Prospective study comparing the conventional and same-day strategies to diagnose pulmonary tuberculosis.

OBJECTIVE: The WHO recommends same-day sputum smear microscopy for the diagnosis of smear-positive tuberculosis (TB) in countries with high TB burden for earlier diagnosis and treatment, a cornerstone to prevent air-borne transmission. We aimed to compare the conventional strategy (sputum collection on three consecutive days) and the same-day strategy (hour h, h+1, h+2) in France, a country with low TB burden. PATIENTS AND METHODS: Over a six-month period, all adult individuals presenting with presumptive smear-positive TB were eligible for the study, registered in https://clinicaltrials.gov/ ID (NCT02961569). Sputum specimens were collected three times the first day, then once on the second day and once on the third day. The concordance between the two strategies regarding smears and cultures were assessed. RESULTS: Of the 131 eligible individuals, 34 were given a TB treatment. Smears from hour h, h+1, h+2, day two and three were negative in 19 of these 34 patients. Positive smears were obtained in 15, 14, 15, 14, and 14 patients at hour h, h+1, h+2, on day two and three, respectively. Concordance regarding smear or culture was good, with Kappa 0.69 and 0.64, respectively. CONCLUSION: The same-day strategy seems to be a good alternative to the conventional strategy.

[Influenzae and pneumococcal vaccination rate in an internal medicine ward]. / Couverture vaccinale antigrippale et antipneumococcique dans un service de médecine interne.

INTRODUCTION: Vaccination against influenza virus and Streptococcus pneumoniae is a global health priority and authorities, on the basis of recent publications, have recently updated French recommendations. The aim of this study was to describe the influenzae and pneumococcal vaccination's rate in an internal medicine ward. MATERIAL AND METHODS: All patients consecutively hospitalized during a 10 week-period in an internal medicine ward were included. The reasons for non-vaccination and the impact of an educational program for corrective measures were reported. RESULTS: Overall, 198 consecutive patients were included; 93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of them were vaccinated against these microorganisms, respectively. Prior pneumococcal vaccination was more frequently observed in immunocompromised patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but no significant difference was observed for influenza vaccine. Corrective measures were initiated in 46 patients (39%), non-immunized against S. pneumoniae. CONCLUSION: These results underline the very low prevalence of pneumococcal vaccination rate in at-risk hospitalized patients, as compared with influenza, despite recent recommendations.

Anterior lumbar sagittal alignment after anterior or lateral interbody fusion.

PURPOSE: Anterior or lateral interbody fusion is a treatment option for lumbar disc disease. A segmental change occurs after such surgery. This study was designed to evaluate the changes in the lumbar regional alignment after a single or two-level standalone anterior or lateral interbody fusion (ALIF or LLIF). METHODS: Data from patients referred to our institution between March 2013 and November 2015 for standalone ALIF or LLIF for low-grade isthmic spondylolisthesis or degenerative discopathy were retrospectively included in our analysis. Patients with a history of spinal fusion were excluded. Global and regional alignments were analyzed pre- and postoperatively. Pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), lumbar lordosis (LL), index segmental lordosis (ISL) and L4S1 lordosis were compared. Three groups according to the pelvic incidence (PI) (low, normal and high) were separately analyzed then compared. RESULTS: Forty-one women and 27 men (mean age was 46 years; range 25-66) were included. The mean follow-up was 10.8 (range 3-34 months). The patients were globally well balanced preoperatively and remained after surgery (SVA stagnated from 16.76±28.42mm to 15.97±28.20mm, P=0.75). PT and LL did not vary. L4S1 lordosis, and ISL were significantly increased respectively from 30.56±8.59 to 34.58±7.47 (P=0.0026) and from 5.94±5.25 to 12.99±5.87 (P<0.0001) at latest follow-up. CONCLUSION: Despite effective changes in the segmental lordosis at the index levels, our findings suggest that one or two-levels standalone ALIF or LLIF had no effect on the global balance and the lumbar lordosis. The three groups behaved similarly, the regional lordosis was redistributed in a better harmony (L4S1/LL ratio went up from 55% to 61%, P=0.01). STUDY TYPE: Retrospective study. LEVEL OF EVIDENCE: 4.

Polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) induce apoptotic and autophagic cell death of DU145 cells.

