Search

Malignant melanoma can occur in various ocular structures and accounts for 70% of all primary eye malignancies. At the time of initial diagnosis of uveal melanoma, most patients have no demonstrable evidence of metastatic disease. However, within 5 years, metastases appear in 19-35% of patients. The median relapse-free interval for these patients is 2-4 years. Unlike cutaneous melanoma, uveal melanoma most commonly metastasises to the liver. In fact, the liver is the sole site or the initial site of metastasis in more than 50% of patients. This paper reviews major studies that evaluated different treatment options for metastatic uveal melanoma, including surgery, systemic chemotherapy, intra-arterial chemotherapy, chemoembolisation and chemoimmunotherapy. Surgery and systemic chemotherapy offer minimal benefits for these patients. However, the use of intra-arterial fotemustine demonstrated a 40% response rate for patients with liver metastases of uveal melanoma. Additionally, chemoimmunotherapy with a four-drug chemotherapy regimen and interferon alfa has provided response rates of approximately 20% and may contribute to prolonged survival. Ongoing multicentre trials are expected to determine the feasibility of this regimen. The activity of immunotherapy, particularly interferon, encourages its use in combination with other active therapies, such as intra-arterial fotemustine.

Oestrogens can regulate immune functions, and due to this females have more effective immune responses than males. Oestrogens and anti-oestrogens enhance T-cell-dependent antibody production of B cells in vitro. The cytokine mediators which are behind oestrogen and anti-oestrogen induced effects are not yet known. The authors studied whether anti-oestrogens (tamoxifen and toremifene) can regulate PMA-induced cytokine production of B-, T- or myeloid cell lines. Anti-oestrogens, tamoxifen and toremifene, stimulated overall cytokine production on a B-cell line (Ball), whereas on a T-cell line (Molt-4) tamoxifen stimulated IL-1 beta, IL-6 and IFN-gamma production and toremifene inhibited it. Anti-oestrogens did not have any significant effect on cytokine production of myeloid cells.

Two hundred and thirty-nine patients with squamous cell carcinoma of the penis were grouped into the existing different clinical classifications and staging systems, i.e. the UICC-TNM (1978 and 1987), Jackson's and that used in Heidelberg. Because of shortcomings observed in the previous systems, a new classification and staging system was developed. The present authors' classification and staging system were found applicable and all patients except 2 with unknown tumor size were classifiable. The distribution into different stages was more even in the proposed staging system than in the previous ones. A good correlation and a gradient for survival rate according to stages were also obtained. We propose that the systems presented should be examined and applied prospectively for clinical classification and staging of carcinoma of the penis.

Tumour markers are molecules occurring in blood or tissue that are associated with cancer and whose measurement or identification is useful in patient diagnosis or clinical management. The ideal marker would occur only in patients with malignancy, and would correlate with stage and response to treatment, however, to date there are few reliable prognostic markers in colorectal cancer (CRC), consequently much research is focused on identifying such markers. This review aims to summarise the most important currently available markers in CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed in tumour tissue such as thymidylate synthase and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices such as apoptotic index is discussed.

To compare the risk of cancer between BRCA1 or BRCA2 mutation-positive and -negative families.We assessed standardized incidence ratios (SIR) in 107 Finnish breast cancer families (12 BRCA1, 11 BRCA2, 84 non-BRCA1/2) with confirmed genealogy. The observed numbers of cancer cases were compared to the expected ones; both numbers were based on the population-based Finnish Cancer Registry.Risk of ovarian cancer for first-degree relatives was high in BRCA1 (SIR 29, 95% confidence interval 9.4-68) and in BRCA2 families (SIR 18. 8.3-35), but not increased for non-BRCA1/2 families (SIR 1.0, 0.2-2.9). The SIR for subsequent ovarian cancer among breast cancer patients was 61 (20-142), 38 (11-98), and 0 (0-4.2), respectively. The risk of subsequent new breast cancer among breast cancer patients was equally high in BRCA1 families (SIR 11, 3.6-26) and in BRCA2 families (SIR 10, 3.3-24) and somewhat lower in mutation-negative families (SIR 3.7, 2.1-6.1). The risk of breast cancer among relatives was markedly increased in all three groups. The only elevated SIR, besides breast and ovarian, was that for prostate cancer in BRCA2 families (SIR 4.9, 1.8-11).The excess risk of breast cancer in non-BRCA1/2 families suggests the existence of another predisposition gene which seems not to be linked with increased risk of ovarian cancer.

Interferon-alpha has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-alpha2a (IFN-alpha) in metastatic renal cell carcinoma (RCC). Interferon-alpha was administered intermittently for outpatients.Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-alpha dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years.The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10-28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed.Prolonged and intermittently administered IFN-alpha2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC.

We evaluate the validity of the family history of breast cancer reported by the patient and the number of families and individuals at risk and potentially benefiting from surveillance. Family history of cancer was systematically screened in three different series of breast cancer patients. Breast cancer families were defined by the selection criterion of at least three first- or second-degree relatives with breast or ovarian cancer (including the proband) and their genealogy and cancer diagnoses were confirmed. Family history of breast or ovarian cancer was reported by approximately 30% of the patients and 7-9% were classified as breast cancer families. On average, there were 3.1 healthy female (age: 20-70 years) first degree relatives per family potentially at high risk. Index patients reported 87% of all confirmed diagnoses and the primary site was correct in 93-95% of the reported cases. The incompleteness and errors in accuracy should be considered in epidemiological studies and verification of the diagnoses is important when deciding clinical management.

Meta-analysis of all clinical data was conducted to compare toremifene 40-60 mg/day (TOR) with tamoxifen 20-40 mg/day (TAM) in postmenopausal women with estrogen receptor (ER) positive or ER unknown advanced breast cancer and assess factors predicting treatment outcome. Data from five randomized parallel group studies (all studies) were combined. Efficacy variables were the response rate in all studies and also the time to treatment failure and survival in the three major studies (pivotal studies). Of the 1421 patients, 725 received TOR and 696 TAM. Response rates were 24.0% and 25.3%, respectively (p = 0.675) with 95% confidence interval (95% CI) for the difference -5.3 to 3.4. Of the 1157 patients in the pivotal studies, 75% had progressed and 50% expired. Median treatment times were 4.9 months in TOR and 5.3 months in TAM groups (p = 0.762, hazard ratio 0.98 with 95% CI 0.87-1.11). Median survival times were 31.0 (TOR) and 33.1 (TAM) months (p = 0.758, hazard ratio 0.98 with 95% CI 0.83-1.15). All results are consistent with the criteria of statistical equivalence between TOR and TAM. More patients in TAM (20%) than in TOR (14%, p = 0.007) discontinued the treatment prematurely but overall the treatments were well tolerated. As the treatments were equally effective all data were analyzed together for predictive factors. High tumor ER concentration, long disease free time, soft tissue metastases, few metastatic sites, and good performance status all independently predicted longer survival (p0.001). Previous adjuvant tamoxifen predicted shorter survival (p = 0.008). Objective response to treatment or disease stabilization for at least 12 months both predicted prolonged survival (p = 0.001). TOR 60 mg/day and TAM are equally effective and well tolerated in the treatment of advanced breast cancer in postmenopausal women. Probability of survival may be predicted based on patient characteristics and on the initial response to the treatment.

46 postmenopausal women with estrogen receptor positive breast cancer entered a phase II study with a novel antiestrogen, toremifene. Patients had either recurrent or primarily inoperable advanced disease. No prior or concurrent cytostatic or hormonal treatment was allowed. Eight patients (17%) achieved complete response (CR), 17 (37%) partial response (PR) and 13 (28%) had stabilization or their disease at least for three months. The mean durations of responses were 52+, 53+ and 27+ weeks, respectively, with 5 patients in CR, 6 in PR and 1 with no change (NC) still continuing the treatment. No significant differences could be seen in response rates according to the concentration of estrogen receptors or presence of progesteron receptors in this group of patients. Toxicity was not a problem, in general, the treatment was well tolerated. Two side effects (sweating and vertigo) were classified as severe and one patient after achieving PR interrupted the treatment because of tremor.

The clinical role of vascularity was examined in metastatic melanoma, analyzing the correlation of the blood vessel density and prognosis. Our study included 51 specimens of metastatic melanoma tissue samples from 31 patients treated with combined chemo-immunotherapy. PECAM-1 (CD31) was used for assessing vascularity by immunohistochemical staining. On the basis of blood vessel counts, patients were classified into 2 main groups: low and high vascularity. A higher blood vessel density was found to be associated with shorter survival, estimated from the primary diagnosis of the disease (38 months), compared with patients with low blood vessel counts (68 months). A similar tendency was observed when vascularity was correlated to the survival period after the detection of the first metastases (13 vs. 30 months) and with survival since the initiation of chemo-immunotherapy (8 vs. 16 months). When vascularity and some common prognostic factors, such as age, sex, DNA ploidy and WHO tumor response, were used for a Cox multivariate analysis, vascularity turned out to be the most significant independent prognostic factor. Our results suggest that counting the blood vessels identified by immunohistochemical staining for the endothelial cell-specific CD31 is a powerful predictor for prognosis in patients with metastatic melanoma and should be considered when selecting patients for therapy.

