Paeoniflorin inhibits excitatory amino acid agonist-and high-dose morphine-induced nociceptive behavior in mice via modulation of N-methyl-D-aspartate receptors.

BACKGROUND: Pain, the most common reasons for physician consultation, is a major symptom in many medical conditions that can significantly interfere with a person's life quality and general functioning. Almost all painkillers have its untoward effects. Therefore, seeking for a safe medication for pain relieve is notable nowadays. Paeonia lactiflora is a well-known traditional Chinese medicine. Paeoniflorin is an active component found in Paeonia lactiflora, which has been reported to inhibit formalin-induced nociceptive behavior in mice. Aims of this present study were to investigate effects of paeoniflorin on excitatory amino acid agonist- or high-dose morphine-induced nociceptive behaviors in mice. RESULTS: Paeoniflorin (100, 200, 500 nmol, i.c.v.) alone and combined with glutamatergic antagonists (MK-801 14.8 pmol, or NBQX 5 nmol, i.t.) inhibited nociception. Those agents also inhibited the clonic seizure-like excitation induced by high-dose morphine (250 nmol, i.t) in mice. Antisense oligodeoxynucleotides of NMDA receptor subunits NR1, NR2A, NR2B significantly enhanced the inhibition of paeoniflorin on excitatory amino acid-and high-dose morphine-induced nociception. Docking energy data revealed that paeoniflorin had stronger binding activity in NR2A and NR2B than NR2C of NMDA receptors. CONCLUSIONS: Results of this study indicate that paeoniflorin-induced inhibition of excitatory amino acid agonist- and high-dose morphine-induced nociceptive behaviors might be due to modulation of NMDA receptors, specifically the NR2B subunit.

The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study.

BACKGROUND: Lung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual's lung function is lacking. RESEARCH QUESTION: What is the normal range and the upper limit of normal (ULN) decline in lung function in adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease? STUDY DESIGN AND METHODS: A retrospective analysis of healthy individuals who have never smoked (N = 1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed effects model and estimated to a 6-year interval. The ULN decline was defined as the 95th percentile. RESULTS: The mean follow-up between spirometry examinations was 5.5 years, whereas the mean follow-up between diffusing capacity for carbon monoxide studies was 5.9 years. Decline in FEV1, FVC, and D accelerated with age, whereas decline in FEV1/FVC decelerated with age. Decline varied with sex, age, and height. Over a 6-year period, the ULN decline in FEV1 ranged from 383 to 667 mL, and the ULN decline in Dlco ranged from 3.6 to 9.5 mL/min/mm Hg. Overall, male individuals had faster absolute rates of decline than female individuals, whereas relative (%) rates of decline were similar between sexes. INTERPRETATION: Lung function decline is nonlinear and accelerates with age. In this cohort, the ULN decline over 6 years often exceeded current guidelines for interpreting significant longitudinal change in lung function.

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

BACKGROUND: Chronic inflammation may increase susceptibility to pneumonia. RESEARCH QUESTION: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. METHODS: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. RESULTS: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). CONCLUSIONS: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

Background: Chronic inflammation may increase susceptibility to pneumonia. Research Question: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. Methods: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. Results: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). Conclusions: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition.

Early oncological outcomes for bladder urothelial carcinoma patients treated with robotic-assisted radical cystectomy.

OBJECTIVE: • To determine oncological outcomes including early survival rates among unselected bladder urothelial carcinoma (BUC) patients treated with robotic-assisted radical cystectomy (RRC). PATIENTS AND METHODS: • Clinicopathologic and survival data were prospectively gathered for 85 consecutive BUC patients treated with RRC. • The decision to undergo a robotic rather than open approach was made without regard to tumor volume or surgical candidacy. • Kaplan-Meier survival rates were determined and stratified by tumor stage and LN positivity, and multivariate analysis was performed to identify independent predictors of survival. RESULTS: • Patients were relatively old (25% >80 years; median 73.5 years), with frequent comorbidities (46% with ASA class ≥ 3). Of these patients 28% had undergone previous pelvic radiation or pelvic surgery, and 20% had received neoadjuvant chemotherapy. • Extended pelvic lymphadenectomy was performed in 98% of patients, with on average 19.1 LN retrieved. • On final pathology, extravesical disease was common (36.5%). • Positive surgicalmargins were detected in five (6%) patients, all of whom had extravesical tumors with perineural and/or lymphovascular invasion, and most of whom were >80 years old. • At a mean postoperative interval of 18 months, 20 (24%) patients had developed recurrent disease, but only three (4%) patients had recurrence locally. Disease-free, cancer-specific and overall survival rates at 2 years were 74%, 85% and 79%, respectively. Patients with low-stage/LN(-) cancers had significantly better survival than extravesical/LN(-) or any-stage/LN(+) patients, with stage being the most important predictor on multivariate analysis. CONCLUSION: • RRC can achieve adequately high LN yields with a low positive margin rate among unselected BUC patients. • Early survival outcomes are similar to those reported in contemporary open series, with an encouragingly low incidence of local recurrence, however long-term follow-up and head-to-head comparison with the open approach are still needed.

