Stage Lymph Node Research Articles

Speckle reduction in ultrasound endoscopy using refraction based elevational angular compounding

Endoscopic ultrasonography (EUS) is a safe, real-time diagnostic and therapeutic tool. Speckle noise, inherent to ultrasonography, degrades the diagnostic precision of EUS. Elevational angular compounding (EAC) can provide real-time speckle noise reduction; however, EAC has never been applied to EUS because current implementations require costly and bulky arrays and are incompatible with the tight spatial constraints of hollow organs. Here we develop a radial implementation of a refraction-based elevational angular compounding technique (REACT) for EUS and demonstrate for the first time spatial compounding in a radial endoscopy. The proposed implementation was investigated in cylindrical phantoms and demonstrated superior suppression of ultrasound speckle noise and up to a two-fold improvement in signal- and contrast- ratios, compared to standard image processing techniques and averaging. The effect of elevational angular deflection on image fidelity was further investigated in a phantom with lymph node-like structures to determine the optimum elevational angular width for high speckle reduction efficiency while maintaining image fidelity. This study introduces REACT as a potential compact and low-cost solution to impart current radial echo-endoscopes with spatial compounding, which could enable accurate identification and precise sizing of lymph nodes in staging of gastrointestinal tract cancers.

LncRNA TPT1‑AS1 knockdown inhibits liver cancer cell proliferation, migration and invasion.

Long non-coding RNA (lncRNA) tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) serves as an oncogene in several tumors, including ovarian and cervical cancer. However, the functional role of TPT1-AS1 in liver cancer (LC) is not completely understood. The present study aimed to explore the role of TPT1-AS1 in LC. In this study, the reverse transcription-quantitative PCR results demonstrated that TPT1-AS1 expression was significantly upregulated in LC tissues and cell lines compared with adjacent paracancerous tissues and THLE-3 cells, respectively. Elevated TPT1-AS1 expression was significantly associated with TNM stage lymph node metastasis and poor prognosis in patients with LC, as determined via χ2 and Kaplan-Meier survival analyses. By constructing TPT1-AS1 knockdown LC cell lines (HepG2 and SNU-182), loss-of-function experiments, including Cell Counting Kit-8, colony formation, flow cytometry, wound healing and Transwell assays, were performed to explore the function role of TPT1-AS1 in LC in vitro. The results demonstrated that TPT1-AS1 knockdown inhibited LC cell proliferation, G1/S transition, migration and invasion compared with the small interfering RNA (si)-negative control (NC) group. Mechanistically, TPT1-AS1 knockdown markedly decreased CDK4, N-cadherin and Vimentin expression levels, but notably increased p21 and E-cadherin expression levels compared with the si-NC group. Therefore, the results of the present study suggested that TPT1-AS1 might serve as a promising therapeutic target for LC treatment.

Can anesthetic effects and pain treatment influence the long-term prognosis of early-stage lymph node-negative breast cancer after breast-conserving surgery?

BackgroundBreast cancer is currently the leading cause of women’s death. It is crucial to further improve the approach to treatment and the long-term survival rate of breast cancer patients, and to reduce the rates of recurrence and metastasis. It has been reported that the possibility of tumor metastasis depends on the metastatic potential of the tumor and the host defense against tumor metastasis, in which cellular immunity and the function of natural killer (NK) cells are critical to maintaining this balance. Surgical stress response and postoperative pain inhibit perioperative immune function in patients and increase the likelihood of dissemination and metastasis of cancer cells after cancer surgery. The study aims to investigate the effect of anesthetic factors and pain treatment on the long-term prognosis of patients with early stage lymph node negative breast preservation surgery.MethodsA total of 337 patients with early-stage lymph node negative breast cancer (ASA I-II) who had undergone successful breast-conserving surgery in our hospital were included in this retrospective analysis. Cases were divided into general anesthesia with postoperative analgesia group (GA + PCA), general anesthesia without postoperative analgesia group (GA), epidural anesthesia with postoperative analgesia group (EA + PCA), and epidural anesthesia without postoperative analgesia group (EA). The 5-year survival rate and 5-year disease-free survival were recorded in the 4 groups.ResultsThe general condition and length of hospital stay of the patients were not statistically different between the 4 groups. However, the 5-year survival rate and 5-year disease-free survival rate of the 4 groups were statistically different. The 5-year survival rate and 5-year disease-free survival rate were the lowest in the GA group, while the EA + PCA group had the highest 5-year disease-free survival rate. The 5-year survival rate and 5-year disease-free survival rate in the GA + PCA group were significantly higher than those in the GA group. The 5-year disease-free survival rate in EA group was significantly higher than GA group.ConclusionsEpidural anesthesia and postoperative pain treatment maybe beneficial to the long-term prognosis of patients with early-stage lymph node-negative breast cancer.

Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer.

The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

Diagnostic Value of Multimodal Magnetic Resonance in Cervical Cancer Staging and Pelvic Lymph Node Metastasis

Objective. To investigate the diagnostic value of multimodal magnetic resonance imaging (MRI) in cervical cancer patients with disease stage lymph node metastasis. Method. A total of 46 patients diagnosed with cervical cancer admitted to our hospital from January 2018 to December 2020 were selected. All the patients were confirmed by postoperative pathological examination. Figo staging and lymph node metastasis were determined based on the pathological examination results. Multimodal MRI examination was used to complete conventional MRI plain scan, diffusion weighted imaging (DWI) and dynamic enhanced scanning (DCE). Multimodal MRI staging results, lymph node metastasis and pathological results were compared. To evaluate the diagnostic value of multimodal MRI in cervical cancer patients. Result. According to the results of postoperative pathological examination, stage I patients accounted for 26.1%(12/46), stage II patients accounted for 43.5%(20/46), stage III patients accounted for 17.4%(8/46), and stage IV patients accounted for 10.9%(5/46). Multimodal MRI showed stage I in 13 cases, stage II in 18 cases, stage III in 10 cases, and stage IV in 5 cases. Compared with postoperative pathological examination results, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of multimodal MRI in patients with stage IV cervical cancer were all 100.00%, which were higher than those in patients with stage III, II and I cervical cancer (P<0.05). A total of 131 lymph nodes were examined in 46 patients after surgery, of which 63 lymph nodes had metastasis and 68 lymph nodes had no metastasis. After multimodal MRI examination, 60 lymph nodes were diagnosed with metastasis, with diagnostic accuracy of 93.1% and sensitivity of 95.00%. The diagnostic specificity was 91.56%. Conclusion. Multimodal MRI examination has a high accuracy in the diagnosis of the disease stage and lymph node metastasis of cervical cancer patients, and can clearly and comprehensively display the lesions and effectively identify the disease stage. It can be used as an important means for the diagnosis of cervical cancer and is worthy of clinical promotion.

Abstract 665: Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery

Abstract Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival rate of 21%. New treatment options are thus required, and the endogenous cannabinoid system is a potential new therapeutic target. We therefore analysed the expression of cannabinoid 1 and 2 receptor (CB1 and CB2) genes in NSCLC tissue and its influence on survival following radical surgery. Method: CB1 and CB2 gene expression in tumor tissue samples collected from 100 NSCLC patients was analysed using the quantitative real-time polymerase chain reaction. Since gene expression may not correlate with protein production, the presence of the CB2 protein was validated by immunohistochemistry. CB2 gene expression was correlated with disease stage, the presence of lymph node and distant metastases, tumor size, tumor grade, and survival. Result: Patients with tumors expressing CB2 gene had significantly longer overall survival (OS) (p&amp;lt;0.001), cancer-specific survival (CSS) (p=0.002), and disease-free survival (DFS) (p&amp;lt;0.001). They also had less advanced disease stage (p=0.047) and fewer lymph node metastases (p=0.011) at the time of surgery. A multivariate analysis showed that CB2 tumor tissue gene expression was a positive prognostic factor for OS (Hazard ratio (HR) = 0.402, p=0.013), CSS (HR=0.344, p=0.025), and DFS (HR=0.274, p=0.003). CB1 gene expression had no effect on survival. CB1 and CB2 gene expression was detected in 50% and 79.6% of the tumor tissue samples, respectively, and immunohistochemistry confirmed a correlation between CB2 gene expression and the presence of the CB2 protein in tumor tissues. Conclusion: In NSCLC patients undergoing radical surgery, CB2 gene expression in tumor tissue is associated with less advanced disease stage, fewer lymph node metastases, and longer survival (OS, CSS, DFS). Acknowledgement: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132), Palacky University Olomouc (LF 2020_007), Technological Agency of the Czech Republic (TN01000013), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Monika Vidlarova, Emil Berta, Petr Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch. Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 665.

Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting

Abstract Background: Accumulation of systemically administered nanoparticles (NPs) in lymph nodes has been exploited clinically for diagnostic imaging (e.g., USPIOs for lymph node metastasis) and therapeutic applications (e.g., vaccine delivery). However, the combination of diagnostic and therapeutic functionalities into a single theranostic NP has obliged undesirable trade-offs between either the imaging or drug delivery of the NP and their specific accumulation in lymph nodes. To overcome these trade-offs, we conducted a screen of various lipid-based theranostic NPs focusing on differing NP design and their resulting pharmacokinetic behaviours in healthy and diseased lymph node models. Methods: Lipid-based theranostic NPs with varying physicochemical characteristics (e.g., formulation, size and morphology, surface targeting, etc.) were prepared with positron emitting Cu-64 and administered systemically at equivalent NP doses in healthy and diseased rodent models (i.e., mice and rats). NP types were assessed for time-dependent accumulation in major lymph node basins via non-invasive whole-body PET/MR imaging at two or more timepoints per animal. 72-hours post-injection the animals were sacrificed, and lymph nodes and major organs were excised for gamma counting and pathological evaluation. Pharmacokinetic behaviour of NPs in healthy versus diseased lymph nodes were calculated in individual animals and in naïvely pooled datasets using non-compartmental analysis. Results: Preliminary analysis identified a leading NP candidate with specific lymph node targeting in healthy and diseased rodents: a discoidal, 35-nm peptide-targeted HDL-mimetic. In comparison with a spherical, 100-nm PEGylated NP, the discoidal NP obtained greater absolute (%ID) and relative (%ID/g) amounts of injected dose in anatomically matched lymph nodes than the spherical NP, regardless of lymph node pathology. At greatest measured concentration in healthy lymph nodes, typically 24-hpi, the differences between the discoidal and spherical NPs were on average 3-fold greater (2.893 vs. 0.864, %ID/g). Differences in other pharmacokinetic parameters such as AUC (%ID/g*h) and MRT (h) were equally pronounced. Conclusions: Our preliminary analysis uncovered a discoidal, peptide-targeted HDL-mimetic with remarkable accumulation in lymph nodes of healthy and diseased models. Future investigations will focus on the biochemical and cellular mechanisms underlying their unique lymphatic pharmacokinetics. These preliminary results provide key insights for design of theranostic NPs for non-invasive imaging and staging lymph node pathologies, and for applications in delivery of therapeutics to lymph nodes following systemic administration. Citation Format: Michael S. Valic, Mark Zheng, Lili Ding, Michelle Lai, Chris J. Zhang, Tina Ye, Jenny Ma, Michael Halim, Pamela Schimmer, Wenlei Jiang, Juan Chen, Gang Zheng. Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 307.

How many number of retrieved lymph nodes is required for accurate N-staging in resected pancreatic cancer?

