A Case of Severe Falciparum Malaria in a Returned Traveler.

Primary care providers should be alert to travel-related infections. Around 10-40% of returning travelers from all destinations and 15-70% of travelers from tropical settings experience ill health, either overseas or upon returning home.1 A systematic approach concentrating on possible infections should be undertaken based on the patient's travel location, immunization history, presence of malaria chemoprophylaxis at the destination, other potential exposures, incubation period, and clinical presentation.2-3 The World Health Organization (WHO) website is constantly being updated on specific travel-related infections and recent geographical outbreaks. In this paper, we report a case of severe falciparum malaria in a returned traveler.

Does intra-tumoural fat on MRI predict visibility of small (≤3 cm) hepatocellular carcinomas during ultrasound-guided tumour ablation?

AIM: To assess if intra-tumoural fat on magnetic resonance imaging (MRI) affects the ultrasonographic (US) visibility of small (≤3 cm) hepatocellular carcinomas (HCC) during radiofrequency ablation (RFA). MATERIALS AND METHODS: Institutional review board approval was obtained. A retrospective review of all patients who underwent image-guided ablation between 1 January 2010 and 31 April 2015 was performed. Patients with HCC who underwent US RFA were included. Inclusion criteria included small tumours (≤3 cm), treatment-naive cases or new focus of HCC in a different and untreated segment, and pre-procedural MRI. The presence of intra-tumoural fat was determined retrospectively via in-and-out-of-phase MRI. Other factors that potentially affect ultrasonographic visibility, such as background fatty liver, presence of cirrhosis, tumour size, and distance from diaphragm, were recorded. RESULTS: Ninety procedures performed on 74 patients (62 men and 12 women; mean age: 67.3 years; range: 39-88 years). Seventy-two tumours were visible on US (hypoechoic n=35, hyperechoic n=28, heterogeneous n=9). Intra-tumoural fat was seen in 23 tumours (25.6%, hyperechoic n=17, hypoechoic n=6). The presence of intra-tumoural fat (p=0.005) and distance from diaphragm (p=0.007) were found to be statistically significant factors affecting tumour visibility on planning US. The presence of background fatty liver (p=0.485), cirrhosis (p=0.48), and tumour size (p=0.15) were not found to be significant. CONCLUSION: The present study shows that the presence of intra-tumoural fat in small HCCs on pre-procedural MRI can accurately predict their visibility on planning US during percutaneous tumour ablation.

Resting-state abnormalities in amnestic mild cognitive impairment: a meta-analysis.

Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer's disease (AD). As no effective drug can cure AD, early diagnosis and intervention for aMCI are urgently needed. The standard diagnostic procedure for aMCI primarily relies on subjective neuropsychological examinations that require the judgment of experienced clinicians. The development of other objective and reliable aMCI markers, such as neural markers, is therefore required. Previous neuroimaging findings revealed various abnormalities in resting-state activity in MCI patients, but the findings have been inconsistent. The current study provides an updated activation likelihood estimation meta-analysis of resting-state functional magnetic resonance imaging (fMRI) data on aMCI. The authors searched on the MEDLINE/PubMed databases for whole-brain resting-state fMRI studies on aMCI published until March 2015. We included 21 whole-brain resting-state fMRI studies that reported a total of 156 distinct foci. Significant regional resting-state differences were consistently found in aMCI patients relative to controls, including the posterior cingulate cortex, right angular gyrus, right parahippocampal gyrus, left fusiform gyrus, left supramarginal gyrus and bilateral middle temporal gyri. Our findings support that abnormalities in resting-state activities of these regions may serve as neuroimaging markers for aMCI.

The prevalence of lower urinary tract symptoms and treatment-seeking behaviour in males over 40 years in Singapore: a community-based study.

BACKGROUND: This study was performed to report the prevalence of lower urinary tract symptoms (LUTSs), bother and related quality of life (QOL) and health-seeking behaviour in men 40 years old or older in Singapore. METHODS: The study was a community-based, cross-sectional study targeting males 40 years and above in the township of Bedok North, Singapore. An interviewer-administered questionnaire inclusive of the International Prostate Symptom Score (IPSS) was used to score symptom severity objectively. RESULTS: There were a total of 644 respondents. In all, 16.5% of patients with LUTS had moderate-to-severe LUTS (IPSS ≥8). The prevalence of LUTS was found to be significantly associated with age, diabetes mellitus and hypertension. The impact on QOL because of LUTS was proportional to the severity of LUTS. Nocturia was associated with the most bother. Out of the respondents with moderate-to-severe LUTS, 71.7% of them did not seek help for their symptoms. CONCLUSION: The investigators thus conclude that LUTS is common in our population and has significant impact on QOL. However, <30% of patients with moderate-to-severe LUTS sought medical attention for symptoms. We believe that steps should be taken to increase public awareness and variability of treatment options to address this problem facing the growing number of elderly men in the population.

