Ebbe Lindegaard Madsen

Surveillance following orchidectomy for stage I seminoma of the testis

From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.

Effect of prophylactic sucralfate suspension on stomatitis induced by cancer chemotherapy. A randomized, double-blind cross-over study.

We have studied whether mouth-swishing with sucralfate, a well-known gastric mucosal protective agent, may be used as prophylaxis against chemotherapy-induced stomatitis. Using radioactively labelled sucralfate we found that 20-30% was still bound to the oral mucosal lining 2 1/2 h after mouth-swishing. Forty patients receiving cisplatin and continuous infusion with 5-fluorouracil (5-FU) for 5 days entered a double-blind placebo-controlled cross-over study. Among 23 evaluable patients a significant reduction (p = 0.04) in an objective score of edema, erythema, erosion and ulcerations was seen during treatment with sucralfate. Patient preference favored sucralfate, but this preference failed to reach statistical significance (p = 0.06). Seven patients were inevaluable for reasons not associated with the study treatment. However, ten patients did not complete the study since the swishing procedure aggravated chemotherapy-induced nausea. An equal rate of non-compliance was seen with sucralfate and placebo. To overcome this problem, the oral medication should have a neutral taste, the solution should not be swallowed after the swishing, which should not be started until the nausea had ceased.

Anxiety and depression in cancer patients' spouses.

The spouse has been identified as a primary source of support for patients in coping with cancer. Therefore, attention must be given to problems faced by the spouses. In this study, 120 spouses were asked to fill in the Hospital Anxiety and Depression Scale and a questionnaire containing 51 items. A response rate of 83% was obtained. Eighteen percent scored as cases on the anxiety dimension and 6% on the depression dimension. No differences were seen according to sex, age, patients diagnosis, treatment and performance status. Significantly more spouses identified as cases regarding anxiety and depression had problems which they had never talked about, physical symptoms, or feelings of anger. Generally, the level of contact with family and friends was maintained, but the perception of support from family and friends was low. Only 23% sought professional support and only a fraction of the spouses identified as cases did so. Therefore the professional team must be aware of signals from spouses since help seeking does not seem to be part of their coping strategy.

Serum lactate dehydrogenase isoenzyme 1 and tumour volume are indicators of response to treatment and predictors of prognosis in metastatic testicular germ cell tumours

44 patients with metastatic testicular germ cell tumours treated with cisplatin-based chemotherapy were evaluated for prognostic implications of clinical characteristics. 22 obtained complete remission by the initial chemotherapy, and 30 are disease-free. S-LDH-1 had an overall predictive value regarding the response of 80%, S-LDH of 64%, S-AFP of 62%, and S-hCG of 62%. In multivariate analysis regarding response, only tumour volume classified according to the Royal Marsden system (P = 0.0036) and S-LDH-1 (P = 0.0069) yielded information. Regarding survival, S-LDH-1 (P = 0.0141) and an estimate of total tumour mass (P = 0.0171) had most impact with additional information from S-hCG only (P = 0.0536). We conclude that S-LDH-1 may be used as a tumour marker in addition to S-hCG and S-AFP in patients with metastatic testicular germ cell tumour.

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals

Abstract The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis. A reference group of 37 men had a near ln-Gaussian distribution for the absolute S-LD-1 catalytic concentration. The geometric mean was 76 U/l and an S-LD-1 > 128 U/l (99.72 percentile, the decision limit) indicated a high risk of a relapse of TGCT. We have previously shown that an S-LD-1 > 160 U/l (treatment limit) was associated with a suboptimal outcome from the treatment of metastatic TGCT. The maximum allowable analytical positive bias was 5 U/l, and the maximum allowable analytical negative bias was −32 U/l. The maximum allowable analytical coefficient of variation, CVA, was 11 % (≈14 U/l) at a bias = −5 U/l. For S-LD-1 measurements not corrected for hemolysis, the decision limit was 145 U/l, the maximum allowable negative bias −19 U/l, and CVA 8 % (≈12 U/l). A routine correction for hemolysis had a large impact on the analytical quality specifications.

Influence of Adjuvant Irradiation on Shoulder Joint Function After Mastectomy for Breast Carcinoma

The influence of postoperative radiation therapy on ipsilateral shoulder function following mastectomy was evaluated from a series of 52 women with primarily operable carcinoma of the breast. Mastectomy and partial axillary dissection were carried out in all patients. In addition, 29 of the patients received postoperative irradiation with 36.6 Gy applied mid-axillarily in 12 fractions with irradiation twice a week. A significant impairment of the active shoulder mobility was found in the irradiated group (p less than 0.01). The passive mobility did not differ significantly between the two groups. The impairment of active shoulder mobility is suggested to be caused by radiation induced subcutaneous fibrosis.

Serum lactate dehydrogenase isoenzyme 1 as a prognostic predictor for metastatic testicular germ cell tumours

Serum lactate dehydrogenase isoenzyme 1 as a prognostic predictor for metastatic testicular germ cell tumours

Lactate Dehydrogenase Isoenzyme 1 in Testicular Germ Cell Tumors

In his thesis, Zondag (1964) described the lactate dehydrogenase (l-lactate: NAD+-oxidoreductase EC 1.1.1.27, LDH) isoenzyme patterns of human malignant diseases. Among other findings, he drew attention to the characteristic LDH isoenzyme pattern in germ cell tumors, which showed a predominance of LDH isoenzyme 1 (LDH-1), being deviant from those of other cancers. This LDH-1 pattern in tumor tissue has been confirmed in later investigations (Murakami and Said 1984; Takeuchi et al. 1979). Similarly, the serum activity is frequently raised in patients with tumors (von Eyben 1983). The increased LDH-1 level in testicular tumors could be due to polyploidization involving the gene locus encoding LDH-B, as LDH-1 is a homotetrameric combination of this subunit. The LDH-B gene is localized on the short arm of chromosome 12 (12p12.1–12p12.2), and multiple copies of isochromosome i(12p) are often present in human testicular germ cell tumors (Atkins and Baker 1982). The raised tissue LDH-1 could also be related to an increase in the rate of transcription of the LDH-B gene, an increased stability of the LDH-B mRNA, an increase in the translation of the LDH-B mRNA, or a combination of all these factors (Fig. 1).

Vinorelbine as first-line or second-line therapy for advanced breast cancer: a Phase I-II trial by the Danish Breast Cancer Co-operative Group.

Introduction. This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. Patients and methods. Patients had histologically proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks’ schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. Results. Fifty-five patients were included in the dose-escalation study, which defined 40 mg/m2 as the MTD. Neutropenia of short duration and autonomic neuropathy causing constipation were the most common dose-limiting toxicities. At the 35 mg/m2 dose-level 60 patients were included in total. Seven (12%; 95% CI 6 to 22) had a partial response and 16 additional patients had stable disease. 27% had stable disease (clinical benefit rate 38%, 95% CI 27 to 51). The median overall survival was 45 weeks and 39% of the patients were alive after one year. Discussion. The clinical benefit rate was 38% with an overall intention to treat response rate of only 12%. The results were, however, achieved with low subjective burdens of toxicity.

Weekly oral idarubicin in advanced prostatic cancer : a phase II study

Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty-three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment.