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Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Chi-Square Distribution↗

Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density.

PURPOSE: We evaluated the clinical outcomes and risk factors for progression in a large cohort of patients with lymph node metastases following en bloc radical cystectomy and bilateral pelvic lymphadenectomy. MATERIALS AND METHODS: From July 1971 through December 1997, 1,054 patients underwent radical cystectomy and bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66 years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the 244 patients (57%) received some form of chemotherapy. At a median followup of greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate analysis according to tumor grade, carcinoma in situ, primary bladder tumor stage, pathological subgroups, total number of lymph nodes removed and involved with tumor, and lymph node density (total number of positive lymph nodes/total number removed). In addition, the form of urinary diversion and the administration of chemotherapy were also evaluated. Multivariate analysis was then performed to analyze these variables independently. RESULTS: The incidence of positive lymph nodes increased with higher p stage and pathological subgroups. Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%) with extravesical tumor extension had involved lymph nodes. The median number of lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96), while the median number of positive lymph nodes was 2 (range 1 to 63). Overall recurrence-free survival at 5 and 10 years for the 244 patients with lymph node positive disease was 35% and 34%, respectively. Patients with lymph node positive disease and an organ confined primary bladder tumor had significantly improved 10-year recurrence-free survival compared with those with extravesical tumor extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25% 10-year recurrence-free survival compared with 36% when greater than 15 lymph nodes were removed. Recurrence-free survival at 10 years for patients with 8 or less positive lymph nodes was significantly higher than in those with greater than 8 positive lymph nodes (40% vs 10%, p <0.001). The novel concept of lymph node density was also a significant prognostic factor. Patients with a lymph node density of 20% or less had 43% 10-year recurrence-free survival compared with only 17% survival at 10 years when lymph node density was greater than 20% (p <0.001). On multivariate analysis the total number of lymph nodes involved, pathological subgroups of the primary bladder tumor, lymph node density and adjuvant chemotherapy remained significant and independent risk factors for recurrence-free and overall survival. CONCLUSIONS: Patients with lymph node tumor involvement following radical cystectomy may be stratified into high risk groups based on the primary bladder tumor, pathological subgroup, number of lymph nodes removed and total number of lymph nodes involved. Lymph node density, which is a novel prognostic indicator, may better stratify lymph node positive cases because this concept collectively accounts for the total number of positive lymph nodes (tumor burden) and the total number of lymph nodes removed (extent of lymphadenectomy). Future staging systems and the application of adjuvant therapies in clinical trials should consider applying lymph node density to help standardize this high risk group of patients following radical cystectomy.

Adult↗

Interval nodes: the forgotten sentinel nodes in patients with melanoma.

BACKGROUND: Any sentinel lymph node that receives lymph drainage directly from a primary melanoma site, regardless of its location, may contain metastatic disease. This is true even if the sentinel node does not lie in a recognized node field. Interval (in-transit) nodes that lie along the course of a lymphatic vessel between a primary melanoma site and a recognized node field are sometimes seen during lymphatic mapping for sentinel node biopsy. If drainage to such interval nodes is ignored by the surgeon during sentinel node biopsy, metastatic melanoma will be missed in some patients. HYPOTHESIS: When lymph drains directly from a cutaneous melanoma site to an interval node, that sentinel node has the same chance of harboring micrometastatic disease as a sentinel node in a recognized node field. DESIGN: Preoperative lymphoscintigraphy with technetiumTc 99m antimony trisulfide colloid was performed to define lymphatic drainage patterns and, since 1992, to locate the sentinel lymph nodes for surgical biopsy or for permanent skin marking of their location with point tattoos. SETTING: Melanoma unit of a university teaching hospital. PATIENTS: A total of 2045 patients with cutaneous melanoma were studied in 13 years. RESULTS: Interval nodes were found in 148 patients (7.2%). The incidence of interval nodes varied with the site of the primary melanoma. Interval nodes were more common with melanomas on the trunk than with those on the lower limbs. Micrometastatic disease was found in 14% of interval nodes that underwent biopsy as sentinel nodes. This incidence is similar to that found in sentinel nodes located in recognized node fields, confirming the potential clinical importance of interval nodes. CONCLUSIONS: Interval nodes should be removed surgically along with any additional sentinel nodes in standard node fields if the sentinel node biopsy procedure is to be complete. In some patients, an interval node will be the only lymph node that contains metastatic disease.

Female↗

Laparoscopic detection of sentinel lymph nodes followed by lymph node dissection in patients with early stage cervical cancer.

OBJECTIVE: The purpose of this study was to investigate the feasibility of sentinel node detection through laparoscopy in patients with early cervical cancer. Furthermore, the results of laparoscopic pelvic lymph node dissection were studied, validated by subsequent laparotomy. METHODS: Twenty-five patients with early stage cervical cancer who planned to undergo a radical hysterectomy and pelvic lymph node dissection received an intracervical injection of technetium-99m colloidal albumin as well as blue dye. With a laparoscopic gamma probe and with visual detection of blue nodes, the sentinel nodes were identified and separately removed via laparoscopy. If frozen sections of the sentinel nodes were negative, a laparoscopic pelvic lymph node dissection, followed by radical hysterectomy via laparotomy, was performed. If the sentinel nodes showed malignant cells on frozen section, only a laparoscopic lymph node dissection was performed. RESULTS: One or more sentinel nodes could be detected via laparoscopy in 25/25 patients (100%). A sentinel node was found bilaterally in 22/25 patients (88%). Histological positive nodes were detected in 10/25 patients (40%). One patient (11%) had two false negative sentinel nodes in the obturator fossa, whereas a positive lymph node was found in the parametrium removed together with the primary tumor. In seven patients (28%), the planned laparotomy and radical hysterectomy were abandoned because of a positive sentinel node. Bulky lymph nodes were removed through laparotomy in one patient, and in six patients only laparoscopic lymph node dissection and transposition of the ovaries were performed. These patients were treated with chemoradiation. In two patients, a micrometastasis in the sentinel node was demonstrated after surgery. Ninety-two percent of all lymph nodes was retrieved via laparoscopy, confirmed by laparotomy. Detection and removal of the sentinel nodes took 55 +/- 17 min. Together with the complete pelvic lymph node dissection, the procedure lasted 200 +/- 53 min. CONCLUSION: Laparoscopic removal of sentinel nodes in cervical cancer is a feasible technique. If radical hysterectomy is aborted in the case of positive lymph nodes, sentinel node detection via laparoscopy, followed by laparoscopic lymph node dissection, prevents potentially harmful and unnecessary surgery.

Adult↗

[Reproducibility of electrophysiological tests of sinus node function in patients with sick sinus syndrome. Reproducibility of tests of sinus node recuperation time, corrected sinus node recuperation time and sino-atrial conduction time].

In order to clarify whether SNRT, CSNRT and SACT are reproducible tests, 20 patients with sick sinus syndrome underwent two successive electrophysiological studies with an interval of 24 hours; mean sinus cycle, SACT, SNRT, CSRNT were evaluated. Although no significant differences were found between the mean values of the two studies, in isolated cases remarkable variations of one or more parameters were observed. We conclude that SNRT, CSNRT and SACT are reproducible tests only if mean values in a large number of patients are considered, while they are not as useful in quantifying sinus node dysfunction in single cases. In conclusion, while SNRT, CSNRT and SACT are reproducible and useful in comparing data from relatively large number of patients, great caution should be used before drawing conclusions of potentially serious diagnostic and prognostic consequence in the single patient.

Aged↗

Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection.

OBJECTIVE: To assess the status of the regional and paraaortic lymph nodes in hilar cholangiocarcinoma and to clarify the efficacy of systematic extended lymphadenectomy. SUMMARY BACKGROUND DATA: There have been no studies in which regional and paraaortic lymphadenectomies for hilar cholangiocarcinoma have been routinely performed. Therefore, the metastasis rates to the regional and paraaortic nodes, the mode of lymphatic spread, and the effect of extended lymph node dissection on survival remain unknown. METHODS: This study involved 110 patients who underwent surgical resection for hilar cholangiocarcinoma with lymph node dissection including both the regional and paraaortic nodes. A total of 2,652 nodes retrieved from the surgical specimens were examined microscopically. RESULTS: Of the 110 patients, 52 (47.3%) had no involved nodes, 39 (35.5%) had regional lymph node metastases, and 19 (17.3%) had regional and paraaortic node metastases. The incidence of positive nodes was significantly higher in the patients with pT3 disease than in those with pT2 disease. The pericholedochal nodes were most commonly involved (42.7%), followed by the periportal nodes (30.9%), the common hepatic nodes (27.3%), and the posterior pancreaticoduodenal nodes (14.5%). The celiac and superior mesenteric nodes were rarely involved. The 3-year and 5-year survival rates were 55.4% and 30.5% for the 52 patients without involved nodes, 31.8% and 14.7% for the 39 patients with regional node metastases, and 12.3% and 12.3% for the 19 patients with paraaortic node metastases, respectively. Of the 19 patients with positive paraaortic nodes, 7 had no macroscopic evidence of paraaortic disease on intraoperative inspection. The survival in this group was significantly better than in the remaining 12 patients. CONCLUSION: The paraaortic nodes and the regional nodes are frequently involved in advanced hilar cholangiocarcinoma. Whether extended lymph node dissection provides a survival benefit requires further study. However, the fact that long-term survival is possible despite pN2 or pM1 disease encourages the authors to perform an aggressive surgical procedure with extended lymph node dissection in selected patients with hilar cholangiocarcinoma.

Aorta↗

Clinical evaluation of pN-stage (TNM) in gastric cancer: an analysis of distribution of regional lymph nodes in node-positive patients.

BACKGROUND: The aims of the present study were to identify the distribution of regional lymph nodes in gastric cancer patients based on the number of nodes and to assess the influence of the examined area of lymph nodes on the determination of node stage according to TNM in node-positive patients with gastric cancer. MATERIALS AND METHODS: A total of 346 node-positive patients with primary solitary carcinoma of the stomach (210 males and 136 females; age range, 27 to 84 years; mean, 58.5 years), who underwent curative gastric resection combined with D2 or more extended lymph node dissection, were enrolled in the present study. The anatomical distribution of regional lymph nodes at each station classified according to the JCGC was assessed from pathology records. RESULTS: The number of first tier and all regional nodes dissected was < 15 in 7 patients (2%) of all patients and <15 in 37 patients (11%), respectively. Metastasis to first tier nodes was found in 2129 nodes (21%) but not in 8199 nodes (79%) and to second tier nodes in 375 nodes (9%) but not in 4028 nodes (91%), representing a significant difference between the two node groups (p<0.0001). No metastasis to first tier nodes was found in 12 patients (5%) out of 229 patients with pN1 tumor. Similarly, the number of metastases to first tier nodes in 15 patients (21%) out of 73 patients with pN2 tumor and in 13 patients (29%) out of 44 patients with pN3 tumor were 1-6 and 7-15, respectively. CONCLUSION: The present findings suggest that the extent of lymph node dissection does affect node stage as classified according to TNM and that restriction of the number of dissected regional lymph nodes (> or = 15 lymph nodes) may not be essential for practical staging of TNM.

Adult↗

Detection of pelvic lymph node metastases in patients with clinically localized prostate cancer: comparison of [18F]fluorocholine positron emission tomography-computerized tomography and laparoscopic radioisotope guided sentinel lymph node dissection.

PURPOSE: Accurate detection of lymph node metastases in prostate cancer has important implications for prognosis and approach to treatment. We investigated whether preoperative [18F]fluorocholine combined in-line positron emission tomography-computerized tomography and intraoperative laparoscopic radioisotope guided sentinel pelvic lymph node dissection can detect pelvic lymph node metastases in patients with clinically localized prostate cancer as reliably as extended pelvic lymph node dissection. MATERIALS AND METHODS: A total of 20 patients (mean age 63.9 +/- 6.7 years, range 52 to 75) with clinically localized prostate cancer, prostate specific antigen greater than 10 ng/ml, and/or a Gleason score sum of 7 or greater and negative bone scan were enrolled in the study. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was performed before surgery. Sentinel pelvic lymph node dissection preceded extended pelvic lymph node dissection including the area of the obturator fossa, external iliac artery/vein and internal iliac artery/vein up to the bifurcation of the common iliac artery. Laparoscopic radical prostatectomy was performed afterward. RESULTS: In 10 of the 20 patients (50%) lymph node metastases were detected, and were exclusively found outside the obturator fossa in 62%. These metastases would not have been identified with standard lymph node dissection of the obturator fossa only. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was true positive in 1, false-positive in 2, false-negative in 9 and true negative in 8 patients. The largest lymph node metastasis not seen with [18F]fluorocholine combined in-line positron emission tomography-computerized tomography was 8 mm. Laparoscopic sentinel guided lymph node dissection revealed lymph node metastases in 8 of 10 patients. In the other 2 patients sentinel lymph node dissection was not conclusive. In 1 patient normal nodal tissue was completely replaced by cancer and, therefore, there was no tracer uptake in the involved pelvic sidewall/node, and the other patient had no tracer activity at all in the involved pelvic sidewall. Extended pelvic lymph node dissection missed 1 lymph node metastasis (2 mm diameter near pudendal artery) which was detected by sentinel pelvic lymph node dissection only. CONCLUSIONS: Extended pelvic lymph node dissection reveals a higher number of lymph node metastases as described for obturator fossa dissection only. [18F]fluorocholine combined in-line positron emission tomography-computerized tomography is not useful in searching for occult lymph node metastases in clinically localized prostate cancer. Sentinel guided pelvic lymph node dissection allows the detection of even small lymph node metastases. The accuracy of sentinel pelvic lymph node dissection is comparable to that of extended pelvic lymph node dissection when the limitations of the method are taken into consideration.

Aged↗

Sentinel node identification and the ability to detect metastatic tumor to inguinal lymph nodes in squamous cell cancer of the vulva.

OBJECTIVES: The goal of this study was to identify one or more inguinal sentinel nodes in patients with primary squamous cell carcinoma of the vulva and to determine the ability of the sentinel node to predict metastasis to the inguinal lymphatic basin. METHODS: Techniques employing technetium-99m (Tc-99m) sulfur colloid and isosulfan blue dye were utilized to identify sentinel nodes in the inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally at the tumor margins 90-180 min preoperatively followed by a similar injection of isosulfan blue dye 5-10 min before the groin dissection. A handheld collimated gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic tracts that had taken up blue dye and their corresponding sentinel node were also identified and retrieved. A completion inguinal dissection was then performed. Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and blue. The sentinel nodes were subjected to pathologic examination with step sections and nonsentinel nodes were evaluated in the standard fashion. RESULTS: Twenty-one patients with a median age of 79 were entered onto protocol and a total of 31 inguinal node dissections were performed. A sentinel node was identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin dissections were found to have metastatic disease, and in 4 of these dissections, the sentinel node was the only positive node. Lymph nodes in 22 groin dissections had no evidence of metastasis. No false-negative sentinel lymph nodes were obtained (sentinel node negative and a nonsentinel node positive). CONCLUSION: Tc-99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel nodes in inguinal dissections of patients with vulvar cancer. A sentinel node dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal dissections. Pathologic examination with step sections has shown the sentinel node to be an accurate predictor of metastatic disease to the inguinal nodal chain.

Carcinoma, Squamous Cell↗

Is a lymph node detected by the dye-guided method a true sentinel node in gastric cancer?

PURPOSE: A sentinel node is defined as the initial lymph node, to which cancer cells metastasize from a primary tumor. Recently, sentinel node navigation surgery has been done using the dye-guided method. However, no study has shown that a lymph node detected by the dye-guided method is the true sentinel node from the viewpoint of micrometastasis. Micrometastases of lymph nodes, in which no metastasis was found by H&E staining, were examined to establish whether a lymph node detected by the dye-guided method is the true sentinel node. EXPERIMENTAL DESIGN: Isosulfan blue was injected endoscopically as the dye-guided method at a submucosal lesion of early gastric cancer. Total 345 lymph nodes, including 150 blue-dyed lymph nodes and 195 nondyed lymph nodes were collected from 57 patients and each was quartered. Two quarters were examined histologically by H&E staining and cytokeratin staining. The other specimens were used for quantitative reverse transcription-PCR of CEA and CK20 mRNAs. RESULTS: Lymph node disease was not found in any of 345 lymph nodes from the 57 patients by routine H&E staining. By contrast, either CEA or CK20 mRNA expression was detected in 21 of 345 lymph nodes obtained from the 10 (18%) of 57 patients by quantitative reverse transcription-PCR. Eight of the 21 micrometastasis-positive lymph nodes were confirmed to be positive for cytokeratin staining. Although micrometastasis of nondyed lymph nodes was found in three cases, these were included in the 10 cases with micrometastasis of blue-dyed nodes, such that there was no patient who only had micrometastasis in nondyed nodes. Six of 10 cases were micrometastasis-positive in a single node; all six were blue-dyed nodes. CONCLUSION: A lymph node detected by the dye-guided method should be a true sentinel node to which cancer cells metastasize initially.

Adult↗

Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.

