Papers by George Thalmann
Bladder Cancer, 2016
Background: Results of a dynamic multimodality mapping study showed no lymphatic drainage of the ... more Background: Results of a dynamic multimodality mapping study showed no lymphatic drainage of the lateral bladder wall to the contralateral internal iliac region. Objectives: To validate whether pathoanatomical mapping in bladder cancer (BC) patients can confirm these results. Methods: Between 01/2000 and 07/2013, 825 BC patients preoperatively staged ≥pT1 and without clinical signs of metastases (cN0 cM0) underwent extended pelvic lymph node dissection (ePLND) and radical cystectomy at our department. Of these patients, 23% (193/825) were lymph node (LN) positive in the pathological specimen; 26% (51/193) of this subgroup had strictly unilateral BC. Pathoanatomical mapping was used to retrospectively validate the distribution of LN involvement in these 51 patients. Results: A median of 35 LNs were removed per patient (range: 13-80 LNs), with a median of 2 positive LNs (range: 1-14 LNs). 27% (14/51) of patients presented with LN metastases on the contralateral side. No positive LNs were found in the contralateral internal iliac region or the contralateral fossa of Marcille. 10% (5/51) of patients had LN metastases only on the contralateral side without evidence of metastases on the tumor-bearing side. Conclusions: Our findings corroborate the data of a dynamic mapping study showing bilateral lymphatic drainage in almost one third of patients with strictly unilateral BC, but no lymphatic drainage from the lateral bladder wall to the contralateral internal iliac region. If prospective studies confirm these results, the contralateral internal iliac region may be omitted during ePLND in patients with strictly unilateral BC.
Once tumors became measurable, blood samples for sequential PSA measurements were obtained by dor... more Once tumors became measurable, blood samples for sequential PSA measurements were obtained by dorsal tail vein incision every 10 days. Samples were collected in 75-mm microhematocrit capillary tubes and centrifuged in a microcapillary centrifuge, model MB (IEC, Ncedham Heights, MA) for 3
Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition,... more Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity. Because epithelial-to-mesenchymal transition is involved in cancer, we investigated whether BMP7 plays a role in prostate cancer growth and metastasis. BMP7 expression in laser-microdissected primary human prostate cancer tissue was strongly down-regulated compared with normal prostate luminal epithelium. Furthermore, BMP7 expression in prostate cancer cell lines was inversely related to tumorigenic and metastatic potential in vivo and significantly correlated to E-cadherin/vimentin ratios. Exogenous addition of BMP7 to human prostate cancer cells dose-dependently inhibited transforming growth factor -induced activation of nuclear Smad3/4 complexes via ALK5 and induced E-cadherin expression. Moreover, BMP7-induced activation of nuclear Smad1/4/5 signaling transduced via BMP type I receptors was synergistically stimulated in the presence of transforming growth factor , a growth factor that is enriched in the bone microenvironment. Daily BMP7 administration to nude mice inhibited the growth of cancer cells in bone. In contrast, no significant growth inhibitory effect of BMP7 was observed in intraprostatic xenografts. Collectively, our observations suggest that BMP7 controls and preserves the epithelial phenotype in the human prostate and underscore a decisive role of the tumor microenvironment in mediating the therapeutic response of BMP7. Thus, BMP7 can still counteract the epithelial-to-mesenchymal transition process in the metastatic tumor, positioning BMP7 as a novel therapeutic molecule for treatment of metastatic bone disease.
BJU International, 2015
To evaluate the long term oncological and functional outcomes after readaptation of the dorsolate... more To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (<cT4, cN0, cM0) between April 2006 and September 2009. Patients were randomised into two groups: group A with readaptation of the dorsolateral peritoneal layer (n=100; 73 male, 27 female; median age 68 yrs, range 35-86 yrs) and group B without readapation (n=100; 66 male, 34 female; median age 65 yrs, range 30-86 yrs). Regular postoperative follow-up was performed at our outpatient clinic. Median follow-up was 59 months (range 3-100 months), five patients were lost to follow-up in group A, seven in group B. Bowel function was evaluated using the validated Gastrointestinal Quality of Life Index questionnaire and an institutional questionnaire regarding post-cystectomy outcome. Local recurrences and distal metastases were evaluated using computed tomography and bone scan at the regular follow-up visits. There was no significant difference between the two groups in terms of the rate of local (pelvic) recurrence (5/95 [5.3%] in group A; 7/93 [7.5%] in group B; p = 0.53), the rate of distant metastases (21/95 [22.1%] in group A; 23/93 [24.7%] in group B; p = 0.67), cancer-specific survival (p = 0.37), and overall survival (p = 0.59). Group A had significantly better bowel function at 3 (p < 0.001), 6 (p < 0.006), 12 (p <0.006) and 24 months (p = 0.04), and significantly less postoperative abdominal pain and bloating at 3 (p = 0.002) and 6 months (p = 0.01). Readaptation of the dorsolateral peritoneal layer following PLND and cystectomy has a beneficial long-term impact on bowel function and postoperative pain without compromising oncological radicality. This article is protected by copyright. All rights reserved.
European Urology Supplements, 2010
The Journal of urology, Jan 8, 2015
Blood loss and blood substitution are associated with higher morbidity after major abdominal surg... more Blood loss and blood substitution are associated with higher morbidity after major abdominal surgery. During major liver resection, low local venous pressure, has been shown to reduce blood loss. Ambiguity persists concerning the impact of local venous pressure on blood loss during open radical cystectomy. We aimed to determine the association between intraoperative blood loss and pelvic venous pressure (PVP) and determine factors affecting PVP. In the frame of a single-center, double-blind, randomized trial, PVP was measured in 82 patients from a norepinephrine/low-volume group and in 81 from a control group with liberal hydration. For this secondary analysis, patients from each arm were stratified into subgroups with PVP <5 mmHg or ≥5 mmHg measured after cystectomy (optimal cut-off value for discrimination of patients with relevant blood loss according to the Youden's index). Median blood loss was 800 ml [range: 300-1600] in 55/163 patients (34%) with PVP <5 mmHg and 120...
The Journal of urology, 2015
FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is... more FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases. We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis. Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (...
Histology and histopathology, 2012
We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pi... more We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic pos...
Biomedical optics express, 2011
We investigated vapor bubbles generated upon irradiation of gold nanoparticles with nanosecond la... more We investigated vapor bubbles generated upon irradiation of gold nanoparticles with nanosecond laser pulses. Bubble formation was studied both with optical and acoustic means on supported single gold nanoparticles and single nanoparticles in suspension. Formation thresholds determined at different wavelengths indicate a bubble formation efficiency increasing with the irradiation wavelength. Vapor bubble generation in Bac-1 cells containing accumulations of the same particles was also investigated at different wavelengths. Similarly, they showed an increasing cell damage efficiency for longer wavelengths. Vapor bubbles generated by single laser pulses were about half the cell size when inducing acute damage.
Urologic oncology, Jan 2, 2015
To evaluate risk factors for urethral recurrence (UR) in women with neobladder. From 1994 to 2011... more To evaluate risk factors for urethral recurrence (UR) in women with neobladder. From 1994 to 2011, 297 women (median age = 54y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116). Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumo...
Journal of Urology, 2006
We evaluated the incidence of pathological findings of the ureter at cystectomy for transitional ... more We evaluated the incidence of pathological findings of the ureter at cystectomy for transitional cell carcinoma of the bladder and assessed the usefulness of intraoperative frozen section examination of the ureter. Histopathological findings of ureteral frozen section examination were compared to the corresponding permanent sections and the diagnostic accuracy of frozen section examination was evaluated. These segments were then compared to the more proximal ureteral segments resected at the level where they cross over the common iliac arteries. The histopathological findings of the ureteral segments were then correlated for upper urinary tract recurrence and overall survival. Transitional cell carcinoma or carcinoma in situ was found on frozen section examination of the distal ureter in 39 of 805 patients (4.8%) and on permanent sections in 29 (3.6%). In 755 patients the false-negative rate of frozen section examination of the ureters was 0.8%. Of the patients with carcinoma in situ diagnosed on the first frozen section examination 80% also had carcinoma in situ in the bladder. Transitional cell carcinoma or carcinoma in situ in the most proximally resected ureteral segments was found in 1.2% of patients. After radical cystectomy there was tumor recurrence in the upper urinary tract in 3% of patients with negative ureteral frozen section examination and in 17% with carcinoma in situ on frozen section examination. Routine frozen section examination of the ureters at radical cystectomy is only recommended for patients with carcinoma in situ of the bladder, provided the ureters are resected where they cross the common iliac arteries.
The development,of novel anti-cancer strategies requires,more,sensitive and less invasive methods... more The development,of novel anti-cancer strategies requires,more,sensitive and less invasive methods,to detect ,and ,monitor ,in vivo minimal ,residual ,disease ,in cancer ,models. ,Bone marrow,metastases,are indirectly detected,byradiography,as osteolytic and/or osteoscle- rotic lesions. Marrow micrometastases elude radiographic detection and, therefore, more sensitive methods ,are needed ,for their direct identification. Injection of cancer ,cells into the left cardiac ventricle of mice closely mimics,micrometastatic,spread.
The Journal of urology, Jan 5, 2015
Management of ureteral stones remains controversial. To determine whether optimizing extracorpore... more Management of ureteral stones remains controversial. To determine whether optimizing extracorporeal shock wave lithotripsy (ESWL) delivery rates improves treatment of solitary ureteral stones, we compared outcomes of two SW delivery rates in a prospective, randomized trial. From July 2010 to October 2012, 254 consecutive patients were randomized to undergo ESWL at SW delivery rates of either 60 pulses (n=130) or 90 pulses (n=124) per min. The primary endpoint was stone-free rate at 3-month follow-up. Secondary endpoints included stone disintegration, treatment time, complications, and the rate of secondary treatments. Descriptive statistics were used to compare endpoints between the two groups. Adjusted odds ratios and 95% confidence intervals were calculated to assess predictors of success. The stone-free rate at 3 months was significantly higher in patients who underwent ESWL at a SW delivery rate of 90 pulses per min than in those receiving 60 pulses (91% vs. 80%, p=0.01). Patien...
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Papers by George Thalmann