Willem Meinhardt

Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure.

PURPOSE We evaluated the so-called dynamic sentinel node procedure in patients with penile cancer. This new staging technique consists of excisional biopsy of the first lymph node onto which a tumor drains the so-called sentinel node, based on individual mapping of lymphatic drainage. MATERIALS AND METHODS From 1994 to 1998, 55 consecutive patients with stage T2 or greater bilateral or unilateral node negative squamous cell carcinoma of the penis were prospectively entered in this study. Tumor stage was T2N0 in 42, T2N1 in 4 and T3N0 in 9 cases. To locate the sentinel node each patient underwent lymphoscintigraphy with 99mtechnetium nanocolloid injected intradermally around the tumor. The following day the sentinel node was identified intraoperatively using patent blue dye injected intradermally around the tumor and a gamma detection probe. Regional lymph node dissection was restricted to patients with a tumor positive sentinel node only. RESULTS Scintigraphy revealed 125 sentinel nodes in 107 inguinal regions, including no sentinel node in 2 patients, 1 or more unilateral nodes in 10 and bilateral drainage in 43. At surgery 108 sentinel nodes were removed. In 8 patients with 2 or more sentinel nodes on lymphoscintigraphy only 1 was noted intraoperatively and in 9 an additional sentinel node was removed, which was not identified by scintigraphy. All nodes were identified with the gamma detection probe. In 1 patient a wound abscess developed. Regional lymph node dissection was performed in 11 patients with sentinel node metastasis. Median followup was 22 months (range 4.1 to 61). In 1 patient lymph node metastasis was noted at followup despite prior excision of a tumor-free sentinel node. CONCLUSIONS The dynamic sentinel node procedure is a promising staging technique to detect early metastatic dissemination of penile cancer based on individual mapping of lymphatic drainage, and enables identification of patients with clinically node negative disease requiring regional lymph node dissection.

SPECT/CT for preoperative sentinel node localization.

The value of SPECT/CT for detection and localization of sentinel nodes is reviewed. SPECT/CT depicts extra sentinel nodes and identifies non‐nodal tracer accumulation. SPECT/CT is indicated in patients with complex lymphatic drainage as often present in patients with head, neck and scapular melanoma, breast cancer patients with extra‐axillary sentinel nodes and patients with tumors draining to pelvic nodes. SPECT/CT also clarifies the drainage pattern of inconclusive conventional images (non‐visualization or unclear location of the nodes). J. Surg. Oncol. 2010;101:184–190.

SEXUALITY PRESERVING CYSTECTOMY AND NEOBLADDER: INITIAL RESULTS

PURPOSE Standard cystectomy for bladder cancer in males and females includes removal of organs that are vital to normal sexual function. We report the initial results of modified cystectomy in males and females meant to preserve all sexual function, called sexuality preserving cystectomy and neobladder. MATERIALS AND METHODS Sexuality preserving cystectomy and neobladder consists of pelvic lymph node dissection followed by cystectomy alone with preservation of the vasa deferentia, prostate and seminal vesicles in males, and all internal genitalia in females. An ileal neobladder is anastomosed to the margins of the prostate in males and urethra in females. Indications for this type of surgery are bladder cancer stages T1-T3 with absent tumor growth in the bladder neck in males and females, absent tumor in the prostatic urethra in males and absent invasive tumor in the trigone in females. Further requirements are patient motivation for the preservation of sexual function, no prostate cancer and no cervical/uterine abnormalities. Preoperative evaluation in males involves prostate specific antigen measurement and transrectal ultrasound with sextant prostate biopsies, while females undergo gynecological examination with a cervical smear and transvaginal ultrasound. Voiding and sexual function are assessed by a structured interview with preoperative urodynamics. Erectile function is evaluated by RigiScan (UroHealth Systems, Inc., Laguna Niguel, California) nocturnal penile erection measurement. A short course of 20 Gy. external radiation therapy to the bladder is given shortly before surgery. No patient has been lost to followup, which involves repeat RigiScan examination and regular endoscopy. All patients were entered in a prospective clinical trial approved by the medical ethics committee. RESULTS From 1995 to 1998, 10 males and 3 females 38 to 71 years old (mean age 55) were enrolled in this protocol. Bladder cancer was stage T carcinoma in situ N0M0 in 1 case, Ta multiple grade 3 N0M0 in 1, T1 multiple grade 3 N0M0 in 4, T2 grade 3 N0M0 in 5, T2 grade 3 N1M0 in 1 and T3 grade 3 N1M0 in 1. Mean followup was 3.5 years (range 3 to 6). Two patients died of widespread metastasis without local recurrence. In 1 case prostate cancer developed 5 years after sexuality preserving cystectomy and neobladder, which was treated with external radiation therapy. Erection was normal in 7 men with antegrade ejaculation in 5 and vaginal lubrication was reported to be normal in all women. Daytime continence was achieved in 9 of the 10 males and 2 of the 3 females, while nighttime continence was achieved in 7 and 2, respectively. One woman and 3 men perform intermittent catheterization because of post-void residual urine after voiding. Postoperatively a vaginal fistula and ureteral stenosis developed in 1 case each. CONCLUSIONS Sexuality preserving cystectomy and neobladder achieves maximal tissue conservation, resulting in preserved normal sexual function and satisfactory urinary tract reconstruction. Using strict criteria oncological results have not been jeopardized to date.

Phase I Clinical and Pharmacokinetic Study of Kahalalide F in Patients with Advanced Androgen Refractory Prostate Cancer

Purpose: The purpose is to determine the maximum tolerated dose, profile of adverse events, and dose-limiting toxicity of Kahalalide F (KF) in patients with androgen refractory prostate cancer. Furthermore, the pharmacokinetics after KF administration and preliminary antitumor activity were evaluated. KF is a dehydroaminobutyric acid–containing peptide isolated from the marine herbivorous mollusk, Elysia rufescens. Experimental Design: Adult patients with advanced or metastatic androgen refractory prostate cancer received KF as an i.v. infusion over 1 hour, during five consecutive days every 3 weeks. The starting dose was 20 μg per m2 per day. Clinical pharmacokinetics studies were done in all patients using noncompartmental analysis. Prostate-specific antigen levels were evaluated as a surrogate marker for activity against prostate cancer. Results: Thirty-two patients were treated at nine dose levels (20-930 μg per m2 per day). The maximum tolerated dose on this schedule was 930 μg per m2 per day. The dose-limiting toxicity was reversible and asymptomatic Common Toxicity Criteria grade 3 and 4 increases in transaminases. The recommended dose for phase II studies is 560 μg per m2 per day. Pharmacokinetics analysis revealed dose linearity up to the recommended dose. Thereafter, a more than proportional increase was observed. Elimination was rapid with a mean (SD) terminal half-life (t1/2) of 0.47 hour (0.11 hour). One patient at dose level 80 μg per m2 per day had a partial response with a prostate-specific antigen decline by at least 50% for ≥4 weeks. Five patients showed stable disease. Conclusions: KF can be given safely as a 1-hour i.v. infusion during five consecutive days at a dose of 560 μg per m2 per day once every 3 weeks.

Laparoscopic sentinel node dissection for prostate carcinoma: technical and anatomical observations

To report experience with sentinel node (SN) lymphadenectomy which allows an assessment of the exact location of radioactive and of tumour‐bearing lymph nodes, and evaluate differences in timing of the scintigraphy and surgery.

Paraaortic Sentinel Lymph Nodes: Toward Optimal Detection and Intraoperative Localization Using SPECT/CT and Intraoperative Real-Time Imaging

Paraaortic sentinel node biopsy may be a challenging procedure because the sentinel nodes are located retroperitoneally in close proximity to vital structures. The purpose of this study was to describe and evaluate the value of preoperative SPECT/CT for lymphatic mapping, and a portable γ-camera for intraoperative radioguidance, in patients with paraaortic sentinel nodes. Methods: We evaluated our practice in 18 patients, who were treated at The Netherlands Cancer Institute with sentinel lymphadenectomy for different urologic malignancies and showed paraaortic drainage on preoperative images. After intratumoral injection of 99mTc-nanocolloid, the patients underwent sequential planar lymphoscintigraphy, hybrid SPECT/CT, and sentinel lymphadenectomy. Intraoperative node detection and localization were guided by a laparoscopic γ-probe and a portable γ-camera. This γ-camera was set to display both the 99mTc signal and the 125I-seed signal. This 125I seed was placed on top of the γ-probe, functioning as a pointer on screen, thus enabling real-time sentinel node localization with the γ-camera. Results: In 16 patients with midabdominal drainage on planar images and in 2 patients with nonvisualization on planar images, SPECT/CT showed clear localization of paraaortic sentinel nodes in relation to the abdominal vessels. Five patients underwent open surgery, and 13 patients underwent laparoscopy. The paraaortic sentinel nodes were successfully localized and removed in 15 patients with the help of the portable γ-camera and γ-probe and in 3 patients with the γ-probe only. In 1 patient, the paraaortic sentinel node showed a metastasis. Conclusion: If retroperitoneal drainage is expected, SPECT/CT provides good detection and clear localization of sentinel nodes in relation to anatomic structures. Detection and removal of paraaortic sentinel nodes by means of a laparoscopic γ-probe and real-time imaging with a portable γ-camera is a successful method with high intraoperative detection rates.

