/or serum tumour markers, 12 patients had a seminoma and 36 a non-seminoma. At diagnosis, 33 and 15 patients were classified as having abdominal and mediastinal EGGCT respectively. At the time of diagnosis 13 patients, all with non-seminomatous tumours, had metastases to bone, liver or brain. One patient with abdominal seminoma was cured by radiotherapy alone, whereas cisplatin-based chemotherapy (with or without surgery) was planned in the 47 remaining patients. Twenty-seven out of 42 patients receiving four or more chemotherapy cycles were rendered tumour free by induction chemotherapy, including 5 of the 13 patients with extralymphatic non-pulmonal disease. An additional tumour-free patient died of septicaemia after only two cycles of chemotherapy. Late relapses (after > 2 years) were observed in three patients, and a testicular primary was diagnosed during follow-up in three cases. Seven patients died of treatment-related complications, five of these because of neutropenic septicaemia. The median age of these patients was 52 years compared with 35 years in the remaining 41 patients (P < 0.05). The 5-year overall survival for all 48 patients was 60% (95% CI 46-74%) [cancer-specific 5-year survival 71% (95% CI 50-92%)]. EGGCT is a potentially curable disease, even in patients with very advanced disease. Special attention should, however, be devoted to patients above the age of 40 years because of an increased risk of treatment-related side-effects. Late relapses and the subsequent development of testicular tumours indicate the need for long-term follow-up.     

The usefulness of detecting thyroglobulin in fine-needle aspirates from patients with neck lesions using a sensitive thyroglobulin assay

The aim of this study was to assess the diagnostic utility of thyroglobulin (Tg) in fine needle aspirates (Tg-FNAB) of nonthyroidal neck masses using a sensitive in-house method for detecting Tg in washout specimens. A total of 256 samples from 145 patients were evaluated for Tg in washout specimen from FNAB and compared to corresponding cytological smear and histology of 46 surgical specimens. Tg was measured by a sensitive in-house time-resolved immunofluorometric assay. The sensitivity for Tg-FNAB alone or in combination with cytological findings was found to be 100% in both the follow-up group and before primary surgery. In the follow-up group the specificity of Tg-FNAB was 100%. Fifty-nine of 60 follow-up specimens with malignant cytology were Tg-FNAB positive (n = 195). Histological examination of one lymph node with malignant cytology and negative Tg-FNAB showed metastasis from carcinoma of the salivary gland. Tg-FNAB was positive in 25 specimens with suspicious or cystic cytology. Tg-FNAB values were high (median 4557 microg/l, range 122-37200 microg/l) in washout specimen from cystic metastasis from which cytology did not confirm malignancy. Of the 20 lymph nodes with histology confirming metastasis from differentiated thyroid carcinoma (DTC), the Tg-FNAB was positive in 19 and intermediate in one. However, before primary surgery, two Tg-FNABs were false positive compared to the histology of the lymph nodes. TgAb in serum did not interfere with FNAB-Tg measurements. Tg-FNAB measurement is accurate with high sensitivity (100%) and of great importance in detecting cystic metastasis when cytology is not conclusive. Even metastases to small neck lymph nodes may be detected by using sensitive Tg-assay. Serum thyroglobulin antibodies appear to have ignorable effect on the clinical performance of Tg-FNAB.     

Clinical significance of routine follow-up examinations in patients with metastatic cancer of the prostate under hormone treatment

The results of clinical examination, skeletal X-ray, bone scan and phosphatase determinations in serum were analyzed in 30 patients with metastatic prostatic cancer prior to and during anti-androgenic treatment. Bone scan revealed skeletal metastases in all 30 patients, whereas X-ray showed bone metastases in only 22 patients. Radiological pseudoprogression and scintigraphic flair reaction were relatively frequent findings during the first 3-8 months of effective hormone therapy. Later on progressive changes on X-ray and bone scan were well related to clinical progression of the disease and indicated a poor prognosis in the individual patient. Soft tissue metastases most often responded well to the initial hormone treatment, but regrew only rarely during later disease progression. Changes of the radioimmunologically determined prostatic acid phosphatase seemed most often to indicate the presence of advanced disease and subsequent disease progression. Second line treatment of hormone-unresponsive prostatic cancer is at best palliative and has not been proved to prolong the survival in most of the patients. In routine clinical practice, the need for such second line therapy is dependent on the patient's symptoms and not on the early detection of progressive changes on X-ray, bone scan or blood tests. Therefore it seems unnecessary to perform these examinations regularly in hormone-treated asymptomatic patients with advanced prostatic cancer unless the patient is entered into a clinical research program.     

