Sentinel node staging in colon carcinoma: value of sentinel lymph node biopsy with radiocolloid and blue staining.

BACKGROUND: Nodal staging accuracy is important in the prognosis and selection of patients for chemotherapy. This prospective study aims to assess the feasibility and accuracy of the sentinel lymph node procedure (SNP) using radiocolloid and blue dye in colon carcinoma. METHODS: In 56 patients, lymphatic mapping was accomplished by means of intraoperatively injecting patent blue and nanocoll subserosally around the tumour. Sentinel nodes (SNs) were harvested ex-vivo. Nodes were stained with H&E. If lymph nodes were interpreted as negative for metastatic tumour, serial sectioning and immunohistochemical staining were performed. RESULTS: At least one SN was detected in 49 of 53 patients (92.5%). Three patients were excluded because of preoperatively detected metastases. Overall, 121 SN were harvested with a mean of 2.2 SN/patients. Eighteen patients had tumour positive nodes. In four patients, pathological nodes were palpable during operation and were excluded. The SN was histologically negative in 2 of 14 patients with positive nodes (false-negative rate 14.3%). In 5 of 14 patients with positive nodes, the SN was the exclusive site of regional nodal metastasis. Four patients were upstaged by immunohistochemical staining (28.6%). The negative predictive value was 93.9% and the overall accuracy 95.6%. Scintigraphy was done in 17 patients. In three patients the SN was detected only by this modality. DISCUSSION: The SN biopsy with the combined technique proved a feasible technique with a steep learning curve. It can change the initial staging from stage II to stage III colon carcinoma. Scintigraphy can improve the success rate of the technique.

Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Lymphoscintigraphic details of sentinel lymph node detection in 82 patients with squamous cell carcinoma of the oral cavity and oropharynx.

Lymphoscintigraphy for sentinel node (SN) detection has been studied extensively in melanoma and breast cancer. In head and neck squamous cell carcinoma (HNSCC), however, experience in this field is relatively meagre. The purpose of this study was to document and evaluate lymphoscintigraphic findings in HNSCC patients. Eighty-two patients with clinical T1-T4 N0 SCC of the oral cavity or oropharynx received peritumoral injections of 25-75 MBq 99mTc-colloidal albumin (CA). Dynamic lymphoscintigraphy was performed in lateral projection for 20 min, followed by 2 min static imaging in anterior projection. In 26 patients, additional static images were obtained 2-6 h after injection of the tracer. In four of 82 patients, both early and late imaging revealed no tracer transport. In 78 of 82 patients, one (60), two (14) or three (4) SNs could be visualized, either by dynamic scintigraphy (73) or delayed static imaging (5). In 48 of 78 (62%) patients, the SN was visualized within the first minute of dynamic imaging. In particular, SNs of tumours of the mobile tongue were visualized within the first minute. No effect of T-stage or 99mTc-CA dose on the transport time of the tracer towards the SN was seen. The distribution of the SNs in the various levels of the neck relative to the primary tumour sites within the oral cavity was in concordance with the patterns of lymph node metastases reported traditionally for patients with SCC in the oral cavity. This study demonstrates the different variables affecting SN identification with lymphoscintigraphy using 99mTc-CA in HNSCC patients.

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Predictive factors for metastatic involvement of nonsentinel nodes in patients with breast cancer.

BACKGROUND: The potential morbidity of an axillary lymph node dissection in patients with breast cancer can be avoided in patients with a negative sentinel node (SN). HYPOTHESIS: It may be possible to identify a subset of patients with a positive SN and without metastases in the remaining axillary lymph nodes. DESIGN: Case-control study. SETTING: Both primary and referral hospital care. PATIENTS: Data were studied for 255 consecutive patients with stage T1 or T2 breast cancer who had a successful identification of the SN. INTERVENTIONS: In patients with a positive SN, histological examination of all non-SNs that were negative by routine examination was the same as that for SNs (multiple sectioning and immunohistochemical analysis). MAIN OUTCOME MEASURES: The incidence of non-SN metastases was correlated with the surface area and number of SN metastases and primary tumor characteristics. A micrometastasis was defined as less than 1 mm(2). RESULTS: Of 255 patients, the SN appeared to be positive in 93 (36%). Subsequent axillary lymph node dissection revealed positive non-SNs in 46 patients (49%). Patients with a single positive SN and patients with metastases less than 1 mm(2) in the SN had significantly less non-SN involvement than patients with more than 1 positive SN (40% vs. 78%) and patients with macrometastases (27% vs. 49%). CONCLUSIONS: The incidence of non-SN metastases seemed to be related to the number of positive SNs and the size of SN metastases. However, in the group of patients with a positive SN, it was not possible to identify a subset of patients without non-SN metastases.

No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm.

In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it is relevant to perform the SN procedure - seems to depend on the Breslow thickness of the primary tumour. However, a Breslow thickness cut-off point has not yet been established. We evaluated a melanoma population that had undergone an SN procedure to determine this point, so that the procedure can be restricted to a smaller group of patients in future. In a total of 348 patients with proven American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of preoperative visualization of the lymph channels from the initial site of the melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval 0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31 months. Our data suggest that this procedure need no longer be indicated for almost a quarter of the patient population, because the cut-off point for nodal involvement appears to be a Breslow thickness of 0.90 mm.

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

BACKGROUND: In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient. METHODS: In 263 consecutive patients with proven American Joint Committee on Cancer Stages I and II cutaneous melanoma, the triple technique SLN procedure was used, i.e., preoperative visualization of the lymph channels from the initial site of the melanoma toward the SLN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and lymph nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabeled lymph nodes. Median follow-up time was 48 months (range, 36-84 months). Multivariate logistic regression analysis was performed to examine the influence of the SLN status and several other prognostic factors on a minimum 3-year disease free survival. RESULTS: In 20% of patients, the SLN proved to be tumor positive. For SLN negative patients, the 5-year disease free survival rate was 91% (+/- 2.4%), and for SLN positive patients it was 49% (+/- 9%). Five variables showed a strong and statistically significant independent prognostic association with outcome, i.e., SLN status (P = 0.0007), thickness of primary melanoma (1.01-2.0 mm; P = 0.04), ulceration (P = 0.05), and lymphatic invasion (P = 0.01) of primary melanoma, and age (40-50 years; P = 0.01). CONCLUSIONS: The SLN status-along with Breslow thickness, ulceration, lymphatic invasion, and age--seems to have strong additional value in predicting a minimum 3-year disease free period after the SLN procedure. Patients with a positive SLN have a poorer prognosis than those with a negative SLN.

Head and neck squamous cell carcinoma: US-guided fine-needle aspiration of sentinel lymph nodes for improved staging--initial experience.

Ultrasonography (US)-guided fine-needle aspiration with cytologic examination was combined with lymphoscintigraphy for the identification of sentinel lymph nodes (SLNs) in 12 patients with a squamous cell carcinoma of the oral cavity or oropharynx. Dynamic lymphoscintigraphy and a hand-held gamma probe were used to depict the SLNs to be aspirated. Cytologic examination of the aspirated SLNs revealed neck lymph node status in patients who underwent neck dissection (n = 6). In patients who underwent only transoral excision, one false-negative cytologic result was observed. This combined approach is expected to improve the detection of occult neck lymph node metastases.

Sentinel node detection in cervical cancer.

BACKGROUND: For superficial tumors such as melanoma, breast, and vulvar cancer, sentinel node detection prevents unnecessary extensive lymph node dissections. Sentinel node detection has not yet proved feasible in tumors, such as cervical cancer, that drain to deep pelvic lymph nodes. TECHNIQUE: We injected technetium-99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy and intraoperative gamma probe detection of sentinel nodes. For visual detection, blue dye was injected at the start of surgery. EXPERIENCE: In six of 10 eligible women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe detection was successful in eight of ten women, whereas visual detection found sentinel nodes in only four. They were found as far as the common iliac level. One woman had positive lymph nodes, of which one was a sentinel node. CONCLUSION: Identification of sentinel nodes using radionuclide is possible in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided.

Reliability of the sentinel node procedure in melanoma patients: analysis of failures after long-term follow-up.