BACKGROUND: Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. METHODS: In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumour site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held gamma-ray detector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. FINDINGS: From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97.5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1.5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. INTERPRETATION: In the large majority of patients with breast cancer, lymphoscintigraphy and gamma-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.

Adult↗

Pilot study comparing the accuracy of lymphoscintigraphy sentinel lymph node localisation with axillary node dissection in women with operable breast cancer.

AIM: To evaluate the use of lymphoscintigraphy sentinel lymph node mapping with scintillation gamma probe detection and blue dye assisted sentinel lymph node biopsy in patients with invasive breast cancer. To compare the lymph nodes detected lymphosintigraphically and at surgery for invasive breast cancer and the accuracy of sentinel node prediction of axillary status. METHODS: A prospective pilot study was performed on 36 women diagnosed with invasive breast cancer requiring axillary node dissection. Lymphoscintigraphy involving peritumoral injection of 99mTechnetium antimony sulphide or rhenium sulphur colloid was performed prior to surgery. Sentinel lymph node biopsy was then performed using gamma probe and blue dye localisation. RESULTS: Sentinel lymph nodes were identified on lymphoscintigrams in 100% of cases, and sentinel nodes located surgically in 34/36 (94.4%) of patients. All women with positive axillary lymph nodes on axillary dissection were correctly identified on sentinel node biopsy. Eight patients demonstrated internal mammary (IM) node radiocolloid uptake, one returning positive IM histology in the presence of positive axillary sentinel node metastasis. CONCLUSION: A high proportion of sentinel nodes were demonstrated by lymphoscintigraphy and were subsequently removed surgically. When internal mammary nodes are identified surgical removal should be considered. In this small series sentinel lymph node status correctly predicted axillary node status in 100% of patients for whom sentinel nodes were retrieved supporting the concept of sentinel node biopsy only for women with normal sentinel lymph nodes. Evidence from randomised trials that sentinel node based management does not compromise regional control of breast cancer or survival, is awaited.

Adult↗

Sentinel Node Biopsy in Breast Cancer Patients with Clinically Negative Lymph-Nodes.

BACKGROUND: The purpose of the present study is to evaluate the usefulness ofdye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla. METHODS: Sentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node andcomplete axillary lymph-node dissection specimens were examined separately, andthe incidence of metastases was compared. RESULTS: We identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one toeight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle. CONCLUSIONS: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were locatednear the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.

Journal Article↗

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes.

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.

Adult↗

Submission of lymph node tissue for ancillary studies decreases the accuracy of conventional breast cancer axillary node staging.

Pathologists are under increasing pressure to submit fresh tissue for ancillary studies and research protocols. In several tumor types (breast, lung, melanoma, colorectal, prostate), increased interest in detecting submicroscopic nodal metastases through reverse transcriptase polymerase chain reaction analysis of mRNA from portions of lymph nodes has precluded histologic analysis of the entire node for metastases. A retrospective review was undertaken of 227 breast cancer patients prospectively entered on a research protocol examining the usefulness of sentinel lymph node surgery. All of the patients ultimately underwent complete lymph node dissection. The research protocol required that all nodes greater than 8 mm in size be bisected and submitted separately. Positive lymph nodes were evaluated for unilateral or bilateral involvement in the node sections. Sixty node-positive patients were identified, yielding 230 positive nodes. One hundred seven of these nodes were confirmed to have been bisected. Carcinoma was identified in both lymph node sections in 64 (59.8%) nodes and in only one-half of the bisected lymph node in 43 (40.2%) nodes. Involvement of both sections was more likely when patients had multiple nodes positive. In 12 patients, involvement of one-half of the bisected nodes was the only evidence of metastatic disease (20.0% of node-positive patients). This evidence suggests that submission of less than the complete lymph node for histologic evaluation of metastatic disease decreases the accuracy of lymph node staging. Furthermore, a significant proportion of patients may be erroneously classified as histologically node negative.

Adult↗

Prediction of tumour involvement in remaining axillary lymph nodes when the sentinel node in a woman with breast cancer contains metastases.

