Faculty Bibliography

We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3'-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.

OBJECTIVE: * To describe six steps for haemostasis and collecting system closure ('six degrees of haemostasis') that are reproducible and that minimize the two most concerning complications of laparoscopic partial nephrectomy: haemorrhage and urine leakage. METHODS: * A retrospective study of 23 consecutive laparoscopic partial nephrectomy cases performed by a single surgeon between 2005 and 2008 using the 'six degrees of haemostasis' was carried out. RESULTS: * There were no cases of intraoperative, postoperative or delayed bleeding. * There were no cases of urine leakage. CONCLUSION: * The 'six degrees of haemostasis' technique for laparoscopic partial nephrectomy described in the present study provides a reliable and reproducible method to reassure the surgeon of haemostasis and provide a decreased risk of urine leakage.

OBJECTIVE To assess a prototype ureteric 'buoy' stent with a 10 F upper body tapering to a 3F tail, developed to potentially reduce stent-related irritative symptoms while providing an adequate mould for healing after endopyelotomy. MATERIALS AND METHODS Eighteen Yucatan minipigs had the stent placed either into the intact ureter (phase I) or after Acucise proximal endoureterotomy (phase II). Buoy stents were compared to 10/7 F endopyelotomy stents and to standard 7 F stents in phases I and II, respectively. The pigs were assessed for vesico-ureteric reflux, hydronephrosis and infection, before stent insertion and at harvest. Stents were weighed before and after placement and the removal force was measured. Pressure/flow studies, antegrade nephrostograms and specimens for histopathology from the renal pelvis, ureter and vesico-ureteric junction (VUJ) were obtained at harvest. RESULTS Thirteen minipigs survived the entire study. Ureteric flow with the stents in situ was better for buoy stents than for 10/7 F stents (P < 0.005). Ureteric flow after endoureterotomy and subsequent stent removal was similar for buoy stents and standard 7 F stents. None of the stents refluxed. There was no difference between stents in removal force, weight change or incidence of hydronephrosis. At 1 and 12 weeks, buoy stents tended to produce lower histopathological alteration scores than control stents, especially at the VUJ (phase I, 2.0 vs 3.9, P = 0.092; phase II, 0.6 vs 1.7, P = 0.18). CONCLUSIONS The novel buoy stents are easily placed and removed via the urethra. They can cause less VUJ inflammation than standard stents while allowing for adequate ureteric flow and healing after proximal endoureterotomy.

INTRODUCTION: Bowel injury is an uncommon, although potentially devastating, intraoperative laparoscopic complication. Questions have been raised about the possible use of a tissue adhesive to repair injured bowel. We compared glued repair and sutured repair of both large bowel (LB) and small bowel (SB) electrosurgical injuries in a rabbit model. METHODS: Pneumoperitoneum was obtained, and four laparoscopic ports were placed in each of 48 New Zealand rabbits. The hook electrode was used in a specified manner to create an equal number of uniform full-thickness injuries to either the SB or the LB. Laparoscopic repair was performed with a 3-0 silk Lembert suture (LS), fibrin glue (FG), or BioGlue (BG), or repair was not performed (i.e., no repair, NR); the animals were monitored for 3 weeks. Adverse clinical outcomes and findings at laparotomy were recorded. Pathologic assessment included an objective scaled evaluation of the intensity of the inflammatory response and degree of healing. RESULTS: In the SB injury group, deteriorating clinical condition necessitated early euthanasia in one animal repaired with FG, one animal repaired with BG, and two animals with NR. LS repair animals had no adverse clinical outcomes. The LB injury group had no adverse clinical outcomes regardless of the method of repair, including the control group. Of the animals that survived for 3 weeks, the animals repaired with BG had more intraabdominal adhesions (100%) than LS (33%), FG (55%), and NR (50%) (p = 0.001). The pathologic assessment revealed that BG induced a more intense inflammatory response (p < 0.05). CONCLUSION: In the rabbit, suture repair of an electrosurgical SB injury appears to have improved outcomes when compared with a glued repair. In contrast, LB injury responded well to any form of treatment. The data suggest that suture is superior to biological glues when dealing with a laparoscopic electrosurgical bowel injury.

PURPOSE: Sealing the lymphatic vessels during abdominal and pelvic surgery is important to prevent the leakage of lymphatic fluid and its resultant sequelae. To our knowledge we compared for the first time the quality of lymphatic sealing by each of 4 commonly used laparoscopic dissection devices. MATERIALS AND METHODS: A total of 12 domestic pigs were used to test dissecting devices, including monopolar scissors (Ethicon Endo-Surgery, Cincinnati, Ohio), Harmonic ACE Scalpel, LigaSure V, EnSeal and Trissector. A midline incision was made from mid sternum to umbilicus, the diaphragm was divided and the porcine thoracic duct was isolated. In all animals each device was used to seal an area of the duct and each seal was placed at least 2 cm from the prior seal. In group 1 the thoracic duct of 6 pigs was cannulated with a 5Fr catheter and the seal was subjected to burst pressure testing using a burst pressure measuring device (Cole-Parmer, Vernon Hills, Illinois). In the 6 pigs in group 2 each seal was immediately sent for histopathological evaluation. Specimens were given a score for the extent of cautery damage, including 0-none, 1-minimal, 2-moderate, 3-severe and 4-extreme. RESULTS: A total of 64 seals were created, of which 35 were subjected to burst pressure testing. Mean size of the thoracic duct was 2.6 mm. No acute seal failures were observed with any bipolar device or the harmonic shears. However, 2 immediate failures (33%) were seen with monopolar scissors. Mean burst pressure for monopolar scissors, Harmonic ACE Scalpel, LigaSure V, EnSeal and Trissector was 46 (range 0 to 165), 540 (range 175 to 795), 258 (range 75 to 435), 453 (range 255 to 825) and 379 mm Hg (range 175 to 605), respectively (p <0.05). Trissector, Harmonic ACE Scalpel and EnSeal generated seals with significantly higher burst pressure than that of monopolar scissors (p <0.05). Histopathological evaluation revealed that LigaSure caused less thermal damage than Trissector and EnSeal (p <0.05). CONCLUSIONS: Each device tested except monopolar scissors consistently produced a supraphysiological seal and should be suitable for sealing lymphatic vessels during laparoscopic surgery.