Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.

Trends in Sentinel Lymph Node Biopsies in Patients With Inflammatory Breast Cancer in the US.

Importance: The standard of care for inflammatory breast cancer (IBC) is neoadjuvant chemotherapy, total mastectomy with axillary lymph node dissection (ALND), and postmastectomy radiation therapy. Existing studies suggest that sentinel lymph node biopsy (SLNB) may not be reliable in IBC. The use and frequency of SLNB in women with IBC is not well characterized. Objective: To determine the frequency and temporal trend of SLNB in patients with IBC. Design, Setting, and Participants: This retrospective cohort study used the National Cancer Database, a nationwide hospital-based cancer registry, and included women who were diagnosed with nonmetastatic IBC and underwent axillary surgery from 2012 to 2017. Data were analyzed from January 2021 to May 2021. Exposures: Any SLNB, including SLNB alone and SLNB followed by ALND, and ALND alone. Main Outcomes and Measures: Scatterplot fit with a linear regression model were used to evaluate the yearly increase of any SLNB use. Multivariable logistic regression models to evaluate the association of study variables with the outcome of any SLNB. Results: This study included a total of 1096 women (mean [SD] age, 56.1 [12.9] years) who were 18 years or older with nonmetastatic IBC diagnosed between 2012 and 2017. Of the 186 of 1096 women (17%) who received any SLNB, 137 (73.7%) were White individuals; and of the 910 of 1096 women (83%) who received an ALND only, 676 (74.3%) were White individuals. Among women undergoing any SLNB, 119 of 186 (64%) did not undergo a completion ALND. There was a statistically significant increasing trend in the use of SLNB from 2012 to 2017 (22 of 205 patients [11%] vs 32 of 148 patients [22%]; P = .004). In multivariable analysis, the use of SLNB was associated with diagnosis year (2017 vs 2012; odds ratio [OR], 2.26; 95% CI, 1.26-4.20), clinical nodal status (cN3 vs 0; OR, 0.39; 95% CI, 0.22-0.67), and receipt of reconstructive surgery (OR, 1.80; 95% CI, 1.09-2.96). Conclusions and Relevance: The findings of this cohort study suggest that there is frequent and increasing use of SLNB in patients with IBC that is not evidence-based or supported by current treatment guidelines.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Sentinel lymph node biopsy for stage II endometrial cancer: Recent utilization and outcome in the United States.

OBJECTIVE: To examine trends and outcomes related to sentinel lymph node (SLN) biopsy for stage II endometrial cancer. METHODS: This is a retrospective observational cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 6,314 women with T2 endometrial cancer who underwent hysterectomy from 2010-2018. Exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n=4,915, 77.8%), SLN biopsy (n=340, 5.4%), or no surgical nodal evaluation (n=1,059, 16.8%). The main outcomes were (i) trends and characteristics related to nodal evaluation assessed by multinomial regression, and (ii) overall survival (OS) assessed by an inverse probability of treatment weighting propensity score analysis. A sensitivity analysis was performed to examine concurrent LND in women who underwent SLN biopsy. RESULTS: The utilization of SLN biopsy increased from 1.6% to 16.1%, while the number of LND decreased from 81.5% to 65.7% between 2010-2018 (P<0.05). In multivariable analysis, the utilization of SLN biopsy increased 45% annually (adjusted-odds ratio 1.45, 95% confidence interval [CI] 1.37-1.54, P<0.001). The frequency of SLN biopsy alone exceeded the frequency of SLN biopsy with concurrent LND in 2017 (6.8% versus 3.4%), followed by continued increase in SLN biopsy alone (11.2% versus 4.9%) in 2018. In the weighted model, the 3-year OS rate was 79.9% for the SLN biopsy group and 78.6% for the LND group (hazard ratio 0.98, 95%Cl 0.80-1.20, P=0.831). Similarly, the SLN biopsy alone without concurrent LND had comparable OS compared to the LND group (hazard ratio 0.90, 95%CI 0.59-1.36, P=0.615). CONCLUSION: Utilization of SLN biopsy in stage II endometrial cancer increased significantly over time, and SLN biopsy-incorporated nodal assessment was not associated with worsened short-term survival outcome.

Does failed mapping predict sentinel lymph node metastasis in cN0 breast cancer?

