Optimizing the colloid particle concentration for improved preoperative and intraoperative image-guided detection of sentinel nodes in prostate cancer.

PURPOSE: Lymphatic mapping for prostate cancer can be used to determine therapeutic strategies. Sentinel node visualization requires sufficient nodal tracer uptake. We evaluated the effect of an increase in particle concentration on preoperative and intraoperative sentinel node depiction. METHODS: Enrolled in the study were 50 consecutive patients with prostate cancer. The first 25 patients (group A) received nanocolloid with standard labelling (0.4 ml (99m)Tc per 0.1 mg nanocolloid). The last 25 patients (group B) received nanocolloid with a reduced labelling dilution volume (0.4 ml (99m)Tc per 0.2 mg nanocolloid). The aimed injected volume and dosage were the same for both groups (225 MBq in 0.4 ml). Intratumoral tracer injection was followed by planar lymphoscintigraphy (15 min and 2 h), SPECT/CT and laparoscopic sentinel lymphadenectomy. Lymph node visualization was evaluated using a four-point scoring system (0 nonvisualization to 3 intense visualization) and count quantification on the 2-h anterior lymphoscintigram. In addition to the gamma ray detection probe, a portable gamma camera was used for intraoperative sentinel node visualization. RESULTS: Preoperative visualization in group A was 88% (mean 2.0 sentinel nodes per patient) versus 100% in group B (mean 2.6 sentinel nodes per patient). Visualization scores (p=0.008), total counts (p=0.001) and maximum counts per pixel (p=0.034) in the sentinel nodes were significantly better in group B. This also led to more efficient intraoperative detection of the sentinel nodes with the portable gamma camera (84% in group A versus 100% in group B). CONCLUSION: Enhancement of the particle concentration may lead to significant improvement in sentinel node visualization and intraoperative localization in patients with prostate cancer. Further research regarding optimization of radiotracer labelling by changing the particle concentration is warranted.

Lymphatic drainage from the treated versus untreated prostate: feasibility of sentinel node biopsy in recurrent cancer.

PURPOSE: The goal of this study was to establish the feasibility of sentinel node biopsy in patients with recurrent prostate cancer after initial local treatment and to compare lymphatic drainage patterns of the treated versus untreated prostate. METHODS: In ten patients with a proven local recurrence after initial local treatment (four external beam radiation, four brachytherapy and two high-intensity focused ultrasound), the radiotracer ((99m)Tc-nanocolloid, GE Healthcare) was injected into the prostate. Planar images after 15 min and 2 h were followed by SPECT/CT (Symbia T, Siemens) to visualize lymphatic drainage. Laparoscopic sentinel lymphadenectomy was assisted by a gamma probe (Europrobe, EuroMedical Instruments) and a portable gamma camera (Sentinella, S102, Oncovision). Sentinel node identification and lymphatic drainage patterns were compared to a consecutive series of 70 untreated prostate carcinoma patients from our institute. RESULTS: Lymphatic drainage was visualized in all treated patients, with a median of 3.5 sentinel nodes per patient. Most sentinel nodes were localized in the pelvic area, although the percentage of patients with a sentinel node outside the pelvic para-iliac region (para-aortic, presacral, inguinal or near the ventral abdominal wall) was high compared to the untreated patients (80 versus 34%, p = 0.01). In patients with recurrent prostate cancer, 95% of the sentinel nodes could be harvested and half of the patients had at least one positive sentinel node on pathological examination. CONCLUSION: Lymphatic mapping of the treated prostate appears feasible, although sentinel nodes are more frequently found in an aberrant location. Larger trials are needed to assess the sensitivity and therapeutic value of lymphatic mapping in recurrent prostate cancer.

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).

Prostate-sparing cystectomy: long-term oncological results.

OBJECTIVE: To analyse the oncological outcome of prostate-sparing cystectomy (PSC). PATIENTS AND METHODS: Between 1994 and 2006, 63 men were treated with PSC after meeting the inclusion criteria (no tumour at the bladder neck, no prostate cancer). The results were compared with patients who had a standard cystoprostatectomy (SC) during the same study period, after matching for clinical and pathological characteristics. RESULTS: The 3- and 5-year disease-specific survival rates were 77% and 66% in the PSC group, and 68% and 64% in the SC group (log-rank, P = 0.6). The local recurrence rate was 7.9% and 16% for the PSC and the SC groups, respectively, and the respective distant recurrence rate was 29% and 33%. Subsequent prostate cancer was detected in 3% in the PSC group. None of these patients died from prostate cancer. In the SC group the final pathology showed that 18% had prostate cancer. CONCLUSION: Local recurrences were not diagnosed more often in the PSC than the SC group. The outcomes of both procedures are comparable with contemporary cystoprostatectomy series. We consider this procedure oncologically safe and offer this to selected patients. However, selection is the key to success, and our results should further be corroborated by the experience of others.

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

OBJECTIVE: 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. PATIENTS AND METHODS: The study included 35 patients who opted for external beam radiation therapy for prostate carcinoma of intermediate or poor prognosis. Agreement was reached between the participating urologists and the physicians of the nuclear medicine department on the definition of the relevant anatomical areas. The time between a transrectal intraprostatic injection with the radioactive nanocolloid and the laparoscopic SN procedure varied from 5 h to 26 h. Scintigrams were merged with the computed tomography scans until combined methods became available. A laparoscopic gamma-probe was used to identification the SNs, and an extensive laparoscopic node dissection undertaken in the same procedure. Lymph nodes were submitted to the pathologist in such a way that their exact location could be reconstructed. After surgery a graphic report was produced showing the exact location of the lymph nodes. RESULTS: Of the 35 patients 40% were node positive; a mean of 13.5 nodes were resected, and there were no false-negative results. The location of the vast majority of the tumour-positive SNs was around the bifurcation of the external and internal iliac artery, and so involved nodes from the internal iliac, external iliac, communis and obturator basins. Of the six SNs outside the extended node dissection area, two were positive but only one of them exclusively so (lateral to the external iliac artery). The scintigrams did not change after 4 h, and the operation should be done within 24 h to have sufficient radioactivity in the nodes to be detected by the probe. There were eight complications (23%) but only one could be attributed to the SN procedure; the others were thought to be related to the extended laparoscopic node dissection. CONCLUSION: The laparoscopic SN procedure is a reliable tool for diagnosing prostate cancer-bearing lymph nodes, but the extended laparoscopic node dissection has, in this series and others, too many complications for it to be attractive for diagnostic purposes. The SN procedure makes an extended node dissection unnecessary in most patients.

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

OBJECTIVE: To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: Integrated peTRUS in the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) was used for bladder neck identification and dissection in the initial 80 patients with clinically localized prostate cancer operated by two urologists. The clinical and pathological results were compared with the initial 80 patients who had RALP with no peTRUS. The location of positive margins was recorded. RESULTS: The operative duration, blood loss, hospital stay, catheter dependency, clinical and pathological T-stage and Gleason sum score were no different between the groups. The prostate-specific antigen level at time of diagnosis was slightly higher for patients in the peTRUS group. Basal surgical margins (bladder neck and basal areas of both prostate lobes) were positive for tumour in 9.1% and 2.3% of patients treated without and with peTRUS, respectively (P = 0.001). Although the use of peTRUS improved the basal margin rate in the initial 30 patients in each group, it did not in the last 30 in each group, when the urologist's experience apparently improved. In a multivariate analysis the use of peTRUS and pathological T-stage were the best predictors of basal margin status. Pad use at 6 months after surgery was similar for both groups. CONCLUSION: peTRUS during RALP decreased the positive surgical margin rate at the base of the prostate during the initial experience of RALP.

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 microg per m(2) 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 microg per m(2) per day). The maximum tolerated dose on this schedule was 930 microg per m(2) 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 microg per m(2) 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 (t(1/2)) of 0.47 hour (0.11 hour). One patient at dose level 80 microg per m(2) per day had a partial response with a prostate-specific antigen decline by at least 50% for > or =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 microg per m(2) per day once every 3 weeks.

Intraoperative imaging for sentinel node identification in prostate carcinoma: its use in combination with other techniques.

UNLABELLED: 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 (99m)Tc 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.

Prostatic lymphatic drainage with sentinel nodes at the ventral abdominal wall visualized with SPECT/CT: a case series.

