Human milk fat globule antigen 1 (HMFG1) expression in prostatic carcinoma and immunotargeting with a radiolabelled monoclonal anti-HMFG1 antibody.

BACKGROUND: Prostatic cancer is the leading cause of death in Swedish men. Approximately 50% have disseminated disease at diagnosis. Radiolabelled antibodies could possibly be a treatment modality for disseminated prostatic cancer, so that in this study the expression of the human milk fat globulin 1 (HMFG1) antigen in prostate cancer was examined. MATERIALS AND METHODS: An immunohistochemistry technique with a murine monoclonal antibody was used, as well as the human prostate cancer cell line DU-145, which expresses this cell surface antigen. TUR specimens from patients with prostate cancer were also examined. RESULTS: Eighteen out of 22 (82%) patients exhibited an HMFG1-positive tumour. An inhomogenity in the immunostaining could occasionally be seen, with smaller apparently negative areas. The immunolocalisation properties of the antibody were investigated using a radiolabelled antibody injection into nude mice bearing heterotransplants of the DU-145 cell line. The highest accumulation of the antibody was seen in the tumour tissue and the liver. CONCLUSION: The results obtained form a basis for further investigations with the goal of using the antibodies for staging and therapy for prostate cancer.

Value of sextant biopsies in the assessment of local cure following external beam radiotherapy of prostatic adenocarcinoma.

Between 1982 and 1992, 73 patients received radical external beam radiotherapy (EBR) for prostatic adenocarcinoma at the Central Hospital, Västerås, with an average dose of 68.1 Gy (range 64.5-72.5 Gy) and an average cumulative radiation effect (CRE) of 18.2 (range 17.1-19.9) All patients had a negative bone scan prior to treatment and presented with clinical stage T1-T4,Nx,Mo. Twenty-four out of 36 surviving patients consented to participate in a follow-up study which included transrectal, ultrasonically guided prostate biopsies. The average follow-up from EBR to biopsy was 5.5 years (range 3.6-11.1 years). Sixteen (67%) of the patients had a positive biopsy. The average PSA level in the biopsy-positive group was 35.7 ng/mL (range 3.9-200 ng/mL). In the biopsy-negative group, the average PSA was 3.7 ng/mL (range 0.2-13.0 ng/mL). The conclusion is that the degree of local cure achieved in patients with prostatic cancer treated with external beam radiotherapy is low (33%), and that a higher radiation dose may be required to eradicate this malignancy.

Expression of p21 and mutant p53 gene products in residual prostatic tumor cells after radical radiotherapy.

BACKGROUND: In a previous study, sextant core biopsies revealed residual tumor in the prostate in 37/55 investigated patients, with an average of 6.8 years after external beam radiation therapy (RRT). More than half of the biopsies exhibited Ki-67 and PCNA proliferation activity. METHODS: The present study aims at further characterizing residual tumor cells post-RRT by investigating whether the tumor cells exhibit immunohistochemical expression of p21 and mutant p53 gene products, which reflect the state of cell cycle regulatory mechanisms. RESULTS: Positive p53 staining was observed in 11% and p21 positivity in 47% of biopsies. The proportion of positively stained cells was low for both antigens. The staining patterns point to the existence of wild-type p53-dependent, as well as alternative pathways for p21 protein induction. CONCLUSIONS: A low proportion of tumor cells exhibited p53 protein accumulation post-RRT. G1 arrest, as assessed by p21 immunoexpression, was demonstrated in a low percentage of tumor cells in < 50% of post-RRT biopsies, indicating that the vast majority of residual tumor cells following RRT escape the G1/S checkpoint control and propagate into S-phase, presumably with a maintained malignant potential.

Characterization of residual tumor cells following radical radiation therapy for prostatic adenocarcinoma; immunohistochemical expression of prostate-specific antigen, prostatic acid phosphatase, and cytokeratin 8.

