Making sense of prostate specific antigen: improving its predictive value in patients undergoing prostate biopsy

PURPOSE: The clinical usefulness of PSA for prostate cancer screening is unclear, although the test remains in common use. New methods to interpret PSA are needed. MATERIALS AND METHODS: We examined a cohort of 2,637 men who underwent prostate biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for prostate cancer, including patient age, ethnicity, family history of prostate cancer, previous negative biopsy, voiding symptoms and prostate volume, we developed risk groups for prostate cancer using recursive partitioning modeling independent of PSA or DRE. We then compared prostate cancer probabilities by PSA ranges by risk group. RESULTS: Of the 2,637 men 1,282 (48.6%) had prostate cancer. Age, ethnicity, family history, previous negative biopsy and prostate volume were predictive for cancer. We constructed 6 risk groups by combining these factors and created tables to assign patients to these groups. Independent of PSA and DRE the probability of cancer ranged from 15% in patients in group 1 to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk group prostate cancer probabilities were refined from 0% to 100%. Patients in the higher risk groups also had higher grade cancer (p <0.0001). CONCLUSIONS: We generated 6 risk groups based on simple risk factors for prostate cancer. When used in the right context and patient, PSA is highly accurate for predicting prostate cancer and permitting rational decision making in patients with abnormal PSA.     

Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma

OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes predispose women to ovarian and/or breast cancer. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Korean women remains to be elucidated. In addition, genetic polymorphisms may affect not only cancer development but also cancer progression and, as a result, could influence cancer phenotypes. The purposes of this study were, first, to investigate the presence of BRCA1 and BRCA2 mutations in women with ovarian cancer who were unselected for family history and, second, to evaluate the relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. METHODS: We studied 37 women who were diagnosed with epithelial ovarian cancer and treated at the Yonsei University Hospital between August 2002 and March 2004. Genomic DNA was analyzed for BRCA mutations using a PCR-DHPLC-sequencing method. The relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features was examined. RESULTS: Most mutations of BRCA1 and BRCA2 associated with ovarian and/or breast cancer result in truncated proteins. We found one frameshift mutation in BRCA1 (3746insA) that led to premature termination. The patient had no family history of breast or ovarian cancer. There was no relationship between ovarian cancer susceptibility gene polymorphisms and clinicopathological features. CONCLUSION: Our results were consistent with the hypothesis that BRCA1 and BRCA2 mutations have a limited role in sporadic ovarian carcinogenesis in the Korean population. Furthermore, polymorphisms of certain, selected ovarian cancer susceptibility genes were not associated with the clinicopathological phenotypes of ovarian cancer.     

Efficacy assessment of CellSlide in liquid-based gynecologic cytology

OBJECTIVE: To evaluate the efficacy of CellSlidetrade mark (CS) method in liquid-based gynecologic cytology. METHODS: We compared 1221 specimens prepared by both CS and conventional techniques to evaluate specimen adequacy and cytologic diagnoses. Sensitivity and specificity of these techniques were analyzed in 54 cases using the available histological data. RESULTS: Quality limiting factors, such as obscuring inflammation or blood, were markedly reduced in CS (0.2%) compared to the conventional smear (4.9%). There was a complete agreement in the Bethesda 2001 diagnosis between these methods in 1132 cases (92.7%) out of 1221. 16.7% more ASC cases and 37.5% more low-grade squamous intraepithelial lesions (LSIL) and 21.4% more high-grade SIL (HSIL) were detected on the CS slides than on the conventional smears. Sensitivity rates, relative to histological data, were 91.4% (CS) and 74.3% (conventional) and specificity rates were same (89.5%) for ASC and more severe lesions. Infectious organisms (Trichomonas and Candida, etc.) were readily identifiable in both methods. CONCLUSIONS: CS preparation is more sensitive and equally specific in detecting epithelial abnormalities when compared to the conventional smear. In addition, it has a lower incidence of unsatisfactory results with hypocellularity or >75% obscuration of cells.     