Polyphenols extracted from many plants have shown antiproliferative and antitumor activities in a wide range of carcinogenesis models. The antiproliferative effects of polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) were investigated on the androgen-insensitive DU145 human prostatic carcinoma cell line. A F3 fraction purified from leaf extract inhibited the DU145 cell proliferation more than 30-fold compared to the crude extract. By flow cytometric analysis, the polyphenol fraction was demonstrated to induce G0/G1 cell growth arrest and cell apoptosis. This apoptosis was evidenced by caspase 3 stimulation in F3-treated cells as compared to crude extract treated cells. The acid phosphatase activity of lysosomes was strongly activated in the lysosomal fraction of the F3-treated DU145 cells. This lysosomal activation, together with the appearance of autophagic vacuoles, suggests that "type 2 physiological cell death" was also involved in this antiproliferative effect. HPLC analysis of this F3 fraction showed 18 different subfractions. Among these subfractions, F3-3, F3-7 and F3-13 strongly inhibited DU145 cell proliferation in a dose-dependent manner. However, the nature of these polyphenols remains unknown since only one (Isoquercitrin) of the tested pure polyphenols co-migrated with F3-13. Since lysosomotropic drugs are considered as possible regulators of lysosome activity, aroeira polyphenols could target lysosomes of prostatic cancer cells to induce autophagic cell death.

Apoptotic conversion: evidence for exchange of genetic information between prostate cancer cells mediated by apoptosis.

Changes in the outer membrane of apoptotic cells can induce neighboring cells to become phagocytic. Using genetically marked prostate cancer cell lines, we explored the possibility that genetic information might be transferred from an apoptotic cell to a phagocytic neighbor. Neomycin-resistant LNCaP cells that overexpress bcl-2 (LNCaP(bcl-2/neo-r)) were cocultured with hygromycin-resistant LNCaP cells (LNCaP(hygr-r)). The cocultures were then transiently exposed to serum starvation to induce apoptosis of LNCaP(hygr-r) cells. Surviving cells were then coselected in medium containing both antibiotics. Whereas monocultures of LNCaP(bcl-2/neo-r) or LNCaP(hygr-r) treated this way yielded no colonies, cocultures yielded dual-antibiotic-resistant clones at a frequency of approximately 1 in 10(5). Pre-exposure to an apoptotic agent was required; cocultures not exposed to serum starvation yielded no dual-selectable colonies. Analysis of DNA extracted from a dual-resistant clone demonstrated that the restriction endonuclease pattern of the neo-r gene was unaltered when compared with the parental LNCaP(bcl-2/neo-r). However the hygr-r gene demonstrated an altered restriction endonuclease pattern in the dual-resistant derivative compared with the parental LNCaP(hygr-r) cell line. This is evidence that genetic information can be transferred from one prostate cancer cell to another through the process of apoptosis, and we term this form of genetic transfer "apoptotic conversion."

Expression of human chorionic gonadotropin beta subunit genes in superficial and invasive bladder carcinomas.

Increased serum levels of human chorionic gonadotropin beta subunit (hCG beta) were described previously in patients with bladder cancer. To obtain insight into such production of hCG beta, the expression of hCG beta 7, 8, 5, and 3 genes in bladder carcinomas and normal urothelia was investigated by reverse transcription PCR. Surprisingly, hCG beta mRNAs were detected in both normal urothelial and carcinomatous cells. However, tumor progression was characterized by different patterns of transcription of the hCG beta genes; the beta 7 gene was the only gene transcribed in normal urothelia and Ta tumors included in this study, whereas in addition to beta 7, genes beta 5, 8, and 3 were transcribed in T1 to T4 tumors. Moreover, transcription levels of the latter three genes increased with the stage of the disease. These observations showed that dramatic modifications in the expression of hCG beta genes accompany progression of bladder carcinomas.

Reduction and fusion in high-grade L5-S1 spondylolisthesis by a single posterior approach. Results in 50 patients.

