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PURPOSE: To assess whether therapeutic and toxic effects of intravesical lidocaine are determined by coincident serum levels. MATERIAL AND METHODS: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times. RESULTS: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.16±0.3 mg/L at 5 min in bladder cancer patients coinciding with the rapid onset of pain relief (<5 min) and blood pressure drop (≥10 mm Hg) in spinal cord injured patients. Serum levels at 5 min are raised five-fold by alkalinization for a tertiary amine with pKa of 7.8 and a linear rise in F with longer dwell time (r2 = 0.80; P<0.005) conforms to passive, paracellular diffusion of amphiphilic lidocaine (log P of 1.68) around umbrella cell borders with absorption rate at least five times faster than the terminal elimination rate, and therefore the delay in blood sampling after instillation is unwarranted. A rapid resolution of therapeutic and toxic effects is predicated on the extensive dilution of absorbed lidocaine with a rapid distribution half-life of 3.6 min in body weight dependent Vd - 15 times larger than blood volume, 0.13-4.5 L/kg which necessitates dose adjustment in children. CONCLUSION: Whether rapid absorption of instilled lidocaine is complicated by an equally rapid and extensive dilution in body weight dependent Vd can be resolved by early blood sampling (<30 min) for: evidence-based medicine, avoidance of lidocaine toxicity in children and to educate the evolution of lidocaine solution to gel and devices.
ABSTRACT
Electronic cigarette (EC) use is gaining popularity as a substitute for conventional smoking due to the perception and evidence it represents a safer alternative. In contrast to the common perception amongst users that ECs represent no risk initial studies have revealed a complex composition of e-cigarette liquids. Conventional cigarette smoking is a known risk factor for developing bladder cancer and prior reports raise concern some of those causative compounds may exist in EC liquids or vapor. Urine samples were collected from 13 e-cigarette using subjects and 10 non e-cigarette using controls. Five known bladder carcinogens that are either present in conventional cigarettes, products of combustion, or solvents believed to be used in some e-cigarette formulations were quantified by liquid chromatography - mass spectrometry (LC-MS). Analysis of e-cigarette user urine revealed the presence of two carcinogenic compounds, o-toluidine and 2-naphthylamine, at a mean 2.3 and 1.3 fold higher concentration (p-value of 0.0013 and 0.014 respectively). Many of these subjects (9/13) were long term nonsmokers (>12 months). Further study is needed to clarify the safety profile of e-cigarettes and their contribution to the development of bladder cancer given the greater concentration of carcinogenic aromatic amines in the urine of e-cigarette users.
Subject(s)
Carcinogens/analysis , Electronic Nicotine Delivery Systems , 2-Naphthylamine/analysis , Adult , Case-Control Studies , Chromatography, High Pressure Liquid , Female , Humans , Male , Mass Spectrometry , Middle Aged , Toluidines/urine , Young AdultABSTRACT
Adenocarcinoma of the rete testis is a rare and aggressive malignancy arising from the epididymal epithelium. We present a case of a 66-year-old male who presented with left testis mass. Histopathological analysis of orchiectomy specimen was consistent with adenocarcinoma of the rete testis. Subsequent retroperitoneal lymph node dissection revealed metastatic disease not detected on preoperative PET-CT. Prior reports have suggested poor response rates to both systemic chemotherapy and radiation therapy. Aggressive surgical management of the retroperitoneum should be considered even in clinically node-negative patients given the paucity of other effective treatment regimens.
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Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70-98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office-based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases ("Ammps") is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin-conjugated alginate (Fe(II)) nanoparticles by collagenases generates free-floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation.
Subject(s)
Hematuria/diagnosis , Hematuria/urine , Molecular Diagnostic Techniques/methods , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/urine , Female , Humans , Male , Middle Aged , Pilot Projects , Point-of-Care Systems , Sensitivity and SpecificityABSTRACT
INTRODUCTION: To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer. MATERIALS AND METHODS: We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups. RESULTS: There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses. CONCLUSIONS: Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.
