Wael Khoder

A New Concept for Early Recovery after Surgery for Patients Undergoing Radical Cystectomy for Bladder Cancer: Results of a Prospective Randomized Study

PURPOSE Early recovery after surgery concepts have gained wide acceptance in various surgical specialties. However, limited data are available for radical cystectomy. A new early recovery after surgery concept was compared to a more conservative regimen in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS A total of 101 consecutive patients were prospectively randomized to early recovery after surgery (62) or a conservative regimen (39) (intended randomization ratio was 2 early recovery after surgery-to-1 conservative regimen). Primary end points were differences in quality of life, and secondary end points included postoperative morbidity, demand for analgesics, time spent in the intermediate care unit, mobility and number of gastrointestinal events during hospital stay. RESULTS Quality of life parameters, as measured by the EORTC (European Organization for the Research and Treatment of Cancer) Quality of Life questionnaire QLQ-30 did not change significantly between postoperative days 3 and 7 and at discharge from hospital in the conservative regimen group, whereas a significant improvement was observed in the early recovery after surgery group. Postoperative morbidity was lower in the early recovery after surgery group in terms of wound healing disorders (p = 0.006), fever (p = 0.004) and thrombosis (p = 0.027). The demand for analgesics was significantly lower in the early recovery after surgery group. The amount of food consumed in relation to the amount of food offered was significantly higher for the early recovery after surgery group as early as day 3 (p = 0.02). Time spent in the intermediate care unit was significantly shorter for the early recovery after surgery group (p <0.001). There were no significant differences between the groups with respect to gastrointestinal events. The main limitations of this study were the lack of long-term data as well as the single center approach. CONCLUSIONS Early recovery after surgery of patients who underwent radical cystectomy appears to have significant benefits compared to a conservative regimen in terms of postoperative morbidity, quality of life, use of analgesics and time spent in the intermediate care unit.

18F-Fluoroethylcholine PET/CT Identifies Lymph Node Metastasis in Patients with Prostate-Specific Antigen Failure After Radical Prostatectomy but Underestimates Its Extent

BACKGROUND The detection of lymph node metastases (LNMs) is one of the biggest challenges in imaging in urology. OBJECTIVE To evaluate the accuracy of combined 18F-fluoroethylcholine (FEC) positron emission tomography (PET)/computed tomography (CT) in the detection of LNMs in prostate cancer (PCa) patients with rising prostate-specific antigen (PSA) level after radical prostatectomy. DESIGN, SETTINGS, AND PARTICIPANTS From June 2005 until November 2011, 56 PCa patients with biochemical recurrence after radical prostatectomy underwent bilateral pelvic and/or retroperitoneal lymphadenectomy based on a positive 18F-FEC PET/CT scan. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The findings of PET/CT were compared with the histologic results. RESULTS AND LIMITATIONS Median PSA value at the time of 18F-FEC PET/CT analysis was 6.0 ng/ml (interquartile range: 1.7-9.4 ng/ml). In 48 of 56 (85.7%) patients with positive 18F-FEC PET/CT findings, histologic examination confirmed the presence of PCa LNMs. Of 1149 lymph nodes that were removed and histologically evaluated, 282 (24.5%) harbored metastasis. The mean number of lymph nodes removed per surgical procedure was 21 (standard deviation: ± 18.3). A lesion-based analysis yielded 18F-FEC PET/CT sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 39.7%, 95.8%, 75.7%, and 83.0%, respectively. A site-based analysis yielded sensitivity, specificity, PPV, and NPV of 68.4%, 73.3%, 81.3%, and 57.9%, respectively. Patients with negative PET/CT did not undergo surgery, thus sensitivity, specificity, and negative predictive value on a patient basis could not be calculated. CONCLUSIONS A positive 18F-FEC PET/CT result correctly predicted the presence of LNM in the majority of PCa patients with biochemical failure after radical prostatectomy but did not allow for localization of all metastatic lymph nodes and therefore was not adequately accurate for the precise estimation of extent of nodal recurrence in these patients.