BACKGROUND: Our knowledge about the nature and biological activity of tumor cells residing in the prostate gland after radical radiotherapy (RRT) is limited. METHODS: In the present study, residual tumor in core biopsies taken from 37 patients after an average of 6.8 years follow-up after radiation, were investigated with immunohistochemistry for the biochemical markers prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial marker, cytokeratin 8 (CK8). RESULTS: Tumor cells were cytokeratin-positive in 33 of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in 94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation was observed between PSA/PAP expression and tumor grade after treatment. Endocrine treatment administered in addition to RRT in 12 of the 37 patients did not affect the expression of PSA or PAP. The expression of both biochemical markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and post-treatment specimens were available. CONCLUSIONS: Tumor cells retain their epithelial characteristics immunohistochemically after radiation, though their morphology sometimes suggests an altered phenotype after treatment. PSA and PAP reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy, which indicates that these cells maintain their biochemical integrity and protein synthesis to a certain extent. Furthermore, endocrine treatment did not abolish PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression provides independent prognostic information needs to be further investigated.

Assessment of proliferation indicators in residual prostatic adenocarcinoma cells after radical external beam radiotherapy.

BACKGROUND: Fifty-five patients who had received radical external beam radiotherapy (RRT) for clinically staged, localized prostatic adenocarcinoma were examined with systematic sextant mapping with the help of transrectal ultrasound-guided core biopsies. The average follow-up after RRT was 6.8 years. Residual cancer was found histopathologically in 67% (37/55) of the patients investigated. METHODS: In the present report, the viability of these tumor cells was studied using immunohistochemical staining methods with the monoclonal antibodies MIB1 and PC10, which are specific for the proliferation-associated antigens Ki-67 and PCNA. RESULTS: Available data concerning proliferating activity in the pretreatment situation in 12 of these patients revealed that proliferating activity was substantially reduced in the majority of cases after RRT. Post-RRT, Ki-67, and PCNA activity was nonetheless found to varying degrees in 64% and 94% of the 36 evaluable tumor-harboring specimens, respectively. In the majority of cases, the proportion of proliferating cells, designated "score", was low. However, Ki-67 scores of up to 8% and PCNA scores of up to 50% were obtained in 35% (8/23) and 97% (33/34) of the specimens, respectively, with proliferative activity. There was no significant correlation between tumor grade and proliferative score in the follow-up biopsies. In the 36 cases investigated, endocrine treatment did not influence the proliferation results. CONCLUSIONS: The present study demonstrates a proliferative capacity in residual tumor cells in a long-term follow-up after RRT, suggesting that these cancer cells might have a biological significance.

Adverse effects after radical external beam radiotherapy of localized prostatic adenocarcinoma using two-dimensional dose-planning and a limited field technique.

Adverse effects were assessed after definitive limited field, 2-dimensional CT-planned radiation treatment of localized prostatic adenocarcinoma. In 66 surviving patients, out of a total of 176 treated patients, personal interviews were performed and self-administered questionnaires distributed. The average follow-up was 6.6 years. Adverse effects with regard to bowel function and micturition were investigated, and graded 0-4 with increasing severity and impact on performance status, essentially according to the RTOG toxicity scoring system. Sexual functions were registered on visual analogue scales. The majority of adverse effects were considered minor (grade 1) and did not require any treatment. Late adverse effects on bowel and bladder or urethra that required treatment (grade 2-4) were reported in up to 8% (n = 5) of cases respectively. Late bowel side-effects that interfered with life style (grade 3-4) occurred in up to 3% (n = 2) of patients; the majority were rectal complications. Corresponding urinary side-effects were registered in up to 6% (n = 4) of the patients. Major surgical interventions were not required. Sexual functions were substantially affected in 60% of cases not administered endocrine treatment. Multivariate analyses could not identify patient or treatment risk factors related to complications.

Transrectal ultrasonically-guided core biopsies in the assessment of local cure of prostatic cancer after radical external beam radiotherapy.

Fifty-five patients were included in an extended follow-up after radical radiation therapy (RRT) for localized prostatic cancer (T1-3, Nx, M0). Local cure was assessed by a combination of digital rectal examination (DRE), transrectal ultrasound (TRUS) and systematic 'mapping' with TRUS-guided core biopsies (TGCB). After a mean follow-up of 6.8 years, 33% (18/55) of the patients were locally free of tumour, while in 67% (37/55) of cases residual cancer was demonstrated in the biopsies. Endocrine treatment did not influence the local cure rate, nor did the T stage of tumour grade at diagnosis or the cumulative radiation effect (CRE) values within the range of the present study. The sensitivity of DRE and TRUS was low; 37% and 20% respectively, while the specificity of the DRE and TRUS methods was 83% and 94% respectively. The conclusion of the study is that residual tumour was found in the high proportion of biopsied patients nearly 7 years after RRT and that multiple, TRUS-guided core biopsies are mandatory in the assessment of local cure in patients irradiated for prostatic cancer; both DRE and TRUS on their own are less reliable.

The symmetry of the breasts in normal and scoliotic girls.

Mammary asymmetry was estimated visually by different investigators in three series of scoliotic girls and in three control groups. The breasts of each girl were classified as being equal in size or as being obviously different in size, note being made of which breast was the larger. Breast asymmetry was significantly more common among the scoliotic than the normal girls. Moreover, the left breast was significantly more often larger in the scoliotic series of girls. On the other hand, there was no significant difference in the frequency of breast asymmetry in respect of the classifications according to curve type (right convex thoracic vs. other types) and to Cobb angle (35 degrees or less vs. more than 35 degrees).

Anthropometric data relating to normal and scoliotic Scandinavian girls.

The increase in height and weight and the age at the menarche have been determined in girls with idiopathic scoliosis and in age-matched normal girls. The scoliotic girls were classified according to the position of the curve. The menarche was found to occur significantly later in girls with either a thoracolumbar or a double primary curve than in the control group; it was also significantly later in those two groups combined than in the girls with a right convex thoracic curve. At the time of the menarche, the girls with a thoracolumbar or a double primary curve were significantly taller than those in the control group. The girls with a double primary curve, and these together with girls with a thoracolumbar curve, were also significantly taller than those with a right convex thoracic curve. Those in the control group were significantly heavier, and in some age groups significantly taller, than children born during the period 1953-1958 and providing earlier Swedish research data. The average age at the menarche did not differ from that for a normal population for this country. The observed differences between the group with a right convex thoracic curve and that with a thoracolumbar or a double primary curve indicate that the pathomechanism, and even the etiology, may vary with the form of idiopathic scoliosis.

Impact of a mandatory second-opinion program on medicaid surgery rates.

The effect of the Massachusetts second-opinion program on the volume of elective surgery in the Medicaid population was assessed using two approaches: a study of the program experience and surgery decisions of 2,501 program referrals, and an analysis of Medicaid surgery rates before and after program implementation. Nonconfirmation rates, which averaged 14.5 per cent, varied by procedure from 4 per cent for cholecystectomy to 26 per cent for disc surgery. The patient's surgery decision was related to the outcome of the second-opinion consultation: 85.5 per cent of the confirmed patients had the originally proposed operation, as compared with 31 per cent of the nonconfirmed patients. In the year after program implementation, the program was associated with a 20 per cent reduction in the volume of those procedures covered by the program. The greatest percentage declines were for hysterectomies, meniscectomies, hemorrhoidectomies and tonsillectomies/adenoidectomies. The decline in surgery rates was attributed both to a direct effect on patients referred to the program and to a sentinel effect whereby fewer operations were proposed. We conclude that the mandatory second-opinion program in Massachusetts saved Medicaid $3 to $4 for every dollar spent.

The effect of a thirty per cent reduction in physician fees on Medicaid surgery rates in Massachusetts.

In this paper, we use an interrupted time series analysis to assess the effect of a 30 per cent reduction in the Medicaid reimbursement fee for physician services on the rate at which eight elective surgical procedures were performed in the Massachusetts Medicaid population. Tonsillectomy/adenoidectomy is the only procedure in which there was a statistically significant decline in the rate of surgery in most areas of the state following the fee cut. There is some evidence of an increase in the rate of disc surgeries/spinal fusions. The rate of other procedures increased in some areas of the state and decreased in other areas in the period after the fee cut.