Subject(s)
Arginine/therapeutic use , Cystectomy , Postoperative Complications/microbiology , Postoperative Complications/prevention & control , Preoperative Care/methods , Urinary Bladder Neoplasms/surgery , Aged , Cystectomy/methods , Female , Humans , Male , Middle Aged , Pilot Projects , Postoperative Complications/immunologyABSTRACT
Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non-tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee-approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material-enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 µm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. (©) RSNA, 2016 Online supplemental material is available for this article.
Subject(s)
Bacteriochlorophylls/pharmacology , Kidney/drug effects , Liver/drug effects , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , Animals , Contrast Media , Female , Immunohistochemistry , Kidney/diagnostic imaging , Liver/diagnostic imaging , Models, Animal , Necrosis , Optical Fibers , Swine , Tomography, X-Ray ComputedABSTRACT
The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome.
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Purpose. To determine whether total psoas area (TPA), a simple estimate of muscle mass, is associated with complications after radical cystectomy. Materials and Methods. Patients who underwent radical cystectomy at our institution from 2011 to 2012 were retrospectively identified. Total psoas area was measured on preoperative CT scans and normalized for patient height. Multivariable logistic regression was used to determine whether TPA was a predictor of 90-day postoperative complications. Overall survival was compared between TPA quartiles. Results. 135 patients were identified for analysis. Median follow-up was 24 months (IQR: 6-37 months). Overall 90-day complication rate was 56% (75/135). TPA was significantly lower for patients who experienced any complication (7.8 cm(2)/m(2) versus 8.8 cm(2)/m(2), P = 0.023) and an infectious complication (7.0 cm(2)/m(2) versus 8.7 cm(2)/m(2), P = 0.032) than those who did not. On multivariable analysis, TPA (adjusted OR 0.70 (95% CI 0.56-0.89), P = 0.003) and Charlson comorbidity index (adjusted OR 1.34 (95% CI 1.01-1.79), P = 0.045) were independently associated with 90-day complications. TPA was not a predictor of overall survival. Conclusions. Low TPA is associated with infectious complications and is an independent predictor of experiencing a postoperative complication following radical cystectomy.
ABSTRACT
OBJECTIVES: To test a novel porcine two-kidney model for evaluating the effect of controlled acute kidney injury (AKI) related to induced unilateral ischaemia on both renal units (RUs) To use neutrophil gelatinase-associated lipocalin (NGAL) and physiological serum and urinary markers to assess AKI and renal function. METHODS: Twelve female Yorkshire pigs had bilateral cutaneous ureterostomies placed laparoscopically with identical duration of pneumoperitoneum for all cases. An experimental group (n = 9) underwent induced unilateral renal ischaemia with left hilar clamping of timed duration (15, 30, 60 min) and a control group (n = 3) had no induced renal ischaemia. Urine was collected and analysed from each RU to assess creatinine and NGAL concentration preoperatively and at multiple postoperative time points. Serum was collected and analysed daily for creatinine and NGAL levels. Statistical comparisons were made using the rank-sum and sign-rank tests. RESULTS: Three pigs were excluded because of intra-operative and postoperative complications. In the RUs that experienced renal ischaemia (n = 7),the median urine volume was lower (P = 0.04) at 6, 12, 24 and 48 h and the median NGAL concentration was higher (P = 0.04) at 12 and 48 h compared with the RUs of control pigs that experienced no renal ischaemia (n = 2). When comparing the ischaemic (left) RU of the pigs in the experimental group with their contralateral non-ischaemic (right) RU, ischaemic RUs had a lower median cumulative urine volume at 6, 12, 24 and 48 h (P = 0.05) and a higher median NGAL concentration at 12, 24 and 48 h (P < 0.05). At 48 h, no significant increase was found in serum NGAL in pigs in the experimental group compared with controls (P = 0.2). Creatinine clearance (CC) was lower in ischaemic RUs compared with non-ischaemic RUs 1 day after surgery (P = 0.04) with decreasing CC as the duration of ischaemia increased. CONCLUSIONS: We have developed a promising novel small-scale pilot surgical model that allowed the evaluation of bilateral RU function separately during and after unilateral renal ischaemia. The induction of unilateral renal ischaemia corresponds with physiological changes in both the ischaemic and contralateral RU. AKI as measured by increases in NGAL and decreased renal function as measured by decreases in CC, are specific to the RU exposed to ischaemia.
