Sashi S. Kommu

Laparo-endoscopic single-site surgery: preliminary advances in renal surgery

We reviewed the preliminary advances in laparo‐endoscopic single‐site surgery (LESS) as applied to renal surgery, and analyzed current publications based on animal models and human patients. We searched published reports in major urological meeting abstracts, Embase and Medline (1966 to 25 August 2008), with no language restrictions. Keyword searches included: ‘scarless’, ‘scar free’, ‘single port/trocar/incision’, ‘intraumbilical’, and ‘transumbilical’, ‘natural orifice transluminal endoscopic surgery’ (NOTES), ‘SILS’, ‘OPUS’ and ‘LESS’. The lessons learnt from the studies using the porcine model are that further advances in instrumentation are essential to achieve optimum results, and that testing survival in animals is also necessary to further expand the NOTES and LESS techniques. Further advances in instrument technology together with increasing experience in NOTES and LESS approaches have driven the transition from porcine models to human patients. In the latter, studies show that the techniques are feasible provided that both optimal surgical technical expertise with advanced skills, and optimal instrumentation, are available. The next step towards minimal access/minimally invasive urological surgery is NOTES and LESS. It is inevitable that LESS will be extended to involve more complex and technically demanding procedures such as laparoscopic radical prostatectomy and partial nephrectomy.

LAPAROENDOSCOPIC SINGLE‐SITE SURGERY (LESS) AND NOTES; STANDARDISED PLATFORMS IN NOMENCLATURE

J O U R N A L C O M P I L A T I O N

INITIAL TREATMENT COSTS OF ORGAN-CONFINED PROSTATE CANCER: A GENERAL PERSPECTIVE

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

Laparoendoscopic single-site surgery and natural orifice translumenal endoscopic surgery in urology: trainee-directed tools in tandem with rapid surgical advances.

Sir, There is increasing evidence that lymphovascular invasion (LVI) is one of important prognostic indicators in upper urinary tract urothelial carcinoma (UUT-UC) [1]. A recent report from Akao et al. [2] in the BJU Int suggested LVI status might be a better predictive marker for cancer-specific survival in patients UUT-UC and treated by radical surgery. They also reported that patients with pT3N0M0 disease without LVI had a significantly better prognosis than those who were pT3N0M0 with LVI. The presence of LVI represents a higher probability of metastasis, so many investigators who respectively evaluated the role of retroperitoneal lymph node dissection in UUT-UC concluded that lymphadenectomy has a therapeutic effect, especially for patients with advanced UUTUC [3–5]. We totally agree with the conclusion of the authors, as LVI is a good prognostic factor for predicting the outcome of pT3 disease, especially for patients who have a primary tumour in the renal pelvis. Traditionally, the prognosis of UUT-UC is strongly correlated with pathological stage, especially with invasion of the muscularis. The muscular layer of the ureter is much thinner than in the renal pelvis. Ureteric UC is associated with a greater local or distant failure rate than renal pelvic UC [6]. However, the TNM staging system combines renal pelvic and ureteric carcinomas, despite their different anatomy. However, different from the ureter and the urinary bladder, lamina propria is lacking beneath the urothelial lining, and the renal papillae in the renal pelvis, and is quite thin along the minor calyces. Moreover, within the renal sinus, the muscularis propria might be very thin or imperceptible near the calyces, and is surrounded by sinus fat. Renal sinus fat invasion is not addressed in the TNM staging system. Guinan et al. [7] suggested a modification of the TNM staging system, separating renal pelvic and ureteric tumours, and reported a significant survival difference between stage T3 and stage T4N + M + in renal pelvic tumours. They concluded that renal parenchyma is a relative anatomical barrier to the spread of renal pelvic tumours, and that stage T3 renal pelvic tumours invading the renal parenchyma are not comparable with stage T3 ureteric tumours invading peri-ureteric tissues. Wu et al. [8] evaluated 72 patients with pT3 UUT-UC and concluded that superficial renal parenchymal invasion should be considered as a lower-stage disease. They also indicated that vascular involvement is the only independent prognostic factor for pT3 disease. The concept could be supported by the findings of Akao et al. , who indicated that LVI status is the most useful independent factor for predicting cancer-specific survival by multivariate analysis using Cox proportional hazard model. We could consider LVI status for risk stratification of patients with pT3 UUT-UC, to decide whether adjuvant chemotherapy will be added [9]. PUBLIC INTEREST WARNING: SHOULD WE BAN WOODEN/ORNAMENTAL TOILET SEATS FOR MALE INFANTS?

The Clinical Genetics of Prostate Cancer

Prostate cancer is the most common cancer in men and the second highest cause of cancer-related mortality in the U.K. A genetic component in predisposition to prostate cancer has been recognized for decades. One of the strongest epidemiological risk factors for prostate cancer is a positive family history. The hunt for the genes that predispose to prostate cancer in families has been the focus of many research groups worldwide for the past 10 years. Both epidemiological and twin studies support a role for genetic predisposition to prostate cancer. Familial cancer loci have been found, but the genes that cause familial prostate cancer remain largely elusive. Unravelling the genetics of prostate cancer is challenging and is likely to involve the analysis of numerous predisposition genes. Current evidence supports the hypothesis that excess familial risk of prostate cancer could be due to the inheritance of multiple moderate-risk genetic variants. Although research on hereditary prostate cancer has improved our knowledge of the genetic aetiology of the disease, a lot of questions still remain unanswered.This article explores the current evidence that there is a genetic component to the aetiology of prostate cancer and attempts to put into context the diverse findings that have been shown to be possibly associated with the development of hereditary prostate cancer. Linkage searches over the last decade are summarised. It explores issues as to why understanding the genetics of prostate cancer has been so difficult and why despite this, it is still a major focus of research. Finally, current and future management strategies of men with Hereditary Prostate Cancer (HPC) are discussed.