Although N stage is important factor in survival of resected pancreatic cancer, appropriate number of retrieved lymph nodes for accurate staging is still controversial. From 1993 to 2019, 446 patients underwent pancreatectomy for pancreatic cancer were included. The binomial probability law was applied to define the minimum number of examined LNs (minELN). The prognostic factors for overall survival were analyzed. According to binomial probability law, 12 and 20 retrieved lymph nodes were found to be required accurate staging for pancreatic cancer. With node-positive disease, the median OS of patients with less than 12 ELNs was not significantly different to those with 12 or more ELNs (20 v. 18 months, p = 0.326). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes even when finding fewer than 12 ELNs (26 v. 19 months, p = 0.04) and more than 12 ELNs (22 v. 18 months, p = 0.01). On the other hand, with node-positive disease, the median OS of patients with less than 20 ELNs was not significantly different to those with 20 or more ELNs (20 v. 20 months, p = 0.78). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes in fewer than 20 ELNs (23 v. 17 months, p = 0.015), but SHOWED no significant IN MORE THAN 20 ELNs (22 v. 18 months, p = 0.07). AJCC (8TH) N-staging system in independent prognostic factor for long-term survival of resected pancreatic cancer.Retrieving 12 lymph nodes are appropriate for Nodal staging PDAC by using AJCC (8th) N stage.

Comparing practice patterns and outcomes for early-stage hormone receptor-positive and node-positive breast cancer patients with high-intermediate-risk Oncotype Dx scores in the National Cancer Database.

e12520 Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS &lt; 25 in the ER+/HER2-/node positive breast cancer population.

164P Usefulness of positron emission tomography for determination of axillary metastasis of breast cancer

Breast cancer is one of the most common cancer types for women worldwide. Metastatic status of axillary lymph nodes in breast cancer staging is very important. Axillary dissection and sentinel lymph node biopsies are currently the gold standard methods for axillary evaluation. In this study, the use of positron emission tomography as an alternative or as an adjunct to invasive methods for the detection of axillary metastasis of breast cancer has been evaluated.

Clinicopathological characteristics and prognostic factors of cervical adenocarcinoma

We aimed to assess the clinicopathological features and to determine the prognostic factors of cervical adenocarcinoma (AC). Relevant data were extracted from surveillance, epidemiology and end results database from 2004 to 2015. The log-rank test and Cox proportional hazard analysis were subsequently utilized to identify independent prognostic factors. A total of 3102 patients were identified. The enrolled patients were characterized by higher proportion of early FIGO stage (stage I: 65.9%; stage II: 14.1%), low pathological grade (grade I/II: 49.1%) and tumor size ≤ 4 cm (46.8%). The 5- and 10-year cancer-specific survival rates of these patients were 74.47% and 70.00%, respectively. Meanwhile, the 5- and 10-year overall survival (OS) rates were 71.52% and 65.17%, respectively. Multivariate analysis revealed that married status, surgery as well as chemotherapy were independent favorable prognostic indicators. Additionally, aged > 45, tumor grade III/IV, tumor size > 4 cm, advanced FIGO stage and pelvic lymph node metastasis (LNM) were unfavorable prognostic factors (all P < 0.01). Stratified analysis found that patients without surgery could significantly benefit from chemotherapy and radiotherapy. In addition, chemotherapy could significantly improve the survival in stage II–IV patients and radiotherapy could only improve the survival in stage III patients (all P < 0.01). Marital status, age, grade, tumor size, FIGO stage, surgery, pelvic LNM and chemotherapy were significantly associated with the prognosis of cervical AC.

