Bone metastasis from colorectal cancer in autopsy cases

The incidence of bone metastasis from colorectal cancer is reported to be 10.7% in autopsy cases. However, the characteristics of the primary cancers, as well as the patterns of bone metastasis, remain unclear. We analyzed the clinical and autopsy records of 118 patients with primary colorectal cancer treated either surgically or conservatively and eventually autopsied between 1970 and 1987 at Toranomon Hospital in Tokyo. Bone metastasis was detected in 23.7% (28/118). The average age of patients with bone metastasis was lower than that in patients without bone metastasis (P < 0.02). Cancers to the rectum and cecum were accompanied by bone metastasis more frequently than cancers of other portions of the colon. Signet-ring cell carcinoma showed a high incidence of bone metastasis (P = 0.041). Bone metastasis from colorectal cancer was associated with liver or lung metastases (P < 0.0001). These results indicated that bone metastasis from colorectal cancer is not as infrequent as previously described.     

Bilateral testicular metastasis of cancer of the prostate

Testicular metastasis of prostate cancer rarely occurs. Bilateral localization is exceptional. We report a new case of prostate adenocarcinoma with bilateral testicular metastasis. The diagnosis was made on clinical and ultrasonic arguments, and confirmed on the pathological specimen. Treatment consisted in a bilateral orchidectomy, associated with nonsteroid androgens.     

Bone metastasis in patients with urogenital neoplasms

The clinical data of 91 patients with bone metastases were reviewed. The renal cell carcinoma and prostatic carcinoma were diagnosed respectively in 53% and 47% of the patients. 48% of the patients had tumour size stage T3 and 71% had histopathological stage II (G2). 21% of the patients presented a bone pain. In patients with renal cell carcinoma, the level of serum bone alkaline phosphatase and erythrocyte sedimentation rate were correlated with the concentration of serum ferritin (respectively p = 0.008 and p = 0.055). The relationship between the histopathological grade (G) and the stage of tumour size (T), and the concentration of serum ferritin was noted. In patients with prostatic carcinoma, the relationship between general condition and the concentration of prostatic specific antigen (PSA) as well as the relationship between PSA and the intensity of bone pain were observed. Only relationship between the histopathological grade and the concentration of PSA had a statistical significance (p < 0.05).     

Intraoperative radiotherapy combined with external beam radiation for prostate cancer without metastasis

Between 1989 and 1996, 35 patients with prostate cancer without metastasis received intraoperative radiotherapy combined with external beam radiation. 10 of 16 stage B patients and all of 19 stage C patients received additional endocrine therapy for the initial treatment. The radiation therapy included 25-30 Gy of intraoperative radiotherapy for prostate and 30 Gy of external beam radiotherapy for small pelvic region. One patient of stage C was dead for cancer and 4 patient were dead for other causes during 15-99 (mean: 41.6) months follow up period. The overall actuarial survival at 5 years by Kaplan-Meier method were 92.3% for stage B and 87.2% for stage C. Although cystitis, proctitis and anal bleeding were observed as the adverse effects of radiotherapy, both acute and chronic symptoms were not critical. In conclusion, intraoperative radiotherapy combined with external beam radiotherapy was revealed as an effective treatment for prostate cancer without metastasis.     

Lymph node size does not correlate with the presence of prostate cancer metastasis

Prostate carcinoma (PC) is the second leading cause of cancer death in men in the western world. Although the role of oncogenes and growth factors in prostate carcinoma is still unclear, overexpression of the epidermal growth factor receptor (erbB-1) and the proto-oncogene erbB-2 have been reported in prostate tumors, and erbB-2 related to poor prognosis and distant metastasis. Recent allelotyping studies in prostate cancer have shown chromosomal gains in 7p and 17q, regions where erbB-1 and erbB-2 are localized respectively, although no direct evidence of an increased gene copy number of either erbB-1 or erbB-2 has been reported. To address this question, we analyzed 20 benign prostatic hyperplasia (BPH) samples and 36 samples of metastatic and non-metastatic PC by means of semiquantitative PCR. Thus, 64% (11/17) and 52% (10/19) of metastatic and non-metastatic tumors respectively showed gains of the relative genomic content of erbB-1 and an association of erbB-1 with prostate cancer but not with metastasis. Additionally, 41% (7/17) of metastatic samples showed gains of erbB-2 genomic content, suggesting an association of erbB-2 with metastasis and poor prognosis (p<0.005). No gains of erbB-1 or erbB-2 genomic content were detected in the BPH samples.     

