Friedhelm Wawroschek

The Sentinel Lymph Node Concept in Prostate Cancer – First Results of Gamma Probe-Guided Sentinel Lymph Node Identification

Objective: The goal of this study was to show lymphatic drainage and to verify the validity of lymphoscintigraphy for the identification of the sentinel lymph node (SLN) in prostate cancer. Furthermore, the question is to be raised whether the standardized pelvic lymphadenectomy is a sufficient means for also detecting solitary micrometastases. Patients and Methods: Eleven patients with prostate cancer received a sonographically controlled, transrectal administration of a technetium-99m colloid injected directly into the prostate 1 day prior to pelvic lymphadenectomy. 20 min later the dynamic lymphoscintigraphy was carried out. During surgery, the SLNs were identified by using a gamma probe. The standard pelvic lymphadenectomy was performed after removal of the SLN. Results: In 3 of 4 patients with micrometastasis the spread of the tumor could exclusively be found in those nodes which had been identified as SLNs by means of scintigraphy by combining preoperative lymphoscintigraphy and intraoperative gamma probe detection. In 2 cases, the pathologically proved SLNs were situated at the anteromedial region of the internal iliac artery, thus being located outside of the standard pelvic lymphadenectomy area. In 1 patient, however, the micrometastasis was found beyond those nodes which had been identified as SLN intraoperatively. Conclusions: In the future, we expect the restriction of pelvic staging lymphadenectomy to scintigraphically proved SLN. The perioperative morbidity may be reduced by increasing the sensitivity of the detection of micrometastases. Our data confirm earlier perceptions, according to which even modified standardized pelvic lymphadenectomy is considered insufficient in terms of the detection of micrometastases.

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 90– 400 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.

Low dose unenhanced helical computerized tomography for the evaluation of acute flank pain.

PURPOSE Unenhanced helical computerized tomography (CT) has proved to be an excellent diagnostic tool for evaluating acute flank pain with reported 95% to 100% sensitivity, 92% to 100% specificity, 96% to 100% positive and 91% to 100% negative predictive values. The diagnostic value of a new low dose protocol was prospectively studied and compared with the results of conventional unenhanced helical CT in a previous series with an effective dose equivalent (HE) of 3.1 to 4.3 mSv. and in current literature with an estimated HE of 4.3 to 4.7 mSv. MATERIALS AND METHODS In 109 patients 18 to 86 years old with acute flank pain we performed low dose unenhanced helical CT in addition to abdominal ultrasound and urinalysis with new CT parameters (120 kV. 70 mA., 5 mm. collimation, pitch 2 and incremental reconstruction each 5 mm.) that led to a more than 50% decrease in radiation exposure to 1.50 mSv. in females and 0.98 mSv. in males. Ureteral calculi were confirmed or excluded by retrograde ureteropyelography in 51 cases. In the other cases the diagnosis was verified by the clinical and ultrasound course, and/or stone asservation. RESULTS In 80 of the 109 patients the flank pain was caused by a ureteral calculus. Low dose unenhanced helical CT precisely identified 77 ureteral calculi with 1 false-positive finding. Thus, the sensitivity and specificity of low dose unenhanced helical CT were 96% and 97% with a 99% positive and 90% negative predictive value. In 15 of 29 patients with CT findings negative for stone disease different causes of pain were established by low dose unenhanced helical CT. CONCLUSIONS Even with the significantly decreased radiation exposure of the low dose protocol unenhanced helical CT is still an excellent and rapid diagnostic tool for evaluating acute flank pain with lower radiation exposure than excretory urography (HE 1.3 to 2.3 mSv.) at our departments. Only in obese patients with a body mass index of greater than 31 kg./m.2 is conventional unenhanced helical CT with higher radiation exposure recommended to achieve adequate image quality.

