Is adjuvant chemotherapy for bladder cancer safer in patients with an ileal conduit than a neobladder?

OBJECTIVE: To assess the safety of adjuvant chemotherapy in patients with neobladder reconstruction in comparison to ileal conduit, as radical cystectomy and urinary diversion is an effective curative surgical treatment for muscle-invasive and high-risk superficial bladder cancer, and adjuvant chemotherapy is usually considered for patients with clinical stage > T2 and nodal metastasis. PATIENTS AND METHODS: We analysed retrospectively patients who had had a radical cystectomy and urinary diversion between 1992 and 2004. Patients with high-risk disease who had adjuvant chemotherapy were identified and stratified based on the type of urinary diversion (ileal conduit or neobladder). The chemotherapy regimen, complications from the adjuvant chemotherapy and other relevant data were analysed. RESULTS: Overall, 343 patients had radical cystectomy, 40 had adjuvant chemotherapy; 25 had an ileal conduit and 15 had a neobladder. Patient characteristics including age, stage and follow-up were similar. In all, 55% of patients had grade 1 toxicity, 23% grade 2, 18% grade 3, and 13% grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the toxicity among the two groups. CONCLUSIONS: Adjuvant chemotherapy appears to be safe in patients with a neobladder and equally safe in patients with an ileal conduit. Hence neobladder reconstruction should not be denied to patients with bladder cancer who are at high risk of recurrence and who might require adjuvant chemotherapy.     

Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker “fingerprint” to assess sperm quality on the basis of molecular parameters.     

Femoral lengthening over an intramedullary nail using the external fixator: risk of infection and knee problems in 22 patients with a follow-up of 2 years or more

BACKGROUND: The time for femoral lengthening is shortened if external fixation is combined with intramedullary nailing. However, several complications have been reported with this procedure. PATIENTS AND METHODS: We retrospectively reviewed the outcome of femoral lengthening performed over an intramedullary nail using external fixation in 22 patients. These patients were followed for a mean of 3.2 (2-5.2) years. The mean age was 22 (13-35) years at the time of the index procedure. The mean lengthening was 5 (2.7-8.1) cm and the external fixator was removed after median 20 (8-30) weeks. The mean external fixation index was 24 (11-35) days/cm and the mean consolidation index was 43 (26-55) days/cm of lengthening. RESULTS: 3 patients who had a past history of infection or open trauma developed osteomyelitis which required removal of the nail. There were 4 knee joint complications when the lengthening was over 20%, including posterior knee subluxation and patella subluxation. In 1 patient, the lengthened segment collapsed with breakage of locking screws. INTERPRETATION: Although lengthening over a nail can reduce the duration of external fixation, caution is required to prevent major complications.     

Successful use of Thoratec biventricular support in a small child awaiting cardiac transplantation

The use of paracorporeal mechanical biventricular support devices either as a bridge to transplantation or while awaiting recovery of the failing heart has been well described in the literature. The majority of these reports detail conditions specific to the adult population. We describe use of the Thoratec ventricular assist device (Thoratec Corp, Pleasanton, CA) in the smallest known cardiomyopathy patient to date to be successfully supported with an emergent biventricular device before subsequent cardiac transplantation. The operative technique, pump settings, and modifications utilized to optimize peripheral perfusion are detailed.     

Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo

BACKGROUND: Tumor necrosis factor related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo-2L) is a novel anticancer agent, capable of inducing apoptosis preferentially in tumor and transformed cells. TRAIL-R1/death receptor (DR)4 and TRAIL-R2/DR5 are members of the tumor necrosis factor (TNF) receptor family, and can be activated by the TRAIL. We examined the clinical potential of chemotherapeutic drugs and TRAIL for the treatment of prostate cancer. METHODS: Prostate and bladder cancer cells were exposed to chemotherapeutic drugs (paclitaxel, vincristine, vinblastine, etoposide, doxorubicin, and camptothecin) and TRAIL. Cell viability was measured by sodium 3'[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) assay; expressions of death receptors and Bcl-2 family members were measured by Western blotting, ELISA and ribonuclease protection assay. PC-3 tumor cells xenografted athymic nude mice were exposed to chemotherapeutic drugs and TRAIL, either alone or in combination, to measure tumor growth and survival of mice. Apoptosis was measured by annexin V-FITC/propidium iodide staining, and terminal deoxynucleotidyltransferase-mediated nick end labeling assay. Caspase-3 activity was measured by the Western blotting and immunohistochemistry. RESULTS: TRAIL induced apoptosis with varying sensitivity. Chemotherapeutic drugs (paclitaxel, vincristine, vinblastine, etoposide, doxorubicin, and camptothecin) significantly augmented TRAIL-induced apoptosis in cancer cells through up-regulation of DR4, DR5, Bax, and Bak, and induction of caspase activation. Mitochondrial pathway enhanced the synergistic interactions between drugs and TRAIL. The sequential treatment of mice with chemotherapeutic drugs followed by TRAIL induced caspase-3 activity, and apoptosis, inhibited angiogenesis, completely eradicated the established tumors, and enhanced survival of mice. CONCLUSIONS: Chemotherapeutic drugs can be used to enhance the therapeutic potential of TRAIL in prostate cancer.     

Buccal mucosal urethroplasty: a versatile technique for all urethral segments

OBJECTIVE: To present our experience with buccal mucosa urethroplasty for substitution of all segments of the anterior urethra, as the buccal mucosal graft (BMG) has emerged as the tissue of choice for single-stage reconstruction of bulbar urethral strictures, but its use for reconstructing meatal, pendulous and pan-urethral strictures has not been widely reported. PATIENTS AND METHODS: Between January 1998 and October 2003, 92 patients had a BMG substitution urethroplasty at our institution; 75 had a single-stage dorsal onlay BMG urethroplasty (bulbar 41, pendulous 16 and pan-urethral 18; six combined penile skin flap and BMG) and 17 (pendulous five, pan-urethral 10, bulbar two) a two-stage urethroplasty. Recurrence rates, complications and cosmetic outcomes were analysed retrospectively. RESULTS: Over a median (range) follow-up of 34 (8-72) months, 66 (88%) patients with a one-stage reconstruction (14/16 pendulous; 37/41, 90%, bulbar; 15/16 pan-urethral) remained stricture-free. The mean (range) time to recurrence was 9.4 (3-17) months. Of the nine recurrent strictures, six were managed by one-stage optical urethrotomy and three required a repeat urethroplasty. In patients who had a staged procedure, after a mean follow-up of 24.2 (9-56) months, one had complete graft loss, requiring re-grafting, five required stomal revision after stage 1, and only two (12%) developed a recurrent stricture after the two-stage urethroplasty. CONCLUSION: A one-stage dorsal onlay BMG urethroplasty provides excellent results for strictures involving any segment of the anterior urethra. The BMG appears to be the most versatile urethral substitute, as it can be successfully used for both one- and two-stage reconstruction of the entire anterior urethra.     

Backpropagation Artificial Neural Network Detects Changes in Electro-Encephalogram Power Spectra of Syncopic Patients

This paper presents an effective application of backpropagation artificial neural network (ANN) in differentiating electroencephalogram (EEG) power spectra of syncopic and normal subjects. Digitized 8-channel EEG data were recorded with standard electrodes placement and amplifier settings from five confirmed syncopic and five normal subjects. The preprocessed EEG signals were fragmented in two-second artifact free epochs for calculation and analysis of changes due to syncope. The results revealed significant increase in percentage δ and α (p<0.5 or better) with significant reduction in percentage θ activity (p<0.05). The backpropagation ANN used for classification contains 60 nodes in input layer, weighted from power spectrum data from 0 to 30 Hz, 18 nodes in hidden layer and an output node. The ANN was found effective in differentiating the EEG power spectra from syncopic EEG power spectra and the normal EEG power spectra with an accuracy of 88.87% (85.75% for syncopic and 92% for normal). Certificate of Originality—This is to certify that the article submitted for publication in ‘Journal of Medical Systems’ has not been publ-ished, nor is being considered for publication, elsewhere. (Rakesh Kumar Sinha)     

Comparison of clinical and microbiological profiles in smear-positive and smear-negative cases of suspected microbial keratitis

PURPOSE: To examine the hypothesis that initial smear examination results have a significant bearing on the management and outcome of suspected microbial keratitis. MATERIALS AND METHODS: One hundred and seventy consecutive patients with suspected microbial keratitis were included in a prospective nonrandomized comparative study and their detailed clinical and microbiological data (smears and cultures of corneal scrapings) were captured on a predesigned corneal ulcer database. Patients were divided into two groups: Group 1 included 68 patients with corneal scrapings negative in smears while Group 2 included 102 patients with corneal scrapings positive in smears. The two groups were compared for their clinico-microbiological profile, management and clinical outcome. The outcome was noted at three months. Fisher's exact test was applied for statistical analysis. RESULTS: Cultures were sterile in 57.3% of patients in Group 1 compared to 17.6% in Group 2. Scrapings that grew S. pneumoniae, gram-negative organisms, fungi and Acanthamoeba were more often positive in smears (18.6%, 11.8%, 19.6% and 2.9% respectively). While data on duration of prior treatment was not available, prior medication made no significant difference to smear results. More (79.3%) patients of Group 1 had small infiltrate size (CONCLUSIONS: Initial smear examination helps in instituting specific therapy thereby improving the outcome in cases of microbial keratitis. Positive smears indicate greater severity of disease and prior medication may not be a significant cause of smear negativity.