Cornelis A. Hoefnagel

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.

Metaiodobenzylguanidine and somatostatin in oncology: role in the management of neural crest tumours

Two recently developed radiopharmaceuticals, iodine-131 metaiodobenzylguanidine (MIBG) and indium-111 pentetreotide, are currently being used for the diagnosis and therapy of neural crest tumours by interaction with the characteristic features of these tumours, such as an active uptake-I mechanism at the cell membrane and the presence of vesicles or neurosecretory granules in the cytoplasm and of specific receptors at the cell membrane. This review focusses on the role of MIBG and somatostatin analogues in the management of neural crest tumours. A number of aspects of both tracers are compared and the cumulative results are reviewed. Other uses of these radiopharmaceuticals are mentioned. It is concluded that both 111In-pentetreotide and 123I/131-MIBG are sensitive indicators of neural crest tumours, and have a complementary role. Unlike MIBG, 111In-pentetreotide is not specific for neural crest tumours, as scintigraphy is also positive in many other tumours, granulomas and autoimmune diseases. 131I-MIBG is effective in the therapy of several neural crest tumours; the biodistribution of 111In-pentetreotide at present does not allow radionuclide therapy using a beta-emitting label. However, as an indicator of somatostatin receptors, 111In-pentetreotide scintigraphy may be a predictor of response to palliative treatment with unlabelled octreotide. Recommendations for the use of these procedures are given.

Localizing the sentinel node in cutaneous melanoma: gamma probe detection versus blue dye

AbstractBackground: Sentinel node (SN) biopsy can be used to select patients with melanoma for therapeutic lymphadenectomy. We investigated the value of two methods to locate the SN: patent blue dye (PBD) and gamma probe detection of99mTc-nanocolloid. Methods: One hundred ten patients with cutaneous melanoma were studied. Lymphoscintigraphy with99mTc-nanocolloid was performed to determine the position of the SN. Before operation, PBD was injected at the same site as the radiopharmaceutical. When a blue node was identified intraoperatively, its radioactivity level was measured with the probe. In the absence of blue coloration, the probe was used to trace the SN. Results: Scintigrams visualized a total of 219 SNs in 141 basins. Eight SNs were not explored. One SN was not found. The remaining 210 and 27 additional intraoperatively identified SNs were excised. From the total of 237 removed SNs, 200 (84%) were found using PBD only. All 37 nodes that were not found with the PBD were localized with the probe so that the probe combined with PBD identified 99.5% of all SNs. In 23 patients the SN contained tumor. In three patients the SN was false-negative for metastasis. Conclusion: The gamma probe together with PBD can identify more SNs (99.5%) than lymphatic mapping with PBD alone (84%).

Review and Evaluation of Sentinel Node Procedures in 250 Melanoma Patients With a Median Follow-Up of 6 Years

Background: The aim of this study was to evaluate the results of sentinel node biopsy in cutaneous melanoma at our institute.Methods: A total of 250 patients with cutaneous melanoma were studied prospectively. Preoperative lymphoscintigraphy was performed after injection of 99mTc-nanocolloid intradermally around the primary tumor or biopsy site (.32 mL, 65.5 MBq [1.8 mCi]). The sentinel node was surgically identified with the aid of patent blue dye and a gamma ray detection probe. The median follow-up was 72 months.Results: Lymphoscintigraphic visualization was 100%, and surgical identification was 99.6%. In 60 patients (24%), 1 or more sentinel nodes were tumor positive at initial pathology evaluation. Late complications after sentinel node biopsy of the remaining 190 patients were seen in 35 patients (18%). The false-negative rate was 9%. In-transit metastases were seen in 7% of sentinel node–negative and 23% of sentinel node–positive patients. The estimated 5-year overall survival rates were 89% and 64%, respectively (P < .001).Conclusions: This study confirms that the status of the sentinel node is a strong independent prognostic factor. The false-negative rate and the incidence of in-transit metastases in sentinel node–positive patients are high and have to be weighed against the possible survival benefit of early removal of nodal metastases.

Sentinel node biopsy for melanoma in the head and neck region

Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region.

Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry

Since the introduction of radioiodinated metaiodobenzylguanidine in 1980, considerable research has been performed, both in the chemical field and in medical sciences. However, despite the wide use of radioiodinated metaiodobenzylguanidine, knowledge about its pharmacology is still limited. This paper reviews the biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry of radioiodinated metaiodobenzylguanidine. Iodine-131 metaiodobenzylguanidine therapy is in general well tolerated, but its effectiveness needs improvement. Also whole-body dosimetry as part of treatment planning needs to be improved. Future prospects on these items are included in this review.