BACKGROUND: In a significant proportion of women with breast cancer, the sentinel node is the only involved node in the axilla. The purpose of this study was to identify factors associated with histologically positive non-sentinel lymph nodes. METHODS: Between 1997 and 2002, 800 women with early breast cancer underwent sentinel node biopsy. In 263 patients the node contained metastases, including 83 with micrometastases detected by immunohistochemistry (IHC), 40 micrometastases detected on haematoxylin, eosin and safranine (HES) staining, and 140 macrometastases. All clinical and histological criteria were recorded and analysed with reference to histology of the non-sentinel node. RESULTS: The risk of metastasis in the non-sentinel lymph node was related to the volume of the tumour in the sentinel node. Non-sentinel nodes were involved in five (6.0 per cent) of 83 women when the sentinel node contained only micrometastatic cells detected on IHC, and in three (7.5 per cent) of 40 women when micrometastases were detected by HES, compared with 55 (39.3 per cent) of 140 when the sentinel node contained macrometastases on HES staining. Univariate analysis revealed a significant association between non-sentinel node involvement and type of metastasis within the sentinel node, clinical primary tumour size, palpable axillary lymph nodes before operation, pathological primary tumour size and the presence of peritumoral lymphovascular invasion. On multivariate analysis, the type of metastasis within the sentinel node (P < 0.001), histological tumour size greater than 20 mm (P = 0.017) and the presence of palpable axillary nodes before operation (P = 0.014) remained significant. CONCLUSION: Clinical and pathological factors associated with sentinel node histology can reliably predict women for whom further axillary clearance is recommended, but it is not yet possible to determine a subgroup of patients in whom the sentinel node is the only involved node and for whom further axillary treatment may be unnecessary.

Adult↗

Predictive factors for the status of non-sentinel nodes in breast cancer patients with tumor positive sentinel nodes.

In patients with tumor positive sentinel nodes, axillary lymph node dissection is routinely performed while a majority of these patients have no tumor involvement in the non-sentinel nodes. The authors tried to identify a subgroup of patients with a tumor positive sentinel node without non-sentinel node tumor involvement. In 135 consecutive patients with tumor positive sentinel nodes and axillary lymph node dissection performed, the incidence of non-sentinel node involvement according to tumor and sentinel node related factors was examined. The size of the sentinel node metastasis, size of primary tumor and number of tumor positive sentinel nodes were the three factors significantly predicting the status of the non-sentinel nodes. The size of the sentinel node metastasis was the strongest predictive factor (P < 0.0001). In a subgroup of 41 patients with a stage T1 tumor and micrometastatic involvement in the sentinel node only 2 patients (5%) had non-sentinel node involvement. In patients with small primary tumors and micrometastatic involvement of the sentinel nodes, the chance of non-sentinel node involvement is small but cannot be discarded. Because the clinical relevance of micrometastases in lymph nodes is still unclear it is not advisable to omit axillary lymph node dissection even in these patients.

Adult↗

Lymphoscintigraphy in penile cancer: limited value of sentinel node biopsy in patients with clinically suspicious lymph nodes.

The staging lymph node dissection in patients with penile carcinoma is accompanied with a high morbidity. As many patients are free of nodal metastases the lymphoscintigraphic sentinel node biopsy is supposed to minimize perioperative morbidity in these patients. In the current study the accuracy of the lymphoscintigraphic sentinel node biopsy was verified against the gold standard of radical inguinal dissection. In particular, patients with enlarged lymph nodes have also been included since one half of these patients is known to have histologically negative lymph nodes. Between 2000 and 2004 fifteen patients with penile carcinoma were elected to undergo bilateral groin dissection, thus 30 inguinal areas have been dissected. Nine patients have had clinically palpable nodes. All patients underwent lymphoscintigraphy after injection of Tc99-nanocolloid subcutaneously into the peritumoral area. Intraoperatively the sentinel nodes were identified with the aid of a gamma ray detection probe and excised. Afterwards a standard groin dissection was performed and the different lymph nodes were histopathologically assessed separately. In all patients lymph nodes with high radioactivity uptake were detected bilaterally. In 10 out of 30 inguinal areas histopathologically positive lymph nodes were present. In four of them the sentinel node was positive for tumor but in six dissection areas lymph node metastases were found despite a negative sentinel node. These patients had clinically palpable lymph nodes in their histologically positive inguinal regions. If no palpable nodes were present dynamic sentinel biopsy detected the positive nodes. The current study showed that dynamic sentinel node biopsy in patients with clinically suspicious lymph nodes is of low value for detection of lymphatic spread in penile cancer. Therefore the gold standard in these patients remains the radical groin dissection. However, dynamic sentinel node biospy is still a promising strategy to identify lymphatic spreading in clinically N0 patients and therefore to prevent unnecessary groin dissection.

Adult↗