Lymphatic drainage from the prostate is mainly directed towards pelvic sentinel lymph nodes, although presacral and para-aortic sentinel nodes have also been found with lymphatic mapping. In this case series, we describe direct lymphatic drainage towards the anterior abdominal wall in 3 patients with prostate cancer. In one patient, the sentinel node at the anterior abdominal wall contained metastasis. Sentinel node sampling provides the possibility to map all nodes on a direct drainage pathway, in contrast to regional pelvic nodal dissection with which some sentinel nodes may be missed.

Paraaortic sentinel lymph nodes: toward optimal detection and intraoperative localization using SPECT/CT and intraoperative real-time imaging.

UNLABELLED: 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 gamma-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 (99m)Tc-nanocolloid, the patients underwent sequential planar lymphoscintigraphy, hybrid SPECT/CT, and sentinel lymphadenectomy. Intraoperative node detection and localization were guided by a laparoscopic gamma-probe and a portable gamma-camera. This gamma-camera was set to display both the (99m)Tc signal and the (125)I-seed signal. This (125)I seed was placed on top of the gamma-probe, functioning as a pointer on screen, thus enabling real-time sentinel node localization with the gamma-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 gamma-camera and gamma-probe and in 3 patients with the gamma-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 gamma-probe and real-time imaging with a portable gamma-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.

Dynamic sentinel node biopsy in penile carcinoma: evaluation of 10 years experience.

PURPOSE: The aim of this study was to evaluate the results of 10 years dynamic sentinel node biopsy experience in penile carcinoma at our institute. PATIENTS AND METHODS: 140 patients with clinically node-negative groins were prospectively included. Lymphoscintigraphy was performed after injection of 99mTechnetium-nanocolloid around the primary tumour. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma ray detection probe. Lymph node dissection was performed only if sentinel node metastasis was found. Median follow-up was 52 months (range 5-129). RESULTS: Lymphoscintigraphy visualized at least 1 sentinel node in 138 patients. Sentinel node metastasis was found in 37 inguinal regions of 31 patients. The sentinel node was the only tumour-positive node in 78% (29/37) of the dissection specimens. Complications occurred in 8% (17/206) of the operated groins. False-negative results were encountered in 6 patients resulting in a false-negative rate of 16% (6/37 patients). 5-year disease-specific survival was 96% and 66% for patients with a tumour-negative sentinel node and tumour-positive sentinel node, respectively (p=0.001). CONCLUSION: Dynamic sentinel node biopsy in penile carcinoma is of important diagnostic, prognostic, and therapeutic value at the cost of only minor morbidity.

Infiltration of activated dendritic cells and T cells in renal cell carcinoma following combined cytokine immunotherapy.

OBJECTIVES: In a phase I study the feasibility, toxicity and immunological effects of peri-operative cytokine immunotherapy of renal cell carcinoma were studied. Main goals were to determine the maximal tolerable dose and detailed in situ analysis of tumor infiltrates. METHODS: Fifteen patients with renal cell carcinoma, undergoing nephrectomy, received subcutaneous immunotherapy, consisting of low-dose IL-2, IFNalpha and GM-CSF, from day -3 prior, until day +5 following surgery in a dose escalation study. Infiltrates from resected tumor tissues from patients undergoing immunotherapy or control patients that underwent nephrectomy only, were examined using quantitative immunohistological analysis and 3-color immunofluorescence staining and confocal laser scanning microscope analysis. RESULTS: Toxicity was limited and the maximal tolerable dose was established. In peripheral blood an increase was found in total lymphocytes, (activated) T cells, NK cells and monocytes. Quantitative immunohistological analysis of tumor infiltrates showed enhanced numbers of CD3+ T cells, S100+ DC, CD83+ DC and IL-2 receptor positive cells (4-fold, 2-fold, 10-fold and 20-fold, respectively, compared to controls). In treated patients preferential invasion was observed of TNFalpha positive CD8+ T cells and DC, positive for DC-SIGN (CD209), CD83, CD80, IL-12 and the DC specific chemokine, DC-CK1 (CCL18). CONCLUSIONS: These findings show increased infiltration of activated, mature DC and functionally active CD8+ T cells in renal tumors, which may suggest clinical potential of cytokine immunotherapy.