Bone metabolism and phosphorus metabolism in patients with prostate cancer: paracrine and endocrine effects produced by prostate neoplasm

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P < 0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p < 0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P < 0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.     

Brain metastasis as a sole recurrence of prostate cancer after total prostatectomy

Postsynaptic density-95 (PSD-95) is a palmitoylated peripheral membrane PDZ protein that organizes signaling molecules at synaptic sites. Here we find the amino terminal region of PSD-95, containing the three PDZ domains is necessary and sufficient to localize PSD-95 to caveolar-like domains. In transfected COS cells, a subpopulation of PSD-95 is buoyant in sucrose gradients, and co-migrates with caveolin, a marker for caveolar domains. Sucrose gradient separation of brain extracts showed that some neuronal PSD-95 protein is present in buoyant fractions as well. Analysis of truncated forms of the PSD-95 indicated that the N-terminal PDZ-containing region localizes to caveolae, but the C-terminal region, containing the SH3 and the guanylate kinase domains does not. The mechanism by which the N-terminal region targets PSD-95 to buoyant lipid domains remains unknown. PSD-95 does not interact with caveolin and palmitoylation of PSD-95 is not required for caveolar fractionation.     

Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone

Coordination between karyokinesis and cytokinesis in the cell division cycle is fundamental to a precise transmission of duplicated genome into dividing daughter cells. byr4, a previously isolated essential gene, affects the mitotic cell cycle and cytokinesis in S. pombe. Phenotypic analyses of the null alleles and the overexpression of byr4 suggest that byr4 is a dosage-dependent coordinator of karyokinesis and cytokinesis (Song et al., 1996). In this study, the functional mechanisms of byr4 were investigated using a byr4 mutant that exhibits byr4 overexpression phenotypes in thiamine deficient media. Genetic suppression analyses of this byr4 mutant with other cytokinesis regulatory genes in S. pombe, cdc16, cdc7, cdc15, cdc14, and plo1, show that byr4 overexpression phenotypes are suppressed by the overexpression of cdc16 and cdc7, but not by plo1, cdc14, and cdc15. Also, the basal expression of byr4 and cdc7 suppresses the temperature-sensitive cdc16 mutation. However, the basal expression of either byr4 or cdc16 does not suppress the temperature-sensitive cdc7 mutation. The results of these suppression tests suggest that byr4 genetically interacts with cdc16 and cdc7: byr4 functions at the same level with or downstream of cdc16 and upstream of cdc7. In the present study, we also show that Byr4 interacts with Cdc16 and Spg1 in the yeast two-hybrid assays. Recent reports suggest a possible small GTPase pathway to regulate the timing of cytokinesis where Cdc16 functions as a GAP (GTPase activating protein), Spg1 as a GTPase, and Cdc7 as a downstream effector. Combined genetic and two-hybrid analyses of this study strongly suggest that Byr4 directly interacts with this possible small GTPase pathway including Cdc16, Spg1, and Cdc7 to regulate cytokinesis in S. pombe.     