INTRODUCTION: Treatment strategies in high-grade L5-S1 spondylolisthesis are controversial. Reduction of slippage, correction of lumbosacral kyphosis and the necessity of a complementary anterior approach are debated in the literature. The present study reports clinical and radiological outcome for reduction and instrumented fusion on a single posterior approach. MATERIAL AND METHOD: A retrospective study included all consecutive adolescent and young adult patients operated on by a single surgeon (D.C.) for high-grade (Meyerding 3-4-5) L5-S1 spondylolisthesis. The technique consisted in reduction of lumbosacral kyphosis and posterolateral fusion on a single posterior approach without resection of the sacral dome or complementary anterior approach. Only cases of adult ptosis required impacted tibial interbody graft. Clinical complications, radiologic lumbopelvic results and sagittal balance were analyzed at last follow-up. RESULTS: Fifty patients, with a mean age at surgery of 21±11 years, were followed up for a mean 5.5±4.6 years. Mean lumbosacral angle was reduced by 25° (from 76° to 101°; P<0.05), and mean listhesis grade by >50% (from 75% to 23%; P<0.0001), without correction loss at last follow-up. C7 sagittal offset was corrected (from 8° to 4°; P<0.05), with harmonization of lumbar (from 57° to 64°; P<0.001) and thoracic curvature (from 37° to 44°; P=0.1). Seventeen patients (34%) showed postoperative radicular deficit, without sequelae at last follow-up. There were no cauda equina lesions. Bone fusion was achieved in 42 patients (84%), in the same surgical step. After revision by complementary interbody graft, there was no residual non-union. CONCLUSION: Surgery on a single posterior approach gave reliable results in high-grade spondylolisthesis in adolescents and young adults. The technique is not however, free of risk (transient neurologic deficit and non-union), and patients should be forewarned. Complementary interbody graft can be reserved to adult ptosis with incomplete reduction of lumbosacral kyphosis and to revision surgery for non-union. LEVEL OF EVIDENCE: IV, retrospective study.

Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder.

Loss of heterozygosity (LOH) on chromosome 10 has been observed in several human cancers including glioblastomas, meningiomas, melanomas and endometrial and prostate carcinomas. We have investigated the incidence of LOH on chromosome 10 in 36 human transitional cell carcinomas (TCCs) of the bladder, three upper urinary tract TCCs and one lymph node metastasis, using a panel of 27 highly polymorphic markers spanning 10p (short arm) and 10q (long arm). Fourteen bladder tumours (39%), the three upper urinary tract tumours and the lymph node metastasis showed LOH for at least one locus on chromosome 10. Remarkably, LOH on chromosome 10 was observed mainly in muscle-invasive (P = 0.01) and high grade tumours (P = 0.03). For five tumours and the lymph node metastasis, LOH was found at all informative loci, indicating monosomy or isodisomy of chromosome 10. The deletion mapping of the tumours with partial loss delineated two minimal regions of loss on chromosome 10q. One region, the most telomeric, was bounded by markers D10S214 and D10S169 and the other, the most proximal, was bounded by markers D10S222 and D10S531. Our results demonstrate that chromosome 10q LOH is common in muscle-invasive bladder cancers and that two potential tumour suppressor loci, at 10q24.1-q24.3 and 10q26.1-q26.2, may contribute to the malignant progression of these tumours. Localization of the smallest common regions of loss in bladder tumours provides a starting point for the identification of the genes involved.

Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas.

Growth factors and growth factor receptors are involved in tumor progression. The fibroblast growth factor receptor 2 gene encodes distinct isoforms. The isoforms which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epithelia and is involved in the control of epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi-quantitative RT-PCR using TFIID and GAPDH as internal standards. In normal bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying stroma. In TCCs, the level of KGF-R mRNA was generally either normal or low. Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium. This decrease in KGF-R mRNA was not accompanied by an increase in BEK (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor receptor 2 gene. Expression of the KGF-R was also monitored by immunohistochemistry using a functional KGF-immunoglobulin chimera. The receptor was uniformly expressed throughout the normal urothelium except for the umbrella cells. Immunoreactivity for KGF-R was found to be negative in tumors with low levels of KGF-R mRNA, while the peritumoral normal urothelium was positive. Among patients with muscle invasive tumors, those exhibiting a low level of KGF-R mRNA had a significantly higher proportion of cancer deaths. Our results suggest that decreased expression of KGF-R can be considered as a marker of tumor progression in muscle invasive TCCs.

Androgen suppressed apoptosis is modified in p53 deficient mice.