BACKGROUND: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability of this procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years. METHODS: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date. RESULTS: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases. CONCLUSIONS: With a 99% success rate and a 1.5% rate of failed SN procedures (7% false-negative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.

Radioimmunotherapy with intravenously administered 131I-labeled chimeric monoclonal antibody MOv18 in patients with ovarian cancer.

UNLABELLED: We investigated the safety and pharmacokinetics of (131)I-labeled chimeric monoclonal antibody MOv18 ((131)I-c-MOv18 IgG) in patients with ovarian cancer and the estimated radiation dose to cancer-free organs and tumor. METHODS: Three patients were injected intravenously with 3 GBq (131)I-c-MOv18. Toxicity was evaluated according to the World Health Organization toxicity scales. Blood sampling was performed for 12 wk after injection. Whole-body and SPECT imaging was performed frequently. Dose rates were obtained with a portable dose-rate measure. Quantitative activity analysis of several organs was performed with the region-of-interest technique. Absorbed doses were calculated using MIRDOSE3. RESULTS: Transient changes in hematologic profiles were seen in 2 patients. Pancytopenia developed in 1 patient; on analysis, she entered the study probably with exhausted bone marrow reserves. Nonhematologic toxicity was mild. No human antichimeric antibody responses were observed. Mean isolation time was 12 d. The plasma elimination half-life increased almost 3-fold compared with that after tracer doses of c-MOv18. Dosimetry showed mean absorbed doses of 163, 380, 276, 338, 781, and 216 cGy, for whole-body, liver, kidney, spleen, lung, and red marrow, respectively. Tumor-absorbed doses ranged from 600 to 3800 cGy. All patients achieved a stable disease state, as confirmed by CT and carcinoma-associated antigen CA 125, lasting from 2 to >6 mo. CONCLUSION: (131)I-labeled c-MOv18 can safely be given to patients with noncompromised bone marrow reserves and may have therapeutic potential particularly in patients with minimal residual disease.

The implementation of the sentinel node biopsy as a routine procedure for patients with breast cancer.

BACKGROUND: The sentinel node procedure for breast cancer allows for accurate staging of the axilla while the axillary node dissection can be avoided in patients with no sentinel node metastasis. This study describes those patients in whom an axillary dissection is performed, depending on the outcome of the sentinel node procedure, with particular emphasis on the use of strict criteria for the procedure and its practical limitations. METHODS: Preoperative lymphoscintigraphy was performed in 115 consecutive patients. The sentinel nodes were located with the use of a gamma probe and blue dye. Axillary dissection was performed at the same time when the sentinel node procedure was positive by frozen section or not successful by the criteria used. RESULTS: The sentinel node procedure was successful in 106 patients, with the sentinel node being both radioactive and blue in 94% of these patients. The frozen section was positive in 21 of 37 patients with sentinel node metastases. Axillary dissection could be avoided in 69 patients. CONCLUSIONS: The triple technique (with the use of lymphoscintigraphy, the gamma probe, and the blue dye) gives a high success rate of the sentinel node procedure, even when strict criteria for a successful sentinel node procedure are used. Palpation of the open axilla for metastatic nonsentinel nodes is advocated.

Functional lymphatic anatomy for sentinel node biopsy in breast cancer: echoes from the past and the periareolar blue method.

OBJECTIVE: To simplify and improve the technique of axillary sentinel node biopsy, based on a concept of functional lymphatic anatomy of the breast. SUMMARY BACKGROUND DATA: Because of their common origin, the mammary gland and its skin envelope share the same lymph drainage pathways. The breast is essentially a single unit and has a specialized lymphatic system with preferential drainage, through select channels, to designated (sentinel) lymph nodes in the lower axilla. METHODS: These hypotheses were studied by comparing axillary lymph node targeting after intraparenchymal peritumoral radiocolloid (detected by a gamma probe) with the visible staining after an intradermal blue dye injection, either over the primary tumor site (90 procedures) or in the periareolar area (130 procedures). The radioactive content, blue coloring, and histopathology of the individual lymph nodes harvested during each procedure were analyzed. RESULTS: Radiolabeled axillary nodes were identified in 210 procedures, and these were colored blue in 200 cases (94%). The targeting concordance between peritumoral radiocolloid and intradermal blue dye was unrelated to the breast tumor location or the site of dye injection. Radioactive sentinel nodes were not stained blue in 10 procedures (5%), but this mismatching could be explained by technical problems in all cases. In two cases (1%), the (pathologic) sentinel node was blue but had no detectable radiocolloid uptake. CONCLUSIONS: The lessons learned from this study provide a functional concept of the breast lymphatic system and its role in metastasis. Anatomical and clinical investigations from the past strongly support these views, as do recent sentinel node studies. Periareolar blue dye injection appears ideally suited to identify the principal (axillary) metastasis route in early breast cancer. Awareness of the targeting mechanism and inherent technical restrictions remain crucial to the ultimate success of sentinel node biopsy and may prevent disaster.

Vital dye and radiolabelled colloids--complement or alternative?

Several different protocols for retrieval of the sentinel node (SN) have been described: gamma probe (GP) and/or dye guided biopsy, preceded by lymphoscintigraphy or not. Especially in American studies, predominantly executed by surgeons, dye or GP guidance only is used with good results. The disadvantages of applying dye only are: an extensive learning curve, lower retrieval rate of the SN and, especially in the learning phase, a higher rate of false negative biopsies. If only GP guidance is applied, the technique seems more simple to master. A recent multicentre study, however, revealed an unacceptably high false negative rate. It must be considered that most published studies were executed by highly experienced surgeons. In most European studies, scintigraphy is a standard part of the procedure. Lymphoscintigraphy provides the surgeon with a "road map", revealing the number and approximate location of the SNs in the lymphatic basin(s). Scintigraphy proves useful especially if an SN is situated close to the injection site (breast cancer), or if SNs are situated at unexpected locations (head-and-neck or trunk melanoma). A combination of all three available steps results in the highest number of successful procedures with the lowest false negative rate. This may prove to be especially important for general hospitals where the number of biopsy procedures is often smaller compared to specialized centres.

Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer.

AIMS: The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN. METHODS AND RESULTS: Seventy-four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1-2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty-one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not. CONCLUSIONS: Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.

[Follow-up after melanoma resection is more extensive than recommended in the practice guidelines, primarily for reassurance of the patient]. / Follow-up na melanoomverwijdering uitgebreider dan aanbevolen in de consensus, ter geruststelling van de patiënt.

OBJECTIVE: To determine to what extent the follow-up after resection of melanoma in practice corresponds to the relevant guidelines in the first revised version of the consensus 'Melanoma of the skin'. DESIGN: Descriptive, retrospective. METHOD: For 67 patients, who had a melanoma resected in September 1993-April 1995 in the Academic Hospital, Vrije Universiteit, Amsterdam, the Netherlands, data were collected in May-August 1997 on the first two years of follow-up from the medical records (n = 42) and through communication in writing with the referring physicians and the physicians involved in the follow-up in other hospitals in the Netherlands (n = 25). The frequency of physical examination and routine diagnostics by the doctor was evaluated. To gain insight into the reasons why in some cases the guidelines were not followed, we set up an inquiry among the 20 doctors involved in the follow-up in August 1998. RESULTS: The mean frequency of outpatient visits and physical examinations was 3-4 times per year, practically consistent with the guideline. Routine blood testing was performed in 17 patients (25%) and diagnostic imaging (X-ray or CT scan of the chest, ultrasonography of the liver) in 51 patients (76%) in deviation from the guideline. Non-compliance with the guideline could not be explained by unfamiliarity with the consensus, disagreement with the contents or existence of local protocols. Extra diagnostics were mostly meant to reassure patients. No metastases or recurrences were encountered during routine follow-up examinations, but some were found (in 8 patients) at interim visits to the outpatient clinic. CONCLUSION: The national guidelines regarding diagnostic tests in the follow-up of melanoma patients are insufficiently followed. Because redundant routine diagnostics probably have more disadvantages than benefits, a more active implementation of (future) guidelines appears necessary.