A Novel Method for Intraoperative Sentinel Lymph Node Detection in Prostate Cancer Patients Using Superparamagnetic Iron Oxide Nanoparticles and a Handheld Magnetometer: The Initial Clinical Experience

BACKGROUND: A sentinel lymph node (SLN) biopsy using superparamagnetic iron oxide nanoparticles (SPIOs) as a tracer instead of radioisotopes was first applied successfully in breast cancer. This study determined the feasibility of this new technique using SPIOs and a handheld magnetometer to detect SLNs in prostate cancer (PC). METHODS: Enrolled 20 patients with intermediate and high-risk PC (PSA >10 and/or Gleason score >7) in a prospective study (12/2013–1/2014; DRKS00005473), following an ethics committee approval. After transrectal intraprostatic SPIOs injection a day earlier, patients (19/20) underwent magnetometer-guided sentinel lymphadenectomy (sPLND) and extended PLND, followed by radical prostatectomy. One patient was not operated because of an unrelated coagulation disorder. The ex vivo magnetic activity of all lymph nodes (LNs) removed was measured. The detection rate, rate of in vivo detected SLNs, and sensitivity of sPLND was established. RESULTS: No adverse events attributable to SPIOs injection were observed. Identified 126 SLNs (median 7, IQR 4–9) and resected 334 LNs (median 17, IQR 14–19); 37 % (7/19) of the patients had LN metastases (median 1, IQR 1–3.5). The detection rate and rate of in vivo detected SLNs were 90 % (17/19) and 94 % (118/126) respectively. Using sPLND, all LN metastases were detected (15/15, sensitivity 100 %) in all patients identified with SLNs. One LN + patient showed no SLNs following transurethral prostate resection. CONCLUSIONS: This is the first study using a magnetic tracer and magnetometer to detect SLNs in PC. Initial data indicate that this simple, radiation-free procedure is safe, feasible, and reliably identifies SLN and LN metastases in most patients

Prostate lymphoscintigraphy and radio-guided surgery for sentinel lymph node identification in prostate cancer - Technique and results of the first 350 cases

Introduction: Having in mind the promising results of lymphoscintigraphy and intraoperative gamma probe application for the detection of sentinel lymph nodes (SLN) in malignant melanoma, breast and penis cancer, we tried to identify the SLN in prostate cancer by applying a comparable technique. Materials and Method. 350 patients with prostate cancer were examined after providing informed consent. The day before pelvic lymphadenectomy technetium-99m nanocolloid was transrectally injected into the prostate under ultrasound guidance. A single central application was done per prostate lobe in most cases. Activity attained 90400 MBq, and the total injected volume was about 2-3 ml. Hereafter, lymphoscintigraphy was carried out. Those lymph nodes having been identified as SLN by means of gamma probe detection and lymphoscintigraphy were removed intraoperatively. Later, most of the cases had different types of pelvic lymphadenectomy. SLN received serial sections and immunohistochemistry, non-SLN step sections. Results: 335 patients showed at least 1 SLN in lymphoscintigraphy. 24.7% had lymph node metastases. In 2 patients, metastases in non-SLN were found without at least one SLN being affected (false-negative patient). Conclusion:Our experience suggests that the SLN identification is not only feasible in breast cancer and malignant melanoma, but also in prostate cancer with a comparable technique. Copyright (C) 2003 S. Karger AG, Basel

Complete PSA Remission without Adjuvant Therapy after Secondary Lymph Node Surgery in Selected Patients with Biochemical Relapse after Radical Prostatectomy and Pelvic Lymph Node Dissection

Introduction. To evaluate whether secondary resection of lymph node (LN) metastases (LNMs) can result in PSA remission, we analysed the PSA outcome after resection of LNM detected on PET/CT in patients with biochemical failure. Materials and Methods. 11 patients with PSA relapse (mean 3.02 ng/mL, range 0.5–9.55 ng/mL) after radical prostatectomy without adjuvant therapy were included. Suspicious LN (1–3) detected on choline PET/CT and nearby LN were openly dissected (09/04–02/11). The PSA development was examined. Histological and PET/CT findings were compared. Results. 9 of 10 patients with histologically confirmed LNM showed a PSA response. 4 of 9 patients with single LNM had a complete permanent PSA remission (mean followup 31.8, range 1–48 months). Of metastasis-suspicious LNs (14) 12 could be histologically confirmed. The additionally removed 25 LNs were all correctly negative. Conclusions. The complete PSA remissions after secondary resection of single LNM argue for a feasible therapeutic benefit without adjuvant therapy. For this purpose the choline PET/CT is in spite of its limitations currently the most reliable routinely available diagnostic tool

Role of Pelvic Lymph Node Dissection in Prostate Cancer Treatment

Pelvic lymph node dissection (PLND) is the most accurate and reliable staging procedure for detecting lymph node invasion (LNI) in prostate cancer. Recently, [11C]-choline positron emission tomography imaging and magnetic resonance imaging with lymphotropic superpara-magnetic nanoparticles have shown potential for detecting LNI but are still under investigation. The risk of LNI in low-risk groups could be underestimated by use of the current nomograms, which rely on data collected from patients who underwent only limited PLND. Extended PLND (ePLND) shows higher lymph node yield, which leads to the removal of more positive nodes and fewer missed positive nodes. It may be possible to refrain from performing PLND on low-risk patients with a prostate-specific antigen value <10 ng/ml and a biopsy Gleason score ≤6, but the risk of biopsy-related understaging should be kept in mind. Theoretically, meticulous ePLND may also impact prostate cancer survival by clearing low-volume diseases and occult micrometastasis even in pN0. The therapeutic role of PLND in prostate cancer patients is still an open question, especially in individuals with low-risk disease. Patients with intermediate- to high-risk disease are more likely to benefit from ePLND

Protocol for a Randomized Phase II Trial for Mesh Optimization by Autologous Plasma Coating in Prolapse Repair: IDEAL Stage 3

Introduction: Mesh-related complications especially after vaginal implantation have raised awareness lately because of severe adverse reactions and legal aspects. About 20% of patients suffer from complications after mesh insertion in the anterior vaginal wall. Autologous plasma coating of meshes prior to implantation has shown potential to improve the biocompatibility of meshes in vivo and in vitro. This innovative approach has been developed according to the IDEAL recommendations for surgical innovations. The method has still to be assessed at stage 3 accordingly. Methods: A protocol is developed for a prospective single-blinded randomized controlled phase II trial for biocompatibility optimization of anterior vaginal meshes for prolapse repair by autologous plasma coating versus non-coated meshes. Results: The protocol aims at fulfilling the requirements for stage 3 (assessment) according to IDEAL. Eligible for inclusion are women with primary cystocele, requiring a surgical procedure, suitable for randomization, and willing to be randomized. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomization) and will also be reviewed in clinic 12 and 24 months post surgery. Primary endpoint is the assessment of mesh-related complications following the Clavien–Dindo classifications. QoL, sexual function assessment, efficacy, and validation of an already developed long-term register are considered secondary endpoints. To afford a calculated 10% reduction of postoperative complications through plasma-coated meshes vs. non-coated meshes at 1-year follow-up, a total 214 women in each arm will be necessary to achieve 80% power at a significance level of 5%. Conclusion: The protocol for this randomized clinical trial represents the conditions to assess the surgical innovation of plasma coating of meshes in order to improve the meshes’ biocompatibility at stage 3 according to the IDEAL recommendations. © 2017 Springer Healthcar

Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition

BACKGROUND: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging. METHODS: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5–3 hours after injection of 250 MBq (99m)Tc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 × 1.8 Gy / week) to the pelvis and 70.0 Gy (5 × 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed. RESULTS: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred. CONCLUSION: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients

Does Intensity Modulated Radiation Therapy (IMRT) prevent additional toxicity of treating the pelvic lymph nodes compared to treatment of the prostate only?

<p>Abstract</p> <p>Background</p> <p>To evaluate the risk of rectal, bladder and small bowel toxicity in intensity modulated radiation therapy (IMRT) of the prostate only compared to additional irradiation of the pelvic lymphatic region.</p> <p>Methods</p> <p>For ten patients with localized prostate cancer, IMRT plans with a simultaneous integrated boost (SIB) were generated for treatment of the prostate only (plan-PO) and for additional treatment of the pelvic lymph nodes (plan-WP). In plan-PO, doses of 60 Gy and 74 Gy (33 fractions) were prescribed to the seminal vesicles and to the prostate, respectively. Three plans-WP were generated with prescription doses of 46 Gy, 50.4 Gy and 54 Gy to the pelvic target volume; doses to the prostate and seminal vesicles were identical to plan-PO. The risk of rectal, bladder and small bowel toxicity was estimated based on NTCP calculations.</p> <p>Results</p> <p>Doses to the prostate were not significantly different between plan-PO and plan-WP and doses to the pelvic lymph nodes were as planned. Plan-WP resulted in increased doses to the rectum in the low-dose region ≤ 30 Gy, only, no difference was observed in the mid and high-dose region. Normal tissue complication probability (NTCP) for late rectal toxicity ranged between 5% and 8% with no significant difference between plan-PO and plan-WP. NTCP for late bladder toxicity was less than 1% for both plan-PO and plan-WP. The risk of small bowel toxicity was moderately increased for plan-WP.</p> <p>Discussion</p> <p>This retrospective planning study predicted similar risks of rectal, bladder and small bowel toxicity for IMRT treatment of the prostate only and for additional treatment of the pelvic lymph nodes.</p

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology