Ex vivo sentinel lymph node mapping in colon cancer: improving the accuracy of pathologic staging?

BACKGROUND: A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution. METHODS: Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody. RESULTS: Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4-54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%. CONCLUSIONS: The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.     

Sentinel Lymph Node Evaluation Does Not Improve Staging Accuracy in Colon Cancer

BACKGROUND: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer. METHODS: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test. RESULTS: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41). CONCLUSIONS: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.     

Use of sentinel node mapping for cancer of the colon: 'to map or not to map"

Sentinel lymph node (SLN) mapping has become a cornerstone of oncologic surgery because it is a proven method for identifying nodal disease in melanoma and breast cancer. In addition, it can ameliorate the surgical morbidity secondary to lymphadenectomy. However, experience with SLN mapping for carcinoma of the colon and other visceral malignancies is limited. This study represents an update to our initial pilot experience with SLN mapping for carcinoma of the colon. Consenting patients over the age of 18 diagnosed with adenocarcinoma of the colon were included in this study. At the time of operation, 1 to 2 mL of isosulfan blue was injected with a 25-gauge needle into the subserosa at 4 sites around the edge of the palpable tumor. The SLN was identified visually and excised followed by a standard lymphadenectomy and surgical resection. SLNs were evaluated by standard hematoxylin and eosin (H&E) evaluation as well as immunohistochemical (IHC) techniques for carcinoembryonic antigen and cytokeratin if the H&E was negative. Sixty-nine patients underwent SLN mapping. A SLN was identified in 93 per cent (64 of 69) of patients. Nodal metastases were identified in 38 per cent (26 of 69) of patients overall. In 5 patients, the only positive node identified was the SLN, 2 of which were positive by IHC criteria alone. Therefore, 3 per cent (2 of 69) of patients were upstaged by SLN mapping. This technique was 100 per cent specific while being 46 per cent sensitive. Fourteen patients had false-negative SLNs. Metastasis to regional lymph nodes remains the key prognostic factor for colon cancer. SLN mapping is feasible for colon cancer and can identify a subset of patients who could benefit from adjuvant chemotherapy. Although SLN mapping did not alter the surgical management of colon cancer, it does make possible a more focused and cost-effective pathologic evaluation of nodal disease. We do not suggest routine utilization of SLN mapping for colon cancer, but we believe that the data supports proceeding with a national trial.     

Can Methylene Blue Only Be Used in Sentinel Lymph Node Biopsy for Breast Cancer?

Sentinel lymph node biopsy (SLNB) has become an accepted standard of care to stage the axilla for clinically node-negative early stage breast cancer. In experienced hands, studies have shown an acceptable rate of identification of the sentinel lymph node (SLN) with blue dye only. Lymphazurin is occasionally associated with severe allergic reaction, including anaphylaxis and death. The use of methylene blue alone as a method of identifying the SLN in breast cancer has been reported once previously in the literature. Methylene blue may be an acceptable alternative with fewer deleterious side effects. Medical records of patients, who underwent sentinel node mapping between September 2003 and March 2005 by two surgeons at an academic medical center were reviewed. SLN mapping was performed by periareolar injection of 5 cc of 1% methylene blue. All patients with positive SLNs underwent completion axillary node dissection. During the study period, 141 consecutive patients with clinically node-negative axillas and without evidence of inflammatory breast cancer underwent SLNB with injection of methylene blue only. A SLN was identified in 136 of 141 patients (96.5%). Thirty-three of 136 SLNs (24%) harbored metastatic disease. No cases of anaphylaxis were noted. In experienced hands, methylene blue alone is a highly sensitive method of detecting SLNs. Avoiding the greater frequency of allergic reactions seen with lymphazurin is an important advantage of methylene blue.     

A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer.

