Macroscopic Quality Control Improves the Reliability of Blue Dye–Only Sentinel Lymph Node Biopsy in Breast Cancer

Background: One of the problems of sentinel lymph node (SLN) biopsy is the risk of false negatives. At the Institut Curie, to reduce the false-negative rate, we have developed a histological quality control of the SLN performed by blue dye alone, which consists of verification of the SLN blue stain by the pathologist.Methods: A total of 324 patients underwent an SLN biopsy procedure with patent blue dye only followed by an immediate axillary dissection. Initially, SLNs were checked to ensure that they were blue by macroscopic examination. Finally, a search for immunohistochemistry micrometastasis was performed.Results: In 277 (85.5%) of 324 patients, an SLN was identified by the surgeon. After standard examination, the false-negative rate was 11.1% (10 of 90). After macroscopic checking of the 197 negative SLNs, 167 of the 197 were confirmed blue, and there were 5 false negatives, which brought the false-negative rate down to 5.6% (5 of 90). Sixty SLNs out of the 167 confirmed blue SLNs were then proved to be immunohistochemically micrometastatic, and there were 3 false negatives, giving a final false-negative rate of 2.2% (2 of 90; P = .002).Conclusions: In this series, the procedure of pathologic analysis of the SLN has resulted in a significant reduction of the false-negative rate.     

Does Blue Dye Contribute to Success of Sentinel Node Mapping for Breast Cancer?

Background

We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node (SLN) mapping at a high-volume institution.

Methods

Using a prospectively maintained database, 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified. Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review. Statistical analysis was performed with Student t test and chi-square analysis.

Results

2,049 (60.2%) patients underwent mapping with dual technique, and 1,353 (39.8%) with radioisotope only. Blue dye use decreased gradually over time (69.8% in 2002 to 48.3% in 2006, p < 0.0001). Blue dye was used significantly more frequently in patients with lower axillary counts, higher body mass index (BMI), African-American race, and higher T stage, and in patients not undergoing skin-sparing mastectomy. There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone (both 98.4%). Four (0.8%) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN. None of these four had significant counts detected in the axilla intraoperatively. Nine (0.4%) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye.

Conclusions

Blue dye use has decreased with increasing institutional experience with SLN mapping. In patients with adequate radioactive counts in the axilla, blue dye is unlikely to improve the success of sentinel node mapping.

     

Is Blue Dye Indicated for Sentinel Lymph Node Biopsy in Breast Cancer Patients With a Positive Lymphoscintigram?

Background The use of isosulfan blue dye in sentinel node biopsy for breast cancer has been questioned because of its risk of allergic reaction. We hypothesized that blue dye could be safely omitted in the subgroup of patients who have evidence of successful sentinel node localization by lymphoscintigraphy.Methods A retrospective review of patients with breast cancer and sentinel node biopsy was conducted. Information was collected on lymphoscintigraphy results, use of blue dye, and intraoperative and pathologic findings of sentinel nodes.Results We identified 475 patients with breast cancer who underwent 478 sentinel node biopsies. Both dye and isotope were given in 418 cases, of which 380 had a positive lymphoscintigram. In 5 of the 380 cases with a positive lymphoscintigram, the sentinel nodes obtained were blue but not hot, for a 1.3% marginal benefit of dye in the technical success of the procedure. Sentinel nodes positive for metastasis were found in 102 of 380 cases; in 3 cases, the only positive sentinel node was blue but not hot. Omission of the blue dye tracer would have increased the false-negative rate of the sentinel node procedure by approximately 2.5%.Conclusions Even in sentinel node biopsy cases with a positive lymphoscintigram, the use of blue dye is beneficial for both improving the technical success of the procedure and reducing the false-negative rate of the procedure. Because the marginal benefits of dye justify its routine use, strategies to minimize the toxicity of blue dye are warranted.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

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.     

Sentinel Lymph Node Detection for Breast Cancer: Which Patients Are Best Suited for the Patent Blue Dye Only Method of Identification?

