Pelvic lymph node dissection in the context of radical cystectomy: a thorough insight into the connection between patient, surgeon, pathologist and treating institution

Pelvic lymph node dissection (PLND) in patients with bladder cancer varies widely in extent, technique employed, and pathological workup of specimens. The present paper provides an overview of the existing evidence regarding the effectiveness of PLND and elucidates the interactions between patient, surgeon, pathologist, and treating institution as well as their cumulative impact on the final postoperative lymph node (LN) staging. Bladder cancer patients undergoing radical cystectomy with extended PLND appear to have better oncologic outcomes compared to patients undergoing radical cystectomy and limited PLND. Attempts have been made to define and assess the quality of PLND according to the number of lymph nodes identified. However, lymph node counts depend on multiple factors such as patient characteristics, surgical template, pathological workup, and institutional policies; hence, meticulous PLND within a defined and uniformly applied extended template appears to be a better assurance of quality than absolute lymph node counts. Nevertheless, the prognosis of the patients can be partially predicted with findings from the histopathological evaluation of the PLND specimen, such as the number of positive lymph nodes, extracapsular extension, and size of the largest LN metastases. Therefore, particular prognostic parameters should be addressed within the pathological report to guide the urologist in terms of patient counseling.

Salvage Radiotherapy After Radical Prostatectomy

Salvage radiation therapy is the sole curative treatment for patients experiencing biochemical relapse after radical surgical treatment of prostate cancer. The main dilemma in salvage radiation therapy is, whether or not biochemical relapse represents purely localized recurrent disease in the prostatic fossa or systemic micrometastasis. Initiating salvage radiation therapy at an early time point raises its chances of success, but may lead to overtreatment of patients. Target volume definition and treatment techniques are a matter of current research, with still many questions unanswered. Strategies of treatment escalation either by increasing the treatment dose or combining radiation therapy with androgen deprivation therapy are being addressed in clinical trials.

AIDS talk

The observations of Michel Foucault, noted Twentieth Century French philosopher, regarding modern power relations and orders of discourse, form the framework utilized to analyze and interpret the power struggles of AIDS activists and their opponents--the religious and radical right, and the administrative agencies of the 'Liberal' welfare State. Supported by the tools of sociolinguistic inquiry, the analysis highlights the success of a safer sex campaign in Houston, Texas to illustrate the dynamics of cultural and political change by means of discursive transformations initiated by the gay micro-culture. The KS/AIDS Foundation, allied with both the biomedical community and gay entertainment spheres, was successful in conveying biomedical cautions that resulted in altered personal behavior and modified public attitudes by using linguistic conventions consonant with the discourse of the Houston gay micro-culture. The transformation of discursive practices transgressed not only the Houston gay micro-culture's boundaries, but the city boundaries of Houston as well. In addition to cultural and political change, moderate and confrontational gay activists also sought to change the cognitive boundaries surrounding 'the gold standard' for clinical research trials.^ From a Foucauldian perspective, the same-sex community evolved from the subordinated Other to a position of power in a period of five years. Transformations in discursive practices and power relations are exemplified by the changing definitions employed by AIDS policy-makers, the public validation of community-based research and the establishment of parallel track drug studies. Finally, transformations in discursive practices surrounding the issues of HIV antibody testing are interpreted using Foucault's six points of power relations. The Montrose Clinic provides the case study for this investigation. The clinic turned the technical rationalities of the State against itself to achieve its own ends and those of the gay micro-culture--anonymous testing with pre and post test counseling. AIDS Talk portrays a dramatic transformation in discursive practices and power relations that transcends the historical moment to provide a model for future activists. Volume 2 contains copies of fugitive primary source materials largely unavailable elsewhere. Original documents are archived in the Harris County Medical Archives in the Houston Academy of Medicine located in the Texas Medical Center Library, Houston, Texas. ^

Radical chain reactions involving 9-alkyl-9-borafluorenes

The preparation of 9-alkyl-9-borafluorenes and their use as radical precursors in chain reactions were investigated. These organoboranes were found to be excellent precursors of primary and secondary alkyl radicals. Reactions were readily initiated by traces of oxygen and efficient processes involving sulfonyl-based radical traps were discovered. Due to the very high reactivity of the intermediate 9-H and 9-alkyl-9-borafluorenes, problems of reproducibility were identified.

Der Liberalismus macht selig und der Sonntagsgottesdienst macht liberal : ein Wort z. Verständigung an Herrn Gustav Levinstein

von Heinrich Loewe

Populism and Liberal Democracy: Populists in Government in Austria, Italy, Poland and Switzerland

The enduring electoral success of populist parties across Europe and the increasing opportunities they have gained to access government in recent years bring once more into relief the question of whether populism and democracy are fully compatible. In this article we show how, despite playing different roles in government within very different political systems, and despite the numerous constraints placed upon them (for instance, EU membership, international law and domestic checks and balances), populist parties consistently pursued policies that clashed with fundamental tenets of liberal democracy. In particular, the idea that the power of the majority must be limited and restrained, the sanctity of individual rights and the principle of the division of powers have all come under threat in contemporary Europe. This has contributed to the continuing erosion of the liberal consensus, which has provided one of the fundamental foundations of the European project from its start.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

Best Practices in Robot-assisted Radical Cystectomy and Urinary Reconstruction: Recommendations of the Pasadena Consensus Panel

CONTEXT Robot-assisted surgery is increasingly used for radical cystectomy (RC) and urinary reconstruction. Sufficient data have accumulated to allow evidence-based consensus on key issues such as perioperative management, comparative effectiveness on surgical complications, and oncologic short- to midterm outcomes. OBJECTIVE A 2-d conference of experts on RC and urinary reconstruction was organized in Pasadena, California, and the City of Hope Cancer Center in Duarte, California, to systematically review existing peer-reviewed literature on robot-assisted RC (RARC), extended lymphadenectomy, and urinary reconstruction. No commercial support was obtained for the conference. EVIDENCE ACQUISITION A systematic review of the literature was performed in agreement with the PRISMA statement. EVIDENCE SYNTHESIS Systematic literature reviews and individual presentations were discussed, and consensus on all key issues was obtained. Most operative, intermediate-term oncologic, functional, and complication outcomes are similar between open RC (ORC) and RARC. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC generally requires longer operative time than ORC, particularly with intracorporeal reconstruction. Robotic assistance provides ergonomic value for surgeons. Surgeon experience and institutional volume strongly predict favorable outcomes for either open or robotic techniques. CONCLUSIONS RARC appears to be similar to ORC in terms of operative, pathologic, intermediate-term oncologic, complication, and most functional outcomes. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC can be more expensive than ORC, although high procedural volume may attenuate this difference. PATIENT SUMMARY Robot-assisted radical cystectomy (RARC) is an alternative to open surgery for patients with bladder cancer who require removal of their bladder and reconstruction of their urinary tract. RARC appears to be similar to open surgery for most important outcomes such as the rate of complications and intermediate-term cancer-specific survival. Although RARC has some ergonomic advantages for surgeons and may result in less blood loss during surgery, it is more time consuming and may be more expensive than open surgery.

Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. OBJECTIVE To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

BACKGROUND Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. METHODS This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7·0 years (IQR 5·2-8·7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0·78, 95% CI 0·56-1·08; p=0·13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0·54, 95% CI 0·4-0·73, p<0·0001), with 5-year progression-free survival of 47·6% (95% CI 38·8-55·9) in the immediate treatment group and 31·8% (24·2-39·6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. INTERPRETATION Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING Lilly, Canadian Cancer Society Research.