Unexpectedly high serum methotrexate levels in cystectomized bladder cancer patients with an ileal conduit treated with intermediate doses of the drug

The pharmacokinetics of serum methotrexate were studied in 45 bladder cancer patients receiving 250 mg. per m.2 as part of the initial cycle of combination chemotherapy. Serum methotrexate was determined routinely 43 to 49 hours after administration. If the methotrexate levels remained at more than 80 nmol. per l. measurements were repeated daily until the serum levels decreased below this point. The patients were classified into group 1-23 with a bladder in situ and no ureteral obstruction, group 2-11 with a bladder in situ and unilateral hydronephrosis, and group 3-11 who had had cystectomy and ileal conduit diversion before chemotherapy. Of the patients in groups 1 and 2, 5 and 6, respectively, had serum methotrexate levels of 80 nmol. per l. or more 43 to 49 hours after administration, which decreased to below this level on the next day. Of the 11 patients in group 3, 8 had elevated methotrexate levels at the initial determination. Daily methotrexate analyses showed a delayed elimination in 4 of 7 patients and levels of more than 80 nmol. per l. for 3 to 9 days. Low creatinine clearance but, in particular, the previous performance of an ileal conduit predicted high methotrexate levels on day 2 after treatment. The most likely explanation for this observation is the resorption of methotrexate by the small bowel mucosa in the ileal conduit. Patients with an ileal conduit performed 2 years or less before chemotherapy and/or those with a long ileal segment seem to have a particularly high risk for delayed methotrexate elimination. Bladder cancer patients with an ileal conduit who receive methotrexate-containing chemotherapy have a high risk of delayed methotrexate elimination and increased clinical methotrexate toxicity. Leukovorin rescue should be used liberally in these patients together with other prophylactic means (intensive hydration and alkalization of the urine).     

Ultrasound-guided fine needle cytology of retroperitoneal masses in patients with malignant germ cell tumours: diagnosis and therapeutic impact

PURPOSE: There are few reports on the use of fine needle cytology (FNC) for the detection of retroperitoneal lymph node metastases from malignant germ cell tumours (MGCT). In order to determine efficiency of the procedure and its impact on therapeutic approaches, this study reviews experience with ultrasound-guided transabdominal FNC in patients with MGCT. PATIENTS AND METHODS: Twenty-four patients with known malignant germ cell tumour and four patients without previous histology, presented with retroperitoneal masses. They underwent ultrasound-guided fine needle cytology (aspirations were done twice in two patients). Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In metastatic cases, the cytologic findings were correlated with the histology of the primary tumour. RESULTS: Twenty-one of 30 specimens (70%) were diagnosed as malignant, 6 (20%) were benign, and 3 (10%) were unsatisfactory for the cytologic diagnosis. Five of the 21 malignant lesions were < or =10mm. FNC yielded the correct diagnosis in all four cases of extragonadal malignant germ cell tumours. In four other patients, FNC solved significant staging problems at the diagnosis. In 7 of 11 patients with the suspicion of retroperitoneal recurrence and normal serum tumour markers during follow-up, FNC confirmed the malignant morphology of the lesions. CONCLUSIONS: In experienced hands, ultrasound-guided FNC can be a valuable method for the morphological diagnosis of retroperitoneal manifestations from MGCT. FNC should be added in follow-up and staging procedures (radiological imaging and serum tumour markers) in selected patients in whom the histological verification of such lesions is critical for the patient's management.     

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study.

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks'' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.