Background: The objectives of this study were, first, to define the preoperative criteria for using solely the blue dye method and, second, to decrease its operator dependence in predicting axillary lymph node status.Methods: Two hundred fifty-three women consecutively identified with operable breast cancer underwent sentinel lymph node (SLN) detection by the patent blue dye method followed by completion axillary lymph node dissection. A standard pathological examination was performed for all SLN. Then, a pathological color quality assessment (PCQA), which checked for the presence of the blue dye, was performed on the paraffin blocks of the nonmetastatic SLN. Six preoperative identifiable variables likely to influence the detection rate were examined.Results: The surgical detection (sd) rate was 84% (213 of 253) and the PCQA rate was 73% (185 of 253). Only breast size (sd, P = .0005; PCQA, P = .0007) and body mass index 30 (sd, P = .005; PCQA, P = .0007) were significant for SLN identification. Multivariate analysis revealed two independent factors influencing SLN identification: breast size (sd, P = .0001; PCQA, P = .002) and the timing of injection—injection prior to lumpectomy (sd, P =.04).Conclusions: The optimal patient features for identifying the SLN by the patent blue dye method are small or medium-sized breasts, low body fat, and that the procedure is carried out prior to tumor excision. The PCQA offers a useful second assessment of the surgically removed SLN, introducing an independent element of quality control.     

Three–Axillary Lymph Node Sampling for the Prediction of Nonsentinel Node Metastases in Breast Cancer Patients With Sentinel Node Metastases

Background In half of breast cancer patients with positive sentinel nodes, the sentinel nodes are the only metastatic nodes. Such patients have no more metastatic nonsentinel nodes and do not need to undergo axillary lymph node dissection. The purpose of this study was to investigate whether three–axillary lymph node sampling after sentinel node biopsy predicts the status of nonsentinel nodes in patients with sentinel node metastases. Methods Sentinel node biopsy was performed with dye and radioisotope. When the sentinel nodes were diagnosed as metastasis positive by using intraoperative imprint cytology, three–axillary lymph node sampling was performed, followed by axillary lymph node dissection. Results Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as metastasis positive on their final histological examination and were analyzed. The status of the sampled nodes was significantly associated with the status of nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose sampled nodes were negative were found to have additional nodal metastases. The sensitivity, specificity, and accuracy of the sampled nodes for the prediction of nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively. Conclusions We demonstrated that three-node sampling may be useful for predicting the status of nonsentinel nodes and avoiding axillary lymph node dissection in patients with only sentinel node metastases.     

Role for Lymphatic Mapping and Sentinel Lymph Node Biopsy in Patients With Thick (≥4 mm) Primary Melanoma

Background: Historically, patients with thick (4 mm) primary melanoma have not been considered candidates for elective lymph node dissection, because their risk for occult distant disease is significant. Sentinel lymph node (SLN) biopsy offers an alternative approach to assess disease in the regional nodal basin, but no studies have specifically addressed the role for this technique in patients with thick melanoma. Although adjuvant therapy benefits patients who develop nodal metastases, data that supports its routine use in all patients with thick melanoma is both limited and controversial. This study was performed to determine whether pathological status of the SLN is an important risk factor in this heterogeneous group and, thus, provides a rationale for SLN biopsy.Methods: The records of 131 patients with primary cutaneous melanoma whose primary tumors were at least 4 mm thick and who underwent lymphatic mapping and SLN biopsy were reviewed. Several known prognostic factors, i.e., tumor thickness, ulceration, Clark level, location, sex, as well as SLN pathological status were analyzed with respect to disease-free and overall survival.Results: Lymphatic mapping and SLN biopsy was successful in 126 (96%) of 131 patients who underwent the procedure. In 49 patients (39%), the SLN biopsy was positive by conventional histology, although it was negative in 77 patients (61%). The median follow-up was 3 years. Although presence of ulceration and SLN status were independent prognostic factors with respect to disease-free and overall survival, SLN status was the most powerful predictor of overall survival by univariate and multivariate analyses.Conclusions: Lymphatic mapping and SLN biopsy is a highly accurate method of staging lymph node basins at risk for regional metastases in patients with thick melanoma and identifies those patients who may benefit from earlier lymphadenectomy as well as patients with a more favorable prognosis. Pathological status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for survival and is essential to establish stratification criteria for future adjuvant trials in this high-risk group.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Tumor-Positive Sentinel Node Biopsy of the Groin in Clinically Node-Negative Melanoma Patients: Superficial or Superficial and Deep Lymph Node Dissection?