Several in vitro studies have provided evidence that the tumor suppressor protein, p53, is involved in the cell death process referred to as apoptosis. The recent development of p53 knock-out mice has enabled further investigation into the function of p53 for apoptosis, in vivo. Radiation-induced apoptosis is suppressed in such mice, yet other forms of apoptosis do not seem to be significantly affected. In this report, we present evidence that such male p53 nullizygous mice have less apoptosis in the prostate glands associated with the first 4 days following castration. Ventral prostate glands were obtained from normal, heterozygous p53-null and p53 nullizygous mice at daily intervals after castration. These tissues were stained for apoptosis with the use of the in situ and labeling method and apoptotic bodies were quantified by microscopy. Although labeled apoptotic bodies were observed in post-castrated tissues from all of these genetic variant mice, the onset of apoptosis was delayed and the occurrence of apoptosis was significantly reduced in the p53 nullizygous mice when compared to normal controls. Heterozygous p53-null mice were intermediate for these criteria. Examination of the internucleosomal DNA fragmentation pattern at 2 days of castration supports a significant diminution of prostate cell apoptosis in nullizygous p53 mice. Additionally, large nucleated and multinucleated cells were detected in the prostate epithelium of noncastrated p53 nullizygous mice and these abnormal cells were increased after castration. Flow cytometric analysis of these tissues confirmed a high number of 4C and 8C DNA content cells in the p53 nullizygous prostates and their frequency was increased by castration. In concordance with an earlier study, we conclude that functional p53 protein is not essential for prostate epithelial cells to undergo castration-induced apoptosis. However, wild-type p53 does appear to enhance this process, especially in the early period following castration, and this protein may regulate an aberrant prostate cell cycling activity that follows castration.

Relationship between E-cadherin and fibroblast growth factor receptor 2b expression in bladder carcinomas.

E-cadherin is a cell-cell adhesion molecule expressed predominantly by epithelial cells. Reduction or loss of E-cadherin immunoreactivity has been associated with tumour progression in many epithelial cancers, including bladder carcinomas. The fibroblast growth factor receptor 2b (FGFR2b) recognized specifically by FGF7 is expressed only by epithelial cells. Recently, decreased expression of FGFR2b protein and mRNA was found to be associated with tumour progression in bladder carcinomas. The purpose of this investigation was to look for a possible relationship between E-cadherin and FGFR2b expression in bladder carcinomas. As decreased E-cadherin immunoreactivity was found to correlate directly with decreased expression at the mRNA level, the possible relationship between E-cadherin and FGFR2b was investigated at the mRNA level using semi-quantitative RT - PCR in 92 transitional cell carcinomas (TCCs) and four lymph node metastases. All tumours with low E-cadherin expression had low expression of FGFR2b, whereas tumours with low FGFR2b mRNA could express any level of E-cadherin mRNA. The same observation was equally valid for bladder and colon cancer cell lines suggesting that, besides bladder tumours, this relationship could apply to other carcinomas types. These results suggest that a relationship exists between the transcription of the E-cadherin and FGFR2b genes preventing high expression of FGFR2b where expression of E-cadherin is low. We suggest that reduced expression of FGFR2b in conjunction with decreased expression of E-cadherin may contribute to the aggressive behaviour attributable to high grade TCCs.

Tumour suppressive properties of fibroblast growth factor receptor 2-IIIb in human bladder cancer.

FGFRs (fibroblast growth factor receptors) are encoded by four genes (FGFR1-4). Alternative splicing results in various receptor isoforms. The FGFR2-IIIb variant is present in a wide variety of epithelia, including the bladder epithelium. Recently, we have shown that FGFR2-IIIb is downregulated in a subset of transitional cell carcinomas of the bladder, and that this downregulation is associated with a poor prognosis. We investigated possible tumour suppressive properties of FGFR2-IIIb by transfecting two human bladder tumour cell lines, J82 and T24, which have no endogenous FGFR2-IIIb expression, with FGFR2-IIIb cDNA. No stable clones expressing FGFR2-IIIb were isolated with the J82 cell line. For the T24 cell line, stable transfectants expressing FGFR2-IIIb had reduced growth in vitro and formed fewer tumours in nude mice which, in addition, grew more slowly. The potential mechanisms leading to decreased FGFR2-IIIb mRNA levels were also investigated. The 5' region of the human FGFR2 gene was isolated and found to contain a CpG island which was partially methylated in more than half the cell lines and tumours which do not express FGFR2-IIIb. No homozygous deletion was identified in any of the tumours or cell lines with reduced levels of FGFR2-IIIb. Mutational analysis of the entire coding region of FGFR2-IIIb at the transcript level was performed in 33 bladder tumours. In addition to normal FGFR2-IIIb mRNA, abnormal transcripts were detected in two tumour samples. These abnormal mRNAs resulted from exon skipping which affected the region encoding the kinase domain. Altogether, these results show that FGFR2-IIIb has tumour growth suppressive properties in bladder carcinomas and suggest possible mechanisms of FGFR2 gene inactivation.

Report from the 2014 Scoliosis Research Society Travelling Fellowship.