Subject(s)
Acute Kidney Injury , Disease Models, Animal , Acute-Phase Proteins , Animals , Gelatinases , Ischemia , Kidney/blood supply , Lipocalins , Neutrophils , Pilot Projects , Proto-Oncogene Proteins , SwineABSTRACT
BACKGROUND: The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear. OBJECTIVE: Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo. INTERVENTION: RC with mapping PLND. MEASUREMENTS: We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression. RESULTS AND LIMITATIONS: Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04-3.46], p=0.036; versus HR: 4.3 [95% CI, 2.25-8.34], p<0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10-42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22-54] and 35% [95% CI, 11-60], respectively). This study is limited by the lack of prospective randomization and a control group. CONCLUSIONS: The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.
Subject(s)
Carcinoma/pathology , Carcinoma/surgery , Cystectomy/methods , Lymph Node Excision/methods , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Aged , Carcinoma/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Prognosis , Prospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/mortalityABSTRACT
PURPOSE: To evaluate two methods of scanning and tissue processing to achieve accurate magnetic resonance (MR)-histologic correlation in human prostate specimens. MATERIALS AND METHODS: Two prostates had acrylic paint markers injected to define the plane of imaging and serve as internal fiducials. Each was placed on a polycarbonate plane-finder device (PFD), which was adjusted to align the imaging and cutting planes. Three prostates were aligned by use of a plane finder key (PFK), a polycarbonate plate that locks the specimen in a cylindrical carrier. Markers were injected for registration analysis. Prostates were imaged, then sectioned. Imaging software was used to create registration maps of the MR and histology images. Measurements between control points were made and compared. RESULTS: Accurate correlation was achieved between MR and histologic images. The mean displacement (MD) between the corresponding registration points using the PFD technique ranged from 1.11-1.38 mm for each section. The MD for all sections was 1.24 mm. The MD using the PFK technique ranged from 0.79-1.01 mm for each section, and the MD across all sections for the PFK was 0.92 mm. CONCLUSION: We describe two methods that can achieve accurate, reproducible correlation between MR imaging and histologic sections in human prostatectomy specimens.
Subject(s)
Biopsy/methods , Fiducial Markers , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Prostate/pathology , Subtraction Technique/instrumentation , Equipment Design , Equipment Failure Analysis , Humans , Image Enhancement/instrumentation , Image Enhancement/methods , In Vitro Techniques , Male , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
PURPOSE: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. MATERIALS AND METHODS: Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. RESULTS: Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. CONCLUSIONS: Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.
Subject(s)
Carcinoma, Transitional Cell/physiopathology , Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/physiopathology , Kidney/physiopathology , Nephrectomy/methods , Ureter/surgery , Ureteral Neoplasms/physiopathology , Ureteral Neoplasms/surgery , Aged , Female , Humans , Kidney Function Tests , Kidney Neoplasms/surgery , Male , Retrospective Studies , Treatment OutcomeABSTRACT
CONTEXT: The optimal treatment strategy for muscle-invasive bladder cancer remains controversial. OBJECTIVE: To determine optimal combination of chemotherapy and surgery aimed at preserving survival of patients with locally advanced bladder cancer. EVIDENCE ACQUISITION: We performed a critical review of the published abstract and presentation literature on combined modality therapy for muscle-invasive bladder cancer. We emphasized articles of the highest scientific level, combining radical cystectomy and perioperative chemotherapy with curative intent to affect overall and disease-specific survival. EVIDENCE SYNTHESIS: Locally invasive, regional, and occult micrometastases at the time of radical cystectomy lead to both distant and local failure, causing bladder cancer deaths. Neoadjuvant and adjuvant chemotherapy regimens have been evaluated, as well as the quality of cystectomy and pelvic lymph node dissection. CONCLUSIONS: Prospective, randomized clinical trials argue strongly for neoadjuvant cisplatin-based chemotherapy followed by high-quality cystectomy performed by an experienced surgeon operating in a high-volume center. Adjuvant chemotherapy after surgery is also effective when therapeutic doses can be given in a timely fashion. Both contribute to improved overall survival; however, many patients receive only one or none of these options, and the barriers to receiving optimal, combined, systemic therapy and surgery remain to be defined. An aging, comorbid, and often unfit population increasingly affected by bladder cancer poses significant challenges in management of individual patients.