Inhibition of angiogenic and non-angiogenic targets by sorafenib in renal cell carcinoma (RCC) in a RCC xenograft model.

BACKGROUND: It is widely recognised that sorafenib inhibits a range of molecular targets in renal cell carcinoma (RCC). In this study, we aim to use patient-derived RCC xenografts to delineate the angiogenic and non-angiogenic molecular targets of sorafenib therapy for advanced RCC (aRCC). METHODS: We successfully generated three patient RCC-derived xenografts in severe combined immunodeficient mice, consisting of three different RCC histological subtypes: conventional clear cell, poorly differentiated clear cell RCC with sarcomatoid changes, and papillary RCC. This study also used clear cell RCC cells (786-0/EV) harbouring mutant VHL to investigate the clonogenic survival of cells transfected with survivin sense and antisense oligonucleotides. RESULTS: All three xenografts retain their original histological characteristics. We reported that sorafenib inhibited all three RCC xenograft lines regardless of histological subtypes in a dose-dependant manner. Sorafenib-induced growth suppression was associated with not only inhibition of angiogenic targets p-PDGFR-ß, p-VEGFR-2, and their downstream signalling pathways p-Akt and p-ERK, cell cycle, and anti-apoptotic proteins that include cyclin D1, cyclin B1, and survivin but also upregulation of proapoptotic Bim. Survivin knockdown by survivin-specific antisense-oligonucleotides inhibited colony formation and induced cell death in clear cell RCC cells. CONCLUSION: This study has shed light on the molecular mechanisms of sorafenib in RCC. Inhibition of non-angiogenic molecules by sorafenib could contribute in part to its anti-tumour activities observed in vivo, in addition to its anti-angiogenic effects.

Electroacupuncture versus celecoxib for neuropathic pain in rat SNL model.

Though acupuncture has long been used to treat various kinds of pain, its mechanisms remain partly understood. Our recent study has shown that it may inhibit cyclooxygenase-2 (COX-2) in the spinal dorsal horn where COX-2 is upregulated after the development of neuropathic pain following spinal nerve ligation (SNL). The current study directly compared the effect of acupuncture with COX-2 inhibitor celecoxib in the spinal cord after SNL in rats. After L5 SNL, the rats were treated either with acupuncture applied to Zusanli (ST36) and Sanyinjiao (SP6) bilaterally with or without electrical stimulation (2 Hz, 0.5-1-2 mA) four times over 22 days, and/or celecoxib fed daily. Paw-withdrawal-threshold to mechanical stimulation and paw-withdrawal-latency to thermal test were tested for neuropathic pain at four intervals following the treatments in comparison with the pre-treatment and non-treatment controls. The results demonstrate that electroacupuncture (EA) had a long lasting and better analgesic effect than celecoxib in reducing neuropathic hypersensitivity. Though COX-2 expression in the spinal L4-L6 dorsal horn by immunostaining was significantly reduced by acupuncture just as well as by celecoxib, the superior analgesic mechanism of acupuncture appears well beyond COX-2 inhibition alone.

Robotic ultrasound-guided prostate intervention device: system description and results from phantom studies.

BACKGROUND: We introduce the first robotic ultrasound-guided prostate intervention device and evaluate its safety, accuracy and repeatability. METHODS: The robotic positioning system (RPS) determines a target's x, y and z axes. It is situated with a biplane ultrasound probe on a mobile horizontal platform. The integrated software acquires ultrasound images for three-dimensional (3D) modelling, coordinates target planning and directs the RPS. RESULTS: The egg phantom evaluates the software's safety and workflow protocol. Two random targets are planned in each quadrant and biopsy needles are inserted. All were within three separate eggs. Metal wire tips are targeted and their distances from the biopsy needle tips are measured. With 20 wires, < 1 mm accuracy is obtained. Repeatability is demonstrated when previous positions are returned to with similar accuracy. CONCLUSION: Our device demonstrates safety in a defined boundary with a repeatable accuracy of < 1 mm. It can be used for accurate prostate biopsy and treatment delivery.

Electroacupuncture inhibits cyclooxygenase-2 up-regulation in rat spinal cord after spinal nerve ligation.

Electroacupuncture (EA) has long been used to treat pain including neuropathic pain, but its mechanisms remain to be delineated. Since cyclooxygenase-2 (COX-2) has been reported to increase in the spinal dorsal horn following spinal nerve ligation (SNL) and it may play a role in the neuropathic pain, we hereby tested the hypothesis that EA may affect COX-2 expression and hence neuropathic nociception after SNL. The results showed that EA (2 Hz) can significantly reduce mechanical and thermal hypersensitivity following lumbar L5 SNL in rats. Immunostaining demonstrated suppression of COX-2 expression in the spinal L4-L6 dorsal horn after EA. The present results suggest that EA may alleviate neuropathic hypersensitivity by, at least partially, inhibiting COX-2 expression in the spinal cord.

Inverted papilloma of urinary bladder: is long-term cystoscopic surveillance needed? A single center's experience.

OBJECTIVES: To review all cases of urinary bladder inverted papilloma (IP) in our institution and determine the need for cystoscopic surveillance. IP is an uncommon benign tumor of the urinary tract. Its multiplicity, recurrence, and association with transitional cell carcinoma (TCC) suggest possible malignant potential, leading to conflicting clinical conclusions regarding the need for surveillance. METHODS: All consecutive patients from January 1991 to December 2004 with IP were included in this study. A single pathologist performed the histologic review. The patients had undergone cystoscopy and ultrasound evaluation of the kidneys every 6 months. RESULTS: Of the 52 patients, 45 were men and 7 were women. The average age at presentation was 58.9 +/- 11.8 years (range 30 to 79). No patient had a synchronous or previous bladder tumor. The most common complaint was macroscopic hematuria. Ten cases were incidental findings during bladder ultrasonography or cystoscopy. All were solitary tumors, most commonly found at the bladder neck. The average follow-up period was 62 +/- 23 months, with no recurrence. One case of subsequent noninvasive papillary TCC developed 15 months later. The initial histologic findings had revealed cytologic atypia, with suspicious urine cytology findings. On review, it was more compatible with TCC with an inverted pattern. CONCLUSIONS: Although our cases exhibited benign biologic behavior, the presence of cytologic atypia and suspicious urine cytology require exclusion of TCC with an inverted pattern. Thus, in histologically proven solitary bladder IP with no associated TCC, cystoscopic surveillance may not be necessary.

Predictors of androgen independence in metastatic prostate cancer.

OBJECTIVE: To assess the factors that influence the onset of androgen independence (AI, which heralds a dismal outcome) in patients with metastatic prostate carcinoma. PATIENTS AND METHODS: The records of 361 consecutive patients with prostate carcinoma diagnosed and treated in the authors' institution from 1 January 1996 to 31 December 1999 were reviewed retrospectively; 92 with metastatic prostate carcinoma were assessed (median age 71.0 years, range 42-93). Patients were included if they developed metastatic disease from prostate cancer at the time of diagnosis. The nadir for prostate specific antigen (PSA) level was defined as the date of the lowest PSA level after hormonal therapy, and AI was defined as the date of the third consecutive PSA increase above the nadir value by any threshold. RESULTS: The median Gleason sum was 8 and the modal Gleason score 4 + 5. The median (range) pretreatment PSA level was 274.0 (1.3-2179) ng/mL. Of the 92 men, 57 (62%) attained a nadir PSA, including 23 with a nadir of < 2 ng/mL; 32 (35%) progressed to AI within 2 years and 27% reached a nadir PSA but did not develop AI. The mean (sd) time from diagnosis to the nadir PSA was 13.7 (11.8) months, while the mean time from diagnosis to progression to AI was 30.3 (15.6) months. Univariate analysis showed that a nadir PSA level after treatment of >/= 1 ng/mL (P = 0.0128) was an early predictor of progression to AI; a nadir PSA level of >/= 2 ng/mL (P = 0.0216) was a predictor of poor overall survival. CONCLUSION: Failure to attain a nadir PSA of < 1 ng/mL after treatment predicts progression to AI and a nadir PSA of > 2 ng/mL predicts poorer overall survival. The development of skeletal events predicts the onset of AI but occurs late in the disease and is unsuitable as an early prognostic marker.

Selective knockdown of gene expression of N-methyl-D-aspartate receptor one ameliorates parkinsonian motor symptom in 6-hydroxydopamine-lesioned rats.

The present study reported the efficacy of antisense oligonucleotides specific for N-methyl-D-aspartate receptor one (NR1) in reduction of motor symptom in a rat parkinsonian model, the unilateral 6-hydroxydopamine-lesioned rat. Significant reductions in apomorphine-induced contralateral rotation were only seen in the NR1 antisense-treated lesioned rats (after a single intraparenchymal dose of antisense to the lesioned neostriatum; 15 nmol in 3 microl of saline) at 1 or 2 days after the treatment. No motor effect was seen in the lesioned animals with control treatments (sham, treatment using NR1 sense oligonucleotides, randomized oligonucleotides or saline, respectively). In contrast, significant increases in expression of NR1 mRNA in the lesioned neostriatum were seen in rats with control treatments but not in rats with NR1 antisense treatment. Importantly, in the lesioned neostriatum that was treated with NR1 antisense, a significant reduction in NR1 protein expression was found and NR1 immunoreactivity was seen to reduce in perikarya of presumed striatal medium spiny neurons. The present data indicate that a single dose of NR1 antisense ameliorates motor symptom in the rat model. The efficacy of NR1 antisense is likely to be mediated by a selective knockdown in expression of NR1 mRNA and proteins in the presumed medium spiny neurons.

Endorectal magnetic resonance imaging and spectroscopy for the detection of tumor foci in men with prior negative transrectal ultrasound prostate biopsy.

PURPOSE: We determined the ability of combined endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) to detect prostate cancer foci prospectively in men with prior negative transrectal ultrasound (TRUS) prostate biopsy. MATERIALS AND METHODS: Endorectal MRI with spectroscopy was performed in 24 consecutive patients with 1 or more prior negative TRUS prostatic biopsies for persistently increased prostate specific antigen and/or abnormal digital rectal examination. All studies were interpreted by a dedicated radiologist who reported areas of interest in the peripheral zone as normal, equivocal or suspicious on MRI and MRSI separately. Equivocal and suspicious areas were then correlated with a 3-dimensional prostate model. All patients underwent a standard TRUS 10-core peripheral zone biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites. RESULTS: Prostate cancer was detected in 7 of 24 subjects (29.2%). Considering the equivocal category as test negative the sensitivity, specificity, positive and negative predictive values, and the accuracy of MRI, MRSI and combined MRI/MRSI for the detection of prostate cancer were 57.1%, 57.1% and 100.0%, 88.2%, 82.4% and 70.6%, 66.7%, 57.1% and 58.3%, 83.3%, 82.1% and 100%, and 79.2%, 75.0% and 79.2%, respectively. The site of positive biopsy correlated correctly in 50% and 28.6% of MRI and MRSI labeled suspicious cores, respectively. CONCLUSIONS: MRI and MRSI have the potential to identify cancer foci and direct TRUS in patients with a previous negative TRUS biopsy. Further, larger studies are required to quantify the amount of benefit.

Contralateral adrenal metastasis of renal cell carcinoma: treatment, outcome and a review.

OBJECTIVE: To report the surgical treatment of patients with renal cell carcinoma (RCC) metastatic to the contralateral adrenal gland and compare our experience with previous reports, as such metastases are found in 2.5% of patients with metastatic RCC at autopsy, and the role of resecting metastatic RCC at this site is not well defined. PATIENTS AND METHODS: We retrospectively identified 11 patients who had surgery for metastatic RCC to the contralateral adrenal gland between October 1978 and April 2001. The patients' medical records were reviewed for clinical, surgical and pathological features, and the patients' outcome. RESULTS: The mean (median, range) age of the patients at primary nephrectomy was 60.9 (64, 43-79) years; all had clear cell (conventional) RCC. Synchronous contralateral adrenal metastasis occurred in two patients. The mean (median, range) time to contralateral adrenal metastasis after primary nephrectomy for the remaining nine patients was 5.2 (6.1, 0.8-9.2) years. All patients were treated with adrenalectomy; there were no perioperative complications or mortality. Seven patients died from RCC at a mean (median, range) of 3.9 (3.7, 0.2-10) years after adrenalectomy for contralateral adrenal metastasis; one died from other causes at 3.4 years, one from an unknown cause at 1.7 years and two were still alive at the last follow-up. CONCLUSIONS: The surgical resection of contralateral adrenal metastasis from RCC is safe; although most patients died from RCC, survival may be prolonged in individual patients. Hence, in the era of cytoreductive surgery, the removal of solitary contralateral adrenal metastasis seems to be indicated.