Bone scintigraphy in the detection of chronic recurrent multifocal osteomyelitis

In this study, we describe the importance of the whole-body bone scan in diagnosing the multifocality of chronic recurrent multifocal osteomyelitis (CRMO) and in distinguishing it from unifocal acute hematogenous osteomyelitis. MATERIALS: The medical records and two-phase, whole-body bone scans of 14 patients (mean age 10.5 yr) with the diagnosis of CRMO, were retrospectively reviewed. The diagnosis of CRMO was based on bone biopsy in 9 patients and clinical course/laboratory findings in 5. Bone scans were evaluated for geographic and anatomic locations of their lesions. Correlative radiographs of areas of abnormal uptake were performed to assess the radiographic appearance of the lesions. RESULTS: The presentation of the disease was localized to one painful, tender and swollen periarticular site 86% of the time. The number of lesions detected by bone scan varied from 1-18 (mean 6). Most lesions were metaphyseal, proximal or distal tibial lesions. Purely sclerotic or mixed (sclerosis and lysis) lesions were found on radiographs. Bilateral lesions were seen in 64% of patients. Biopsies were negative for organisms in all patients and exhibited subacute or chronic histologic changes in most instances. Complications of chronic hyperemia included marked overgrowth (5), diffuse demineralization (1), angular deformity (1) and length discrepancy (1). CONCLUSION: The identification of the multifocal configuration of the disease process by two-phase (soft-tissue and delayed) whole-body bone scintigraphy results in appropriate diagnosis and therapy of CRMO. Additional sites for possible bone biopsy become apparent for exclusion of other diagnoses. Supportive (nonsteroidal, anti-inflammatory medication) instead of antimicrobial therapy can be initiated with significant cost savings.     

The clinical usefulness of urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer

The aims of this study were to investigate the effects of paracentesis on uterine and intraovarian haemodynamics by colour Doppler ultrasound and the influences of repeated paracentesis on pregnancy outcome in severe ovarian hyperstimulation syndrome (OHSS). Forty-one abdominal paracenteses were performed on seven pregnant women with tense ascites and eight thoracocenteses were performed on three pregnant women with pleural effusion. Pulsatility index (PI) and maximum peak systolic velocity (MPSV) of uterine and intraovarian arteries were measured before and after each intervention. The mean PI of uterine arteries was decreased significantly after paracentesis, but not after thoracocentesis. Furthermore, uterine PI was decreased in 13 out of 14 (92.9%) paracenteses with <2500 ml ascites removed, compared with eight out of 13 (61.5%) with >2500 ml ascites removed. After paracentesis, there were no significant changes in the intraovarian PI and MPSV in either group. The 24-hour urine output increased significantly in the paracentesis group, but not in the thoracocentesis group. There were no significant changes in haematocrit and electrolytes as a result of paracentesis. However, gradual falls in serum total proteins and albumin concentrations were observed in all patients after repeated paracentesis, necessitating post-paracentesis albumin infusion. There was no significant difference in miscarriage rates between the two groups. We conclude that repeated abdominal paracentesis increases uterine perfusion and has no adverse effects on pregnancy outcome in severe OHSS. Extraction of 2500 ml of ascitic fluid did not impair uterine perfusion.     

Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies

Prostatic adenocarcinoma commonly metastasizes to bone. Unlike most other bony secondaries, the majority of skeletal prostatic metastases are osteoblastic rather than osteolytic in nature. Several growth factors which are known to stimulate bone formation are expressed in benign and malignant prostate cells, but none has been specifically linked to osteosclerotic metastases. Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo. We have reported previously that BMP-6 mRNA and protein are expressed in the majority of primary prostatic carcinomas with established skeletal metastases but rarely in clinically organ-confined tumours. This study examines the expression of BMP-6 mRNA in matched prostatic primary and secondary bony lesions and in isolated skeletal metastases from prostatic adenocarcinomas, as well as other common human malignancies, by in situ hybridization. BMP-6 mRNA was detected in 11 out of 13 bone metastases from prostate carcinoma and in three paired samples of primary prostate carcinoma and matching skeletal metastasis. Weak signals for BMP-6 were also present in 5 out of 17 skeletal deposits from non-prostatic malignancies. BMP-6 mRNA appears to be strongly expressed in prostatic adenocarcinomas, both in the primary tumour and in bone metastases. It is also expressed, though less frequently, in skeletal metastases from other human carcinomas. Our findings suggest that BMP-6 may hold potential as an attractive marker and possible mediator of skeletal metastases, particularly in prostate carcinoma.     

