Arne M. Olsson

Gonadal and sexual function in men treated for childhood cancer.

BACKGROUND Insofar as a majority of children with malignant diseases are cured, the late effects of treatment are of major importance. PROCEDURE A retrospective study was conducted of gonadal and sexual function of 77 adult male survivors of childhood malignancies treated and cured at a single center from 1970 to 1989 and followed for a median of 13 years. The study included an interview, physical examination, sperm test, and hormonal analyses. RESULTS One-third of the patients were treated for hematological malignancies, one-third for CNS tumors, and one-third for other malignancies. Eleven patients required androgen substitution after treatment for tumors of the pituitary-hypothalamic region or acute lymphoblastic leukemia including testicular irradiation and/or orchiectomy. In three patients the testicles were removed. The other eight had small testicles, and those providing sperm samples had azoospermia, and sexual function was disturbed in most of them. Most of the remaining 66 patients had small testicles. Normozoospermia was found in 63%, oligozoospermia in 20%, and azoospermia in 17%. Although there was a highly significant correlation between testicular volume and sperm test, 25% of patients with testicles of <10 ml had normozoospermia. Sexual function was normal in 46 patients, and they were married at a frequency comparable to the normal population. Twenty-one patients had no signs of gonadal dysfunction. CONCLUSIONS Patients treated for tumors in the hypothalamic-pituitary region or treated with testicular irradiation or with high doses of alkylating agents had severe gonadal and sexual dysfunction. Most of the other patients had good prospects for preserved gonadal and sexual function.

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Impotence, Smoking, and β-Blocking Drugs

Four patients complaining of erectile dysfunction and using tobacco or propranolol were examined with penile blood pressure measurements and Doppler recordings, calculating the penile acceleration ratio (PAR). After a change in regimen, erectile capacity was restored, PAR returned to normal, and blood pressure measurements revealed increased systolic penile blood pressure in three patients. The changes, especially in PAR, indicate a marked penile vascular reaction during smoking and beta-blocking treatment in these men.

Accuracy of radiological staging procedures in non-seminomatous testis cancer compared with findings from surgical exploration and histopathological studies of extirpated tissue

Preliminary and reviewed statements describing results from abdominal CT and US were compared with surgical findings and with the report from the histopathological investigation of extirpated retroperitoneal tissue. No false positive diagnoses of retroperitoneal metastases were made by CT investigation, while US made one false positive but revealed metastases in one patient overlooked by CT. The overall accuracies (correct answers/all patients) were 81% with CT and 80% with US (31 and 21 patients in Group I respectively). Surgical exploration alone was no more sensitive than either of the two other methods. CT and US are highly reliable when positive but the risks of obtaining false negative results are considerable.

Progress in identifying clinical relevance of inhibition, stimulation and measurements of poly ADP-ribosylation

Our laboratory, in collaboration with Oxigene Inc, has been involved in identifying commercially feasible clinical applications of measurement or modulation of ADP-ribosylation as a core technology. For this purpose a pivotal regulatory role for ADP-ribosylation in the repair of DNA lesions leading to cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA repair inhibitors, the N-substituted benzamides, has been identified which can react with radiation to produce reactive intermediates that oxidize thiol amino acids. Their proposed mechanisms of action are two-fold: ie they can interact with radiation: i) to directly enhance DNA damage; and ii) to react with thiols in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant formulation of metoclopramide which is an N-substituted benzamide, has indicated enhancement of tumor response and survival in patients with inoperable squamous cell carcinoma of the lung when it was administered as a radiosensitizer in a phase I/II trial and compared to historical controls. A mechanism of endogenous regulation of human mononuclear leucocyte ADP-ribosylation has been identified to be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N-chloramines are potent oxidants of thiol-containing proteins. Quantitative estimation of N-chloramine sensitive plasma thiols has been identified as an effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory inguinal hernia repair compared with short-stay surgery.