RADIOISOTOPE GUIDED PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER

PURPOSE The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique. MATERIALS AND METHODS In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed. RESULTS Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor. CONCLUSIONS Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

The Influence of Serial Sections, Immunohistochemistry, and Extension of Pelvic Lymph Node Dissection on the Lymph Node Status in Clinically Localized Prostate Cancer

OBJECTIVES Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The aim of the study was to investigate the value of extended histopathological techniques considering the extent of pelvic lymphadenectomy and preoperative risk factors. METHODS Total of 194 patients with prostate cancer were examined. At first all patients had a sampling of the sentinel lymph nodes (SLN) followed in most cases by a modified or extended pelvic lymphadenectomy. Step sections, serial sections and immunohistochemistry (IHC, pancytokeratin antibody) were analyzed in all SLN and so-called non-SLN of the first 100 patients. Later serial sections and IHC of non-SLN were left out. RESULTS In 26.8% lymphatic metastases were found. The detection rate of lymph node-positive patients depend significantly on the chosen extension of pelvic lymphadenectomy. Limiting the histopathological investigation to the lymph node specimen of the obturator fossa only 44.2% of lymph node-positive cases would have been identified. An additional inclusion of all lymph nodes surrounding the external iliac vessels improves the sensitivity to 65.4% (46.7% and 73.3% for the first 100 patients). Compared to the extension of pelvic lymphadenectomy the diagnostic gain of serial section and IHC (13.8% versus 53.3%) was comparably low. CONCLUSIONS The extension of pelvic lymph node dissection is of outstanding value for the identification of node-positive patients. Limiting the number of lymph nodes to the ones with the highest probability of bearing lymphatic spread (SLN) makes the use of extensive histopathological techniques more feasible.

Unenhanced Helical Computed Tomography in the Evaluation of Acute Flank Pain

Objective: The diagnostic value of unenhanced helical computed tomography (CT) for the evaluation of acute flank pain is investigated in a prospective study. Patients and Methods: In 125 patients aged 18–86 years, we performed unenhanced helical CT in addition to abdominal plain film, abdominal ultrasound and urinalysis as a diagnostic measure for acute flank pain. Ureteral calculi were confirmed or, respectively, excluded by retrograde ureteropyelography in 80 cases. In the other cases, diagnosis was verified by clinical course and/or stone asservation. Results: In 91 of 125 patients the flank pain was caused by a ureteral calculus. In 67 of 91 patients with urolithiasis, stones could be collected for analysis. Helical CT was able to precisely identify 90 ureteral calculi. Abdominal plain films led to 8 false–positive and 48 false–negative findings. Thus, sensitivity of plain radiography, ultrasound and urinalysis was 47, 11 and 84% with a specificity 76, 97 and 32%, respectively. Conclusions: Unenhanced helical CT reaches a distinctively increased diagnostic value (sensitivity 99%, specificity 97%) in the evaluation of acute flank pain as compared to plain radiography, ultrasound and urinalysis.

Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of ≤10 ng/mL and biopsy Gleason score of ≤6, and their influence on PSA progression-free survival after radical prostatectomy

To investigate how many men with low‐risk prostate cancer had positive lymph nodes detected by radio‐guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases.

First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy.

Introduction: [11C]choline PET/CT provides the opportunity to detect small lymph node metastases (LNM) (>5 mm) in prostate cancer (PCa) with exact topographic allocation. PSA development after resection of single LN recurrence detected via [11C]choline PET/CT without adjuvant therapy is not yet analyzed. We wanted to evaluate the potential of [11C]choline PET/CT in the diagnosis of single LN recurrence after radical prostatectomy (RPE) and whether secondary resection can result in PSA remission. Methods: We investigated 6 patients with biochemical recurrence (PSA: median 2.04, range 0.67–4.51 ng/ml) after RPE. A single suspicious LN was detected on PET/CT without suspicion of local relapse or distant metastasis. The suspicious and nearby LN were open dissected (09/2004–02/2008). Histological and PET/CT findings were compared and the postoperative PSA development was examined. Results: All metastasis-suspicious LN could be confirmed histologically. The additionally removed 10 LN were all correctly negative for cancer. Three patients showed a complete permanent PSA remission (<0.01 (n = 2), <0.03 ng/ml (n = 1)) without adjuvant therapy (follow-up: median 24, range 21–35 months). Conclusions: In this small selected collective [11C]choline PET/CT achieved reliable results. After resection of single LNM in all patients the oncologic criteria of a remission were fulfilled. Three of 6 patients had a complete PSA remission without adjuvant therapy. Whether cure or a positive influence on the course of disease can be achieved in individual patients has to be shown in further studies.

Micrometastases of Bone Marrow in Localized Prostate Cancer: Correlation With Established Risk Factors

PURPOSE The presence of cytokeratin 18-positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer. PATIENTS AND METHODS Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis. RESULTS In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors. CONCLUSION We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Abstract Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages.