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Biomedical subjects

M E Chen

Publications and source records attributed to M E Chen.

15 recordsLinked to original sources

Detailed mapping of prostate carcinoma foci: biopsy strategy implications.

BACKGROUND: Prostate carcinoma exhibits considerable anatomic heterogeneity. Detailed characterization of prostate carcinoma distribution could lead to improved detection procedures and biopsy strategies. We mapped all 607 tumor foci from 180 serially sectioned whole mount radical prostatectomy specimens and used a computer algorithm to plot and summarize the distribution of these foci. We investigated whether specimen and clinical variables predicted differences in tumor distribution. METHODS: The volume and anatomic location of each tumor focus were determined and digitized. A computer-based algorithm was used to fit the digitized tumor foci to a paradigm prostate. Pseudo-color summary plots of tumor distribution then were computed for selected cases. RESULTS: Of the 180 specimens, 149 (83%) specimens had more than one cancer focus. Most foci (448 of 607 tumor foci, 74%) were in the peripheral zone (PZ). PZ foci near the apex had a significant midline component. Toward the base, PZ foci diverged laterally. Only 3 (2%) of 180 specimens contained foci solely in the transition zone (TZ). Total TZ cancer volume was </= 0.5 cm(3) in 55% (52 of 94) of patients. Computer plots of patients with T1c classification (UICC/AJCC) and specimen Gleason score </= 6 had greater proportions of TZ tumor. CONCLUSIONS: Almost all TZ foci occurred with PZ foci. The small volume of most TZ foci may explain the ineffectiveness of TZ biopsies to detect additional cancers during screening. Further, our results suggested that biopsies may be more effective if laterally directed biopsy samples are obtained nearer to the base of the prostate and if apical biopsy samples are obtained more medially.

Algorithms↗

Intravasal azoospermia: a surgical dilemma.

OBJECTIVES: To determine the incidence of intravasal azoospermia (IVA) and evaluate which factors before and during surgery influence outcome, by prospectively and intentionally performing bilateral vasovasostomies (VVs) only in men with intraoperative IVA. PATIENTS AND METHODS: Using a multilayer technique, 472 men underwent microsurgical reconstructive procedures. Intravasal fluid was examined for sperm by the surgeon and a pathologist. Strict enrolment criteria included total absence of sperm or sperm parts and bilateral VV as a treatment procedure. Patients were followed up by semen analysis and paternity assessed only by naturally conceived pregnancies. RESULTS: Of the 472 patients, 27 (5.7%) had bilateral IVA; 15 of these patients were available for a follow-up of 1-47 months. Eleven patients had identical gross appearance of intravasal fluid bilaterally. Of these patients, five had sperm in the ejaculate after surgery (three with clear intravasal fluid and two with no fluid). Bilaterally different vasal fluid was found in four men. Unilateral clear fluid was present in three patients, two of whom had sperm in semen analysed after VV. Overall, there was sperm in the ejaculate in seven of 15 patients with IVA; five of these seven had clear fluid in at least one vas deferens. One patient with unilaterally clear fluid achieved paternity by a naturally conceived pregnancy. The difference between the mean (SEM) obstruction interval in men who had sperm in a semen sample after VV, at 16.7 (3. 30) years, and in persistently azoospermic patients, at 15.5 (1.89) years, was not statistically significant (P = 0.741). CONCLUSION: The results of VV in patients with IVA are unsatisfactory; the patency rate is higher in men with copious clear fluid in at least one vas. The obstructive interval in patients with IVA does not appear to influence the outcome of VV.

Adult↗

Prostate cancer detection: relationship to prostate size.