Aims: The clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) is unknown. The authors sought to determine the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Patients & methods: A total of 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively studied. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Results: Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p < 0.001). Conclusion: Patients with non-vSLN had an increased risk for SLN metastasis. The detection rate during surgery was consistent, reducing the amount of unnecessary axillary dissection.

Lay abstract To study the clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) in axillary surgery for breast cancer, 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively reviewed with the aim to analyze the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p < 0.001). Patients with non-vSLN had an increased risk for SLN metastasis. The detection rate during surgery was consistent, reducing the amount of unnecessary axillary dissection.

Sentinel lymph node biopsy alone in the management of early cervical carcinoma.

OBJECTIVE: Sentinel lymph node (SLN) biopsy aims to assess lymph node status with reduced surgical morbidity. The aim of the study was to determine the accuracy and safety of SLN biopsy in the management of early cervical carcinoma using a double technique (technetium-99m (Tc-99m) nanocolloid and methylene blue dye injection). METHODS: This was a 10-year study from January 2009 to January 2019 that recruited 103 consecutive women undergoing surgery for early cervical carcinoma, FIGO 2009 stage IA1 (grade 3, and grade 2 with lymphovascular space invasion) to IB1 (<2 cm), at the West Kent Gynaecological Oncology Centre, Maidstone, UK. All patients were given the choice of pelvic node dissection and SLN mapping or SLN only. All patients elected to undergo SLN only. In total 97 patients had SLN mapping performed laparoscopically. We used the combined method (Tc-99m nanocolloid and/or methylene blue dye). All SLN routinely underwent ultrastaging. RESULTS: At least one SLN was detected in all 103 patients, using at least one of the combined methods (Tc-99m nanocolloid or blue dye). Bilaterally SLN were removed in 85/103 women with an 83% bilateral detection rate. The median SLN count was 2.3 (range 1-6) nodes. Of 103 patients, 7 (6.7%) patients had lymph node involvement. There were no pelvic or para-aortic lymph node recurrences with a median follow-up of 53 (range 8-120) months. The specificity and negative predictive value of a negative SLN was 100%. None of our 103 patients reported lower extremity lymphedema. CONCLUSION: In carefully selected patients with early cervical carcinoma, SLN biopsy alone appears to be a safe method for lymph node assessment of women undergoing surgical staging. Ultrastaging is an essential part of histologic examination of SLN.

Is image-guided core needle biopsy of borderline axillary lymph nodes in breast cancer patients clinically helpful?

BACKGROUND: When borderline axillary lymph nodes (bALN) are identified on ultrasound (US) for breast cancer (BC) patients, preoperative management is unclear. We aimed to evaluate if core needle biopsy (CNB) for bALN is clinically helpful or disruptive. METHODS: Retrospective review of BC patients with bALN from 2014 to 2019 was performed. Clinicopathologic data were compared for those who did and did not have CNB. RESULTS: CNB (n = 34) and no CNB (n = 31) were similar with respect to clinicopathologic factors. Surgical LN-positive rate was the same between cohorts (p = 0.26). CNB was disruptive in 58.8 %; all had CNB for pN0 disease. CNB was helpful in 34.2 %: 14.7 % proceeded directly to axillary dissection; 17.6 % had positive LN localized after neoadjuvant chemotherapy. CONCLUSIONS: CNB for bALN is more likely clinically disruptive and did not impact surgical LN positive rate. BC patients with bALN should undergo CNB only if it will change clinical management.

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Patient Selection for Surgery vs Radiotherapy for Early Stage Oropharyngeal Cancer.

Surgery and radiation therapy are both commonly used in the treatment of early stage (AJCC stages T1-T2 N0-M0) oropharyngeal squamous cell carcinoma (OPSCC). Transoral robotic surgery (TORS) and intensity modulated radiation therapy (IMRT) have been reported to result in similar survival and disease control outcomes. However, their side effect profiles widely differ. Nevertheless, patients who experience the worst side effects and quality of life are the ones who receive the combination of TORS and adjuvant radiation or chemoradiation therapy. Thus, appropriate patient selection for surgery to minimize the need for multimodality therapy is key. We propose, in this paper, the use of sentinel lymph node biopsy in the node negative (N0) neck as a means that is worth exploring for selecting patients to either radiation therapy or surgery. Patients with a positive sentinel lymph node (SLN) would be better directed to upfront radiation. On the contrary, patients with a negative SLN biopsy would be more confidently directed towards TORS and neck dissection alone.