Critical analysis of complications after robotic-assisted radical cystectomy with identification of preoperative and operative risk factors.

OBJECTIVE: To better characterize short- and long-term complications in patients after robotic-assisted radical cystectomy (RRC) using standardized complications-reporting systems, and to identify preoperative and operative risk factors predicting their occurrence. PATIENTS AND METHODS: Data were collected for 79 consecutive patients with bladder cancer undergoing RRC with extracorporeal urinary diversion by one surgeon at our institution. Complications occurring < or =90 days after RRC were graded according to two standardized reporting methods (Memorial Sloan Kettering Cancer Center and Modified Clavien), and additionally stratified by organ system. Nineteen preoperative and operative variables were tested by univariate analysis for association with the occurrence of one or more postoperative complications. Variables with a significant (P < 0.05) or near-significant (P < 0.20) association on univariate analysis were included in multivariate analysis to identify independent risk factors. RESULTS: Patients were of relatively poor health, with 58% having an American Society of Anesthesiology class or Charlson Index score of > or =3. Advanced bladder disease was frequent (41% had pT3/pT4). After RRC, one or more complications occurred within 90 days of surgery for 39/79 (49%) patients. The vast majority of complications were low grade (79%), and mostly infectious (41%) or gastrointestinal (27%). Sixteen high-grade complications occurred in 13/79 (16%) patients. Urinary obstruction, abscess, enteric fistula, gastrointestinal bleeding and thromboembolism constituted most of the high-grade complications, nearly half (seven of 16) of which occurred 31-90 days after RRC. On multivariate analysis, only preoperative renal insufficiency and intraoperative intravenous (i.v.) fluids of >5000 mL were significantly associated with postoperative complications of any grade, with respective odds ratios (ORs) of 4.2 and 4.1. For high-grade complications, significant independent risk factors included an age of > or = 65 years, operative blood loss of > or =500 mL and intraoperative i.v. fluids of >5000 mL, with respective ORs of 12.7, 9.7 and 42.1. CONCLUSION: Even among relatively sick patients with frequent advanced disease, the vast majority of complications after RRC are low grade. High-grade complications are infrequent and similar in nature to high-grade events after open RC, and a notable proportion may occur at >30 days after RRC underscoring the importance of longer reporting intervals. The surgeon's ability to limit blood loss and i.v. fluids during RRC may provide effective risk reduction, particularly for high-grade events.

Species identification of ciguatoxin-carrying grouper implicated in food poisoning.

Food poisoning due to ingestion of an unknown red grouper occurred in southern Taiwan. To identify the species of toxic red grouper implicated in food poisoning, a 475-bp sequence of the cytochrome b gene from six species of fresh red grouper meat was amplified by using a pair of primers (L14735/H15149). This fragment could be amplified when fish meat was treated with different heating processes. After sequencing, it was found that no variation in sequences was detected among individuals within each species. The species of toxic red grouper meat implicated in food poisoning was judged to be Lutjanus bohar based on sequence analysis. In addition, restriction enzyme analysis with HaeIII rapidly distinguished these six species of red grouper and the two samples implicated in food poisoning. No toxicity of viscera in 18 specimens of six red grouper species was detected, but two food poisoning samples were found to be toxic. This study indicated that DNA sequence and restriction enzyme analysis are powerful methods for identifying potentially toxic red grouper species as L. bohar.

Accuracy of Algorithms to Identify Pulmonary Arterial Hypertension in Administrative Data: A Systematic Review.

BACKGROUND: The diagnosis of pulmonary arterial hypertension (PAH) is challenging, and there is significant overlap with the more heterogenous diagnosis of pulmonary hypertension (PH). Clinical and research efforts that rely on administrative data are limited by current coding systems that do not adequately reflect the clinical classification scheme. The aim of this systematic review is to investigate current algorithms to detect PAH using administrative data and to appraise the diagnostic accuracy of these algorithms against a reference standard. METHODS: We conducted comprehensive searches of Medline, Embase, and Web of Science from their inception. We included English-language articles that applied an algorithm to an administrative or electronic health record database to identify PAH in adults. RESULTS: Of 2,669 unique citations identified, 32 studies met all inclusion criteria. Only four of these studies validated their algorithm against a reference standard. Algorithms varied widely, ranging from single International Classification of Diseases (ICD) codes to combinations of visit, procedure, and pharmacy codes. ICD codes alone performed poorly, with positive predictive values ranging from 3.3% to 66.7%. The addition of PAH-specific therapy and diagnostic procedures to the algorithm improved the diagnostic accuracy. CONCLUSIONS: Algorithms to identify PAH in administrative databases vary widely, and few are validated. The sole use of ICD codes performs poorly, potentially leading to biased results. ICD codes should be revised to better discriminate between PH groups, and universally accepted algorithms need to be developed and validated to capture PAH in administrative data, better informing research and clinical efforts.

Evaluation of a successful aging promotion intervention program for middle-aged adults in Taiwan.

PURPOSE: This study was to implement and evaluate a successful aging intervention program for middle-aged private insurance beneficiaries. METHODS: The participants were recruited from the staff and middle-aged clients for the experimental and control groups of a private insurance company. The two client (experimental and control) groups were matched by comparable age groups, gender, education, and purchased insurance types. The intervention program provided for the staff and the experimental group consisted of a series of educational courses on the topics about successful aging and preparation for 4 months. In total, there were 40 staff members, in addition to the 74 members of the experimental group and 60 members of the control group participating in the study. RESULTS: After the intervention, the rate of physical activity and exercise significantly improved for the staff and for the intervention group. There were significant improvements in behaviors associated with doing exercise and living a less sedentary lifestyle and in the utilization of health examinations, and improvements in fitness and blood pressure. CONCLUSION: The successful aging intervention program significantly improved awareness of successful aging, exercise behavior and fitness.

Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK signaling pathways.

BACKGROUND: Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing. RESULTS: In this study, we first observed that ethyl acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose-dependent inhibitory effect without cytotoxicity on the mobility and invasion of highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK-Hep1 cells were treated with EAAC at various concentrations and then subjected to gelatin zymography, casein zymography and western blot to study the impacts of EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2 (TIMP-1/2), respectively. Our results showed that EAAC treatment may decrease the expressions of MMP-2 and enhance the expression of TIMP-1/2 in a concentration-dependent manner. EAAC also inhibited effect on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase/serine/threonine protein kinase [or protein kinase B (PI3K/Akt)] and focal adhesion kinase (FAK). CONCLUSIONS: These results indicate that EAAC inhibited SK-Hep1 cell of metastasis by reduced protein level of MMP-2 through the suppression of MAPK and FAK signaling pathway and of the activity of PI3K/Akt. These findings suggest that EAAC may be used as an antimetastatic agent.

Neuroprotection of Gueichih-Fuling-Wan on cerebral ischemia/ reperfusion injury in streptozotocin-induced hyperglycemic rats via the inhibition of the cellular apoptosis pathway and neuroinflammation.

BACKGROUND: Risks of stroke link with complications of hyperglycemia. Gueichih-Fuling-Wan (GFW), according to Chinese Medical Code literature, has the promotion of blood circulation and attenuates the swollen plot. Recent pharmacological studies have pointed out its efficacy in patients with cerebral ischemia or diabetes. Therefore, this study determined whether GFW has the protection against cerebral ischemia/ reperfusion (I/R) injury in streptozotocin (STZ)-induced hyperglycemic rats and LPS-induced inflammation in BV-2 microglial cells. METHODS: Extracts of GFW were filtered and frozen to dry for use. Hyperglycemia was induced by intraperitoneal injection of 70 mg/kg STZ. Fourteen days after STZ injection, GFW (1, 2 and 4 g/kg) was orally administered once daily for seven days. Rats were subjected to cerebral ischemia/reperfusion and sacrificed for infarction analysis and neuronal apoptosis detection twenty-one days after STZ injection. MTT assay was used for cell viability; nitrite quantification and western blot analysis of iNOS and COX-2 were used to explore the effects of GFW on LPS-induced inflammation in BV-2 microglial cells. RESULTS: GFW significantly ameliorated cerebral infarction while dosage was more than 1 g/kg (by 38.03% at 2 g/kg and 52.44% at 4 g/kg), and attenuated neurological deficits by 23.48% (at 2 g/kg) and 47.25% (at 4 g/kg). Furthermore, GFW (2, 4 g/kg) notably decreased TUNEL- and cleaved caspase-3-positive cells in the immunohistochemical stain (P < 0.01 and P < 0.001, respectively). GFW remarkably increased in Bcl-2 and decreased in caspase-3 and Bax/Bcl-2 ratio protein expressions by Western blot. GFW (0.25, 0.5, 1 mg/ ml) significantly reduced LPS-induced NO production in BV-2 microglial cells. And GFW attenuated iNOS and COX-2 expression in LPS-treated BV-2 cells. CONCLUSIONS: In summary, GFW has good bioactivities to protect cerebral I/R injury in hyperglycemic rats, which might be due to inhibition of cellular apoptosis and neuroinflammation.