Two groups of patients operated on for inguinal hernia, one outpatient group and one inpatient group, are compared with respect to subjective distress and immediate postoperative complications. The groups were chosen at random and matched for sex and age. A large number of those who received treatment as outpatients suffered marked distress during the first postoperative days. Some form of intermediary or light nursing should be tried out for the outpatients so that if necessary they can stay the night after operation at the hospital. The number of postoperative complications was equal in the two groups. With suitable patient selection and with a small number of reserve places in a light-care ward, the majority of inguinal hernia operations can be performed on outpatients, resulting in a considerable economic saving and shorter waiting time.

Advanced Cancer of the Prostate Combined with Hypercalcaemia

Despite the high frequency of skeletal metastases from cancer of the prostate, hypercalcaemia is extremely uncommon in this condition. In two patients with advanced, poorly differentiated metastasizing cancer a fairly uniform clinical picture developed, with anaemia, leukocytosis, increased serum creatinine, thrombocytopenia, elevated alkaline and acid phosphatase levels and symptoms secondary to hypercalcaemia. The development of more effective agents against cancer of the prostate will probably afford longer palliation, but evidently at a risk of severe metabolic disturbances in the preterminal state.

A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous-infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.

Early Clinical Stages of Nonseminomatous Testis Cancer Evaluation of the Primary Treatment and Follow-up Procedures of the Swenoteca Project

During a 5-year period, 588 consecutive patients with nonseminomatous testicular germ cell cancer were included by 16 hospitals into the Swedish-Norwegian Testicular Cancer Project (SWENOTECA). A total of 370 (63%) had early clinical stages (CS1, CS1Mk+ and CS2A), and 345 (93%) of these patients underwent pathological staging (PS) by retroperitoneal lymph node dissection (RPLND). The overall clinical staging accuracy was 75%, with no significant difference between hospitals with low, medium or high patient accrual rate. Addition of bipedal lymphography did not improve the clinical staging accuracy compared to evaluation of the retroperitoneum by CT alone. Tumor serum markers before and close monitoring of the levels after orchiectomy gave valuable information regarding risk of retroperitoneal metastases. After a median follow-up period of 5 years 30 (13.8%) of 217 patients with PS1 disease relapsed, only 3 of them later than 18 months from the RPLND. Short orchiectomy to RPLND time interval, vascular invasion and absence of teratoma elements in the primary tumour were significant predictors of relapse in PS1 cases according to multivariate analysis. Unilateral RPLND was not associated with higher relapse rate than a bilateral procedure, but significantly reduced the risk of dry ejaculation after RPLND. None out of 122 PS2 patients who received adjuvant cisplatin-based chemotherapy after RPLND relapsed, despite the fact that 37 of them had only undergone a unilateral RPLND. Repeated CT examinations and most routine blood tests except serum alpha foeto protein (AFP), beta subunit of human chorionic gonadotropin (HCG) and lactate dehydrogenase (LD) may safely be omitted in the follow-up period for patients who have been pathologically staged with RPLND, provided that effective adjuvant chemotherapy has been given to the PS2 patients.

Cholecystostomy for acute cholecystitis

Summary During the decade 1957 through 1966, sixty-three cholecystostomies in sixty-two patients were performed in the Surgical Department, University of Lund. Fifty-five of these sixty-two patients were followed up. The mean age was seventy-one years for both sexes. The primary mortality was 20 per cent: a third died of circulatory and respiratory insufficiency; three quarters died of peritonitis, abscess, and renal failure; half of the surviving patients had delayed wound healing. The mean hospital stay for the survivors was nineteen days. During the follow-up period, sixteen later required cholecystectomy, nine electively and seven for a recurrence of acute cholecystitis. Nine had another attack of cholecystitis after cholecystostomy. Another four had continuous symptoms; five more died of the gallbladder disease. It is concluded that cholecystostomy should be restricted to very ill patients and should be planned and carried out with the patient under local anesthesia. In all other patients, early primary cholecystectomy should be performed with cholangiography performed during the operation.