Data Driven for Early Breast Cancer Staging using Integrated Mammography and Biopsy.

OBJECTIVE: Breast cancer patients who have a rapid diagnosis have been better prognosis than late diagnosis. The popular screening is mammogram or ultrasound. In recent years, researchers try to develop data driven models to predict early cancer staging from the first screening. However, data elements are not complete such as lymph node status. Therefore, the Integrated dataset approach will be challenging. METHODS: Because the data elements are not collected from the same source, joining between mammography and biopsy data were performed using latent variables that determine by tumor severity. The datasets consist of 445 mammography reports and 183 pathological reports. The latent variables of the mammogram dataset were determined by the severity of mass, while latent variables of the pathological dataset were determined by TNM Staging. The latent variables were used to join between two datasets. Then, the prediction models were built using the machine learning technique. The modeling is divided into three steps; staging prediction, lymph node prediction, and prognosis. RESULTS: Integrated dataset from mammography and biopsy extend more factors and built the models to predict breast cancer staging in the mammography process. The staging prediction is 100% accuracy. The lymph node prediction are 72.47% accuracy, 73.94% specificity, and 72.5% sensitivity. An area under ROC curve is 0.74. The prognosis model prediction are 72.72% accuracy, 80% specificity, and 77% sensitivity. An area under ROC curve is 0.87. There are also built the rule for early staging, diagnosis, and prognosis.  Conclusion: This study aims to build the models for early staging, diagnosis, and prognosis using the less aggressive method. The advantages are (1) predict staging from the first screening (2) estimate the lymph node metastases for planning to ALND or SLNB (3) evaluate overall survival time. These advantages help the physician planning the best treatment for cancer patients.

Sentinel Lymph Node Sampling in Robot-Assisted Staging of Endometrial Cancer.

OBJECTIVE: Sentinel lymph node (SLN) sampling in endometrial cancer staging has become an acceptable standard. Indocyanine green dye injected into the cervix and detected by near-infrared light is technically simple and sensitive. We aimed to evaluate SLN sampling in robot-assisted surgical staging of endometrial cancer at a university-affiliated teaching hospital. METHODS: A retrospective chart review, from January 2016 to December 2017, of patients who underwent robot-assisted surgical staging with cervical injection of indocyanine green dye detected by near-infrared light. The map rate, sensitivity, false negatives, and negative predictive value were calculated. RESULTS: A total of 105 charts were reviewed; 79 patients met inclusion criteria. The mean age was 65 (range 38-93) and the mean body mass index was 33.3 (range 16-49). Most patients (72.2%) had stage I disease and grade 1 or 2 histology (77.1%). Eight (10.1%) patients had lymph node metastasis. Seventy-two (91.1%) patients had positive mapping to at least 1 SLN. Sixty-two (78.5%) patients had bilateral mapping. Forty-four patients had concurrent pelvic ± para-aortic lymph node dissection and were included in the sensitivity analysis. Five of 44 cases had LN metastasis. The sensitivity was 80%, and the negative predictive value of SLN sampling was 97.5%. CONCLUSIONS: SLN mapping and sampling at a university-affiliated teaching hospital have comparable map rate, sensitivity, and negative predictive value as demonstrated in multiple trials. The technique has the potential to standardize endometrial cancer staging across different practice settings.

Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer.

INTRODUCTION: Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS: Prospective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS: We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P < .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION: Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

Sentinel Node Biopsy for Conjunctival Melanoma; Single Centre Experience and Review of Current Literature.

PURPOSE: To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). STUDY DESIGN: Retrospective observational cohort study and literature review. SUBJECTS: Slovenian patients with CjM are included in the study. METHODS: Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. MAIN OUTCOME MEASURES: The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. RESULTS: From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77-224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. CONCLUSION: Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

Factors predicting one or two sentinel lymph nodes to be accepted for sentinel lymph node biopsy alone after neoadjuvant therapy in initially node-positive breast cancer patients.