Trans-Cinnamaldehyde, An Essential Oil in Cinnamon Powder, Ameliorates Cerebral Ischemia-Induced Brain Injury via Inhibition of Neuroinflammation Through Attenuation of iNOS, COX-2 Expression and NFκ-B Signaling Pathway.

Trans-cinnamaldehyde (TCA), an essential oil in cinnamon powder, may have beneficial effects as a treatment for stroke which is the second leading cause of death worldwide. Post-ischemic inflammation induces neuronal cell damage after stroke, and activation of microglia, in particular, has been thought as the main contributor of proinflammatory and neurotoxic factors. The purpose of this study was to investigate the neuroprotective effects of TCA in an animal model of ischemia/reperfusion (I/R)-induced brain injury and the neuroprotective mechanism was verified in LPS-induced inflammation of BV-2 microglial cells. Our results showed that TCA (10-30 mg/kg, p.o.) significantly reduced the infarction area, neurological deficit score and decreased iNOS and COX-2 protein expression level in I/R-induced injury brain tissue. It inhibited 0.5 µg/ml LPS-induced NO production in BV-2 microglial cells without affecting cell viability, reduced protein expression of iNOS and COX-2, and attenuated inhibition of p53 protein. TCA also suppressed the effects of LPS-induced nuclear translocation of NF-κB p65 and p50 and increased cytosolic IκBα. It also reduced LPS-induced mRNA expression of iNOS, COX-2, and TNFα. We concluded that TCA has a potential neuroprotective effect to against the ischemic stroke, which may be via the inhibition of neuroinflammation through attenuating iNOS, COX-2 expression and NF-κB signaling pathway.

Left ventricular early inflow-outflow index: a novel echocardiographic indicator of mitral regurgitation severity.

BACKGROUND: No gold standard currently exists for quantification of mitral regurgitation (MR) severity. Classification by echocardiography is based on integrative criteria using color and spectral Doppler and anatomic measurements. We hypothesized that a simple Doppler left ventricular early inflow-outflow index (LVEIO), based on flow velocity into the left ventricle (LV) in diastole and ejected from the LV in systole, would add incrementally to current diagnostic criteria. LVEIO was calculated by dividing the mitral E-wave velocity by the LV outflow velocity time integral. METHODS AND RESULTS: Transthoracic echocardiography reports from Montefiore Medical Center and its referring clinics from July 1, 2011, to December 31, 2011 (n=11 235) were reviewed. The MR severity reported by a cardiologist certified by the National Board of Echocardiography was used as a reference standard. Studies reporting moderate or severe MR (n=550) were reanalyzed to measure effective regurgitant orifice area by the proximal isovelocity surface area method, vena contracta width, MR jet area, and left-sided chamber volumes. LVEIO was 9.3±3.9, 7.0±3.2, and 4.2±1.7 among those with severe, moderate, and insignificant MR, respectively (ANOVA P<0.001). By receiver operating characteristic analysis, area under the curve for LVEIO was 0.92 for severe MR. Those with LVEIO ≥8 were likely to have severe MR (likelihood ratio 26.5), whereas those with LVEIO ≤4 were unlikely to have severe MR (likelihood ratio 0.11). LVEIO performed better in those with normal LV ejection fraction (≥50%) compared with those with reduced LV ejection fraction (<50%) (area under the curve 0.92 versus 0.80, P<0.001). By multivariate logistic regression analysis, LVEIO was independently associated with severe MR when compared with vena contracta width, MR jet area, and effective regurgitant orifice area measured by the proximal isovelocity surface area method. CONCLUSION: LVEIO is a simple-to-use echocardiographic parameter that accurately identifies severe MR, particularly in patients with normal LV ejection fraction.

Multiphoton microscopy in the evaluation of human bladder biopsies.

CONTEXT: Multiphoton microscopy (MPM) is a nonlinear imaging approach, providing cellular and subcellular details from fresh (unprocessed) tissue by exciting intrinsic tissue emissions. With miniaturization and substantially decreased cost on the horizon, MPM is an emerging imaging technique with many potential clinical applications. OBJECTIVES: To assess the imaging ability and diagnostic accuracy of MPM for human bladder biopsies. DESIGN: Seventy-seven fresh bladder biopsies were imaged by MPM and subsequently submitted for routine surgical pathology diagnosis. Twelve cases were excluded because of extensive cautery artifact that prohibited definitive diagnosis. Comparison was made between MPM imaging and gold standard sections for each specimen stained with hematoxylin-eosin. RESULTS: In 57 of 65 cases (88%), accurate MPM diagnoses (benign or neoplastic) were given based on the architecture and/or the cytologic grade. The sensitivity and specificity of MPM in our study were 90.4% and 76.9%, respectively. A positive (neoplastic) diagnosis on MPM had a high predictive value (94%), and negative (benign) diagnoses were sustained on histopathology in two-thirds of cases. Architecture (papillary versus flat) was correctly determined in 56 of 65 cases (86%), and cytologic grade (benign/low grade versus high grade) was assigned correctly in 38 of 56 cases (68%). CONCLUSIONS: The MPM images alone provided sufficient detail to classify most lesions as either benign or neoplastic using the same basic diagnostic criteria as histopathology (architecture and cytologic grade). Future developments in MPM technology may provide urologists and pathologists with additional screening and diagnostic tools for early detection of bladder cancer. Additional applications of such emerging technologies warrant exploration.

Ureteroileal anastomosis with intraluminal visualization: technique and outcomes.

OBJECTIVES: Although the ileal conduit is the most well-established urinary diversion, the optimal technique for ureteroileal anastomosis remains controversial. Here, we present a technique for anastomosis of the ureters from within the lumen of the ileal conduit, under direct visualization. We examine the rate of ureteral stricture using this method, and review the literature regarding ureteroenteric anastomotic complications with various techniques. METHODS: An intraluminal technique for ureteroenteric anastomsosis was performed by opening the conduit on the antimesenteric border to allow direct visualization of the ureteroileal anastomosis. Using our prospectively collected database, we investigated the prevalence of anastomotic stricture in patients undergoing urinary diversion using this method for anastomosis. RESULTS: One-hundred eighteen patients underwent ileal conduit diversion with ureteroileal anastomoses performed as described. Median postoperative follow-up was 15 months. Ureteral strictures were identified in 5/118 patients (4.2%). Of the patients with strictures, one was successfully treated with endoscopic balloon dilatation, three were managed with chronic ureteral stents, and one was managed with a chronic percutaneous nephrostomy. Review of the recent literature reveals stricture rates up to 10% with current techniques. CONCLUSIONS: We conclude from these results that during ileal conduit creation, intraluminal anastomosis of the ureters to the ileal segment under direct vision represents a viable alternative to other techniques, with complication rates that compare favorably with other reported series.

A comparison of postoperative complications in open versus robotic cystectomy.

BACKGROUND: Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer (BCa). However, reduction in postoperative morbidity relative to the open approach has not been demonstrated. OBJECTIVE: To compare complication rates in patients undergoing robotic versus open radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC, 83 robotic RC. INTERVENTION: Open or robotic RC with urinary diversion. MEASUREMENTS: Demographic, perioperative, and complication data were recorded prospectively. Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale. Data were evaluated using chi(2) and multivariate logistic regression analyses. RESULTS AND LIMITATIONS: At 30 d, the open group demonstrated a higher overall complication rate (59% vs 41%; p=0.04) as well as more major complications (30% vs 10%; p=0.007). At 90 d, the overall complication rate was greater in the open group, but this was not statistically significant (62% vs 48%; p=0.07). However, there was a significantly higher major complication rate in the open cohort (31% vs 17%; p=0.03). When subjected to logistic regression analysis, robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists (ASA) score (3-4) and longer surgical time were independent predictors of major complications. Though this is one of the largest published RC series, the sample size is relatively small. Moreover, despite the two patient cohorts being similarly matched, the study was not performed in a randomized fashion. CONCLUSIONS: Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy. Robotic cystectomy is an independent predictor of fewer overall and major complications. Until long-term oncologic results are available, robotic cystectomy should still be considered investigational.

Human bladder cancer diagnosis using Multiphoton microscopy.

At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, non-invasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.