The Additional Value of SPECT/CT in Lymphatic Mapping in Breast Cancer and Melanoma

The recently introduced SPECT/CT integrates the physiologic data of SPECT with the anatomic data of CT into a single image. The purpose of this pilot study was to explore the additional value of SPECT/CT in breast cancer patients and melanoma patients with inconclusive planar image findings. Methods: Thirty-one patients had planar lymphoscintigrams showing unexpected lymphatic drainage, 6 had lymphoscintigrams that were difficult to interpret, and 3 showed no drainage on planar imaging. SPECT/CT was performed immediately after delayed planar imaging. Results: In 4 patients, SPECT/CT showed 6 additional sentinel nodes, of which 2 were tumor-positive and led to upstaging and tailored management in 5% of patients. SPECT/CT depicted sentinel nodes in 3 patients whose delayed planar imaging had shown no drainage. Conclusion: SPECT/CT was of additional value in finding the exact anatomic location of sentinel nodes in patients with inconclusive planar image findings. SPECT/CT also detected sentinel nodes in addition to those found on planar images, and SPECT/CT detected sentinel nodes in patients whose planar images had shown none.

Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors.

PURPOSE To evaluate the therapeutic effect of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) and unlabeled MIBG in patients with carcinoid tumor. MATERIALS AND METHODS A therapeutic dose of 7.4 GBq (200 mCi) 131I-MIBG infused over 4 hours was administered to 30 patients with either carcinoid syndrome (n = 20) or tumor symptoms such as pain and fever due to carcinoid tumor (n = 10). In general, two courses were given, 6 weeks apart. Due to radioactivity, patients had to be isolated for 5 to 7 days. Subsequently, we studied the effect of unlabeled MIBG based on the possible pharmaceutic activity of MIBG and to avoid the isolation procedure. A doseescalation study of 8.5, 17, and 34 mg/m2 MIBG infused over 4 hours at 4-week intervals was performed in 20 patients with carcinoid syndrome who were not suitable for treatment with the radioactive compound. RESULTS Following 131I-MIBG treatment, symptomatic responses were observed in 60% of patients (median duration, 8 months; maximum, 2 years). Side effects were mild and rapidly reversible in 16 patients, and were related to the isolation procedure in seven of these patients. Unlabeled MIBG resulted in symptomatic improvement in 60% of patients (median duration, 4.5 months). Side effects, which included changes in blood pressure, were mild and transient. Symptomatic responses were not accompanied by biochemical responses. CONCLUSION Both MIBG treatment regimens were equally effective in the palliation of symptoms, but duration of response tended to be much longer with the radioactive compound. However, the unlabeled compound provided a simpler treatment, eg, in elderly patients and those in poor condition, without the need for isolation.

Radionuclide therapy revisited

Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different specific tumour-seeking radiopharmaceuticals are being applied both for diagnostic scintigraphy and treatment, using multiple routes and mechanisms to target radionuclides at tumours. After a brief introduction of some basic principles of radionuclide targeting, the therapeutic radiopharmaceuticals available are reviewed according to the accumulation site in relation to the cell nucleus; the results of their current clinical use for therapy are also reviewed. The response observed to a number of these applications, the non-invasiveness of the procedure and the relative lack of toxicity and late effects in comparison with chemotherapy and external beam radiotherapy make radionuclide therapy an attractive and realistic alternative in the management of malignant disease, as well as in the treatment of a few benign disorders.

Scanning with 18F-FDG-PET/CT for Detection of Pelvic Nodal Involvement in Inguinal Node-Positive Penile Carcinoma

BACKGROUND Penile carcinoma patients with inguinal lymph node involvement (LNI) have an increased risk for pelvic nodal involvement with or without distant metastases. OBJECTIVE To evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with computed tomography (CT; 18F-FDG PET/CT) scanning in determining further metastatic spread in patients with tumour-positive inguinal nodes. DESIGN, SETTING, AND PARTICIPANTS Eighteen patients with penile squamous cell carcinoma with unilateral or bilateral cytologically tumour-positive inguinal disease underwent whole-body 18F-FDG-PET/CT scanning for tumour staging. MEASUREMENTS Images were blindly assessed by two nuclear medicine physicians. All scans were evaluated for pelvic nodal involvement per basin and for distant metastases. Histopathology (when available), radiologic imaging, and clinical follow-up (with a minimum of 1 yr) served as a reference standard. The diagnostic value of PET/CT scanning for predicting pelvic nodal involvement was evaluated using standard statistical methods. RESULTS AND LIMITATIONS The reference was available in 28 of the 36 pelvic basins. Of the 11 tumour-positive pelvic basins, 10 were correctly predicted by PET/CT scan, as were all 17 tumour-negative pelvic basins. PET/CT scan showed a sensitivity of 91%, a specificity of 100%, a diagnostic accuracy of 96%, a positive predictive value of 100%, and a negative predictive value of 94% in detecting pelvic nodal involvement. Additionally, PET/CT scans showed distant metastases in five patients. In four patients, the presence of distant metastases could be confirmed, while in one patient, no radiologic confirmation was found for that particular lesion. A potential limitation is that the diagnostic accuracy of PET/CT scanning was calculated on 28 pelvic basins only. Furthermore, no comparison was made with conventional CT scans, as not all patients had undergone contrast-enhanced CT scans. CONCLUSIONS PET/CT scanning appears promising for detecting pelvic lymph node metastases with great accuracy, and it identifies distant metastases in penile carcinoma patients with inguinal LNI. In our practice, PET/CT scanning has become part of routine staging in such patients.