Summary Background In a randomised trial, patients with renal cell carcinoma (RCC) treated with vinblastine alone or in combination with interferon-α (IFN) were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) prior to and during treatment to elucidate the influence of IFN on these cells, and the association of the change in the CD4+/CD8+ ratio with treatment outcome. Patients and methods Blood samples were systematically obtained from 30 patients receiving either vinblastine or vinblastine + IFN-α-2a. Flow cytometry was used to detect CD4+ (T-helper) and CD8+ cells (T-suppressor) with monoclonal antibodies. Results Increasing CD4+/CD8+ ratios were seen in 10 of 17 patients in the vinblastine-IFN group and in 7 of 13 patients in the vinblastine group. Two of three patients achieving a complete response with the vinblastine-IFN treatment showed a dramatic increase in CD4+/CD8+ ratio concomitantly with regression of all metastases. Those treated with vinblastine-IFN who showed an increasing ratio had a better median survival (not reached at 28 months of follow-up) compared to those with a decreasing ratio (6.3-month survival) (P = 0.0037, log-rank). No such difference occurred in patients treated with vinblastine alone. In the multivariate analysis, the increase in CD4+/CD8+ ratio was the most important prognostic factor. Conclusion In a proportion of patients receiving an interferon-based therapy, IFN seems to influence the host’s immune system, resulting in an increased CD4+/CD8+ ratio concomitantly with tumour regression. Changes in the CD4+/CD8+ ratio of patients with metastatic RCC receiving such therapy, may provide valuable prognostic information and a basis for future improvements of immunotherapy.

Angiogenesis of human melanomas has been the focus of intense interest since it was shown that the spread and prognosis of primary tumors is correlated with their vascularization (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1-8, 1991). Basic fibroblast growth factor (bFGF) and its high-affinity receptor FGFR-1 have been implicated in melanoma growth and angiogenesis (R. Halaban, Y. Funasaka, J. Lee, J. Rubin, D. Ron, and D. Birnbaum, Fibroblast Growth Factors in Normal and Malignant Melanocytes, pp. 232-243. New York: The New York Academy of Sciences, 1991). We have studied the expression of the Tie endothelial cell receptor tyrosine kinase mRNA in skin and primary cutaneous melanomas as well as in their skin and brain metastases by in situ hybridization. The Tie probe hybridized very weakly with the vascular endothelium of capillaries of normal skin, while it was detected in larger arteries and veins as well as in capillaries around sweat glands. However, capillaries and medium-sized vessels within cutaneous and brain metastases of melanoma were strongly positive for Tie mRNA. In contrast, endothelial cells contained very little or no FGFR-1 transcripts, whereas abundant FGFR-1 mRNA was present in melanoma tumor cells and in fibrovascular stroma. In agreement with these findings, a Tie-specific amplified cDNA band was obtained by reverse transcription-polymerase chain reaction from melanoma metastases but not from normal skin. These results suggest a role for the Tie receptor in the angiogenesis associated with melanoma metastases.

We performed in situ hybridization (ISH) studies of malignant pleural mesotheliomas to detect numerical aberrations of chromosomes 1 and 7 in interphase nuclei of paraffin sections of 13 cases that had been analyzed previously by conventional karyotyping and flow cytometry. The hybridizations were performed with the biotin-labeled probes recognizing repetitive DNA sequences in the (peri)centromeric regions of chromosomes 1 (1q12) and 7(7cen). Application of histologic sections allowed us to analyze the tumor cells only. Comparison of the karyotype and ISH studies showed that the same chromosome copy numbers were detectable by both methods in 13 (chromosome 1) and in 12 (chromosome 7) cases evaluable by ISH. DNA indexes determined in the paraffin-embedded tumor material corresponded with the ISH findings. As compared with karyotype analysis, ISH showed a larger heterogeneity in chromosome copy numbers. The results can be divided into three groups: 1) Monosomy or disomy of chromosomes 1 and 7 was detected by both methods in two cases; 2) in four cases, disomy of both chromosome 1 and 7 was observed in most of the cells by ISH analysis, and karyotype analysis had shown clear polyploidization in three of these cases; 3) in seven cases, supernumerary copies of chromosomes 1 and/or 7 were present in an evident fraction (27-80%) of the cells analyzed by ISH, and karyotype analysis confirmed the aberrant copy numbers in five of these cases. On the other hand, ISH showed copy numbers not detected by karyotype analysis in six of the seven cases. Thus, by combining karyotype and interphase cytogenetic studies, complementary information about chromosomal aberrations in mesothelioma is obtained.

16 patients with disseminated malignant melanoma (1 with primary ocular melanoma) entered a multicentre phase II study of recombinant interleukin-2, (rIL-2) given by continuous intravenous infusion on days 1–5 at 18 × 10 6 IU/m 2 per day, followed by dacarbazine 850 mg/m 2 on day 8. After a 2 week rest, a second course was given. In the absence of disease progression, monthly maintenance cycles were given for up to four cycles. 16 patients received one cycle, 14 received two and 6 patients three or more. All 16 patients are evaluable for toxicity and 15 for response. 2 patients responded (13%). 1 patient with lung and pleural metastases achieved partial remission after two cycles and went off treatment after six cycles. 3 months later a complete response was noted lasting 396+ days. A second patient with lung metastases had a partial response lasting 153 days. 3 patients (20%) had stable disease. Mean rebound lymphocytosis (24–48 h after the end of rIL-2 therapy), cell count 4.9 × 10 9 /l (2.6–8.8 × 10 9 /l) was within the expected limits. Other toxicity was as expected. Thus sequential treatment with rIL-2 and dacarbazine is feasible but synergy did not occur.

Summary— A system of histological grading based on retrospective analysis of 239 patients with squamous cell carcinoma of the penis is presented. A new scoring system with 4 histological grades was used. The results of this study confirm previous reports that penile cancer is usually a highly (50%) or moderately (29%) differentiated squamous cell carcinoma. Poorly differentiated carcinomas and cancers of other types are very rare. The new grading system was found to be practical and a correlation between histological grade, clinical findings and prognosis was established. Patients with grade 1 tumours had an exceptionally favourable prognosis, with more than 80% being long-term survivors; for these patients, treatment with delayed side effects should be avoided and new forms of treatment should be explored.

Fourteen postmenopausal women with estrogen-receptor positive advanced breast cancer and no prior cytostatic treatment received 20 mg toremifene daily as a single dose after a loading dose (120----60----60 mg) for the first 3 days. All were evaluable and had undergone at least 6 weeks' treatment. Results were: no complete remissions (CR), 3 partial remissions (PR), 8 no change (NC) and 3 cases of progressive disease (PD). Three patients had mild side effects: nausea, insomnia, sweating and arm pain.

A series of 41 individuals were restudied after childhood cancer with a median follow-up time of 17 years after chest irradiation or treatment with cyclophosphamide or Adriamycin (doxorubicin). Radiotherapy of the chest had been used in 21 patients, and in 13 of these irradiation was also directed at the heart. Thirty-five patients received cyclophosphamide and five received Adriamycin therapy. All patients were investigated by a pediatric cardiologist. Investigations included an electrocardiogram (ECG), a chest radiographic film, an echocardiogram, an exercise test, and a 24-hour ECG. Altogether 20 patients (49%) showed some abnormality in cardiac tests. Each additional year of follow-up was associated with a 1.3-fold (95% confidence limits, 1.04-1.66; P less than 0.05) increase in the risk for pathologic cardiac findings. The risk for an abnormal cardiac test result in the 13 patients who had received cardiac irradiation was 12.8-fold (95% confidence limits, 1.8-90.8; P less than 0.02) that of the other patients. However, abnormalities in cardiac function were mild.

To analyse the epidemiological aspects contributing to the transmission of human papillomavirus (HPV) lesions (flat, inverted, and papillomatous condylomas) of the uterine cervix, we recorded the sexual behaviour of 146 women who consecutively attended the department of obstetrics and gynaecology of Kuopio University Central Hospital with a cervical HPV lesion (with or without concomitant cervical intraepithelial neoplasia (CIN]. Similar data were collected from an age matched group of women with no signs of gynaecological infection. The sexual habits of the women infected with HPV differed from those of healthy controls in most aspects studied, including an earlier onset of sexual activity (p less than 0.05), lower number of deliveries (p less than 0.05), less regular use of contraceptive measures (p less than 0.05), and use of the condom instead of intrauterine contraceptive device (IUCD) (p less than 0.0001). They also differed from controls in giving histories of more frequent episodes of: CIN (p less than 0.005), abnormal Pap (Papanicolaou) smears (p less than 0.0001), sexually transmitted disease (STD) (p less than 0.05), and genital warts (p less than 0.001). Furthermore, they had more multiple sexual partnerships (both past and current) than the controls (p less than 0.0001 and 0.005 respectively), they had not established permanent partnerships as often as the controls (p less than 0.001), and they had a higher frequency of casual relationships (p less than 0.0001). In addition, their own and their partners' sexual hygiene was poorer than in the control subjects (p less than 0.05 and 0.001 respectively). The results show the dramatic influence of sexual behaviour on the transmission of cervical HPV lesions, which are known to be intimately associated with CIN in many cases.

A double-blind field trial was performed comparing a subunit influenza vaccine (A/Victoria/75 and B/Hongkong/73) with placebo. A good protection against influenza was induced by the vaccine. On the basis of serological determinations (enzyme immunoassay, EIA) the incidences of influenza A and B infections were reduced within a period from 3 weeks up to 5 months after the vaccination by 88 and 68%, respectively. Three weeks after the vaccination 79% of the vaccines had acquired protective serum antibody levels (greater than or equal to 32 x 10(2) by EIA) against influenza A and 62% against influenza B, while in the control subjects protective antibody levels were measured in frequencies from 4 to 13% in subsequent serum samples. With a few exceptions antibody levels were still present in 5-month samples. Side effects were recorded within the first 3 days following the vaccination. Some minor symptoms like redness and tenderness at the vaccination site and muscle ache were reported more frequently by the vaccines than by the controls, but no more harmful systemic reactions.

Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 per cent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 per cent (10/97) and of the pig sera 13 per cent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 per cent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus.

A 27-year-old man had had Fanconi's anemia (FA) for 20 years. The patient had pancytopenia, retarded growth, hypogonadism, and chromosomal aberrations. He had freckle-like and darker pigmented macules scattered on his chest, shoulders, upper part of the back, and hips, with interspersed, hypopigmented areas. Biopsy specimens taken from both the hyperpigmented and hypopigmented spots showed a derangement of keratinocytes and nuclear abnormalities, more notable on sun-exposed skin sites. The patient also had numerous tumor-like, recalcitrant, viral warts. Immunologic studies showed normal humoral immunity, but there was evidence of depressed cell-mediated immunity. We speculate that the chromosomal aberrations, the depressed cell-mediated immunity, and the increased frequency of malignant neoplasms known to occur in patients with FA also reflect changes related to an increased susceptibility to viral infections.

The subrenal capsule assay (SRCA) in normal immunocompetent mice was performed from 1331 implants of 43 human colorectal carcinomas to evaluate the possible applications for clinical chemosensitivity testing. Also the effect of an immunosuppressive agent, cyclosporine, was tested on the growth of tumours. Histologically in all except one of 23 saline-treated tumours the original tumour tissue was replaced by granulation tissue and inflammatory cells. This was also true in cyclosporine-treated mice since in only one of the nine tests tumour cells were observed. The macroscopic growth of the implants in the cyclosporine-treated mice was significantly less than in the saline-treated mice. Flow cytometric DNA-analysis revealed that the difference between macroscopic growth of saline and cyclosporine-treated groups was observed only in DNA-diploid tumours. We conclude that new methods are required to preserve the viability of human colorectal carcinoma in the SRCA.

Warts were found in 25 out of 56 patients with definite or probable systemic lupus erythematosus (SLE) but in only 19 out of 160 control patients. Warts were particularly prevalent in elderly patients with SLE. The corticosteroid and antimalarial drugs used to treat SLE did not influence the frequency of warts. Wart-virus antibodies were found significantly less often in patients with SLE than in controls: antibodies were detected in 23 out of 51 patients and in 40 out of 54 controls. Ihe findings suggest that some deficiency in the immune mechanisms of patients with SLE predisposes them to develop warts. There was an inverse correlation among the patients with SLE between the occurrence of warts and rheumatoid factor activity. This suggests that rheumatoid factor may interfere with resistance to warts.

Common aetiopathogenic factors were sought in 12 patients with progressive pulmonary apical fibrocystic changes, active human-type tuberculosis excluded. HLA-typing did not reveal any clear-cut trends; only the three patients with ankylosing spondylitis or Reiter's disease were HLA-B27 positive. Six patients had HLA-Cw3, which exceeds the prevalence in referents, antibodies, as well as other tissue antibodies, were mainly negative so that autoimmune aetiology is not likely. Similarly, antimicrobial antibodies were found occasionally, while low-titred influenza antibodies were positive in all patients. Serum proteins, immunoglobulins, rheumatoid factor and C-reactive protein were suggestive of chronic inflammation, as were low positive titres of smooth muscle antibodies in nine patients. In spite of the uniform clinical picture and course of the disease, no uniform aetiopathogenic factors were found, but possible unidentified slow- and low-grade viral or fungal infection is discussed.

Serum immune complex (IC) and rheumatoid factor (RF) levels of 39 patients with a transitional cell tumour of the bladder were analyzed using 4 different IC and 2 RF assays. Elevated serum immune complex and rheumatoid factor levels were observed in the majority of the patients (95%). Conglutinin-binding (KgB), C1q-binding (C1qB), platelet iodinated protein A test (PIPA) and RF-enzyme immunoassay (RF-EIA) gave positive results in 31%, 62%, 23% and 31% of the cases, respectively and separated cancer sera from normal blood donors (p less than 0.001). Elevated titers were also observed with platelet aggregation test (PAT) and latex agglutination for RF in 23% and 67% of the cases, respectively. A negative correlation (p less than 0.01) was observed with the stage of the disease and RF-values. Other IC tests did not correlate significantly with stage, histological grade or progression of the disease. The best prognostic marker was the histological grade of the tumour. Males had more undifferentiated tumours than females. Multivariate analysis was carried out to correlate several laboratory parameters simultaneously with clinical variables and it revealed that elevated IC tests values (KgB, C1qB and PIPA) and low RF-values correlated to stage (p = 0.009) but not to histological grade or progressive course of the disease.

The effect of Tigason (etretinate) in the prevention of the recurrence of superficial bladder tumors (Ta-T1, grade 0 papilloma and grade 1 and 2 carcinoma) was studied in 30 patients in a double-blind, placebo-controlled study. Before beginning treatment, the bladder was cleared from all visible tumors by electrocoagulation or TUR. The duration of treatment ranged from 10 to 26 months. The overall preventive effect was significantly better (p less than 0.01) in Tigason-treated patients than in patients given placebo. Tigason was more effective in preventing the recurrence of grade 1 and 2 carcinoma than placebo. On grade 0 papilloma this difference was not so marked. Side effects were common and disturbing at high doses (50 mg/day), but Tigason was well tolerated at the final maintenance dose (25 mg/day). The results obtained from this first clinical study with Tigason in the prevention of recurrence of superficial bladder tumors are promising.

Serum antibodies against BK virus (BKV) and seven other viruses were studied in 76 patients with renal cell carcinoma using either the haemagglutination inhibition or the complement fixation techneque. BKV and herpes simplex virus (HSV), but no other virus antibodies, showed a clear correlation with the clinical course of renal carcinomas. The patients without BKV antibodies or with marginal antibody titres (titre less than or equal to 10), had a significantly longer observed expectation of life (O.E. life, 44.1 months) than the O.E. life (26.7 months) of the patients with BKV antibodies of titre less than or equal to 20. Similarly, patients with low or undetectable HSV antibodies (titre less than or equal to 8) also had significantly longer O.E. life (54.0 months) than the rest of the patients (32.7 months). The results suggest that BKV and HSV have an as yet underfined relationship to renal cell carcinomas.

Human cryo-IgM rheumatoid factor (RF) preparations blocked the tumor-specific in vitro cytotoxicity of ovarian or bladder carcinoma patients' lymphoid cells in microcytotoxicity assays. The effect was mediated by pretreatment of the effector cells. Cryo-IgM RF free of detectable IgG blocked in a dilution-dependent manner, and immunosorbent purification of contaminating IgG from another preparation did not abrogate the blocking effect. Control IgM preparations lacking RF activity did not block the cytotoxicity, and normal human serum preincubation of the RF preparations rendered them inactive, indicating that the blocking effect was due to the anti-IgG activity of the RF.