Evolving Role of Simulators and Training in Robotic Urological Surgery

Sashi S. Kommu1, Kamran Ahmed, Benjamin Challacombe, Prokar Dasgupta, Mohammed Shamim Khan, STILUS Academic Research Group (SARG) MRC Centre for Transplantation, Kings College London, Kings Health Partners, Department of Urology, Guys Hospital Simulation and Interactive Learning (SaIL) Centre, Guys & St Thomas NHS Foundation Trust Department of Urology, London, and STILUS Academic Research Group (SARG), London, UK

Familial Prostate Cancer

Prostate cancer is one of the common cancers where there is good evidence for a larger genetic component to its etiology, but the genetic models are complex. It is highly likely that the PCa predisposition genes will be polygenic and may be interacting within families. Some PCa predisposition genes are likely to be DNA repair genes (e.g., BRCA2) but these may account for only a small proportion of young cases. However, the discovery of high-risk BRCA2 mutations has led to the first clinical targeted screening trial based on genotype in this disease (the IMPACT study, discussed above), and this trial will serve as a basis for further targeted screening and chemoprevention trials based on genotype as further genes are identified. The lessons learned in IMPACT will be screening uptake in a high-risk male population, the psychological issues of screening men at higher risk of PCa, the utility of PSA in a higher risk population, the identification of new and better biomarkers and the clinical parameters of PCa so identified.

Nanotechnology and Prostate Cancer

Prostate cancer (PCa) is the second leading cause of cancer-related death. Despite its high incidence, many uncertainties related to PCa diagnosis and management remains. Current treatment including surgery, radiation therapy, and chemotherapy are mostly ineffective against advanced-stage PCa [1]. PCa can be largely asymptomatic in the “early” stages. Thus, in some countries, men above the age of 50 are screened regularly by digital rectal examination (DRE) or for elevated serum prostate-specific antigen (PSA) levels. Patients with abnormal test results are recommended for prostatic biopsy, which can confirm a diagnosis of PCa. Despite the use of an advanced protocol, sampling error still can occur in some patients, especially those with large prostate glands. Thus, novel approaches are needed to overcome the limitations of the present methods. At the same time, identification of molecular signatures corresponding to histological subtypes is an essential step toward understanding of the molecular basis of tumor development. There is mounting evidence that a substantial proportion of men with screen-detected PCa would otherwise have not known about the disease during their life in the absence of screening. In these men, cancer treatment may not be beneficial. Thus, it is critically important to establish ways to perform accurate and meaningful assessments of men with a potential to develop the disease.

Prostate Cancer Genetics

Prostate cancer (PCa) is one of the commonest cancers in men and a major cause of cancer-related mortality. Family history is the strongest known risk factor for developing PCa. This is illustrated by the observation that a man with one close relative (such as a father or a brother) with PCa has approximately twice the risk of developing PCa when compared to a man with no family history. A man with two close male relatives affected has a fivefold increase in lifetime risk. This degree of relative risk and the increase in its magnitude indicate a strong genetic component to disease development. However, unlike other cancers such as breast, ovarian, and colonic cancers, the search for mutations in candidate genes is proving to be more elusive. Uncovering the genes that predispose to PCa among families where disease is clustered has been the objective of many research groups over the past 15 years. Epidemiological and twin studies support a role for the genetic predisposition to PCa. Familial cancer loci have been identified, but discovery of the genes that cause familial prostate cancer (FPC) remains largely elusive. Unraveling the genetics of PCa is challenging and is likely to involve the analysis of numerous predisposing factors, which may be manifestations of multiple mutagenic pathways. Increased familial risk of prostate cancer could be due to the inheritance of multiple moderate-risk genetic variants. Although the study of hereditary prostate cancer (HPC) has increased our understanding of its genetic etiology, many issues remain largely unresolved. This difficulty with identification of PCa predisposition genes may be due to a number of reasons. PCa, in terms of total prevalence, is a very common condition, and it may not be far wide of the mark to say that the majority of prostates in the Western world will eventually harbor some cancer cells. The disease varies significantly in the spectrum of aggressiveness. We do not know, with absolute conviction, which patients who have been diagnosed with PCa require treatment. It is against this quandary that genetics could play its influence. PCa is diagnosed in the later years of life; therefore, obtaining DNA samples from living affected men for more than one generation is often not possible, and linkage in large pedigrees may be unfeasible. The presence within high-risk pedigrees of phenocopies (individuals with PCa but without the genetic alteration) weakens the linkage results. The genetic heterogeneity of this complex disease (the fact that different pedigrees may be due to different genetic mutations) and the uncertainty regarding the optimal genetic model could render linkage results inaccurate, making gene identification difficult.

The Proteomic Approach to Prostate Cancer

Prostate adenocarcinoma (PCa) is currently the second most common cause of cancer death in men and is recognized as one of the most important medical problems facing the male population [1].