The Scoliosis Research Society traveling fellowship was conceptualized in 1970, repeated in 1972, and, after a pause, restarted in 1993. International traveling fellows visiting North America first commenced in 2000 and have since alternated annually with the North American fellows. Although a senior fellow had always traveled with them, in 2012 the first senior international fellow traveled with the group. This year, the senior fellow was Daniel Chopin from the Neuro-Orthopedic Spine Unit, Lille University Hospital, France, and past Director of the Spine Center, Institut Calot Berck sur Mer (succeeding Dr. Cotrel). The junior fellows were Meric Enercan from the Florence Nightingale Hospital, Istanbul Spine Center, Turkey; J. Naresh-Babu from Mallika Spine Centre, Guntur, Andhra Pradesh, India; and Nasir A. Quraishi from the Centre for Spine Studies and Surgery, Queen's Medical Centre, Nottingham, UK. The host centers were initially suggested by Dr. Chopin, the senior fellow; after some minor tweaking and extensive planning from the Scoliosis Research Society office, the itinerary was confirmed. The researchers were to visit 7 centers in just over 3 weeks. All of the international fellows were going to have an extraordinary adventure although they had not met each other previously. As it turned out, the trip was indeed sensational-professionally stimulating and socially endearing. The following is a short report on this unforgettable experience.

Evolution of adolescent idiopathic scoliosis: results of a multicenter study at 20 years' follow-up.

INTRODUCTION: To date there is no consensus on therapeutic indications in adolescent idiopathic scoliosis (AIS) with curvature between 30° and 60° at the end of growth. OBJECTIVE: The objective of this study was to assess outcome in patients with moderate AIS. MATERIAL AND METHODS: A multicenter retrospective study was conducted. Inclusion criteria were: Cobb angle, 30-60° at end of growth; and follow-up > 20 years. The data collected were angular values in adolescence and at last follow-up, and quality of life scores at follow-up. RESULTS: A total of 258 patients were enrolled: 100 operated on in adolescence, 116 never operated on, and 42 operated on in adulthood. Mean follow-up was 27.8 years. Cobb angle progression significantly differed between the 3 groups: 3.2° versus 8.8° versus 23.6°, respectively; P < 0.001. In lumbar scoliosis, the risk of progression to ≥ 20° was significantly higher for initial Cobb angle > 35° (OR=4.278, P=0.002). There were no significant differences in quality of life scores. DISCUSSION: Patients operated on in adolescence showed little radiological progression, demonstrating the efficacy of surgical treatment for curvature greater than 50°. Curvature greater than 40° was progressive and may require surgery in adulthood. Lumbar scoliosis showed greater potential progression than thoracic scoliosis in adulthood, requiring fusion as of 35° angulation. LEVEL OF EVIDENCE: IV, retrospective study.

Conservative treatment of bladder carcinoma by partial cystectomy and interstitial iridium 192.

From 1971 to 1984, 85 patients with bladder carcinoma were treated conservatively at the Henri Mondor Hospital by a combination of short course of pre-operative external pelvic irradiation, iliac node dissection, partial cystectomy, and iridium 192 implantation. There were 79 transitional cell carcinomas (G1: 12, G2: 25, G3: 36, Gx: 6) and 6 squamous cell carcinomas. By clinical stage, based on endoscopic resection, there were 43 T1, 30 T2, 5 T3, and 7 Tx. After partial cystectomy the pathologic stage distribution was: 41 pT1, 31 pT2, and 13 pT3. Crude disease-free survival at 5 years is 72% for T1 tumors and 55% for T2, but overall only 16% of patients died of bladder carcinoma. Local failures were seen in 11.5% of T1 and 0% of T2 tumors, and second bladder tumors developed at a distance from the treated site in 11.5% of T1 and 7% of T2. There is a non significant trend for intravesical recurrences (both local failures and second tumors) to occur more frequently for G1 tumors (25%) than for G2 (16%) or G3 (7%). At 5 years 95% of disease-free survivors have a functioning bladder. Regional or distant metastases occurred in 54% of patients with pT3 tumors and 10% of those with pT1 or pT2; within each stage there was no apparent influence of grade on metastatic risk. The four patients with histologically positive iliac nodes received additional post-operative external pelvic irradiation; three died of metastases and one is disease free at 10 years. No abdominal scar recurrences were seen. Late complications occurred in 6% of the population. For T1 tumors we suggest modification of the described protocol, eliminating the pre-operative irradiation and the lymph node dissection. If there is no doubt as to the pathologic stage after complete endoscopic resection, iridium 192 implantation delivering a dose of 60 Gy, without partial cystectomy, may be sufficient management. By contrast, for T2 tumors, all elements of the protocol seem important to obtain optimal results.

