Sentinel Nodes Are Identifiable in Formalin-Fixed Specimens After Surgeon-Performed Ex Vivo Sentinel Lymph Node Mapping in Colorectal Cancer

Background In recent years, the technique of sentinel lymph node (SLN) mapping has been applied to colorectal cancer. One aim was to ultrastage patients who were deemed node negative by routine pathologic processing but who went on to develop systemic disease. Such a group may benefit from adjuvant chemotherapy.Methods With fully informed consent and ethical approval, 37 patients with primary colorectal cancer and 3 patients with large adenomas were prospectively mapped. Isosulfan blue dye (1 to 2 mL) was injected around tumors within 5 to 10 minutes of resection. After gentle massage to recreate in vivo lymph flow, specimens were placed directly into formalin. During routine pathologic analysis, all nodes were bivalved, and blue-staining nodes were noted. These later underwent multilevel step sectioning with hematoxylin and eosin and cytokeratin staining.Results SLNs were found in 39 of 40 patients (98% sensitivity), with an average of 4.1 SLNs per patient (range, 1–8). In 14 of 16 (88% specificity) patients with nodal metastases on routine reporting, SLN status was in accordance. Focused examination of SLNs identified occult tumor deposits in 6 (29%) of 21 node-negative patients. No metastatic cells were found in SLNs draining the three adenomas.Conclusions The ability to identify SLNs after formalin fixation increases the ease and applicability of SLN mapping in colorectal cancer. Furthermore, the sensitivity and specificity of this simple ex vivo method for establishing regional lymph node status were directly comparable to those in previously published reports.Presented at the British Society of Gastroenterology, Glasgow, United Kingdom, 2004; the American Society of Colon and Rectal Surgeons, Dallas, Texas, 2004; and the Association of Coloproctologists of Great Britain and Ireland, Birmingham, 2004.     

Comparison of Ex Vivo and In Vivo Injection of Blue Dye in Sentinel Lymph Node Mapping for Colorectal Cancer

Background  The technique of sentinel lymph node (SLN) mapping in patients with colorectal cancer varies between reports, and the optimal method has not been established. The purpose of this study was to determine the optimal injection technique for SLN mapping. Methods  Sixty-nine consecutive patients who underwent curative surgery for colorectal cancer were enrolled. The SLNs was identified intraoperatively by subserosal blue dye injection (in vivo) or by submucosal injection after standard colectomy (ex vivo). If negative by conventional hematoxylin and eosin staining analysis, all lymph nodes, SLNs and non-SLNs, were subjected to further analysis by multi-level section and immunohistochemical examination. Results  The in vivo and ex vivo injected groups were similar in demographic character, tumor size, and histological grade. The mean number of SLNs identified was 2.3 in the in vivo group and 2.6 in the ex vivo group (p = 0.192). The detection rate of SLNs by blue dye injection was somewhat higher in the ex vivo group than in the in vivo group: 90.6 vs. 81.1% (p = 0.219). The false-negative rate was 23.5% for the in vivo group and 13.3% for the ex vivo group (p = 0.392). The upstaging rate, which was 18.5% overall, was similar in both groups (p = 0.538). Conclusions  These findings suggest that ex vivo blue dye injection is an effective alternative to in vivo injection for identifying SLNs in patients with colorectal cancer. Because of its simplicity and applicability in routine clinical settings, further investigation of the ex vivo mapping technique is warranted. Research was supported by the Chung-Ang University Research Grants in 2008.     

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+.     

Clinical Translation of Ex Vivo Sentinel Lymph Node Mapping for Colorectal Cancer Using Invisible Near-Infrared Fluorescence Light

Background

Sentinel lymph node (SLN) mapping in colorectal cancer may have prognostic and therapeutic significance; however, currently available techniques are not optimal. We hypothesized that the combination of invisible near-infrared (NIR) fluorescent light and ex vivo injection could solve remaining problems of SLN mapping in colorectal cancer.

Methods

The FLARE imaging system was used for real-time identification of SLNs after injection of the NIR lymphatic tracer HSA800 in the colon and rectum of (n = 4) pigs. A total of 32 SLN mappings were performed in vivo and ex vivo after oncologic resection using an identical injection technique. Guided by these results, SLN mappings were performed in ex vivo tissue specimens of 24 consecutive colorectal cancer patients undergoing resection.

Results

Lymph flow could be followed in real-time from the injection site to the SLN using NIR fluorescence. In pigs, the SLN was identified in 32 of 32 (100%) of SLN mappings under both in vivo and ex vivo conditions. Clinically, SLNs were identified in all patients (n = 24) using the ex vivo strategy within 5 min after injection of fluorescent tracer. Also, 9 patients showed lymph node involvement (N1 disease). In 1 patient, a 3-mm mesenteric metastasis was found adjacent to a tumor-negative SLN.

Conclusions

The current pilot study shows proof of principle that ex vivo NIR fluorescence-guided SLN mapping can provide high-sensitivity, rapid, and accurate identification of SLNs in colon and rectum. This creates an experimental platform to test optimized, non-FDA-approved NIR fluorescent lymphatic tracers in a clinical setting.     

Sentinel Lymph Node Dissection in Locally Recurrent Breast Cancer

Annals of Surgical Oncology - The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer. A total of...     

Sentinel Lymph Node Mapping in Colon Cancer: Current Status

Background The primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer. Methods A systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated. Results The literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye. Conclusions Sentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients. Robbert J. de Haas and Dennis A. Wicherts have contributed equally and are mentioned alphabetically.     

Quality of Life After Sentinel Lymph Node Biopsy or Axillary Lymph Node Dissection in Stage I/II Breast Cancer Patients: A Prospective Longitudinal Study

Background  Breast cancer patients’ quality of life (QoL) after surgery has been reported to improve significantly over time. Little is known about QoL recovery after sentinel lymph node biopsy (SLNB) in comparison to axillary lymph node dissection (ALND). Methods  175 of 195 stage I/II breast cancer patients completed the EORTC QLQ-C30: one day before surgery (T0) and after 6 (T1), 26 (T2), 52 (T3) and 104 (T4) weeks. Of these, 54 patients underwent SLNB, 56 SLNB+ALND and 65 ALND. General linear models and paired T-tests between T0–T4 and T1–T4 were computed. Complications, radiotherapy and systemic therapy were added to the model. Results  Significant time effects were found on physical, role and emotional functioning. Physical and role functioning decreased between T0 and T1. At T4, SLNB patients’ functioning had increased to their T0 level; ALND (+/– SLNB) patients’ functioning had increased, but had not improved to T0 level. Emotional functioning increased linearly between T0 and T4. At T4, emotional functioning was significantly higher in all groups as compared with T0. No significant group or interaction (time × group) effects were found. Complications and chemotherapy had a significant negative effect on role, emotional and cognitive functioning. Complications had a significant effect on social functioning also. Effect sizes varied between 0.00 and 0.06. Conclusion  Two years post surgery, breast cancer patients’ QoL is comparable to that shortly before surgery. Women rated their emotional functioning as even better. SLNB is not associated with a better QoL than ALND. However, undergoing systemic therapy and/or experiencing complications affects QoL negatively.     

Axillary Lymph Node Dissection for Sentinel Lymph Node Micrometastases May Be Safely Omitted in Early-Stage Breast Cancer Patients: Long-Term Outcomes of a Prospective Study

Objectives

To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted.

Background

The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate.

Methods

In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 ≤ 3 cm, cN0 M0) between 1998 and 2002. The SLN were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry. None of the patients with negative SLN or SLN micrometastases (International Union Against Cancer classification, >.2 mm to ≤2 mm) underwent a completion ALND or radiation to the axilla. Long-term overall and disease-free survivals were compared between patients with negative SLN and those with SLN micrometastases by log rank tests.

Results

The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median follow-up of 77 months (range, 24–106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = .656), locoregional (P = .174), and axillary and distant disease-free survival (P = .15) between patients with negative SLN and SLN micrometastases.

Conclusions

This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.     

Risk of Limited Lymph Node Dissection in Patients with Clinically Early Gastric Cancer: Indications of Extended Lymph Node Dissection for Early Gastric Cancer

Background

Laparoscopic gastrectomy is usually indicated in T1 N0–1 early gastric cancer (EGC). Limited lymph node dissection, such as D1+, is applied in these cases. However, preoperative staging is not always correct, and the risk of undertreatment thus exists.