Differential expression of N-methyl-D-aspartate receptor subunit messenger ribonucleic acids and immunoreactivity in the rat neostriatum during postnatal development.

The present study was performed to investigate the patterns of gene expression of N-methyl-D-aspartate (NMDA) receptors (NRs) in the rat neostriatum during postnatal development. Reverse transcriptase-polymerase chain reactions (RT-PCR) indicated that levels of NR1, NR2A and NR2D mRNAs reached peak levels between postnatal days 7 (PND 7) and PND 14. The levels of NR2B and NR2C mRNAs were low at PND 1 and their levels increased at PND 7 and remained high in adults. Immunofluorescence combined with image analysis revealed that the levels of NR1 immunoreactivity rose to its maximum at PND 14. In contrast, NR1 immunoreactivity rose progressively in perikarya of striatal neurons. Levels of NR2A immunoreactivity in the neostriatum were highest in adults. However, levels of NR2A immunoreactivity were higher in striatal neurons at PND 1 and PND 7. Levels of NR2B immunoreactivity were highest at PND 7. In the perikarya of striatal neurons however, the highest levels of NR2B immunoreactivity were detected at PND 14 and adult striatal neurons. In addition, double immunofluorescence revealed that the levels of NR1 immunoreactivity increased but the levels of NR2A immunoreactivity were the same in parvalbumin (PV)-positive striatal interneurons of PND 14 and adult rats. NR2B immunoreactivity was not detected in PV-positive neurons of PND 14 rats, but intense NR2B labeling was seen in PV-positive neurons of adult rats. Last but not least, in choline acetyltransferase (ChAT)-positive striatal interneurons of PND 14 and adult rats, levels of NR1 and NR2A immunoreactivity was seen to increase. Level of NR2B immunoreactivity remained the same in ChAT-positive neurons of PND 14 and adult rats. The present results indicate that there are differential patterns of expression of NR mRNAs and immunoreactivity in the neostriatum during different stages of postnatal development. Different combinations of NR have been found in different subpopulations of striatal neurons at different developmental stages. NR1, NR2A and NR2B are the major NMDA receptor subunits expressed during development. The change in patterns of expression of NR may be related to the functional maturation of neurons in the neostriatum.

Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate glutamate receptors in the rat striatum during postnatal development.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type glutamate receptors (GluR1-4) are one of the most important ionotropic glutamate receptors in the striatum, a key region of the basal ganglia. The present study investigated the trend of developmental expression of AMPA receptor subunits in the striatum of rats in different developmental stages, i.e., at postnatal day 7 (PND7), PND21 and adult. Perfuse-fixed striatal sections were used. The expression of AMPA subunits was studied by immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR revealed that the levels of expression of the GluR1 and GluR3 mRNAs were the same among the age groups. The level of GluR2 mRNA was highest in PND21 rats and lowest in adult. The highest level of GluR4 mRNA was detected in rats at PND7. Similar trends of GluR1, GluR2 and GluR2/3 immunoreactivity expression were observed using commercially available specific antibodies. In addition, a large proportion of parvalbumin-immunoreactive GABAergic interneurons in the striatum were found to display GluR1 immunoreactivity in PND21 and adult rats. In contrast, most of the choline acetyltransferase-immunoreactive cholinergic interneurons were found to display GluR2 immunoreactivity but less GluR1 and no GluR2/3 immunoreactivity in PND21 and adult rats. The present study suggests that there is a distinct pattern of expression of AMPA-type receptor mRNAs and proteins in the rat striatum at different stages of development.

A twelve-year review of radical cystectomies in Singapore General Hospital.