BACKGROUND: Among the advocates of blue dye, isotope, or combined dye-isotope mapping of the sentinel lymph node (SLN) for breast cancer, there is no universal consensus as to which technique is optimal and whether the relative value of each method changes with increasing experience. The objective of this study was to examine the relative contributions of blue dye and radioisotope to successful identification of the SLN as the SLN-mapping technique evolved over our first 2,000 consecutive cases. STUDY DESIGN: Using the first 2,000 consecutive SLN biopsy procedures for breast cancer, performed by eight surgeons (none previously experienced in SLN techniques) at one institution, using a combined technique of blue dye and isotope mapping, we report the institutional learning curve and the relative contributions of dye and isotope to identifying both the SLN and the positive SLN, by increments of 500 cases. RESULTS: Comparing the first 500 with the most recent 500 cases, success in identifying the SLN by blue dye did not improve with experience, although success in isotope localization steadily increased, from 86% to 94% (p < 0.00005). With the increasing success of isotope mapping, the marginal benefit of blue dye (the proportion of cases in which the SLN was identified by blue dye alone) steadily declined, from 9% to 3% (p = 0.0001). Parallel to this trend, the proportion of positive SLNs identified by blue dye did not change with experience (89% to 90%), but isotope success steadily increased, from 88% to 98% (p = 0.0015). The proportion of positive SLNs identified by blue dye alone declined from 12% to 2% (p = 0.0015). CONCLUSIONS: Using a combined technique of blue dye and radioisotope mapping, and with refinement of the radioisotope technique, we report 97% success identifying the SLN. Although we continue to recommend the use of both methods in SLN mapping for breast cancer, we observe with experience a declining marginal benefit for blue dye.     

Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or intradermal injection of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that intradermal TSC is the optimal mapping technique and can be used alone to identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94 patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes were identified intraoperatively using a hand-held gamma probe and blue nodes were identified visually. Hematoxylin- and eosin-stained SLN sections were examined by light microscopy for breast cancer metastases. RESULTS: Overall, the SLN mapping procedures were successful in 91% of patients. Peritumoral and intradermal TSC were successful in identifying SLNs in 78% and 97% of patients, respectively. Peritumorally injected isosulfan blue was successful in identifying 83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p = 0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly higher success rate than peritumoral TSC or blue dye. There was minimal benefit in identifying additional SLNs with addition of peritumoral blue dye to intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be used alone to effectively stage the axilla for breast cancer.     

Sentinel lymph node dissection for breast cancer: how many nodes are enough and which technique is optimal?

BACKGROUND: Controversy exists in sentinel lymph node (SLN) mapping in breast cancer regarding the appropriate number of nodes to remove and the best technique for identification of the SLNs. METHODS: A retrospective chart review from January of 1999 to January of 2004 was performed for all patients undergoing a SLN biopsy examination who had at least 1 positive SLN. RESULTS: We identified 167 patients. A mean of 4.4 SLNs were removed per patient. All of the positive SLNs were identified by node 6. Radiotracer used alone identified 19 positive nodes (11.4%) and blue dye used alone identified 14 positive nodes (8.4%). CONCLUSIONS: Our data show that 100% of positive SLNs are found by 6 nodes removed, thereby supporting the concept that the SLN dissection may not be complete by removing only 1 or 2 nodes or only the hottest node. The use of blue dye or radiotracer alone can contribute to the overall false-negative rate.     

A novel lymphatic mapping technique to improve localization and staging of early colon cancer during laparoscopic colectomy

Encouraging results from our previous studies of sentinel lymph node (SLN) mapping in colorectal cancer (CRC) prompted investigation of its feasibility and accuracy during laparoscopic colectomy for early CRC. Between 1996 and 2000, 14 patients with clinically localized colorectal neoplasms underwent colonoscopic tattooing of the primary site and SLN mapping. In each case 0.5 to 1 cm3 of isosulfan blue dye was injected submucosally via the colonoscope. The blue-stained lymphatics were visualized through the laparoscope and followed to the SLN, which was marked with a clip, and laparoscopic colectomy was completed in the routine fashion. All lymph nodes were examined by hematoxylin and eosin (H&E) staining; in addition each SLN was subjected to focused examination by multisectioning and immunohistochemical staining using cytokeratin antibody. In all 14 patients the primary neoplasm and an SLN were identified laparoscopically. An average of 13.5 total lymph nodes and 1.7 SLNs per patient were identified. The SLN correctly reflected the tumor status of the nodal basin in 93 per cent of the cases. In four cases with unexpected lymphatic drainage, the extent of mesenteric resection was altered. In two cases (14%), nodal involvement was micrometastatic, confined to an SLN, and identified only by immunohistochemical staining. Lymphatic mapping caused no complications and added only 10 to 15 minutes to the overall operative time. Comparison of results in this group with results for a matched group of 14 patients undergoing SLN mapping during open colon resection showed that the laparoscopic technique had similar rates of accuracy and success. These preliminary findings indicate that colonoscopic/laparoscopic SLN mapping during laparoscopic colon resection is a feasible and technically simple means of identifying the primary colorectal neoplasm and its SLN. Focused pathologic examination of this node can upstage CRC and thereby may improve selection of patients for adjuvant chemotherapy.     

Intraoperative imprint cytology for evaluation of sentinel lymph nodes from visceral malignancies

Although originally described for breast cancer and melanoma, sentinel lymph node (SLN) mapping techniques are being investigated in the treatment of visceral malignancies. There is no literature evaluating intraoperative analysis of SLNs from visceral sites. We evaluated the utility of touch preparation intraoperative imprint cytology (IIC) in evaluating SLNs harvested in the setting of visceral malignancy. SLN mapping procedures involving 50 cases of visceral malignancy (37 colon, 12 gastric, and 1 small bowel), from February 1999 through August 2001, were studied. In each case, subserosal injections of isosulfan blue were used to identify the SLN. The SLNs were then sent fresh to the pathology laboratory for evaluation by IIC. A standard lymphadenectomy was performed in all cases. Postoperatively, the SLNs were evaluated by means of using hematoxylin and eosin staining. If these stains were normal, immunohistochemical analyses using carcinoembryonic antigen and cytokeratin were subsequently performed. SLNs were successfully identified in 46 cases (92%), and a total of 95 SLNs were harvested. The average number of SLNs was 1.9 with a range of one to six. More SLNs were found with gastric than with colonic lesions (2.8 vs. 1.8; P = .017). Evaluable IIC in 41 cases revealed metastatic disease in 10 SLNs, representing seven patients. Of the 34 patients with normal IIC, five were found to have positive SLNs on hematoxylin and eosin staining. An additional three patients were found to have positive SLNs only on immunohistochemical analysis. The overall sensitivity and specificity of IIC was 64% and 100%, respectively. This resulted in a positive predictive value of 100% and a negative predictive value of 86%. The use of IIC to evaluate SLNs from visceral malignancies is clearly feasible. When the IIC of the SLN is positive, the surgeon may feel confident that disease is actually present in the SLN. If there is a negative result, the technique may miss disease that is present on subsequent permanent sections. We do not recommend routine use of IIC; however, it may be of use in clinical trials. Presented at the Society of Surgical Oncology meeting, Denver, Colorado, March 15–17, 2002. Supported in part by a grant from the Comprehensive Cancer Center of Wake Forest University.     

Lymphatic Mapping With Fluorescence Navigation Using Indocyanine Green and Axillary Surgery in Patients With Primary Breast Cancer

Abstract: The indocyanine green fluorescence (ICGf) navigation method provides real‐time lymphatic mapping and sentinel lymph node (SLN) visualization, which enables the removal of SLNs and their associated lymphatic networks. In this study, we investigated the features of the drainage pathways detected with the ICGf navigation system and the order of metastasis in axillary nodes. From April 2008 to February 2010, 145 patients with clinically node‐negative breast cancer underwent SLN surgery with ICGf navigation. The video‐recorded data from 79 patients were used for lymphatic mapping analysis. We analyzed 145 patients with clinically node‐negative breast cancer who underwent SLN surgery with the ICGf navigation system. Fluorescence‐positive SLNs were identified in 144 (99%) of 145 patients. Both single and multiple routes to the axilla were identified in 47% of cases using video‐recorded lymphatic mapping data. An internal mammary route was detected in 6% of the cases. Skip metastasis to the second or third SLNs was observed in 6 of the 28 node‐positive patients. We also examined the strategy of axillary surgery using the ICGf navigation system. We found that, based on the features of nodal involvement, 4‐node resection could provide precise information on the nodal status. The ICGf navigation system may provide a different lymphatic mapping result than computed tomography lymphography in clinically node‐negative breast cancer patients. Furthermore, it enables the identification of lymph nodes that do not accumulate indocyanine green or dye adjacent to the SLNs in the sequence of drainage. Knowledge of the order of nodal metastasis as revealed by the ICGf system may help to personalize the surgical treatment of axilla in SLN‐positive cases, although additional studies are required.     

High isotope counts and sentinel node positivity in patients with melanoma

BACKGROUND: Radioisotope mapping is an essential technical component of sentinel lymph node (SLN) biopsy, and most authors define success by an arbitrary threshold SLN-background ratio. HYPOTHESIS: Few studies have examined the degree to which the relative level of SLN counts correlates with the presence of metastasis. Having removed the SLN with the highest counts, there are no data suggesting how far the surgeon should persist in removing additional SLNs that contain much lower levels of isotope. METHODS: We performed 134 SLN biopsy procedures in 132 patients with melanoma. Successful isotope localization was defined using an SLN/"hottest" SLN ratio; we defined an SLN as any node containing counts at least 10% of that of the hottest SLN. RESULTS: Of 83 patients with more than 1 SLN site identified, 21 (25%) had SLNs that contained metastasis. In 17 (81%) of these cases, the SLN with the highest countcontained tumor, but in 4 (19%) it was benign. Among these 4 patients, the counts of the hottest benign SLNs exceeded those of SLNs positive for metastasis on histological examination by a ratio of at least 10:1, and the counts of the positive SLNs were less than 4:1 of those of the background counts or the presence of blue dye failed to identify the positive SLN. No optimum ratio of SLN/SLN or SLN/background counts identified the positive SLN in all cases. CONCLUSIONS: Although the SLN with the highest counts contained metastasis in 81% of patients with malignant melanoma and multiple SLNs, neither a relatively high isotope count nor the presence of blue dye consistently predicted SLN positivity. For maximum accuracy, SLN biopsy requires the removal of all nodes containing isotope regardless of the relative magnitude of counts and the concurrent use of blue dye to salvage those procedures in which isotope mapping fails.     

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.     

美蓝染色法乳腺癌前哨淋巴结活检临床应用研究

目的探讨美蓝染色法在乳腺癌前哨淋巴结活检(sentinel lymph node biopsy,SLNB)中的应用价值。方法以68例可手术乳腺癌患者作为研究对象,临床体检腋窝淋巴结阴性,均单独采用美蓝作为前哨淋巴结(sentinel lymph node,SLN)示踪剂。结果全组患者共检出SLN 60例78枚。检出后行乳腺癌改良根治术60例,乳腺区段切除+腋窝淋巴结(axillary lymph node,ALN)切除术8例。60例中22例SLN病理结果为阳性,转移淋巴结数28枚,SLN转移率为35.9%(28/78)。全组患者共检出ALN805枚,其中24例病理结果阳性。SLNB的检出率为88.2%(60/68),60例成功检出患者中,38例SLN阴性,其中经病理检查ALN阳性(假阴性)者1例,8例未找到SLN患者中亦有1例ALN阳性。SLNB灵敏度为91.7%,准确率为98.3%,假阴性率为8.3%,假阳性率为0。结论应用美蓝进行SLN的认定是安全可行的,并有利于简化手术方式,提高患者术后生活质量。     

The breast cancer patient with multiple sentinel nodes: when to stop?

BACKGROUND:

During sentinel lymph node (SLN) biopsy for breast cancer, most authors report identifying a mean of 1 to 3 SLNs, but a range of 1 to 8 (or more) SLNs per patient. A significant minority of patients have 4 or more SLNs. Here we seek to determine the significance for the breast cancer patient of finding multiple SLNs, and whether there is an optimal threshold number of SLNs that should be removed.

STUDY DESIGN:

1,561 patients who underwent successful SLN biopsy using blue dye and radioisotope in combination. Each SLN site was categorized prospectively by the operating surgeon as a dye success, an isotope success, or both. All SLNs containing counts at least four times greater than the postexcision axillary background were considered to be isotope successes.

RESULTS:

Fifteen percent of patients (241) had multiple (> 3) SLNs. Ninety-eight percent of node-positive patients (440 of 449) were identified within the first three SLN sites examined. In 2% of all SLN positive patients (9 of 449) or 4% of patients with multiple SLN (9 of 241), a positive SLN was detected at site four or more. In eight patients the first positive SLN was found at sites four or more. Blue dye and isotope were equally effective in identifying metastases in patients with multiple SLNs.

CONCLUSIONS:

Fifteen percent of patients having SLN biopsy for breast cancer have multiple SLNs. Although 98% of positive SLNs were identified within the first three sites sampled, a small number of patients had their first positive SLN at sites 4 to 8. These data suggest that there is no absolute upper threshold for the number of SLNs that should be removed. Sampling a few additional SLNs probably adds little morbidity to the procedure, yet may significantly alter the treatment of some individuals. SLN biopsy should be continued until all blue and hot nodes are removed.     

L选择素在乳腺癌前哨淋巴结的趋向性表达及其临床意义

目的:探讨L选择素(L-selectin)在乳腺癌前哨淋巴结(SLN)中的表达,分析乳腺癌SLN状况与L选择素表达的关系。方法:选择T1-2N0M0乳腺癌患者68例,以亚甲蓝为示踪剂先行前哨淋巴结活检术(SLNB),应用免疫组织化学法检测本组68例乳腺癌SLN,乳腺癌原发灶,癌旁乳腺组织以及20例III级不典型增生乳腺组织中L选择素的表达。结果:68例乳腺癌患者中SLN检出成功62例,检出率为91.17%(62/68),其中假阴性3例(3/32)。阳性SLN中L选择素阳性表达率明显高于乳腺癌组织、癌旁组织(均P<0.05)。SLN阳性患者其原发灶L选择素阳性表达率明显高于SLN阴性患者(P<0.05)。SLN及非前哨淋巴结(NSLN)均阳性患者其原发灶L选择素阳性表达率明显高于SLN及NSLN均阴性患者(P<0.001)。结论:L选择素在阳性SLN转移癌中表达增高,提示L选择素在乳腺癌细胞的淋巴结趋向性中起重要作用;SLN状态与L选择素阳性表达有密切关系,两者相结合分析可以更全面地反映乳腺癌转移规律及腋淋巴结状态。     

Ex Vivo Sentinel Lymph Node Study For Rectal Adenocarcinoma: Preliminary Study

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7–38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0–3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.     

Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01

BACKGROUND: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial. PURPOSE: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer. PATIENTS AND METHODS: Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging. RESULTS: Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone. CONCLUSION: SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.     

The benefit of using two techniques for sentinel lymph node mapping in breast cancer

Sentinel lymph node (SLN) mapping has revolutionized the way we stage breast cancer. A blue dye technique (BD) and the use of a radiotracer with the assistance of a gamma-detecting probe (GDP) have been used for the identification of the sentinel nodes. Some groups have suggested that only one technique is necessary. The reported false negative rates have been 0 to 12 per cent and success rates as low as 65 per cent. We have prospectively evaluated these techniques and have used both for the identification of the SLN. Ten surgeons participated in this study. From April 1998 through May 1999, 58 patients underwent SLN mapping followed by an axillary lymph node dissection. After the injection of 0.3 to 1.96 mCi of filtered sulfur colloid diluted to 4 mL all patients had preoperative lymphoscintigraphy. Five minutes before surgery 3 to 5 mL of isosulfan blue was injected around the tumor or tumor bed. Even though preoperative lymphoscintigraphy identified an SLN in 35 patients (63%) successful intraoperative detection of an SLN was possible using both techniques in 53 patients (91%). The SLN was detected by the BD and the GDP in 37 (65%) and 45 (80%) respectively. Nineteen patients (33%) were positive for metastatic disease in the axilla. Twenty-two (19%) of 113 SLNs removed were positive for disease. All cases of metastatic disease in the axilla were detected by the mapping technique. False negative rate was 0 per cent. In 11 patients the only positive node was the sentinel node (58%). Furthermore six (32%) patients were upstaged by the use of immunostains for cytokeratin. Twenty-two positive SLNs were detected in the 19 patients. The positive lymph node was identified only by BD in four patients (21%), only by GDP in six patients (31%), and by both techniques in nine patients (47%). We conclude that if only one technique had been used the false negative rate could have been as high as 32 per cent. Both techniques must be used to obtain a low false negative rate and high yield in the identification of the SLN.