Subject(s)
Cystectomy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Evidence-Based Medicine , Humans , Lymph Node Excision , Neoadjuvant Therapy , Neoplasm Invasiveness , Survival Rate , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVES: Tumor volume and percent cancer (ratio of tumor volume/prostate volume) have been proposed as predictors of biochemical recurrence and cancer specific survival after radical prostatectomy. However, their relative merits as prognosticators have not been tested. We therefore evaluated and compared tumor volume and percent cancer as independent predictors of biochemical recurrence and prostate cancer specific death after radical prostatectomy. METHODS AND MATERIALS: A retrospective review of 739 patients who underwent radical prostatectomy for prostate cancer between 1984 and 2004 was conducted. Median follow-up was 91.7 months, and 22 patients died of prostate cancer. Univariate and multivariate analysis evaluated the following factors in predicting biochemical recurrence and prostate cancer specific death: tumor volume, prostate volume, percent cancer, Gleason score, percentage of Gleason grade 4/5, margin status, capsular invasion status, seminal vesicle invasion status, preoperative PSA, and lymph node status. RESULTS: In univariate analysis, both tumor volume (P<0.001) and percent cancer (P<0.001) significantly correlated with biochemical recurrence. Since they are highly correlated, they did not predict outcome independently when included in the same model; however, both were highly predictive for biochemical recurrence in separate multivariate models (P=0.01 for both). Both also correlated with cancer specific survival as single variables; however, in separate multivariate models, only tumor volume (P=0.03) predicted death, while percent cancer did not (P=0.09). CONCLUSIONS: Tumor volume and percent cancer are independent predictors of recurrence after radical prostatectomy. However, in our series, tumor volume predicted cancer specific death better than percent cancer. Therefore, accurate determination of tumor volume, along with other accepted pathologic indices, is sufficient and preferred over percent cancer for prognostication after radical prostatectomy.
Subject(s)
Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Assessment , Survival RateABSTRACT
The rapid adoption of robotic-assisted laparoscopic radical prostatectomy (RALP) has occurred despite a lack of high-quality evidence demonstrating its oncologic advantages, safety, or cost effectiveness compared with open radical retropubic prostatectomy (ORP). This review examines the current literature comparing ORP and RALP, focusing on perioperative, oncologic, functional, and economic outcomes.
Subject(s)
Laparoscopy/methods , Prostatectomy/methods , Robotics , Evidence-Based Medicine , Humans , Male , Prostatic Neoplasms/surgery , Treatment OutcomeABSTRACT
PURPOSE: Confocal laser endomicroscopy is a new endoscopic imaging technology that could complement white light cystoscopy by providing in vivo bladder histopathology. We evaluated confocal laser endomicroscopy by imaging normal, malignant appearing and indeterminate bladder mucosa in a pilot study. MATERIALS AND METHODS: Patients scheduled to undergo transurethral resection of bladder tumors were recruited during a 3-month period. After standard cystoscopy fluorescein was administered intravesically and/or intravenously as a contrast dye. A 2.6 mm probe based confocal laser endomicroscope was passed through a 26 Fr resectoscope to image normal and abnormal appearing areas. The images were collected with 488 nm excitation at 8 to 12 frames per second. The endomicroscopic images were compared with standard hematoxylin and eosin analysis of transurethral resection of bladder tumor specimens. RESULTS: Of the 27 recruited patients 8 had no cancer, 9 had low grade tumors, 9 had high grade tumors and 1 had a low grade tumor with a high grade focus. Endomicroscopic images demonstrated clear differences between normal mucosa, and low and high grade tumors. In normal urothelium larger umbrella cells are seen most superficially followed by smaller intermediate cells and the less cellular lamina propria. In contrast, low grade papillary tumors demonstrate densely arranged but normal-shaped small cells extending outward from fibrovascular cores. High grade tumors show markedly irregular architecture and cellular pleomorphism. CONCLUSIONS: We report the first study to our knowledge of in vivo confocal laser endomicroscopy in the urinary tract. Marked differences among normal urothelium, low grade tumors and high grade tumors were visualized. Pending further clinical investigation and technological improvement, confocal laser endomicroscopy may become a useful adjunct to conventional cystoscopy.
Subject(s)
Urinary Bladder Neoplasms/pathology , Aged , Aged, 80 and over , Biopsy/methods , Cystoscopy , Humans , Microscopy, Confocal , Middle Aged , Pilot ProjectsABSTRACT
PURPOSE: Computerized tomography has a critical role in the surveillance of stage I nonseminomatous germ cell tumors of the testis. Some protocols call for up to 16 computerized tomography scans over 5 years, thereby exposing young patients to a significant amount of radiation. We estimated the lifetime risk of cancer incidence and cancer death from imaging related radiation received during surveillance of stage I nonseminomatous germ cell tumor. MATERIALS AND METHODS: Using a model with a 64-slice computerized tomography scanner obtaining images of the abdomen and pelvis with or without chest in a standardized, phantom male patient, organ specific radiation doses were estimated using Monte Carlo simulation techniques. Lifetime attributable risks of cancer were estimated using the approach outlined in the Biological Effects of Ionizing Radiation VII Phase 2 report. RESULTS: With a 5-year surveillance protocol as suggested by the National Comprehensive Cancer Network, lifetime cancer risk ranged from 1 in 52 (1.9%) for an 18-year-old to 1 in 63 for a 40-year-old patient (1.2%). If chest computerized tomography is also performed the risk increases to 1 in 39 (2.6%) and 1 in 85 (1.6%), respectively. Lung and colon cancer accounted for most of the risk. The relative risk of a secondary malignancy with surveillance compared to a single scan after retroperitoneal lymph node dissection is approximately 15.2. CONCLUSIONS: Computerized tomography used in testicular cancer surveillance protocols imparts large radiation doses and is associated with a significant risk of cancer. This risk should be factored into counseling patients with stage I nonseminomatous germ cell tumor.
Subject(s)
Neoplasms, Radiation-Induced/epidemiology , Radiation Dosage , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/pathology , Tomography, X-Ray Computed/adverse effects , Adolescent , Adult , Age Distribution , Biopsy, Needle , Cohort Studies , Diagnostic Imaging/adverse effects , Diagnostic Imaging/methods , Dose-Response Relationship, Radiation , Follow-Up Studies , Humans , Immunohistochemistry , Incidence , Male , Middle Aged , Monitoring, Physiologic/adverse effects , Monitoring, Physiologic/methods , Monte Carlo Method , Neoplasm Staging , Neoplasms, Radiation-Induced/pathology , Predictive Value of Tests , Registries , Risk Assessment , Survival Rate , Testicular Neoplasms/mortality , Testicular Neoplasms/surgery , Tomography, X-Ray Computed/statistics & numerical data , Young AdultABSTRACT
Recent guidelines for particulate matter and aerosol measurements in the workplace describe sampling criteria for three progressively finer particle-size-selective fractions: inhalable, thoracic, and respirable. For substances like wood dust, for which health concerns usually center on particles that enter and deposit within the nasal passages, the inhalable fraction, which by definition includes particles ranging from 0 to 100 microm in diameter, is of greatest interest. There are a variety of commercially available personal samplers that can be used to measure inhalable dust in the workplace. At this time, however, most of these samplers have received only limited field testing in wood-products facility workplaces. This study compared the performance of three different personal inhalable dust samplers and a personal total dust sampler in several different wood-products industry facilities. Specifically, the study provided information on sampler precision and the relationship between results obtained with the various personal samplers. The personal samplers that were evaluated were the Institute of Occupational Medicine (IOM), the conical inhalable (CIS), and the multi-orifice (7-Hole) inhalable dust samplers and the closed-face filter cassette (CFFC) total dust sampler. Study results suggest that the CIS and CFFC may be more precise than the IOM and 7-hole samplers. Results also indicate that the relative performance of the inhalable samplers as compared to the total dust sampler may vary as a function of particle size distribution in the workplace.