Nodal Staging in Penile Carcinoma by Dynamic Sentinel Node Biopsy After Previous Therapeutic Primary Tumour Resection

BACKGROUND Dynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with penile carcinoma and clinically node-negative groins. This minimally invasive procedure is usually done at the same time as the treatment of the primary tumour. OBJECTIVE Our aim was to evaluate results of so-called postresection DSNB, that is, DSNB after previous resection of the penile tumour. DESIGN, SETTING, AND PARTICIPANTS All 40 patients who had undergone DSNB after previous penile carcinoma resection with histopathologically tumour-negative margins between February 2003 and July 2009 were analysed. Twenty patients (50%) had known unilateral nodal involvement, and DSNB was used to stage the clinically normal contralateral groin. Hence the study concerned 60 groins without palpable nodes. The median time between primary tumour resection and DSNB was 2.8 mo. The technique of postresection DSNB was similar to the standard procedure. MEASUREMENTS The sentinel node visualisation rate, identification rate, histopathologic results, and outcome during follow-up were investigated. RESULTS AND LIMITATIONS A sentinel node was visualised on the lymphoscintigrams of 56 of the 60 eligible groins (93%). A sentinel node was identified intraoperatively in all these 56 groins. A median of two sentinel nodes were removed. Histopathologic analysis revealed involvement of seven groins (12%) in seven patients (18%). The median size of these metastases was 6mm. Additional dissemination was found in one completed ipsilateral inguinal node dissection specimen. No recurrences developed in the groins from which one or more tumour-free sentinel nodes had been taken during a median follow-up of 28 mo after the primary tumour resection. A potential limitation of this study is the short follow-up and relatively small cohort number. CONCLUSIONS Postresection DSNB is a suitable procedure to stage clinically node-negative penile carcinoma after previous therapeutic primary tumour resection. The results seem similar to the favourable experience with DSNB in patients with their tumour still present.

Comparative Tolerability and Efficacy of Treatments for Impotence

Modern pharmacological treatment of impotence is determined by the presenting symptoms. Since this involves symptomatology with a heterogenous aetiology, many different drugs are involved in the treatment of impotence.Drugs used for libido and arousal problems include testosterone, yohimbine, trazodone and apomorphine. Since patient self-assessment is the only parameter that can be used to measure the result of treatment and positive results are seldom affirmed, no positive benefit of these agents can be assumed at present.Oral medications for erectile dysfunction include yohimbine, trazodone, apo-morphine, phentolamine, arginine and sildenafil. Of these drugs, sildenafil has been the most systematically studied for effectiveness, but long term safety data await the results of post-marketing surveillance.Of the ejaculation disorder therapies, treatments for premature ejaculation are the best studied. Favourable results have been obtained with clomipramine, paroxetine and fluoxetine. The safety of these medications has been assessed through their long term use in psychiatry.Intracavernous self-injections for erectile disorders are performed using a variety of drugs and drug mixtures. Only alprostadil and the combination of papav-erine with phentolamine are widely used. Alprostadil is very well tolerated; however, penile pain is a serious problem in a significant proportion of patients. Papaverine in combination with phentolamine is effective, but penile fibrosis and priapism occur more often than with the use of alprostadil. Several new developments in this area are currently under way.Alternative routes for medication for erectile dysfunction include ointments and patches to the penile skin and the glans. Only transurethral alprostadil, ‘MUSE’ (medicated urethral system for erection) has been shown to be effective in large trials. Long term safety still has to be demonstrated, but the 1-year safety profile is encouraging.In general, the end points of impotence treatment studies are very diverse so efficacy data can only be assessed in comparative studies. However, long term comparison studies have not been performed. Safety demands must be set very high for this type of treatment since the disorders being treated present no threat to the patient’s health.

Intraoperative Imaging for Sentinel Node Identification in Prostate Carcinoma: Its Use in Combination with Other Techniques

We evaluated a portable γ-camera for sentinel node identification during laparoscopic sentinel lymphadenectomy for prostate cancer. Methods: We analyzed the portable γ-camera for intraoperative sentinel node visualization in 55 patients after 99mTc injection, preoperative planar lymphoscintigraphy, and SPECT/CT. Results: Sixteen percent of 178 nodes seen on SPECT/CT could not be detected with the portable γ-camera. A seed pointer was useful for localizing sentinel nodes intraoperatively in 27% of patients. Seventeen additional sentinel nodes (2 tumor-positive nodes) were removed by monitoring after excision. The location of each sentinel node was significantly associated with the ability to detect it intraoperatively. Conclusion: Intraoperative imaging leads to excision of more radioactive nodes and can determine the residual radioactivity after excision. The use of a radioactive source as a pointer enables efficient identification of nodes in difficult locations (paraaortic nodes) and in patients with a high body mass index.

Peroperative transrectal ultrasonography-guided bladder neck dissection eases the learning of robot-assisted laparoscopic prostatectomy

To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot‐assisted laparoscopic prostatectomy (RALP).