Abstract GS1-10: Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial

Abstract Rationale and research objective: As a result of neoadjuvant chemotherapy (NAC), approximately 1/3 of clinically node positive (cN+) breast cancer patients convert to a pathologic complete response (pCR) of the axilla. Targeted Axillary Dissection appears to be most accurate to evaluate axillary treatment-response, but evidence to support this is limited. The RISAS trial was set up to determine the accuracy of sentinel lymph node biopsy (SLNB) combined with excision of the pretreatment marked positive lymph node for axillary staging after NAC in cN+ patients. Methods: This prospective, multicenter trial included cT1-4N1,2,3b patients treated with NAC. Prior to NAC, an iodine seed was placed in the pathologically confirmed positive lymph node. After NAC, all patients underwent SLNB together with excision of the marked lymph node (RISAS-procedure) followed by axillary lymph node dissection (ALND). The identification rate and the accuracy (i.e. false negative rate (FNR) and negative predictive value (NPV)) were calculated for the RISAS procedure. Assuming an FNR of 2%, a prevalence of a positive ALND of 64% and a 10% drop-out rate, a sample size of 248 patients was needed to determine non-inferiority. The NULL hypothesis of inferiority would be rejected at a significance level of 5% if the upper bound of the two-sided 90% Clopper-Pearson confidence interval of the observed FNR would be below the non-inferiority margin of 6.25%. Secondary objectives included the accuracy of the SLNB and excision of the marked lymph node separately. Results: A total of 252 pathologically proven cN+ patients provided informed consent of whom 227 underwent the RISAS procedure/Targeted Axillary Dissection (SLNB combined with excision of the marked positive lymph node). The identification rate of the RISAS procedure is 98% (223/227). Preliminary analysis shows a false negative rate of approximately 5% and a negative predictive value of approximately 91%. Furthermore, by combining SLNB with excision of the marked lymph node, both the identification rate and the accuracy are improved compared to either the SLNB alone or the excision of the marked lymph node alone. Conclusion: This prospective multicenter validation trial shows that the RISAS procedure/Targeted Axillary Dissection is most suitable in terms of identification rate and accuracy to replace ALND for axillary staging after NAC in cN+ patients. The trial was funded by the Dutch Cancer Society (KWF, grant number 2015-8023). Citation Format: Janine Simons, Thiemo JA v Nijnatten, Linetta B Koppert, Carmen C van der Pol, Paul J v Diest, Agnes Jager, David v Klaveren, Boen LR Kam, Marc BI Lobbes, Maaike de Boer, Cees Verhoef, Paul RA Sars, Harold J Heijmans, Els RM van Haaren, Wouter J Vles, Caroline ME Contant, Marian BE Menke, Leonie HM Smit, Wendy Kelder, Marike Boskamp, Ingeborg Mares-Engelberts, Ernest JT Luiten, Marjolein L Smidt. Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS1-10.

Abstract PS7-76: Association between metabolic syndrome and immunohistochemical profile at breast cancer diagnosis in postmenopausal women

Abstract Objective: To evaluate the association between metabolic syndrome (MetS) and the immunohistochemical profile of breast cancer (BC) in postmenopausal women.Methods: This cross-sectional cohort study included 189 women, aged 45-75 years and amenorrhea &amp;gt; 12 months, with newly diagnosed BC and no previous cancer treatment. Clinical, anthropometric and biochemical (total cholesterol, HDL, LDL, triglycerides, and glucose) data were collected, as well as data on BC (histopathology, grade, tumor stage, lymph node metastasis hormone status (estrogen receptor, ER; progesterone receptor, PR; human epidermal growth factor receptor 2, HER-2), and epithelial proliferative activity (Ki-67). Tumors were divided into five subtypes: luminal A, luminal B HER-2 negative, luminal B HER-2 positive, non-luminal HER-2, and triple negative. Women with three or more of the following criteria were diagnosed with MetS: waist circumference ≥ 88 cm; triglycerides ≥ 150 mg/dL; HDL-cholesterol &amp;lt; 50 mg/dL; blood pressure ≥ 130/85 mmHg; glucose ≥ 100 mg/dL. The Student t-test, gamma distribution (asymmetric variables), chi-square test, and logistic regression (odds ratio, OR) were used for statistical analysis.Results: Sixty-three (33.3%) of the 189 patients had MetS at the time of diagnosis. The mean age, time since menopause and BMI were 59.0 ± 10.6 years, 11.4 ± 9.6 years and 28.5 ± 5.5 kg/m2, respectively, without difference between women with and without MetS (control). Women with MetS had a higher frequency of tumors ≤ 2 cm than women without MetS (49.2% vs 31.8%) (p=0.038). There were no differences in histological grade, staging, or axillary lymph node metastasis (p&amp;gt;0.05). The proportion of PR-positive (p=0.006), HER-2-negative (p=0.034), and luminal B HER-2-negative tumors was higher among patients with MetS (p=0.038) compared to women without MetS (79.4% vs 61.8%, 89.9% vs 78.6% and 44.5% vs 27.8%, respectively). Multivariate analysis adjusted for age, time at menopause and BMI showed a higher risk for luminal B HER-2-negative tumors among women with MetS (OR 2.00, 95% CI 1.03-3.89), obese patients (OR 2.03, 95% CI 1.06-3.90), and women with abdominal obesity (OR 1.96, 95% CI 1.01-4.03). The other BC subtypes were not associated with MetS or its components.Conclusion: In postmenopausal women with newly diagnosed BC, the presence of MetS was associated with a more favorable immunohistochemical profile of BC, such as a smaller tumor size, PR-positive and HER-2-negative status, and the luminal B tumor subtype. Citation Format: Andre Hideo Motoki, Daniel de AraujoBrito Buttros, Ana LuisaCamolezi Gaspar, Eduardo Carvalho Pessoa, Benedito de Sousa Almeida Filho, Jorge Nahas Neto, Heloisa de Luca Vespoli, Eliana AguiarPetri Nahas. Association between metabolic syndrome and immunohistochemical profile at breast cancer diagnosis in postmenopausal women [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-76.

False negative rate at 18F-FDG PET/CT in para-aortic lymphnode involvement in patients with locally advanced cervical cancer: impact of PET technology

BackgroundThe identification of factors responsible for false negative (FN) rate at 18F- Fluorodeoxyglucose (FDG) Positron Emission Tomography /Computed Tomography (PET/CT) in para-aortic (PA) lymph nodes in the presurgical staging of patients with locally advanced cervical cancer (LACC) is challenging. The aim of this study was to evaluate the impact of PET/CT technology.MethodsA total of 240 consecutive patients with LACC (International Federation of Gynecology and Obstetrics, FIGO, stage IB2-IVA) and negative Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and negative 18F-FDG PET/CT in the PA region, undergoing laparoscopic PA lymphadenectomy before chemoradiotherapy were included. The FN rate in patients studied with Time of flight (TOF) PET/CT (TOF PET) or non-Time of flight PET/CT (no-TOF PET) technology was retrospectively compared.ResultsPatients presented with FIGO stage IB (n = 78), stage IIA-B (n = 134), stage III (n = 18) and stage IVa (n = 10), squamous cell carcinoma (n = 191) and adenocarcinoma (n = 49). 141/240 patients were evaluated with no-TOF PET/CT and 99/240 with TOF PET/CT. Twenty-two patients (9%) had PA nodal involvement at histological analysis and considered PET/CT FN findings. The FN rate was 8.5% for no-TOF PET and 10% for TOF PET subgroup respectively (p = 0.98). Ninety patients (38%) presented with pelvic node uptakes at PET/CT. The FN rate in the PA region was 18% (16/90) and 4% (6/150) in patients with and without pelvic node involvement at PET/CT respectively (19 vs 3% for no-TOF PET and 17 vs 5% for TOF PET subgroup).ConclusionsIn LACC, FN rate in PA lymph nodes detection is a clinical issue even for modern PET/CT, especially in patients with pelvic uptake. Surgical lymphadenectomy should be performed in case of negative PET/CT at PA level in these patients, while it could be discussed in the absence of pelvic uptake.

How many number of retrieved lymph nodes is required for accurate N-staging in resected pancreatic cancer?

Introduction Although N stage is important factor in survival of resected pancreatic cancer, appropriate number of retrieved lymph nodes for accurate staging is still controversial. Methods From 1993 to 2019, 446 patients underwent pancreatectomy for pancreatic cancer were included. The binomial probability law was applied to define the minimum number of examined LNs (minELN). The prognostic factors for overall survival were analyzed. Results According to binomial probability law, 12 and 20 retrieved lymph nodes were found to be required accurate staging for pancreatic cancer. With node-positive disease, the median OS of patients with less than 12 ELNs was not significantly different to those with 12 or more ELNs (20 v. 18 months, p = 0.326). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes even when finding fewer than 12 ELNs (26 v. 19 months, p = 0.04) and more than 12 ELNs (22 v. 18 months, p = 0.01). On the other hand, with node-positive disease, the median OS of patients with less than 20 ELNs was not significantly different to those with 20 or more ELNs (20 v. 20 months, p = 0.78). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes in fewer than 20 ELNs (23 v. 17 months, p = 0.015), but SHOWED no significant IN MORE THAN 20 ELNs (22 v. 18 months, p = 0.07). Conclusions AJCC (8TH) N-staging system in independent prognostic factor for long-term survival of resected pancreatic cancer.Retrieving 12 lymph nodes are appropriate for Nodal staging PDAC by using AJCC (8th) N stage.

Prognostic Value of the Anatomic Region of Metastatic Lymph Nodes in the Current TNM Staging of Gastric Cancer.

PurposeThe numeric N stage has replaced the topographic N stage in the current tumor node metastasis (TNM) staging in gastric carcinoma. However, the usefulness of the topographic N stage in the current TNM staging system is uncertain. We aimed to investigate the prognostic value of the topographic N stage in the current TNM staging system.Materials and MethodsWe reviewed the data of 3350 patients with gastric cancer who underwent curative gastrectomy. The anatomic regions of the metastatic lymph nodes (MLNs) were classified into 2 groups: perigastric and extra-perigastric. The prognostic value of the anatomic region was analyzed using a multivariate prognostic model with adjustments for the TNM stage.ResultsIn patients with lymph node metastasis, extra-perigastric metastasis demonstrated significantly worse survival than perigastric metastasis alone (5-year survival rate, 39.6% vs. 73.1%, respectively, P<0.001). Extra-perigastric metastasis demonstrated significantly worse survival within the same pN stage; the multivariate analysis indicated that extra-perigastric metastasis was an independent poor prognostic factor (hazard ratio=1.33; 95% confidence interval=1.01–1.75). The anatomic region of the MLNs improved the goodness-of-fit (likelihood ratio statistics, 4.57; P=0.033) of the prognostic model using the TNM stage.ConclusionsThe anatomic region of MLNs has an independent prognostic value in the numeric N stage in the current TNM staging of gastric carcinoma.

Laparoscopic liver resections for gallbladder cancer and intrahepatic cholangiocarcinoma: the Mayo clinic experience

Presenter: Ron Pery MD | Mayo Clinic, Rochester Background: Gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (ICC) are aggressive malignancies where surgical resection offers the only meaningful chance of cure. Complete tumor removal with negative margins and adequate porta hepatis lymphadenectomy for tumor staging is the surgical standard of care in resectable cases according to the national comprehensive cancer network (NCCN) guidelines. The safety and oncological adequacy of laparoscopic liver resections for GBC and ICC have been questioned in the past and many surgeons were hesitant to consider it. Being a high-volume center of minimal invasive liver surgeries, this study aimed to describe the Mayo clinic experience with laparoscopic liver resections for GBC and ICC and to specifically ascertain their safety and oncological adequacy. Methods: The Mayo clinic database was used to identify patients who underwent curative intent laparoscopic liver resection for GBC or ICC between 01/2016 to 12/2020. Clinicopathological characteristics, operative details and outcomes of 33 patients were collected and analyzed with specific emphasis on resection margins, porta hepatis lymphadenectomy and post-operative complications. Results: 33 patients with GBC or ICC underwent curative-intent laparoscopic liver resection with or without porta hepatis lymphadenectomy in Mayo clinic between 01/2016 and 12/2020. The median age of patients was 65±11.8. Six (18%) patients underwent major liver resection with porta hepatis lymphadenectomy, fourteen (42%) patients underwent minor liver resection with porta hepatis lymphadenectomy; while five (16%) patients underwent major liver resection and eight (24%) patients underwent minor liver resection without portal lymphadenectomy. The mean operative time was 193 minutes (range 83-881) and the mean estimated blood loss (EBL) was 250cc (range 25-1700). There were two conversions (6%) to laparotomy due to failure to progress. Nineteen (58%) patients had no post-operative complications, five (15%) patients had minor post-operative complications (Clavien Dindo score ≤2) and nine (27%) patients had major post-operative complications (Clavien Dindo score ≥3) including one post-operative mortality (3%) due to portal vein thrombosis leading to fatal liver failure. The median in hospital length of stay was three days (range 1-39). On pathology, the mean tumor size was 36.5mm (range 15-150) and resection margins were negative in all specimens. Amongst the patients who underwent porta hepatis lymphadenectomy, the mean number of harvested lymph nodes was 4.5 (range 1-19) and eight (40%) patients have met the AJCC 8th edition staging manual cutoff of at least six harvested lymph nodes. Conclusion: When done by experienced minimal invasive liver surgeons in a high-volume center, laparoscopic liver resections for GBC and ICC are both feasible, safe and oncologically appropriate. While operative times, EBL and post-operative complications profiles are comparable to historic open controls, the in-hospital length of stay is shorter. As in open surgeries, an effort should be made to meet the AJCC 8th edition recommendation of at least six harvested lymph nodes for adequate tumor staging.

