Alfons J. M. Balm

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%).

Comparing the Hybrid Fluorescent–Radioactive Tracer Indocyanine Green–99mTc-Nanocolloid with 99mTc-Nanocolloid for Sentinel Node Identification: A Validation Study Using Lymphoscintigraphy and SPECT/CT

The purpose of this study was to compare the lymphoscintigraphic drainage patterns of a hybrid sentinel node tracer consisting of the fluorescent dye indocyanine green (ICG) and 99mTc-nanocolloid with the drainage pattern of 99mTc-nanocolloid alone, the current standard tracer in many European countries. Methods: Twenty-five patients with a melanoma in the head and neck region (n = 10), a melanoma on the trunk (n = 6), or penile carcinoma (n = 9) who were scheduled for sentinel node biopsy were prospectively included. First, the standard 99mTc-nanocolloid procedure was performed. After injection at the lesion site, lymphoscintigraphy was performed with a 10-min dynamic study and static planar images at 10 min and 2 h after injection, followed by SPECT/CT. The same scintigraphic procedure was repeated after injection of hybrid ICG–99mTc-nanocolloid the same afternoon in 10 patients or the next morning in 15 patients. The paired images of both injections were evaluated, and count rates in the sentinel nodes were calculated and compared. Sentinel nodes were surgically localized using blue dye, a γ-ray detection probe, a portable γ-camera, and a fluorescence camera. Results: Lymphatic drainage was visualized in all 25 patients using 99mTc-nanocolloid, leading to the identification of 66 sentinel nodes in total. These same sentinel nodes were also identified during the second scintigraphic procedure with ICG–99mTc-nanocolloid. Moreover, a high correlation between the radioactive counting rates in the sentinel nodes of both scintigraphic studies was observed (mean R2 = 0.83). Intraoperatively (4–23 h after the second injection), all preoperatively identified sentinel nodes could be localized using radio- and fluorescence guidance combined. In total, 95% of the sentinel nodes could be intraoperatively visualized by means of fluorescence imaging, whereas merely 54% stained blue. Ex vivo, all radioactive sentinel nodes were fluorescent and vice versa. No adverse reactions were observed. Conclusion: The lymphatic drainage pattern of ICG–99mTc-nanocolloid is identical to that of 99mTc-nanocolloid. This observation, together with the added value of intraoperative fluorescence guidance, warrants wider evaluation of hybrid ICG–99mTc-nanocolloid as a tracer for sentinel node procedures.

HIF-1α, pimonidazole, and iododeoxyuridine to estimate hypoxia and perfusion in human head-and-neck tumors

PURPOSE: Tumor hypoxia measured by microelectrodes has been shown to indicate poor patient outcome. Here we investigated four potentially more widely applicable immunohistochemical parameters of tumor oxygenation and perfusion in human head-and-neck tumors. METHODS: Twenty patients with squamous cell carcinomas of the head and neck treated with primary surgery were injected with pimonidazole and IdUrd the evening before operation. Consecutive paraffin-embedded sections were stained for blood vessels, pimonidazole, IdUrd, and HIF-1alpha. IdUrd labeling and Ki-67 labeling around individual blood vessels were scored. The spatial relationship between HIF-1alpha and pimonidazole was studied, as well as the distribution of both markers as a function of distance from the nearest blood vessel. RESULTS: Measurement of all four parameters (diffusion-limited fraction, pimonidazole fraction, HIF-1alpha fraction, IdUrd-negative vessels) was feasible, and a significant difference between tumors was found for all parameters. IdUrd-labeled cells were absent around some vessels, indicating lack of perfusion, because these regions were positive for Ki-67. There was a positive correlation between diffusion-limited fraction and pimonidazole area for all images from all tumors, although no correlation for mean values per tumor. Colocalization of pimonidazole and HIF-1alpha was low (0.02%-25%). Most expression profiles showed a more homogenous distribution for HIF-1alpha than pimonidazole. There was no significant correlation between the pimonidazole and HIF-1alpha fractions in the 10 tumors studied. CONCLUSIONS: Simultaneous immunohistochemical measurements related to hypoxia and perfusion are feasible (and easily applicable) in resected human tumors. The different geographic distributions of HIF-1alpha and pimonidazole indicate that HIF-1alpha might not be suitable as a marker for chronic hypoxia. Each parameter will be correlated with outcome in a larger ongoing study on head-and-neck tumors treated with surgery with or without postoperative radiotherapy.