INTRODUCTION: Bladder carcinoma is the tenth most common cancer affecting men in Singapore. This study reviews the complication rates and long-term outcome after radical cystectomy for bladder carcinoma. PATIENTS AND METHODS: A retrospective case-record review of 90 consecutive radical cystectomies in the Department of Urology at the Singapore General Hospital from 1 January 1989 to 31 December 2000 was performed. Patients were included if they were operated for muscle-invasive tumour, high-grade tumour with carcinoma in-situ (CIS), recurring multifocal high-grade tumour, CIS unresponsive to intravesical therapy, or endoscopically uncontrollable tumour. Patients were excluded if they had metastatic disease or non-bladder primary carcinomas. RESULTS: The patients were predominantly male (M:F, 80:10) and Chinese (Chinese:Malay:Indian:Others, 70:10:3:7) with a mean age of 64.1 +/- 9.9 years (range, 39 to 83 years). Fifty-one patients underwent ileal conduit creation, 36 had ileal neobladder creation, 2 had ureterosigmoidostomies and 1 had Mainz II pouch creation following radical cystectomy. Perioperative mortality was 2.2% (n = 2). Early complications constituted 39% (n = 35), whilst late complications constituted 14% (n = 13) of cases. The mean follow-up was 27.1 +/- 29.7 months (range, 1 to 137 months). The mean time to recurrence was 26.0 +/- 29.5 months (range, 3 to 137 months). The overall survival was 70%, 43% and 37% at 1, 3 and 5 years, respectively. The disease-free survival was 64%, 35% and 32% at 1, 3 and 5 years, respectively. CONCLUSION: The results of our radical cystectomies for bladder carcinoma are comparable to other established urology units although the morbidity remained significant.

Different trends in modulation of NMDAR1 and NMDAR2B gene expression in cultured cortical and hippocampal neurons after lead exposure.

Exposure to heavy metal lead (Pb(2+)) has been reported to cause problems in cognitive functions of the brain, e.g. memory loss and difficulties in mental development. N-Methyl-D-aspartate receptors (NRs) are important molecules that are known to be involved in mediation of learning and memory. In order to investigate the effects of Pb(2+) on the gene expression of NR1 and NR2B subunits in neurons, primary cell cultures of rat cortical and hippocampal neurons were employed. After treatments with different concentrations of Pb(2+) ions in culture medium (0, 5, 10, 25 and 50 microM), the cellular localization of Pb(2+) in neurons was evaluated by laser scan confocal microscopy by using a Pb(2+) ion specific fluorescence probe. In addition, the gene expression of NR1 and NR2B subunits was determined by reverse transcriptase-polymerase chain reaction, immunofluorescence and Western blotting. The results of the present study showed that both cortical and hippocampal neurons accumulated intracellular Pb(2+) in accordance with the concentrations of Pb(2+) ions present in the culture medium. After Pb(2+) treatments, levels of NR1 mRNA, immunoreactivity and protein were found to be unchanged but levels of NR2B mRNA, immunoreactivity and protein were found to be significantly increased in cortical neurons. In contrast, both NR1 and NR2B mRNAs, immunoreactivity and proteins were found to be significantly decreased in hippocampal neurons. The changes in gene expression were found to be dose dependent in accordance with the Pb(2+) concentrations. The present results indicate that Pb(2+) has a differential effect on the expression of NR1 and NR2B subunits in cortical and hippocampal neurons, respectively. It is likely that the toxic effects of Pb(2+) may cause differential damage to different types of memory that are mediated by cortical and hippocampal neurons, respectively.

Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4.

PURPOSE: We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. CONCLUSIONS: In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.

Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney.

OBJECTIVE: To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney. PATIENTS AND METHODS: Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (< or = 30 days) complications and proteinuria at last follow-up. RESULTS: At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52-1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30-5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively (P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2-11.2; P = .01). CONCLUSIONS: This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS.

Cystoscopic diagnosis of bladder cancer by intravesical instillation of 5-aminolevulinic acid induced porphyrin fluorescence--the Singapore experience.

OBJECTIVES: 1) To determine whether fluorescence cystoscopy after intravesical administration of 5-aminolevulinic acid (5-ALA) is more sensitive in detection of dysplasia and bladder cancer when compared with conventional cystoscopy. 2) To determine the safety of using 5-ALA. MATERIALS AND METHODS: A 3% 5-ALA solution was instilled intravesically before cystoscopy in 41 patients. The 5-ALA-induced porphyrin fluorescence was excited by violet light from a xenon arc lamp (lambda 375-440 mm). RESULTS: Among the 175 biopsies obtained, the sensitivity of the fluorescence cystoscopy was greater than that of conventional cystoscopy (89.1% versus 65.6%, P < 0.05). Specificity was at 64.8% and 83.8% respectively with P < 0.05. Duration of ALA instillation did not seem to affect the sensitivity and specificity of photodynamic diagnosis. The procedures were well tolerated by all patients with no additional complication. CONCLUSIONS: Fluorescence-guided biopsies are more sensitive than random biopsies in detecting dysplasia or bladder cancer without additional risk or complication. The duration of ALA instillation did not seem to affect the accuracy of photodynamic diagnosis.