Photodynamic Therapy by Means of 5-ALA Induced PPIX in Human Prostate Cancer – Preliminary Results

Summary Radical retropubic prostatectomy (RRP), external beam radiation and brachytherapy are considered to be the main treatment modalities in localized prostate cancer (PCA). However, with respect to the incidence of complications, efforts have been made to establish alternative treatment modalities of PCA, such as photodynamic therapy (PDT). In a clinical study, the localisation of 5-ALA induced PPIX in PCA was investigated. Patients (n = 14) with histologically proven prostate cancer underwent RRP. Prior to anaesthesia they received a solution of 5-ALA of 20mg/kg body weight (by oral application). Frozen sections of the removed tissue were examined by fluorescence microscopy. Only in carcinoma cells fluorescence was observed, while the epithelial cells and the stromal tissue showed no fluorescence. In control-prostates the tissue was completely fluorescence-negative. Following this experience 5 patients received interstitial PDT, transurethrally (n = 3) or transperineally (n = 2). Light of a diode laser (λ = 633 nm) was coupled into a fibre with a 1 cm cylindrical diffuser tip which was introduced into the tissue. An irradiation of 250 J/cm of laser light (irradiance: 0.5 W/cm, irradiation time: 500 s) was applied. 6 weeks after interstitial PDT the PSA values were reduced by 20% up to 70%. With regard to the side effects no patient complained about incontinence or dysuria after PDT. The presented study demonstrates that interstitial PDT of prostate cancer by means of 5-ALA induced PPIX is a safe and simple procedure. Further investigations concerning light delivery and dosimetry are warranted, to achieve the goal of a complete and curative treatment of prostate cancer.

Quality of life and perioperative outcomes after retroperitoneoscopic radical nephrectomy (RN), open RN and nephron-sparing surgery in patients with renal cell carcinoma

To prospectively evaluate health‐related quality of life (HRQoL) and perioperative outcomes in patients with T1 and T2 renal cell carcinoma (RCC) after retroperitoneoscopic radical nephrectomy (RRN), open RN (ORN) or open nephron‐sparing surgery (NSS).

Photodynamic Diagnosis of Prostate Cancer Using 5-Aminolevulinic Acid—First Clinical Experiences

OBJECTIVES To study the feasibility of 5-aminolevulinic-acid (5-ALA)-induced photodynamic diagnosis (PDD) for the evaluation of the surgical margins (SMs) during radical prostatectomy (RP) in patients with prostate cancer (PCa). METHODS A total of 18 patients with histologically confirmed PCa (Gleason score 4 to 8, prostate-specific antigen 1 to 20 ng/mL) underwent RP. Of the 18 patients, 16 received 5-ALA (20 mg/kg) orally 2 hours before RP, and 2 served as controls without any application of 5-ALA. To study the protoporphyrin IX (PPIX) accumulation after application of 5-ALA, all harvested specimens were investigated by fluorescence microscopy and spectroscopy. In 10 of 16 patients, PDD of the SMs and the prostate was performed during RP using an incoherent light source filtered for efficient fluorescence excitation. RESULTS In all 16 patients, who had received 5-ALA fluorescence microscopy showed a selective accumulation of PPIX in the PCa cells, and only weak PPIX fluorescence could be detected in benign epithelial cells and none in the adjacent stroma. The 2 patients, who had not received 5-ALA had no PPIX fluorescence in the prostate. Of 10 patients, 8 demonstrated fluorescence-negative and histologically confirmed negative margins during PDD, and 1 each demonstrated a fluorescence-positive SM that was also confirmed by histologic examination and a positive SM that was not confirmed by PPD. CONCLUSIONS This is the first report of PDD for PCa using 5-ALA. These initial results have demonstrated that PPIX is selectively enhanced in malignant tissue, an essential prerequisite of PDD. Additional studies are warranted to validate these preliminary data and the efficacy of PDD for PCa during RP.

Photodynamic Diagnosis Using 5-Aminolevulinic Acid for the Detection of Positive Surgical Margins during Radical Prostatectomy in Patients with Carcinoma of the Prostate: A Multicentre, Prospective, Phase 2 Trial of a Diagnostic Procedure

BACKGROUND Surgical margin status after radical prostatectomy (RP) is a significant risk factor for tumour recurrence. It is an intriguing concept to find a fluorescence marker for photodynamic diagnosis (PDD) to make tumour margins visible during surgery. OBJECTIVE To investigate the feasibility of identification of positive surgical margins (PSM) during open retropubic or endoscopic extraperitoneal RP by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) to enhance surgical radicality. DESIGN, SETTING, AND PARTICIPANTS Thirty-nine patients (Gleason score 6-10, prostate-specific antigen [PSA] 2.3-120 ng/ml) received 20 mg/kg of body weight of 5-ALA orally and underwent RP (24 endoscopic extraperitoneal, 15 open retropubic). MEASUREMENTS A PDD-suitable laparoscopy optic (Karl-Storz GmbH, Tuttlingen, Germany) with a yellow long-pass filter was coupled to a fibre-optic light cord with an excitation light source (380-420 nm, D-Light, Karl-Storz GmbH, Tuttlingen, Germany) for fluorescence excitation of PpIX and to a PDD-suitable camera for video and photo documentation by the AIDA DVD system (Karl-Storz GmbH, Tuttlingen, Germany). RESULTS AND LIMITATIONS There were more false-negative cases in the open group (four vs two) than in the endoscopic group but more false-positive cases in the endoscopic group (two vs none) than in the open group. The overall sensitivity and specificity were 56% and 91.6%, respectively. The sensitivity of the endoscopic cases was much higher (75% vs 38%) than for the open cases, while the specificity was higher for the open group (88.2% vs 100%). CONCLUSIONS PDD with 5-ALA-induced PpIX during RP might be a feasible and effective method for reducing the rate of PSM. The technique seems to be more practicable during endoscopic RP rather than open RP. Further clinical studies with higher patient volumes and further development of the technique seem justified. TRIAL REGISTRATION EudraCT: 2005-004406-93.

Risk factors for pelvic lymphoceles post-radical prostatectomy.

Background:  Lymphoceles (LC) represent a well‐described rare complication post‐radical prostatectomy (RP). Our aim was to determine risk factors and to develop possible prevention strategies for LC in a community‐based study.

Ex vivo comparison of the tissue effects of six laser wavelengths for potential use in laser supported partial nephrectomy.

Laparoscopic/robotic partial nephrectomy (LPN) is increasingly considered for small renal tumors (RT). This demands new compatible surgical tools for RT-resection, such as lasers, to optimize cutting and coagulation. This work aims to characterize ex vivo handling requirements for six medically approved laser devices emitting different light wavelengths (940, 1064, 1318, 1470, 1940, and 2010 nm) amenable for LPN. Incisions were made by laser fibers driven by a computer-controlled stepping motor allowing precise linear movement with a preset velocity at a fixed fiber-tip distance to tissue. Optical parameters were measured on 200 μm tissue slices. Cutting quality depended on power output, fiber velocity and fiber-tip distance to tissue. Contact manner is suitable for cutting while a noncontact manner (5 mm distance) induces coagulation. Ablation threshold differs for each wavelength. Ablation depth is proportional to power output (within limit) while axial and superficial coagulation remains mostly constant. Increased fiber velocity compromises the coagulation quality. Optical parameters of porcine kidney tissue demonstrate that renal absorption coefficient follows water absorption in the 2 μm region while for other spectral regions (900 to 1500 and 1 μm) the tissue effects are influenced by other chromophores and scattering. Tissue color changes demonstrate dependencies on irradiance, scan velocity, and wavelength. Current results clearly demonstrate that surgeons considering laser-assisted RT excisions should be aware of the mentioned technical parameters (power output, fiber velocity and fiber-tip tissue-distance) rather than wavelength only.

The growth rate of large renal masses opposes active surveillance.

Study Type – Therapy (case series)
Level of Evidence 4

Intraoperative photodynamic evaluation of surgical margins during endoscopic extraperitoneal radical prostatectomy with the use of 5-aminolevulinic acid.

PURPOSE Today there are no established techniques to image positive surgical margins (PSM) intraoperatively in endoscopic extraperitoneal radical prostatectomy (EERPE). The intention of this study was to describe the specific technique of photodynamic diagnosis (PDD) in patients undergoing EERPE and report on the potential to detect PSM under PDD. MATERIALS AND METHODS Twenty-four patients with clinically organ-confined prostate cancer received 5-aminolevulinic acid 20 mg/kg body weight orally 3 hours prior to nonnerve-sparing EERPE. An endoscopic PDD system (Karl Storz, Tuttlingen, Germany) including a Tricam PDD 3-chip camera head linked with a straight 10-mm telescope and a D-light C system was used. During EERPE, visualization of the surgical margins was performed by means of both white light and PDD at specific steps during standardized prostatectomy in all patients. Positive PDD areas on the prostate specimen were marked with white ink and consequently processed in pathology. RESULTS In white light endoscopy, no suspicion of a PSM was raised. Six out of the eight PSM were detected by PDD. In two cases, areas of positive PDD findings were free of prostate cancer and two PSM were not detected by PDD ( one bladder neck, one lateral). The overall sensitivity and specificity were 75% and 88.2%, respectively. CONCLUSIONS Laparoscopy offers an appropriate setting for the use of PDD in prostate cancer to visualize possible PSM. Although imaging of PSM by PDD is promising with the technique being feasible and safe, larger series are needed to prove the reproducibility of our results.