Endoscopic tissue liquidisation of the prostate, bladder and kidney

Endoscopic techniques have revolutionised the practice of all specialities of surgery. Endoscopic access has been either via a natural route, such as the urethra, or percutaneously, as in percutaneous intrarenal stone surgery. Potential endoscopic procedures for bulk tissue removal have been limited by the need to reduce that tissue to a size smaller than the endoscopic channel used. An attempt has been made to create a device that will liquidise and aspirate tissue through an endoscope, This Instrument has been called the Endoscopic Liquidiser and Surgical Aspirator (ELSA). This report details the design and development of the ELSA which has led to its clinical application. The device is 5 mm in diameter and is used through a specially made endoscope of 8.5 mm outer diameter (approximately 27 French). It consists of a high speed rotating blade mounted in a housing that provides irrigation for efficient 1iquidisation and a channel for aspiration of the tissue. Laboratory evaluation was measured by the removal rates of different tissues. The optimum parameters of blade speed, irrigation flow and aspiration were established after a series of controlled experiments. Blade shape was also found to be important and a study of the material strengths of different tissues was required to establish that blade design should vary for each tissue used. Under optimum laboratory conditions fresh human prostate could be removed at 2.4 g/min and renal cortex at 14.6 g/min. The resultant aspirate contained particles ranging from 10 microns to 3 mm, but the majority were less than 200 microns. Flow cytometry was required as the only reasonable method of rapid pathological diagnosis. The action of the ELSA did not confer any Inherent haemostatic benefit and a diathermy plate was added to the tip of the instrument. The ELSA was successfully used to remove benign prostatic tissue from 7 patients with bladder outflow obstruction. However the procedures were slow and visualisation was poor once the liquidisation began. The mean operating time was 85 minutes (range 50 - 120). 1 patient suffered a fatal capsular perforation, but otherwise morbidity v/as not dissimilar from a control group undergoing a standard transurethral diathermy resection. 6'7 patients regained an improved stream with good control. The ELSA was used in the same transurethral method for the removal of superficial bladder tumours in 10 patients. The same problem of impaired vision was found, but the removal was very rapid as one would expect with a soft non-fibro\is material. The postoperative morbidity was greater than in a control group using a diathermy resectoscope due to bladder perforation with the ELSA in 1 case. A percutaneous endoscopic nephrectomy has been achieved in 2 dogs. Each kidney was embolised with "Ethibloc" (a material that completely occupies all arterial capillary beds), An Intrarenal approach was compared with an extrarenal, retroperitoneal one; the latter using carbon dioxide insufflation. Both procedures were successful. Haeraostasis was not a problem. These may be suitable clinical techniques for the minimally invasive removal of infected kidneys prior to transplantation. The presence of stones would not be a problem because of the ability of the ELSA to fragment and aspirate stone particles as efficently as any ultrasound device. This was confirmed in a series of laboratory tests on various stone types and in 5 patients with urinary stones. An extension of the concept of minimally invasive bulk tissue aspiration is the integration of robotics into this form of surgery. The ELSA has been attached to an industrial robot. The mechanism of a transurethral prostatectomy has been studied in order to program the robot. A robotic prostatectomy in a simulation model has been performed. Each procedure can be preprogrammed according to the dimensions of the gland. The in vitro study confirmed that the robot was consistent and therefore safe; and rapid (mean removal time 5 rains) because visualisation was not required for orientation. In conclusion, the ELSA has proved to be ati efficient instrument for endoscopic tissue removal but its clinical superiority is only for less fibrous tissues and improved visualisation will be required. It still requires ancillary methods for haemostasis and the use of a capillary embolisation technique in the kidney may have applications elsewhere. The robotic study was not just an academic exercise. Robotics will be a feature of future surgery

Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry preliminary study

Summary The in vivo labelling of urological tumour cells using the S phase marker bromodeoxyuridine (BRdU) for histochemical studies is reported. The use of multiparameter flow cytometry (FCM) with BRdU labelling to study tumour proliferation offers significant advantages. It provides simultaneous measurements of the DNA ploidy (Dl), the duration of the S phase (Ts), the potential doubling time (Tpot) and the total and aneuploid tumour labelling indices (LI) from a single specimen. Heterogenous tumour cell populations can be measured with high sensitivity. We report a preliminary study to evaluate the method in the measurement of the kinetics of transitional cell carcinoma of the bladder (TCCB). Nineteen patients with TCCB, 1 with leukoplakia of the bladder, 2 with renal carcinoma, 1 with prostatic carcinoma and 1 with a squamous carcinoma of the penis were studied. Of the bladder tumours, 3 were aneuploid, Dl = 1.32, 1.58 and 1.89. BRdU uptake was detected in all tumours. The median LI was 1.5% (range 0.5–10.0). In 15/19 tumours the labelling profile was satisfactory for calculation of the Ts and Tpot. The median Ts was 6.2 h and the median Tpot was 17.1 days. This study demonstrates that measurement of multiple parameters of urological tumour proliferation in vivo is possible. These parameters require further assessment as indices of biological aggressiveness and clinical prognosis.</p

PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization

Degenerate polymerase chain reaction against conserved kinase catalytic subdomains identified 15 tyrosine and serine-threonine kinases expressed in surgically removed prostatic carcinoma tissues, including six receptor kinases (PDGFBR, IGF1-R, VEGFR2, MET, RYK, and EPH-A1), six non-receptor kinases (ABL, JAK1, JAK2, TYK2, PLK-1, and EMK), and three novel kinases. Several of these kinases are oncogenic, and may function in the development of prostate cancer. One of the novel kinases is a new member of the sterile 20 (STE20) family of serine-threonine kinases which we have called prostate-derived STE20-like kinase (PSK) and characterized functionally. PSK encodes an open reading frame of 3705 nucleotides and contains an N-terminal kinase domain. Immunoprecipitated PSK phosphorylates myelin basic protein and transfected PSK stimulates MKK4 and MKK7 and activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway. Microinjection of PSK into cells results in localization of PSK to a vesicular compartment and causes a marked reduction in actin stress fibers. In contrast, C-terminally truncated PSK (1-349) did not localize to this compartment or induce a decrease in stress fibers demonstrating a requirement for the C terminus. Kinase-defective PSK (K57A) was unable to reduce stress fibers. PSK is the first member of the STE20 family lacking a Cdc42/Rac binding domain that has been shown to regulate both the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and the actin cytoskeleton