Oxidative phosphorylation by chondrocyte mitochondria

A mitochondrial fraction was isolated from chick epiphyseal cartilage using a Polytron. The oxidative phosphorylating properties and principle dehydrogenase activities of these mitochondria were studied. The highest rate of oxidation was noted when succinate was used as a substrate. Lesser levels of respiration were recorded with isocitrate in the presence of NADP. Succinate, isocitrate, oxoglutarate, malate and glycerol-3-phosphate dehydrogenases were found in chondrocyte mitochondria. Of these, succinate and NADP-linked isocitrate dehydrogenases were the most active. The results indicate that chondrocyte mitochondria have the enzymic capability to perform oxidative phosphorylation. The presence of NADP-linked isocitric dehydrogenase supports the view that this enzyme may play a key role in citrate formation.     

Cytotoxicity of a novel biphenolic compound,bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane against human tumor cellsin vitro

Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BP002-A) was isolated from the fermentation broth ofAspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition of cell growthin vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system cancer cell XF498 were 8.24, 10.60, 8.83, 9.85 μg/ml respectively. GERI-BP002-A has also revealed cytotoxicity against P-glycoprotein-expressed human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein. We have also tested cytotoxicities of structurally related compounds of GERI-BP002-A such as diphenylmethane, 1,1-bis(3,4-dimethylphenyl)ethane, 2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, 4,4′-di-tert-butylphenyl, bibenzyl, 2,2′-dimethylbibenzyl,cis-stilbene,trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenylsulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship, and from these data we could suppose that hydroxyl group of GERI-BP002-A conducted important role in its cytotoxicity.     

Cytotoxicity of trichothecenes to human solid tumor cellsin vitro

The trichothecenes are sesquiterpenoid mycotoxins characterized by the 12,13-epoxytrichothec-9-ene ring system. We have tested cytotoxicity of several naturally-occurring or synthesized trichothecenes against human solid tumor cell lines. Among them, trichothecin (I) and 4-β-Acetoxy-12,13-epoxytrichothec-9-ene (trichodermin, II) exhibited highly cytotoxic activities. 4-β-Hydroxy-12,13-epoxytrichothec-9-ene (trichodermol, III) and 4-β-Methoxy-12,13-epoxytrichothec-9-ene and 4-α-Hydroxy-12,13-epoxytrichothec-9-ene(VI) had no cytotoxicities up to 10 μg/ml. And in the tested cell lines, HCT15 colon cancer cell line was the most sensitive to all tested trichothecenes.     

Automatic stimulus breaker for electric dental pulp tester using pain response

The pulp test provides a means of examining the vitality of dental pulp using physical or chemical stimulation. During electrical pulp testing, an electrical current stimulates the intradental nerve, which may be painful and stressful to patients. The study involved measurement of the electromyogram (EMG) from the anterior belly of the digastric muscle, finger movement and voice response during electrical pulp testing. The excessive stimulus time from the onset time of response (EMG, voice and finger movement) to the end of the stimulation was obtained. The results indicated that the responses occurred in the order: EMG, finger and voice. Based on these results, an automatic stimulus shut-off circuit was developed using the above-mentioned responses to stimulus during electric pulp testing. Excessive stimulus time was reduced by prompt switching-off of the pulp tester output, 64 ms on average after the first detected response (EMG). Consequently, excessive stimulus times were reduced by 284 and 152 ms on average for the subject and examiner disconnection, respectively, using the developed automatic shut-off circuit. Therefore it was possible to minimise pain and stress by reducing excessive pulp stimulation.     

Anatomic basis of sharp pelvic dissection for curative resection of rectal cancer

The optimal goals in the surgical treatment of rectal cancer are curative resection, anal sphincter preservation, and preservation of sexual and voiding functions. The quality of complete resection of rectal cancer and the surrounding mesorectum can determine the prognosis of patients and their quality of life. With the emergence of total mesorectal excision in the field of rectal cancer surgery, anatomical sharp pelvic dissection has been emphasized to achieve these therapeutic goals. In the past, the rates of local recurrence and sexual/voiding dysfunction have been high. However, with sharp pelvic dissection based on the pelvic anatomy, local recurrence has decreased to less than 10%, and the preservation rate of sexual and voiding function is high. Improved surgical techniques have created much interest in the surgical anatomy related to curative rectal cancer surgery, with particular focus on the fascial planes and nerve plexuses and their relationship to the surgical planes of dissection. A complete understanding of rectum anatomy and the adjacent pelvic organs are essential for colorectal surgeons who want optimal oncologic outcomes and safety in the surgical treatment of rectal cancer.