Background The extent of a completion groin dissection in sentinel node–positive melanoma patients was guided by the location of the second-echelon nodes on the preoperative lymphoscintigram. The purposes of the current study were to investigate the pathological findings, the lymph node recurrences and (disease-free) survival associated with this approach. Methods Between June 1996 and April 2007, 42 patients underwent completion groin dissection after a tumor-positive sentinel node biopsy. Eighteen patients had femoro-inguinal second-echelon nodes on their lymphoscintigram and underwent a superficial lymph node dissection. Twenty-four patients had iliac-obturator second-echelon nodes found by scan and underwent a combined superficial and deep dissection. Results The median follow-up time was 61 months. One of the 18 patients who underwent a superficial groin dissection developed a deep (obturator) lymph node recurrence after 12 months. Revision of the lymphoscintigram showed that the images had been interpreted incorrectly and that the second-echelon node was located in the obturator area after all. A combined superficial and deep dissection revealed additional involved nodes in the deep lymph node compartment in 2 of the 24 patients. At 5 years, 77% of all patients were alive, and 56% were alive and free of disease. These figures were 76% and 53%, respectively, in the patients who underwent superficial dissection only, and 80% and 61%, respectively, in the patients who also underwent deep dissection. Conclusions This study suggests that a strategy to determine the extent of the groin dissection that is based on the location of the second-tier nodes may be valid.     

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

Background/Objective

Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND).

Methods

Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined.

Results

From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND.

Conclusion

Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

     

Association of Lymph Node Sampling and Clinical Volume in Lobectomy for Non–Small Cell Lung Cancer

BackgroundSampling of ≥10 lymph nodes during lobectomy for non–small cell lung cancer (NSCLC) was a previous surveillance metric and potential quality metric of the American College of Surgeons Commission on Cancer. We sought to determine guideline adherence and its relationship to hospital lobectomy volume within The Society of Thoracic Surgeons General Thoracic Surgery Database.MethodsParticipant centers providing elective lobectomy for NSCLC within The Society of Thoracic Surgeons General Thoracic Surgery Database (2012-2019) were divided into tertiles according to annual volume. Average hospital nodal harvest of ≥10 nodes per lobectomy defined the primary outcome. Univariable analysis compared average patient and operative characteristics between the participant centers. Multivariable logistic regression was used to determine independent factors associated with average clinical center nodal harvest of ≥10 nodes.ResultsMedian annual lobectomy volume was 6.2, 19.9, and 42.7 for low-, medium-, and high-volume participant centers. Among 305 centers and 43 597 patients, 5.6% of lobectomies occurred in low-volume centers, 24.0% in medium-volume centers, and 70.4% in high-volume centers. Average rates of ≥10 nodes per lobectomy were excised in 44.0% of low-volume centers, 70.6% of medium-volume centers, and 75.2% of high-volume centers (P < .001). On multivariable analysis, average nodal excision of ≥10 nodes was strongly associated with medium-volume (odds ratio, 2.94; CI, 1.57-5.50, P < .01) and high-volume (odds ratio, 3.82; CI, 1.95-7.46; P < .001) participant centers.ConclusionsAlthough higher center volume and increased nodal harvest are associated, 25% of high-volume centers average a rate of <10 lymph nodes per lobectomy for NSCLC. Low nodal yield may underestimate stage, with implications for adjuvant therapy and long-term survival.     

Comparison between Preoperative Versus Intraoperative Injection of Technetium-99 m Neomannosyl Human Serum Albumin for Sentinel Lymph Node Identification in Early Stage Lung Cancer

Purpose  

We aimed to evaluate the results of sentinel lymph node mapping according to injection time (preoperative vs. intraoperative) of technetium-99m neomannosyl human serum albumin (^99mTc-MSA) in patients with lung cancer.     

Is There an Additional Value of SPECT/CT Over Planar Lymphoscintigraphy for Sentinel Node Mapping in Oral/Oropharyngeal Squamous Cell Carcinoma?

Background  

Lymphatic mapping for sentinel node biopsy (SNB) has been shown to be crucial for detection of sentinel lymph nodes (SLN). Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. The aim was to assess whether there is an additional value of SPECT/CT over LS alone for lymphatic mapping of SLNs in oral/oropharyngeal SCC.     

The Role of Radical Prostatectomy and Lymph Node Dissection in Lymph Node–Positive Prostate Cancer: A Systematic Review of the Literature

Context

Because pelvic lymph node (LN)-positive prostate cancer (PCa) is generally considered a regionally metastatic disease, surgery needs to be better defined.

Objective

To review the impact of radical prostatectomy (RP) and pelvic lymph node dissection (PLND), possibly in conjunction with a multimodal approach using local radiotherapy and/or androgen-deprivation therapy (ADT), in LN-positive PCa.

Evidence acquisition

A systematic Medline search for studies reporting on treatment regimens and outcomes in patients with LN-positive PCa undergoing RP between 1993 and 2012 was performed.

Evidence synthesis

RP can improve progression-free and overall survival in LN-positive PCa, although there is a lack of high-level evidence. Therefore, the former practice of aborting surgery in the presence of positive nodes might no longer be supported by current evidence, especially in those patients with a limited LN tumor burden. Current data demonstrate that the lymphatic spread takes an ascending pathway from the pelvis to the retroperitoneum, in which the internal and the common iliac nodes represent critical landmarks in the metastatic distribution. Sophisticated imaging technologies are still under investigation to improve the prediction of LN-positive PCa. Nonetheless, extended PLND including the common iliac arteries should be offered to intermediate- and high-risk patients to improve nodal staging with a possible benefit in prostate-specific antigen progression-free survival by removing significant metastatic load. Adjuvant ADT has the potential to improve overall survival after RP; the therapeutic role of a trimodal approach with adjuvant local radiotherapy awaits further elucidation. Age is a critical parameter for survival because cancer-specific mortality exceeds overall mortality in younger patients (<60 yr) with high-risk PCa and should be an impetus to treat as thoroughly as possible.

Conclusions

Increasing evidence suggests that RP and extended PLND improve survival in LN-positive PCa. Our understanding of surgery of the primary tumor in LN-positive PCa needs a conceptual change from a palliative option to the first step in a multimodal approach with a significant improvement of long-term survival and cure in selected patients.     

Matched-Case Comparison for the Role of Surgery in FIGO Stage Ib1–IIa Squamous Cell Carcinoma of Cervix and Suspicious Para-Aortic Lymph Node Metastasis

We sought to compare the efficacy and toxicity between surgery followed by concurrent chemoradiation and primary concurrent chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ib1–IIa squamous cell carcinoma of cervix and suspicious para-aortic lymph node metastasis by preoperative computed tomographic and magnetic resonance imaging. From January 2000 to December 2007, 48 patients treated with radical hysterectomy with pelvic and para-aortic lymphadenectomy followed by concurrent chemoradiation (group 1) were matched to 16 patients treated with primary concurrent chemoradiation (group 2) from medical records. Primary end points were progression-free survival (PFS) and overall survival, and secondary end points were late complications by concurrent chemoradiation and pattern of disease recurrence. Among 48 patients in group 1, 39 (81.3%) and 35 (72.9%) had histologic pelvic and para-aortic lymph node metastases, respectively. Distant metastasis was more frequent in group 2 than in group 1 (37.6% vs. 12.5%, p = 0.027), although there was no difference in locoregional recurrence between the two groups. Surgery followed by concurrent chemoradiation and FIGO stage Ib1 were only statistically significant factors for improved PFS (adjusted hazard ratio, 0.231 and 0.244; 95% confidence interval, 0.072–0.821 and 0.086–0.697), although there was no prognostic factor for overall survival. Furthermore, there was no difference in grade 3 or 4 late complications between groups 1 and 2 (25.0% vs. 31.3%, p = 0.745). Surgery followed by concurrent chemoradiation may improve PFS and reduce distant metastasis without difference in late complications compared with primary concurrent chemoradiation in patients with FIGO stage Ib1–IIa squamous cell carcinoma of cervix and suspicious para-aortic lymph node metastasis.     

Association Between the Number of Dissected Lymph Nodes During Pelvic Lymphadenectomy and Cancer-Specific Survival in Patients with Lymph Node–Negative Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy

Background

A larger number of dissected lymph nodes (LN) during pelvic lymphadenectomy in patients with muscle-invasive transitional-cell carcinoma of the bladder treated by radical cystectomy (RC) is crucial for exact tumor staging and is associated with a positive oncological outcome.

Methods

Clinical and pathological records of 1291 patients undergoing RC due to LN-negative transitional-cell carcinoma of the bladder were summarized and evaluated in a multi-institutional database. The number of removed LNs and the presence or absence of lymphovascular invasion were assessed. On the basis of multivariate Cox regression analyses, a threshold number of removed LNs was defined that exerted an independent influence on cancer-specific survival (CSS).

Results

In multivariate Cox regression models for different numbers of removed LNs, a statistically significant enhancement of CSS could be demonstrated for a LN count of 16. Furthermore, the integration of the dichotomized LN count of 16 resulted in a statistically significantly enhanced predictive ability of the model for CSS. Patients with <16 and ≥16 removed LNs showed CSS rates after 5 years of 72% and 83%, respectively (P = 0.01). In addition, age, sex, pT stage, and lymphovascular invasion had independent influences on CSS in every Cox regression model.

Conclusions

In patients undergoing RC, removal of a higher LN count is associated with an improved oncological outcome. The information resulting from an assessment of lymphovascular invasion and an extended lymphadenectomy is critical for stratification of risk groups and identification of patients who might benefit from adjuvant treatment.