BACKGROUND: Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients. METHODS: Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model. RESULTS: The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age >52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count >530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991). CONCLUSION: When taxane was administered during NAT, the false-negative rate was predicted at <5% for patients aged <57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Prognostic factors and population-based analysis of melanoma with sentinel lymph node biopsy.

Cutaneous malignant melanoma is a rare but fatal disease in East Asia. Despite its increasing incidence, a general lack of awareness about the disease was noted. This study aims to provide population-based prognostic analysis of melanoma with sentinel lymph node biopsy (SLNB) in Taiwan. We conducted this retrospective cohort study using the data from Taiwan National Health Insurance Research Database during 1997-2013. The study cohort contains 3284 patients. The 5-year survival rates of patients undergoing SLNB and not undergoing SLNB were 45.5% and 33.6%. In multivariate analysis, age ≥ 80 years [adjusted hazard ratio (aHR) = 2.15] and male (aHR = 1.19) were associated with a poorer prognosis, while high social economic status (SES) (aHR = 0.69) and undergoing SLNB (aHR = 0.84) were good prognostic factors. Old age and low SES were associated with lower percentages of patients undergoing SLNB (P < 0.001). E-value analysis suggested robustness to unmeasured confounding. In conclusion, undergoing SLNB was associated with a better prognosis. The poor prognosis of old age and low SES may be due to decreased percentages of patients undergoing SLNB. Therefore, we recommend that SLNB should be performed on patients, especially in old age or low SES, who are candidates for SLNB according to current guidelines to achieve maximal survival.

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. METHODS: An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). RESULTS: Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. CONCLUSION: These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.

Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer.

BACKGROUND: Pelvic lymphadenectomy provides prognostic information for those diagnosed with endometrial (womb) cancer and provides information that may influence decisions regarding adjuvant treatment. However, studies have not shown a therapeutic benefit, and lymphadenectomy causes significant morbidity. The technique of sentinel lymph node biopsy (SLNB), allows the first draining node from a cancer to be identified and examined histologically for involvement with cancer cells. SLNB is commonly used in other cancers, including breast and vulval cancer. Different tracers, including colloid labelled with radioactive technetium-99, blue dyes, e.g. patent or methylene blue, and near infra-red fluorescent dyes, e.g. indocyanine green (ICG), have been used singly or in combination for detection of sentinel lymph nodes (SLN). OBJECTIVES: To assess the diagnostic accuracy of sentinel lymph node biopsy (SLNB) in the identification of pelvic lymph node involvement in women with endometrial cancer, presumed to be at an early stage prior to surgery, including consideration of the detection rate. SEARCH METHODS: We searched MEDLINE (1946 to July 2019), Embase (1974 to July 2019) and the relevant Cochrane trial registers. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of tracers for SLN assessment (involving the identification of a SLN plus histological examination) against a reference standard of histological examination of removed pelvic +/- para-aortic lymph nodes following systematic pelvic +/- para-aortic lymphadenectomy (PLND/PPALND) in women with endometrial cancer, where there were sufficient data for the construction of two-by-two tables. DATA COLLECTION AND ANALYSIS: Two review authors (a combination of HN, JM, NW, RG, and WH) independently screened titles and abstracts for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We calculated the detection rate as the arithmetic mean of the total number of SLNs detected out of the total number of women included in the included studies with the woman as the unit of analysis, used univariate meta-analytical methods to estimate pooled sensitivity estimates, and summarised the results using GRADE. MAIN RESULTS: The search revealed 6259 unique records after removal of duplicates. After screening 232 studies in full text, we found 73 potentially includable records (for 52 studies), although we were only able to extract 2x2 table data for 33 studies, including 2237 women (46 records) for inclusion in the review, despite writing to trial authors for additional information. We found 11 studies that analysed results for blue dye alone, four studies for technetium-99m alone, 12 studies that used a combination of blue dye and technetium-99m, nine studies that used indocyanine green (ICG) and near infra-red immunofluorescence, and one study that used a combination of ICG and technetium-99m. Overall, the methodological reporting in most of the studies was poor, which resulted in a very large proportion of 'unclear risk of bias' ratings. Overall, the mean SLN detection rate was 86.9% (95% CI 82.9% to 90.8%; 2237 women; 33 studies; moderate-certainty evidence). In studies that reported bilateral detection the mean rate was 65.4% (95% CI 57.8% to 73.0%) . When considered according to which tracer was used, the SLN detection rate ranged from 77.8% (95% CI 70.0% to 85.6%) for blue dye alone (559 women; 11 studies; low-certainty evidence) to 100% for ICG and technetium-99m (32 women; 1 study; very low-certainty evidence). The rates of positive lymph nodes ranged from 5.2% to 34.4% with a mean of 20.1% (95% CI 17.7% to 22.3%). The pooled sensitivity of SLNB was 91.8% (95% CI 86.5% to 95.1%; total 2237 women, of whom 409 had SLN involvement; moderate-certainty evidence). The sensitivity for of SLNB for the different tracers were: blue dye alone 95.2% (95% CI 77.2% to 99.2%; 559 women; 11 studies; low-certainty evidence); Technetium-99m alone 90.5% (95% CI 67.7% to 97.7%; 257 women; 4 studies; low-certainty evidence); technetium-99m and blue dye 91.9% (95% CI 74.4% to 97.8%; 548 women; 12 studies; low-certainty evidence); ICG alone 92.5% (95% CI 81.8% to 97.1%; 953 women; 9 studies; moderate-certainty evidence); ICG and blue dye 90.5% (95% CI 63.2.6% to 98.1%; 215 women; 2 studies; low-certainty evidence); and ICG and technetium-99m 100% (95% CI 63% to 100%; 32 women; 1 study; very low-certainty evidence). Meta-regression analyses found that the sensitivities did not differ between the different tracers used, between studies with a majority of women with FIGO stage 1A versus 1B or above; between studies assessing the pelvic lymph node basin alone versus the pelvic and para-aortic lymph node basin; or between studies that used subserosal alone versus subserosal and cervical injection. It should be noted that a false-positive result cannot occur, as the histological examination of the SLN is unchanged by the results from any additional nodes removed at systematic lymphadenectomy. AUTHORS' CONCLUSIONS: The diagnostic test accuracy for SLNB using either ICG alone or a combination of a dye (blue or ICG) and technetium-99m is probably good, with high sensitivity, where a SLN could be detected. Detection rates with ICG or a combination of dye (ICG or blue) and technetium-99m may be higher. The value of a SLNB approach in a treatment pathway, over adjuvant treatment decisions based on uterine factors and molecular profiling, requires examination in a high-quality intervention study.

Absence of prognostic value of lymphovascular space invasion in patients with endometrial cancer and negative sentinel lymph nodes.

OBJECTIVE: To evaluate if the prognostic value of lymphovascular space invasion (LVSI) is different in endometrial cancer patients with negative lymph nodes following sentinel lymph node (SLN) mapping or lymph node dissection (LND) as staging procedure. MATERIAL AND METHODS: A retrospective study of 510 patients diagnosed with endometrial carcinoma in our institution between 2007 and 2014. We excluded patients that were diagnosed with positive nodes (Stage IIIc). We compared patients' characteristics and survival outcomes as function of their LVSI status (positive LVSI vs negative LVSI subgroups) in each cohort separately. RESULTS: 413 patients met the inclusion criteria, out of whom 239 underwent SLN and 174 patients underwent LND only. In the SLN group, life table analysis showed 5-year OS and PFS of 80% and 72% in patients with LVSI compared to 96%, and 93% without LVSI. Same trend was observed among patients with LND with 5-year OS and PFS of 74% and 64% in patients with LVSI compared to 97%, and 90% without LVSI. On multivariable analysis, adjusted for age, FIGO stage, grade and maximal tumor size, the favorable survival of negative LVSI remained only in the LND cohort (SLN cohort: HR 1.2, CI [0.3-4.0], P = 0.8 and HR 1.7, CI [0.7-4.3], p = 0.2 for OS and PFS, respectively; LND cohort: HR 3.1, CI [1.4-6.5], p < 0.001 and HR 2.5, CI [1.2-4.9], p = 0.01 for OS and PFS, respectively). CONCLUSIONS: The prognostic value of LVSI disappears when patients undergo staging with SLN and are found to have negative nodes in contrast to those who have undergone LND. Future studies should confirm our observation on patients with negative sentinel nodes, and plan on tailoring adjuvant treatment to this specific subgroup.