Subject(s)
Dust/analysis , Environmental Monitoring/instrumentation , Occupational Exposure , Wood , Equipment Design , Humans , Industry , Inhalation Exposure , Specimen Handling , WorkplaceABSTRACT
Previously we have shown that treatment with the peroxisome proliferator perfluorodecanoic acid (PFDA) significantly increased hepatic reduced glutathione (GSH) content without altering the activity of selenium-glutathione peroxidase. In this study we examined some potential mechanisms by which PFDA treatment increases GSH levels. Male Sprague-Dawley rats were given a single injection of 0, 8.8, 17.5, and 35 mg PFDA in corn oil per kg body weight. Twelve days later the effects of PFDA on the activities of enzymes associated with GSH synthesis, utilization, and regeneration were assessed. The results showed that in a dose-dependent manner, PFDA treatment significantly decreased the activity of gamma-glutamylcysteine synthetase, while the activities of NADPH-generating enzymes, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were increased. PFDA treatment also dose dependently decreased cytosolic, but not microsomal, glutathione S-transferase activity, and the activity of glutathione reductase was decreased by the highest dose of PFDA. The data obtained suggest that increased hepatic GSH levels following PFDA treatment may result from increased regeneration and/or decreased utilization.
Subject(s)
Decanoic Acids/pharmacology , Fluorocarbons/pharmacology , Glutathione/metabolism , Liver/drug effects , Liver/enzymology , Peroxisome Proliferators/pharmacology , Subcellular Fractions/drug effects , Subcellular Fractions/enzymology , Animals , Dose-Response Relationship, Drug , Glucosephosphate Dehydrogenase/metabolism , Liver/metabolism , Malate Dehydrogenase/metabolism , Male , Phosphogluconate Dehydrogenase/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
The purpose of this study was to determine if differences in antioxidant status between the red blood cells (RBCs) of sickle cell anemia (SCA) patients and controls are responsible for the differential responses to oxidative and osmotic stress-induced hemolysis. Susceptibility to hemolysis was examined by incubating oxygenated and deoxygenated RBCs at 37 degrees C with 73 mM 2,2' azobis (2-amidinopropane) HCl (AAPH), a peroxyl radical generator, for up to 3.5 hours.f The ability of RBCs to maintain membrane integrity under osmotic stress was determined over a range of diluted saline-phosphate buffer. Sickled RBCs showed a lesser degree of AAPH-induced hemolysis than control groups and were more resistant to osmotic stress-induced hemolysis. SCA patients had higher levels of RBC vitamin E and RBC lipids, but lower RBC GSH, plasma lipids and plasma carotenes than those of the hospital controls. No significant differences were observed in the levels of retinol, vitamin C, vitamin E, MDA and conjugated dienes in plasma, or the levels of MDA and conjugated dienes in RBCs. The results obtained suggest that the differences in antioxidant status between sickled RBCs and controls do not appear to be responsible for their different susceptibility to oxidative or osmotic stress-induced hemolysis observed.