Postlaryngectomy Voice Rehabilitation: State of the Art at the Millennium

Total laryngectomy or laryngopharyngectomy remains the procedure of choice for advanced laryngeal/hypopharyngeal carcinoma, either as a primary procedure or as salvage following irradiation alone or concurrent chemoradiation therapy. Over the past 25 years there has been significant improvement in the rehabilitation of these patients, with speech restoration that has dramatically altered and improved their quality of life. This article reviews postlaryngectomy voice rehabilitation with a historical background as well as the present state-of-the-art tracheoesophageal shunt voice with an artificial valve. Finally, this article reviews and compares artificial valve prostheses as to their voice characteristics, patient satisfaction, complications associated with the procedure, and devices used at a center in Europe (The Netherlands Cancer Institute, Amsterdam) and a North American center (The Wharton Head and Neck Center, Princess Margaret Hospital, University of Toronto, Canada).

A portable gamma-camera for intraoperative detection of sentinel nodes in the head and neck region

We introduced and evaluated a portable γ-camera for intraoperative visualization of sentinel nodes in the head and neck region. Methods: Planar lymphoscintigraphy and SPECT/CT were performed after peritumoral injection of 99mTc-nanocolloid in 25 patients (head and neck melanoma or oral cavity carcinoma). Sentinel nodes were localized intraoperatively with a portable γ-camera and a hand-held γ-probe. The portable γ-camera was used to determine the distribution of remaining radioactivity after excision of the sentinel nodes. Results: The portable γ-camera visualized all 70 preoperatively identified sentinel nodes. Sentinel nodes at difficult sites could be localized more efficiently, and in 6 patients, 9 additional nodes (1 tumor-positive) were identified with the portable γ-camera after excision. Conclusion: Intraoperative identification of sentinel nodes in the head and neck region with a portable γ-camera is feasible and might lead to detection of more sentinel nodes.

Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid.

PurposeFor oral cavity malignancies, sentinel lymph node (SLN) mapping is performed by injecting a radiocolloid around the primary tumour followed by lymphoscintigraphy. Surgically, SLNs can then be localized using a handheld gamma ray detection probe. The aim of this study was to evaluate the added value of intraoperative fluorescence imaging to the conventional radioguided procedure. For this we used indocyanine green (ICG)‐99mTc‐nanocolloid, a hybrid tracer that is both radioactive and fluorescent.MethodsFourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-99mTc-nanocolloid. SLNs were preoperatively identified with lymphoscintigraphy followed by single photon emission computed tomography (SPECT)/CT for anatomical localization. During surgery, SLNs were detected with a handheld gamma ray detection probe and a handheld near-infrared fluorescence camera. Pre-incision and post-excision imaging with a portable gamma camera was performed to confirm complete removal of all SLNs.ResultsSLNs were preoperatively identified using the radioactive signature of ICG-99mTc-nanocolloid. Intraoperatively, 43 SLNs could be localized and excised with combined radio- and fluorescence guidance. Additionally, in four patients, an SLN located close to the primary injection site (in three patients this SLN was located in level I) could only be intraoperatively localized using fluorescence imaging. Pathological analysis of the SLNs revealed a metastasis in one patient.ConclusionCombined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-99mTc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour.

Development and Clinical Evaluation of a Second-generation Voice Prosthesis (Provox®2), Designed for Anterograde and Retrograde Insertion

Prosthetic voice restoration has considerably improved the results of vocal rehabilitation after total laryngectomy, and is presently the method of choice for many health-care providers treating laryngectomized patients. The Provox voice prosthesis, developed in the Netherlands Cancer Institute, is an indwelling device that has been applied in recent years with regular success. Its retrograde replacement method, using a disposable guide wire, assures reliable, atraumatic positioning of the prosthesis in the tracheoesophageal fistula. However, the method sometimes may be uncomfortable for the patient; therefore an adapted prosthesis and new replacement equipment were developed, which enable bidirectional insertion, i.e. not only in the traditional retrograde manner through the pharynx, but especially in an anterograde manner through the stoma. This second-generation voice prosthesis (Provox 2) was studied in a prospective clinical trial in 44 patients (33 experienced patients, seven first-time replacements and four primary insertions). The study demonstrated that the anterograde insertion with the Provox 2 system was applicable in all patients, making the voice prosthesis even easier to handle than with the traditional retrograde method. A stenosis of the pharyngoesophageal segment no longer interfered with the replacement. In addition, the patients judged the new method as being favourable, reporting significantly less discomfort during the replacement procedure (paired Students t-test: p < 0.0001). Furthermore, the adapted voice prosthesis could be removed from the tracheoesophageal fistula without excessive force (mean 7.9 N, range 6.0-14.0 N), more easily than the original Provox (mean 20.9 N, range 5.5-25.0 N). It can be concluded that this second-generation indwelling voice prosthesis (Provox 2) seems to be a further improvement in the application of this voice rehabilitation system, not only simplifying the replacement procedure, but also diminishing the discomfort for the patient.

Scintigraphic assessment of salivary function and excretion response in radiation-induced injury of the major salivary glands

Background. Both loss of the secretory function and impairment of the excretion may play a role in radiationinduced injury of the major salivary glands after radiotherapy for head and neck malignancies. Therefore, quantitative 99mTc‐pertechnetate (99mTc) salivary scintigraphy to assess trapping, secretion, and excretion, was used to analyze irradiation‐induced changes in relation to the radiation dose and the time interval after radiotherapy.

Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours

Salivary gland scintigraphy with technetium-99m pertechnetate was used to follow changes in the excretion and uptake function of the major salivary glands until 1 year after irradiation. Twenty-five patients who received radiotherapy for head and neck tumours were included in the study. Seventy-nine salivary glands (39 parotid and 40 submandibular) were evaluated in relation to the average received radiation dose. Salivary gland scintigraphy was performed before and 1, 6 and 12 months after radiotherapy. For each gland the excretion response to carbachol, evaluated by calculation of the salivary excretion fraction (SEF), the cumulative gland uptake (CGU) and the absolute excreted activity (AEA) at various intervals after radiotherapy were compared with the baseline values. The excretion response decreased in 20 of 25 patients at 1 month after radiotherapy. One month after radiotherapy both SEF and AEA decreased significantly in relation to the radiation dose. These decreases in excretion parameters persisted during the follow-up period. Parotid excretion was affected significantly more than submandibular excretion. CGU values did not change significantly until 6 months after radiotherapy, but at 12 months a significant decrease related to radiation dose was observed. Xerostomia was assessed during radiotherapy and on the days of the scintigraphic tests. The incidence of xerostomia did not correspond to the effects observed in the scintigraphy studies. It is concluded that radiotherapy induces early and persistent impairment of salivary gland excretion, related to the radiation dose. This impairment is stronger in parotid glands than in submandibular glands.

Improvements in respiratory and psychosocial functioning following total laryngectomy by the use of a heat and moisture exchanger.

A prospective clinical study in 61 patients was undertaken to investigate the subjective and objective influence of a heat and moisture exchanger (HME) on the respiratory and psychosocial problems following total laryngectomy. Although statistical comparisons failed to detect significant differences between the experimental and the control groups, there was a clear trend toward improvements in respiratory and psychosocial functioning in the experimental group. Analyses of differences over time within the HME user group showed significant reductions in the incidence of coughing, the mean daily frequency of sputum production, forced expectoration, and stoma cleaning. Significant improvements were also found in shortness of breath, fatigue and malaise, sleep problems, levels of anxiety and depression, and perceived voice quality. Pulmonary function tests showed significant improvements in inspiratory flow and volume values following use of the HME. This objective improvement in inspiratory pulmonary function reflects the decrease in sputum production reported by the patients.