Anatomical Retzius-space preservation is associated with lower incidence of postoperative inguinal hernia development after robot-assisted radical prostatectomy.

BACKGROUND: Postoperative inguinal hernia (IH) is a non-negligible sequelae with a wide array of rates after robot-assisted laparoscopic radical prostatectomy (RALP). Our aim was to evaluate the incidence and risk factors of postoperative IH development in men undergoing RALP. METHODS: A retrospective analysis of 839 patients "541 of conventional-RALP (C-RALP), and 298 of Retzius sparing-RALP (RS-RALP)" received treatment of prostate cancer between 2005 and 2016 and met with our inclusion criteria was performed. Primary endpoint was incidence of IH after RALP, while secondary endpoint was to assess risk factors of IH occurrence. RESULTS: Overall incidence of postoperative IH was 6.3% (53 out of 839). Mean follow-up period and median time of IH development were 24.1 and 14.0 months, respectively. Among patients who developed IH, there was a higher incidence in C-RALP compared to RS-RALP, (79.2 vs 20.8%, respectively, P = 0.02). Multivariate analysis showed that BMI group (HR 0.471, P = 0.023) and C-RALP (HR 2.834, P = 0.002) were significant predictors of IH development. Kaplan-Meier curve showed that 3-year IH-disease progression free rate was significantly higher after RS-RALP compared to C-RALP (94.2 vs 71.6%, respectively, P < 0.001), likewise in obese versus non-obese patients (87.7 vs 76.6%, respectively, P < 0.003). CONCLUSION: Our study showed that overall incidence of IH was 6.3% after RALP. Nevertheless, RS-RALP carries a lower incidence of IH after surgery, while C-RALP and low BMI are predictors of IH development.

The prognostic role of tertiary Gleason pattern 5 in a contemporary grading system for prostate cancer.

BACKGROUND: Recently, a new prostate cancer (PC) grading system has been introduced, where Gleason score (GS) 7 (3+4) and GS 7 (4+3) are categorized into two separate groups. However, GS 7 with tertiary Gleason pattern 5 (TGP5) was not incorporated in the new grading system. In the present study, we validated the prognostic role of TGP5 in the new classification. METHODS: We retrospectively reviewed the records of 1396 patients with localized GS 6-8 PC (pT2-3N0M0) who underwent radical prostatectomy at our institution between 2005 and 2014. After excluding patients who received neoadjuvant or adjuvant therapy, or had incomplete pathological or follow-up data, 1229 patients were included in the final analysis. The Kaplan-Meier method was used to estimate and compare the probabilities of biochemical recurrence (BCR). Cox regression models were used to investigate associations between variables and the risk of BCR. RESULTS: Of 732 GS 7 patients, 75 (10.2%) had a TGP5. The BCR-free survival rate for men with TGP5 was significantly worse than for those without TGP5 (P<0.001). In multivariate Cox regression analyses for GS 7 PC, TGP5 was a significant predictor of BCR (hazard ratio 1.750, P=0.027). When the total cohort was stratified into four grade groups according to the new classification, group 2 with TGP5 had a BCR risk comparable to group 3, and group 3 with TGP5 behaved like group 4. CONCLUSIONS: Our study shows that TGP5 increased the BCR risk after RP in GS 7 PC. Moreover, we demonstrated that the presence of a TGP5 in GS 7 upgraded the BCR risk to one comparable with the next higher category under the new classification. These findings support incorporating TGP5 into GS 7 to aid with future risk assessment and follow-up scheduling for PC.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio after radical prostatectomy in localized prostate cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with metastatic castration-resistant prostate cancer receiving systemic therapy. However, the prognostic significance of NLR was never previously evaluated in patients who underwent radical prostatectomy (RP) for prostate cancer. In the present study, we investigated the influence of NLR on survival after a RP for prostate cancer. METHODS: We retrospectively reviewed clinical data of 2301 patients with prostate cancer who underwent RP at our institution between 2000 and 2010. Among these patients, we considered only patients who had a preoperative complete blood count with differential result available. Patients who received neoadjuvant or postoperative adjuvant treatment (radiation, androgen deprivation therapy or both) and those without adequate medical record were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), overall survival (OS) and prostate cancer-specific survival (CSS). Univariate and multivariate Cox regression models were used for each end point. RESULTS: In total, 2067 patients were evaluated; median follow-up time was 78 months (interquartile range (IQR) 65-96), median age at RP was 66 years (IQR 61-70) and median preoperative NLR was 1.76 (IQR 1.35-2.40). A Kaplan-Meier analysis showed a significant association between high NLR (⩾1.76) and decreased CSS (P=0.005) and OS (P=0.003) but not with BCRFS (P=0.223). In the univariate and multivariate regression analyses, a high NLR was a significant predictor of CSS (hazard ratio (HR) 2.012, 95% confidence interval (CI) 1.222-3.310, P=0.006) and OS (HR 1.650, 95% CI 1.127-2.416, P=0.010). CONCLUSIONS: This study shows that in patients with prostate cancer preoperative NLR is an independent prognostic factor for OS and CSS after a RP and suggests that a preoperative hematologic workup should be considered in the risk assessment of these patients.

Efficacy of vasectomy reversal according to patency for the surgical treatment of postvasectomy pain syndrome.

This study was conducted to assess outcomes (according to patency) of vasectomy reversal (VR) in qualified patients with postvasectomy pain syndrome (PVPS). A total of 32 patients with PVPS undergoing VR between January 2000 and May 2010 were examined retrospectively. Of these, 68.8% (22/32) completed a study questionnaire, either onsite at the outpatient clinic or via telephone interview. Preoperative clinical findings, preoperative and postoperative visual analogue scale (VAS) pain scores, patency and pregnancy rate and overall patient satisfaction were analyzed. For the latter, a four-point rating of (1) cure, (2) improvement, (3) no change or (4) recurrence was used. The mean age was 45.09±4.42 years and the mean period of follow-up was 3.22 years (0.74-7.41). Patency rates were 68.2% (15/22) and pregnancy rates were 36.4% (8/22). The mean VAS was 6.64±1.00 preoperatively and 1.14±0.71 postoperatively (P<0.001). The difference in the mean preoperative and postoperative VAS was 6.00±1.25 (4-8) in the patency group and 4.43±0.98 (3-6) in the no patency group (P=0.011). A significant difference in procedural satisfaction with surgical outcome was observed between patency and no patency groups (P=0.014). In conclusion, in PVPS patients requiring VR, a significant difference was observed between the patency and no patency groups in terms of pain reduction and the degree of patient procedural satisfaction.

Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species.

In urban areas, a correlation between exposure to particulate matter (PM) from air pollution and increased cardiovascular morbidity and mortality has been observed. Components of PM include bacterial contaminants, transition metals, salts, polycyclic aromatic hydrocarbons (PAH), and carbonaceous material, which could interact with various cell types to produce systemic responses when inhaled. We examined the effects of PM collected from Fresno, California on activation of human monocytes and their interaction with vascular endothelium, a key event in atherogenesis. PM exposure increased cytokine expression and secretion from monocytes and enhanced monocyte adhesion to human aortic endothelial cells, both of which were attenuated by neutralizing endotoxin. PM also increased monocyte CYP1a1 expression, and inhibition of the aryl hydrocarbon receptor reduced the CYP1a1 and inflammatory responses. PM-treated monocytes accumulated intracellular reactive oxygen species (ROS), and antioxidants attenuated inflammatory and xenobiotic responses. Finally, supernatants from PM-treated pulmonary microvascular endothelial cells induced monocyte inflammatory responses that were not a consequence of endotoxin transfer. These results suggest that certain components of urban PM, namely endotoxin and PAH, activate circulating monocytes directly or indirectly by first stimulating other cells such as pulmonary endothelial cells, providing several mechanisms by which PM inhalation could induce pulmonary and/or systemic inflammation.

Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation.

Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 microg/m(3) of CAPs in a size range less than 2.5 microm for 6 h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFalpha), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.

Laparoscopic cholecystectomy under segmental thoracic spinal anaesthesia: a feasibility study.

BACKGROUND: Laparoscopic surgery is normally performed under general anaesthesia, but regional techniques have been found beneficial, usually in the management of patients with major medical problems. Encouraged by such experience, we performed a feasibility study of segmental spinal anaesthesia in healthy patients. METHODS: Twenty ASA I or II patients undergoing elective laparoscopic cholecystectomy received a segmental (T10 injection) spinal anaesthetic using 1 ml of bupivacaine 5 mg ml-1 mixed with 0.5 ml of sufentanil 5 microg ml-1. Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patients were reviewed 3 days postoperatively by telephone. RESULTS: The spinal anaesthetic was performed easily in all patients, although one complained of paraesthesiae which responded to slight needle withdrawal. The block was effective for surgery in all 20 patients, six experiencing some discomfort which was readily treated with small doses of fentanyl, but none requiring conversion to general anaesthesia. Two patients required midazolam for anxiety and two ephedrine for hypotension. Recovery was uneventful and without sequelae, only three patients (all for surgical reasons) not being discharged home on the day of operation. CONCLUSIONS: This preliminary study has shown that segmental spinal anaesthesia can be used successfully and effectively for laparoscopic surgery in healthy patients. However, the use of an anaesthetic technique involving needle insertion into the vertebral canal above the level of termination of the spinal cord requires great caution and should be restricted in application until much larger numbers of patients have been studied.

Segmental spinal anaesthesia for cholecystectomy in a patient with severe lung disease.

Occasionally patients awaiting heart or lung transplant because of terminal disease require other types of surgery, but present significant challenges to the anaesthetist because of impaired organ function. Regional anaesthesia may have much to offer such patients and we here report one who underwent successfully a laparoscopic cholecystectomy under segmental subarachnoid (spinal) anaesthesia performed at the low thoracic level. The anatomical and physiological consequences of such a technique are discussed.

Facile and efficient total synthesis of (+)-preussin.

[structure] The enantioselective total synthesis of (+)-preussin, a potent antifungal agent, has been achieved. The key steps are a Pd(0)-catalyzed oxazoline-forming reaction from L-phenylalanine, hydrogenolysis, and subsequent diastereoselective reductive cyclization of the intermediate aminoketone to pyrrolidine using Pearlman's catalyst.

Synthesis and characterization of stereospecific 1-propargyl-2-(dimethoxymethyl)-1-cyclohexanols.

Stereochemical isomers with hydroxy groups were synthesized by reacting 2-(dimethoxymethyl)cyclohexanone with propargylmagnesium bromide. The stereo chemical structures were identified by NMR spectral interpretation and the geometry optimization. To assist the NMR interpretation, geometry optimization based on semi-empirical AM1 and PM3 methods was applied. Throughout this study, the structures of the two isomers were all determined and 1H and 13C NMR spectra were fully assigned. It was proven that the less polar isomer is an axial alcohol and the more polar one is an equatorial alcohol.

Total synthesis of (+/-)-homoepibatidine.

Total synthesis of (+/-)-homoepibatidine (2), which contains the 8-azabicyclo[3.2.1] octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3.

Stereoselective synthesis of (+/-)-epibatidine analog:(+/-)-2beta-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1] octane.

Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3.

The facile and efficient synthesis of 8-chloroadenosine 3',5'-cyclic monophosphate by phosphorylative cyclization of 8-chloroadenosine and its characterization by(1)H and (13)C NMR spectroscopy.

Purine nucleosides were chlorinated by the reaction of acyl chloride in DMF with MCPBA under mild conditions with moderate yields. And, satisfactory method for the synthesis of ribonucleoside-3',5'-cyclic phosphates and its characterization by(1)H and(13)C nmr spectroscopy is described.

Conversion factors estimating indicative chronic no-observed-adverse-effect levels from short-term toxicity data.

Data on chronic toxicity are generally required to derive a health-based acceptable exposure limit, such as the acceptable daily intake. However, only acute and/or subacute toxicity data are available for many compounds. In this study, we assessed conversion factors (CFs) to estimate a chronic no-observed-adverse-effect-level (NOAELchronic) from these short-term toxicity data. We evaluated distributions of ratios between (sub)acute and chronic toxicity data for 332 compounds. By defining the CF as the upper 95% confidence limit of the 95th percentile for the relevant ratio distribution, both the variation between compounds (95th percentile) and the estimation error (upper 95% confidence limit) could be taken into account. Dividing a NOAELsubacute or LD50 by the corresponding CF results in a conservative estimate of the chronic NOAEL. We assessed a CF of 87 for a NOAELsubacute and a CF of 1.7 x 10(4) for an LD50. We found the NOAELsubacute to be a better predictor of the NOAELchronic than the LD50. Moreover, the added value of an LD50 in estimating a NOAELchronic appeared to be limited when a NOAELsubacute was available.

Synthesis of antihypertensive agents via coupling reaction of benzothiazepinone and 1,4-dihydropyridine derivatives.

The synthesis of 3a, 3b, 7a and 7b from Benzothiazepinone and 1,4-dihyropyridine derivatives is described. Benzothiazepinone and 1,4-dihydropyridine derivatives were prepared according to literature procedure. The key reactions involve esterification and amidation of benzothiazepinone and 1,4-dihydropyridine derivatives.

Sensitivity to retinal light damage and surgical blood oxygen levels.

Increased oxygen levels decrease the threshold for photochemical retinal damage. We measured arterial oxygen levels in a group of ophthalmic surgical patients. As expected, levels exceeded unanesthetized measurements by one to two times. Based on experimental data, this could decrease the threshold for light-induced retinal damage during ophthalmic surgery by 40% to 50%. While the clinical implications of light-induced retinal damage in surgical eye patients are unclear, it is prudent to take steps to minimize light exposure during surgery.

Evaluation of retinal exposures from repetitively pulsed and scanning lasers.

Threshold damage in the macaque retina is shown to be equivalent for the argon-krypton (Ar-Kr) 647 nm and the helium-neon (He-Ne) 632.8-nm lines for exposures to continuous wave (CW) radiation from 1 to 1,000 s. This equivalence allows interpolation from experiments with 647-nm, exposures at power levels that are unavailable with the He-Ne laser. To simulate He-Ne laser scanner exposures, 40-microseconds pulses of 647-nm light transmitted through a revolving disk with holes in the periphery were used to expose the retinas of monkeys under deep anesthesia at pulse repetition frequencies (PRFs) of 100, 200, 400, and 1,600 Hz for exposure durations of 1, 10, 100, and 1,000 s. The thresholds between laser exposure at 488 nm (Ar-Kr) and between laser exposure at 647 nm (Kr) are compared to assess thermal versus photochemical effects on the retina. The threshold for 488-nm pulses was consistently lower than that for 647-nm pulses at all PRFs and exposure times. The difference in thresholds increased with exposure time and PRF. The sharp decreases in 488-nm thresholds at 100-s exposure times for each PRF can be interpreted as a basically photochemical effect. The radiant exposure required for damage at 647 nm was several orders of magnitude above the radiant exposure from typical He-Ne scanner applications. From the similarity of the macaque retina to the human retina, it is concluded that no realistic ocular hazard exists from exposure to scanning laser systems of 1 mW or less, operating at higher than 100 Hz.