OBJECTIVES: It has been suggested that the lower detection rate for cancer in large prostates is due to the smaller proportion of tissue sampled. To examine this hypothesis, we evaluated whole-mount radical prostatectomy specimens in which the volume of cancer had been determined. We correlated cancer volume to overall gland volume. In addition, we performed stochastic computer simulations of parasagittal sextant biopsies on the same group of radical prostatectomy specimens. We correlated the likelihood of a positive cancer biopsy simulation with tumor volume and gland size. METHODS: Six hundred seven tumor foci from 180 serially sectioned whole-mount prostatectomy specimens were mapped and digitized. Tumor volume was calculated by a step-section planimetry algorithm. Before sectioning, each gland was weighed. Systematic parasagittal sextant biopsies were computer simulated for each case. For each prostate, 40 simulations were performed, with random variations in biopsy location programmed for each run. Overall cancer detection by biopsy was considered positive if 90% of the 40 simulation runs were positive for cancer. Chi-square tests were used to evaluate statistical significance. RESULTS: Small-volume cancers (0.5 cc or less) were twice as frequent in large glands greater than 50 g (P = 0.03). These small-volume tumors comprised 33% (13 of 40) of cancers in prostates greater than 50 g, 16% (5 of 31) in glands less than 30 g, and 14% (15 of 109) in glands 30 to 50 g. The rate of positive sextant biopsy simulation was lower in glands greater than 50 g than in glands 50 g or less (48% versus 67%, P<0.03). Smaller cancers were much less likely to be detected in the simulations. The simulation detection rate for cancers 0.5 cc or less was 18% (6 of 33), compared with a detection rate of 73% (107 of 147) for cancers greater than 0.5 cc (P<0.00001). CONCLUSIONS: The observed lower cancer detection rate in large glands is a result of the higher proportion of low-volume cancers in these glands. This suggests that large prostates are more likely to be biopsied because of an elevated prostate-specific antigen value resulting from benign elements of the gland and not from a significant cancer. Increasing the number of cores solely to compensate for increased prostate size risks a disproportionate increased detection of small-volume tumors with a low clinical likelihood of progression.

Biopsy↗

Comparison of prostate biopsy schemes by computer simulation.

OBJECTIVES: To compare the ability of different biopsy schemes to detect cancer and predict tumor volume using our previously described prostate biopsy simulation system. In addition, we used the simulation system to evaluate the optimal location of transition zone biopsies. METHODS: Digital reconstructions of 180 radical prostatectomy specimens were used. Forty simulations were performed on each prostate for 10 biopsy schemes, including a previously reported five-region peripheral zone biopsy pattern and a new 11-core multisite-directed scheme consisting of sextant, two transition zone, one midline, and two anterior horn biopsies. For simulation of the transition zone biopsies, paired near-midline biopsies were simulated, with needle insertion points from the apex to the base of the prostate and with needle advances of 1 to 4 cm before firing. A total of 1,180,800 individual biopsy tracks were simulated. RESULTS: The 11-core multisite-directed biopsy scheme had the highest detection rate for cancers greater than 0.5 cc. This scheme reliably detected cancer in 94% (138 of 147) of the cases. These results were significantly better than those of the sextant biopsy scheme (P <0.001) and the five-region 18-core peripheral zone scheme (P = 0.03). Compared with other schemes, there were increases in small-volume (0.5 cc or less) cancer detection by both the 11-core multisite-directed and five-region schemes, but they were not statistically significant. The multisite and the sextant plus four transition zone biopsy schemes had the best correlation of mean total core cancer length with total cancer volume. In the simulation of the transition zone biopsies, the highest detection rate was observed when the biopsies were initiated at the most apical section and inserted for a depth of 3 cm before firing. CONCLUSIONS: Our simulation results suggest that the detection rate of prostate biopsies is not related solely to the number of cores taken. Core placement (the regions of the prostate from which samples are taken) is also important. The 11-core multisite-directed biopsy scheme performed the best, with improved cancer detection rates and tumor volume correlation over other schemes. On the basis of our simulations, this scheme has been chosen for clinical evaluation.

Biopsy↗

Isolation and characterization of PAGE-1 and GAGE-7. New genes expressed in the LNCaP prostate cancer progression model that share homology with melanoma-associated antigens.

The LNCaP progression model of human prostate cancer consists of lineage-related sublines that differ in their androgen sensitivity and metastatic potential. A differential display polymerase chain reaction was employed to evaluate mRNA expression differences between the LNCaP sublines in order to define the differences in gene expression between the androgen-sensitive, nontumorigenic LNCaP cell line and the androgen-insensitive, metastatic LNCaP sublines, C4-2 and C4-2B. An amplicon, BG16.21, was isolated that showed increased expression in the androgen-independent and metastatic LNCaP sublines, C4-2 and C4-2B. Hybridization screening of a lambda gt11 expression library with BG16.21 revealed two transcripts, both homologous to BG16.21 at the 3' end. A GenBankTM data base search using the GCG Wisconsin software package revealed the shorter approximately 600-bp transcript (designated GAGE-7) to be a new member of the GAGE family. The second approximately 700-bp transcript was a novel gene (designated PAGE-1, "prostate associated gene") with only 45% homology to GAGE gene family members. RNA blot analysis demonstrated that GAGE-7 mRNA was expressed at equal levels in all lineage related prostate cancer cell sublines, while PAGE-1 mRNA levels were elevated 5-fold in C4-2 and C4-2B as compared with LNCaP cells. Neither GAGE-7 nor PAGE-1 demonstrated any regulation by androgens in the prostate cancer cell lines used in this study. PAGE-1 and GAGE-7 expression was found to be restricted to testes (high) and placenta (low) on human multiple tissue Northern blots. As GAGE/MAGE antigens were reported previously to be targets for tumor-specific cytotoxic lymphocytes in melanoma, these results suggest that PAGE-1 and GAGE-7 may be related to prostate cancer progression and may serve as potential targets for novel therapies.

Amino Acid Sequence↗

Optimization of prostate biopsy strategy using computer based analysis.

PURPOSE: We evaluated and optimized the detection of cancer by prostate biopsies. We developed a stochastic computer simulation model of ultrasound guided biopsies using mathematically reconstructed radical prostatectomy specimens. Use of this technique allows rapid evaluation of a variety of factors for their effect on prostate biopsy results. We used this model to analyze the effectiveness of sextant biopsies, which have been widely adopted in clinical practice. We also analyzed other biopsy schemes. MATERIALS AND METHODS: A total of 607 tumor foci from 180 serially sectioned whole mount radical prostatectomy specimens was mapped and digitized. The cancers had been clinically diagnosed by a variety of biopsy strategies. Simulated parasagittal sextant biopsies were performed for each case. Forty simulation runs (each consisting of a set of 6 biopsies) were performed for each prostate, with realistic random variations in sextant biopsy localization programmed in each run. Cancer detection by biopsy was considered reliable if 90% of the simulation runs for each prostate were positive for cancer. A summary algorithm was used to map the tumor foci. RESULTS: Simulation of sextant biopsies demonstrated reliably detected cancer in only 107 of 147 patients (73%) in whom total tumor volume was greater than 0.5 cc. There was little correlation between total length of cancer in biopsy cores and tumor volume. Change of biopsy angle from 30 to 45 degrees did not result in significantly increased detection rates. Similarly, placing all biopsies more laterally did not increase overall detection rates. When we mapped tumor foci from the 40 cases in which sextant biopsies did not reliably detect tumor, we found that the foci were distributed in areas not biopsied by the sextant method, that is the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone. A 10-core biopsy scheme incorporating these areas as well as the posterolateral prostate reliably detected cancer in 141 of 147 patients (96%) with total tumor volumes greater than 0.5 cc. CONCLUSIONS: Prostate cancer of significant volume can be present in areas not sampled by standard sextant biopsies. Biopsies of the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone should be considered for re-biopsy strategy after negative sextant biopsies. Sampling of these additional areas also can be incorporated in an initial biopsy scheme to increase overall initial rates of detection of prostate cancer.

Biopsy↗

Risk of urethral, vaginal and cervical involvement in patients undergoing radical cystectomy for bladder cancer: results of a contemporary cystectomy series from M. D. Anderson Cancer Center.

PURPOSE: Orthotopic bladder reconstruction in women is the focus of considerable interest. To define suitable candidates for orthotopic reconstruction among women with bladder cancer, we reviewed the risk of secondary urethral, vaginal and cervical involvement by transitional cell carcinoma in patients who underwent radical cystectomy at our institution. MATERIALS AND METHODS: We retrospectively reviewed the charts of women who underwent radical cystectomy for primary transitional cell carcinoma of the bladder between 1985 and 1995. These cases also were reviewed pathologically. RESULTS: Of 115 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder 9 (8%) also had secondary transitional cell carcinoma of the urethra, including 2 with concomitant involvement of the vagina or cervix. In 4 patients (3%) the vagina or cervix was involved but not the urethra. Vaginal and cervical invasion correlated with stages T3b and T4 disease (p = 0.04). By logistic regression analysis the sole significant risk factor for urethral involvement was bladder neck involvement (p = 0.0005). Unlike previous studies 2 of 9 patients with secondary urethral transitional cell carcinoma did not have apparent cancer at the bladder neck. CONCLUSIONS: We report secondary urethral involvement without apparent bladder neck involvement in women with transitional cell carcinoma. Women who are candidates for orthotopic reconstruction should undergo biopsies of the bladder neck and urethra as part of the preoperative evaluation. In patients with palpable masses (stage T3b) on bimanual examination, transvaginal biopsies should also be considered. Intraoperative frozen sections of the urethral and vaginal margins should be obtained.

Adenocarcinoma↗

Antisperm antibodies in cryptorchid boys.

To explore whether the development of antisperm antibodies might play a role in inhibiting the future fertility of cryptorchid boys, 32 boys who underwent orchiopexy and 21 boys who underwent other inguinal surgeries were examined for the presence of antibodies to donor sperm. This group was compared to 23 boys who underwent noninguinal surgery or who had unrelated medical conditions. Using the indirect immunobead assay, 28% of the boys in the study group were found to have antisperm antibodies. These were predominantly of the IgG isotype. In the comparison group, only 1 boy (4%) had antisperm antibodies (P < 0.05).

Adolescent↗

Syndrome of mental retardation and distal arthrogryposis in sibs.

Two sisters presented with a syndrome of characteristic facial anomalies and distal arthrogryposis. The older sister is now 4 years old and is severely mentally retarded. Her sister died of respiratory failure due to hypoplastic lungs shortly after birth. The occurrence of this potentially lethal syndrome in 2 sisters with unaffected parents suggests autosomal recessive inheritance.

Arthrogryposis↗

[Effect of Salvia miltiorrhiza co. on angiotensin II and atrial natriuretic polypeptide in rabbits].

Both angiotensin II (AII) and atrial natriuretic polypeptide (ANP) are related to the function of blood vessels, but differ in their actions. The authors observed the effect of Salvia miltiorrhiza Co. (SMC) on the activities of AII and ANP in rabbits by radioimmunoassay. It was found that the concentration of AII and ANP in plasma were significantly lower (P less than 0.05), and slightly lower in brain and atrial (P greater than 0.05) in SMC group than in control group. It indicated that the effect of SMC on blood vessels is related to changes of AII and ANP, and that the difference of peptide changes in brain and plasma might be due to the blood-brain barrier.

Angiotensin II↗

Applying Yalom's principles to crisis work...some intriguing results.

In this paper, the writer has shared some of the results of an innovative eight- to sixteen-week, open-ended crisis group developed at the Community Mental Health Center at Strong Memorial Hospital. The group has been running for over a year and a half. Some of the significant findings were that process interventions can be creatively used in a modified manner to enhance the group interaction, while maintaining the crisis-oriented focus. There were two dimensions of process commentary described, the sense data material of an individual, interpersonal nature, and the mass group interventions with a broader, group development focus. In addition, the secondary function of the group, which was to serve as an assessment tool for an individual's capabilities in long-term group work, proved to be reliable for eighteen out of the twenty members, eventually referred to other groups. A theoretical framework, based on Yalom's work, as well as the writer's synthesis of previous crisis group theory, was outlined. Two clinical illustrations were described, using the paradigm. In closing, the writer wishes to validate the impression that crisis group work is indeed an exciting, clinical adventure. Each week the gestalt of the group varies, so that the crisis therapist must remain a versatile strategist and sensitive role model of communication theory. The interweaving of process issues with more concrete, content-focused group work provides the members with an in-depth, sharply practical interpersonal arena for growth.

Crisis Intervention↗