Recall and attitudes in patients with prostate cancer

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are important in the regulation of tumor tissue progenesis, cell differentiation, tumor cell motility, and tumor cell invasiveness. We have recently reported that the levels of uPA and uPAR were higher in malignant astrocytomas than in low-grade gliomas. In the present study, we measured the levels of uPA and uPAR during the growth of glioblastomas in nude mice. Using fibrin zymography, densitometry, and an enzyme-linked immunosorbent assay, we found that the enzyme activity and content of uPA were increased 4- to 10-fold during tumor formation. Using a receptor assay and an enzyme linked immunosorbent assay, we found the numbers and content of uPAR were increased 5- to 15-fold during tumor formation. In addition, immunohistochemical staining for uPA and uPAR revealed strong immunoreactivity in tumor cells with the staining more intense on day 28 than on day 14. These results suggest that the upregulation of uPA and uPAR plays a major role in the formation of gliomas.     

Screening of prostate cancer in males with prostatism

Genetic analysis of the population structure of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, was conducted using allozymes. This vector tick transmits the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, in the far-western United States. It ranges from British Columbia to Baja California and disjunct populations are present in Oregon, Nevada, Utah, and Arizona. Host-seeking adult ticks were collected from vegetation across the range of the species and were partially fed on rabbits prior to analysis. Twelve putative loci were resolved using starch gel electrophoresis. One locus, glucose-6-phosphate isomerase, formed an apparent north/south latitudinal cline and showed significant geographic structure. None of the remaining loci exhibited much genetic differentiation. Estimates of gene flow were high relative to other arthropods. Isolation-by-distance analysis suggests a recent and rapid range expansion. We conclude that the overall lack of differentiation is due high rates of gene flow.     

Elderly men with cancer: social work interventions in prostate cancer

Prostate cancer requires the attention of social workers in health care for three reasons: the growing elderly population which will increase the number diagnosed, the recent introduction of new treatments and the lack of social acceptability for this condition. Interventions for prostate cancer are specific to the stage of the disease. These individual, family and group interventions are a model for social work services to elderly men with other forms of cancer. Social workers have opportunity to research quality of life and decision-making issues to enhance medical practise in prostate cancer.     

Liver metastasis rare in colorectal cancer patients with fatty liver

BACKGROUND/AIMS: As no reports in terms of the relationship between fatty liver and liver metastasis of colorectal cancer clinicopathological analysis of colorectal cancer patients with fatty were found a liver was carried out. PATIENTS AND METHODS: Among 839 patients with single colorectal carcinoma who underwent operations at our department between 1985 and 1994, 121 patients were designated as fatty liver using ultrasonography (FL group). The remaining 718 non-fatty liver patients with colorectal cancer (NFL group) were compared to the FL group regarding clinicopathological aspects. RESULTS: (1) There were only two patients who had liver metastasis in the FL group (1.7%), while the NFL group included 115 patients with liver metastasis (16.0%) (p < 0.01). (2) The five-year survival rate of the FL group was 95.7%, which was significantly higher than that in the NFL group (9.8%) (p < 0.001). (3) In the multivariate analysis, the fatty liver was identified as an independent prognostic factor. CONCLUSIONS: The FL group had a much better prognosis compared to the NFL group. Especially, liver metastasis was extremely rare in the FL group. We believe that these results will lead to the clarification of the liver metastasis mechanism.     

Clinical usefulness of blood PICP, PINP and ICTP concentrations as bone metastasis markers in prostate cancer patients

PICP and PINP are considered markers of bone formation, and ICTP is considered to be a marker of bone resorption. We measured these three markers as indicators of bone metastasis of prostatic cancer, and assessed their clinical usefulness. Serum PICP, PINP and ICTP were significant higher in patients with bone metastasis than localized cancer or controlled bone metastasis. Serum PSA increased initially with the LH-RH agonist during the course of bone metastasis. All these markers were subsequently observed to increase. Change in PICP of patients with bone metastasis was slight compared to PINP during endocrine treatment. Serum PICP, PINP and ICTP reflect the extent of metastasis in bone and are useful for monitoring the response of this condition to therapy.