Expression of transforming growth factor beta1 and its receptors in normal human urothelium and human transitional cell carcinomas.

Previous studies indicated that transforming growth factor beta1 (TGFbeta1) is expressed by normal urothelial cells and exerts regulatory autocrine functions in urothelial maintenance and wound healing. However, little is known about the expression patterns of TGFbeta1 and its receptors in bladder tumors. Therefore, we studied the protein and mRNA localization of TGFbeta1 and TGFbeta receptor types I and II (TGFbetaRI and TGFbetaRII) in normal human urothelium and transitional cell carcinomas (TCCs) of different grades and stages. Expression of TGFbeta1 and its receptors was examined by immunocytochemistry and mRNA in situ hybridization in normal urothelium and TCCs using a semiquantitative method. By immunocytochemistry, the expression of TGFbeta1 and TGFbetaRII was higher in superficial and basal cell layers of normal urothelium than in the intermediate layer. A similar localization was seen in superficial TCCs. TGFbetaRI was mainly present in basal and intermediate cell layers of normal urothelium and superficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells stained intensely for all three proteins. No correlation was found between immunostaining and TCC grade. In situ hybridization pointed out that all cell layers in normal urothelium exhibit similar TGFbeta1 mRNA levels. Elevated TGFbeta1 mRNA levels were noted in TCCs irrespective of grade or stage. In conclusion, these data indicate that in normal urothelium TGFbeta1, TGFbetaRI, and TGFbetaRII expression depend on maturation and differentiation. This pattern is particularly lost in muscle invasive TCCs, in which the expression of the three proteins is enhanced. These data suggest autocrine TGFbeta1 mechanisms in human TCC cells that may be more pronounced in muscle invasive TCC cells.

Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.

After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.

Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue.

We studied the expression level and cell-specific expression patterns of 5alpha-reductase (5alpha-R) types 1 and 2 iso-enzymes in human hyperplastic and malignant prostate tissue by semi-quantitative RT-PCR and in situ hybridisation analyses. In situ hybridisation established that 5alpha-R1 mRNA is preferentially expressed by epithelial cells and little expressed by stromal cells whereas 5alpha-R2 mRNA is expressed by both epithelium and stroma. Semi-quantitative RT-PCR has been performed on total RNA from different zones of normal prostate, BPH tissues and liver. We found that 5alpha-R1 and 5alpha-R2 mRNAs expression was near the same in all zones of normal prostate. In BPH tissue, 5alpha-R1 and 5alpha-R2 mRNAs expression was slightly but significantly increased, when it was compared to the levels recorded for normal prostate. In cancer samples, 5alpha-R1 mRNA expression was higher than in normal and hyperplastic prostate but the level of 5alpha-R2 mRNA was not statistically different from that observed in the different zones of normal prostate. In liver, 5alpha-R2 mRNA level was similar to that measured in BPH but 5alpha-R1 mRNA expression was ten times higher. The increase observed in 5alpha-R isoenzymes expression in BPH tissue could play an important role in the pathogenesis and/or maintenance of the disease.

Retroperitoneoscopy: a laparoscopic approach for adrenal and renal surgery.

OBJECTIVES: Retroperitoneoscopy has gained acceptance for urologic surgery. We assessed the safety and efficacy of this procedure for renal and adrenal surgery. METHODS: Since December 1994, 20 patients (18 to 75 years old) have undergone laparoscopic adrenalectomy and nephrectomy, including simple nephrectomy in 8, partial nephrectomy in 1, radical nephrectomy in 2, tumorectomy with cyst excision in 1, and adrenalectomy in 8. The retroperitoneal space was created by blunt dissection with the index finger, completed by insufflation, without balloon dissection. RESULTS: Average kidney size was 65 m (range 50 to 108), and average adrenal tumor size was 31 mm (range 20 to 40). The average operating time was 127 minutes (range 60 to 180) for nephrectomy and 84 minutes (range 45 to 140) for adrenalectomy. The average hospital stay was 3 days (range 1 to 7) for nephrectomy and 2.4 days (range 1 to 4) for adrenalectomy. Average blood loss was 65 mL for both nephrectomy and adrenalectomy. Conversion from the laparoscopic procedure to open surgery was never required. Peritoneal effraction and ureteral injury occurred in only 4 patients and 1 patient, respectively. CONCLUSIONS: The laparoscopic retroperitoneal approach is safe and effective for simple renal nephrectomy and for excision of small adrenal tumors. Perioperative morbidity and hospital stay are reduced.