Methods

Patients with clinically early gastric cancer (cEGC) who underwent gastrectomy with lymph node dissection of D2 and over were selected from 4,021 patients with gastric cancer. The station numbers of all metastatic lymph nodes (MLNs) were identified, and MLNs were classified into groups 1 and 2 (including lymph nodes of second tier and over) on the basis of the system of the Japanese Gastric Cancer Association, irrespective of the number of MLNs. Clinicopathological data were compared according to the existence of lymph node metastasis and the classification of MLNs.

Results

Of 1,308 patients with cEGC who fulfilled the inclusion criteria, 1,184 (90.5 %) were diagnosed pathologically with EGC. Among 126 patients with cEGC who were diagnosed with lymph node metastasis, 93 patients had only group 1 MLNs and 33 patients had group 2 MLNs. Tumor location in the proximal third of the stomach (odds ratio 5.450) and ulceration (odds ratio 11.928) were significant factors for group 2 metastasis.

Conclusions

Extended lymph node dissection is recommended in cEGC with ulceration or disease located in the proximal third of the stomach.     

胃癌的淋巴结清扫及意义

胃癌是目前我国死亡率较高的恶性肿瘤之一。胃癌的浸润深度（T）和淋巴结转移程度（N）是评价肿瘤分期的重要依据,UICC及日本胃癌规约均认为淋巴结转移情况是评价胃癌预后的独立且重要的因素,因此,胃癌的淋巴结清扫程度与胃癌预后关系密切。东西方学者对胃癌淋巴结清扫范围的争论已持续多年,但越来越多的学者趋向于把D2清扫术作为胃癌治疗的标准术式。     

Diagnostic Value of Sentinel Lymph Node Biopsy in Gastric Cancer: A Meta-Analysis

Background  

The possible application and validity of the sentinel lymph node (SLN) concept in gastric cancer (GC) is still debated. A systematic review to evaluate the diagnostic value of SLN biopsy (SLNB) in GC is urgently needed.     

A Prospective Trial Comparing 1% Lymphazurin vs 1% Methylene Blue in Sentinel Lymph Node Mapping of Gastrointestinal Tumors

Background  Methylene blue (M), as a dye in sentinel lymph node mapping (SLNM), has been introduced as an alternative to lymphazurin (L) after the recent shortage of L. M has been evaluated in breast cancer in multiple studies with favorable results. Our study compares L with M in the SLNM of gastrointestinal (GI) tumors. Methods  Between Jan 2005 and Aug 2008, 122 consecutive patients with GI tumors were enrolled. All patients (pts) underwent SLNM with either L or M by subserosal injection of 2–5 mL of dye. Efficacy and rates of adverse reactions were compared between the two dyes. Patients were prospectively monitored for adverse reactions including anaphylaxis, development of blue hives, and tissue necrosis. Results  Of 122 pts, 60 (49.2%) underwent SLNM using L and 62 (50.8%) underwent SLNM using M. Colon cancer (CrCa) was the most common site in both groups. The success rate of L and M in SLNM was 96.6% and 96.7%, respectively, with similar numbers of total number of lymph nodes per pt, SLNs per pt (<3), nodal positivity, skip metastasis, and accuracy. The only adverse reaction in the L group was oxygen desaturation >5% in 5% (3/60) of pts, compared with none in the M group. Cost per vial of L was $210 vs $7 for M. Conclusion  The success rate, nodal positivity, average SLNs per patient, and overall accuracy were similar between L and M. Absence of anaphylaxis and lower cost make M more desirable than L in SLNM of GI tumors.     

Appropriate Gastric Resection with Lymph Node Dissection for Early Gastric Cancer

Background The extent of lymphadenectomy (limited vs. extended) and that of gastric resection (partial vs. total) remain controversial issues in the management of early gastric cancer (EGC). A multicentric study was performed to elucidate the appropriate gastric resection with lymph node dissection for early gastric cancer.Methods From 1979 to 1988, 332 patients with EGC underwent surgery in 23 French centers. Clinicopathological data, the extent of resection, and the number of lymph nodes retrieved were reviewed retrospectively and screened for prognostic effect. The mean follow-up for the 332 EGC patients was 80 months.Results Postoperative mortality was correlated to age (odds ratio [OR], 1.1) and extent of gastric resection (OR,10.3). Examination of survival data (excluding postoperative deaths) with univariate analysis and the Cox proportional hazards model showed that the independent factors for excellent prognosis included no lymphatic involvement (P = .005), 10 or more lymph nodes retrieved (P = .003), site of the tumor in the lower third of the stomach (P = .01), and mucosal lesions (P = .04). The extent of resection did not influence long-term survival.Conclusions Our results suggest that because of the associated good prognosis, the appropriate surgical treatment for EGC is partial gastrectomy with lymphadenectomy retrieving 10 or more lymph nodes.     

Eighteen Sensations After Breast Cancer Surgery: A 5-Year Comparison of Sentinel Lymph Node Biopsy and Axillary Lymph Node Dissection

Background The aim of this study is to evaluate prevalence, severity, and level of distress of 18 sensations at baseline (3–15 days) and 5 years after breast cancer surgery, and compare sensations after sentinel lymph node biopsy (SLNB) with those after SLNB plus immediate or delayed axillary lymph node dissection (ALND). Methods A total of 187 patients with breast cancer completed the Breast Sensation Assessment Scale at baseline and at 3, 6, 12, 24, and 60 months after surgery to assess prevalence, severity, and level of distress of sensations. Of these, 133 had SLNB, and 54 had SLNB and ALND. Additionally, of the 187 patients, 141 had breast-conservation therapy and 46 had total mastectomy. Results Sensations were less prevalent, severe, and distressing after SLNB compared with ALND at baseline and at 5 years. This difference was most evident in those who had breast-conservation therapy. Most sensations after SLNB and ALND, even if prevalent, were not severe or distressing. Some sensations remained notably prevalent at 5 years, including tenderness and twinges after SLNB, and tightness and numbness after ALND. Phantom sensations were frequently reported by mastectomy patients. Conclusions Prevalence, severity, and level of distress of sensations were lower after SLNB compared with ALND, but some morbidity existed after SLNB. Certain sensations remained highly prevalent in both groups for up to 5 years.     

Systematic Review of Sentinel Lymph Node Mapping Procedure in Colorectal Cancer

Background

The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports.

Methods

A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens).

Results

The pooled SN identification rate was 90.7?% (95?% CI 88.2?C93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6?% (95?% CI 64.7?C74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2?% (95?% CI 4.7?C10.7). Subgroups with significantly higher sensitivity could be identified: ??4 SNs versus <4 SNs (85.2 vs. 66.3?%, p?=?0.003), colon versus rectal cancer (77.6 vs. 65.7?%, p?=?0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8?%, p?=?0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9?% (range 0?C50?%). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7?%.

Conclusions

The SN procedure in colorectal cancer has an overall sensitivity of 70?%, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.     

New Sentinel Node Mapping Technologies for Early Gastric Cancer

The sentinel node (SN) concept has revolutionized the surgical staging of both melanoma and breast cancer over the past two decades. The application of this concept can yield benefits for patients by preventing various complications related to unnecessary prophylactic regional lymph node dissection in patients with cancer-negative SNs. Clinical application of SN mapping in patients with early gastric cancer has been a controversial issue for years. However, a recent meta-analysis and a prospective multicenter trial of SN mapping for early gastric cancer have shown acceptable SN detection rates and accuracy of determination of lymph node status. For early stage gastric cancer such as cT1N0M0, for which a better prognosis can be achieved through conventional surgical approaches, the establishment of individualized, minimally invasive treatments that may retain the patients’ quality of life should be the next surgical challenge. Although there are many unresolved technical issues, laparoscopic SN biopsy with laparoscopic minimized gastrectomy or endoscopic mucosal resection/endoscopic submucosal dissection has the potential to achieve this goal.     

临床腋淋巴结阴性乳腺癌前哨淋巴结研究

目的：探讨前哨淋巴结活检术（ｓｅｎｔｉｎｅｌ ｌｙｍｐｈ ｎｏｄｅ ｂｉｏｐｓｙ, ＳＬＮＢ）在乳腺癌治疗中的应用。方法：使用专利蓝和美蓝染色,对１９９９年９月～２００１年４月连续收治的１４５例临床查体腋窝淋巴结阴性乳腺癌病人行前哨淋巴结活检术。结果：ＳＬＮＢ成功率为９６．５％（１４０／１４５）,假阴性率为２３．５％,准确率为９１．４％。病人年龄、肿瘤最大径、肿瘤部位、注射染料类型及是否活检对成功率和假阴性率无影响。结论：ＳＬＮＢ能够准确预测腋窝淋巴结的转移状况,在缩小手术范围、减少术后并发症的同时,提高了腋窝淋巴结分期的准确性;美蓝与专利蓝均可成功确定ＳＬＮ。