Small Molecules for Multi-Wavelength Near-Infrared Fluorescent Mapping of Regional and Sentinel Lymph Nodes in Colorectal Cancer Staging.

Assessing lymph node (LN) status during tumor resection is fundamental for the staging of colorectal cancer. Current guidelines require a minimum of 12 LNs to be harvested during resection and ultra-staging regional lymph nodes by sentinel lymph node (SLN) assessment is being extensively investigated. The current study presents novel near-infrared (NIR) fluorescent dyes for simultaneous pan lymph node (PanLN; regional) and SLN mapping. PanLN-Forte was intravenously injected in mice and assessed for accumulation in regional LNs. SLN800 was injected intradermally in mice, after which the collection and retention of fluorescence in SLNs were measured using indocyanine green (ICG) and its precursor, SLN700, as references. LNs in the cervical, inguinal, jejunal, iliac, and thoracic basins could clearly be distinguished after a low dose intravenous injection of PanLN-Forte. Background fluorescence was significantly lower compared to the parent compound ZW800-3A (p < 0.001). SLN700 and SLN800 specifically targeted SLNs with fluorescence being retained over 40-fold longer than the current clinically used agent ICG. Using SLN700 and SLN800, absolute fluorescence in SLN was at least 10 times higher than ICG in second-tier nodes, even at 1 hour post-injection. Histologically, the fluorescent signal localized in the LN medulla (PanLN-Forte) or sinus entry (SLN700/SLN800). PanLN-Forte and SLN800 appear to be optimal for real-time NIR fluorescence imaging of regional and SLNs, respectively.

Clinical applications of receptor-binding radiopharmaceutical 99mTc-Tilmanocept: sentinel node biopsy and beyond

99mTc-tilmanocept is the first mannose-containing, receptor-directed, radiopharmaceutical for molecular imaging and mapping of sentinel lymph nodes (SLNs) in solid tumor staging. This review focuses on the approved and innovative clinical application of 99mTc-tilmanocept. 99mTc-Tilmanocept is a new-generation radiotracer designed to overcome certain limitations of the conventionally used radiocolloids. The superior efficacy profile of 99mTc-tilmanocept has been demonstrated in several preclinical and clinical studies based on its specific properties like rapid injection site clearance, high uptake in the first node, and low distal node accumulation. The capability of 99mTc-tilmanocept for selective molecular imaging of the CD206 receptor may be used for diagnosis and treatment of several macrophage mediated diseases, including autoimmune diseases, infectious diseases (HIV and tuberculosis), neurodegenerative disorders (dementias) and cardiovascular disease (vulnerable plaque and atherosclerosis).

Assessment of circulating HISLA as a potential biomarker for breast cancer diagnosis and prognosis.

Breast cancer (BC) is the most frequently encountered and aggressive type of malignant tumor and affects the health of females across the globe. Approximately 30% of patients that are newly diagnosed have a high risk of subsequent metastasis and relapse. HIF-1α-stabilizing long noncoding RNA (HISLA) packaged in exosome has been recently identified and revealed as an important oncogenic gene in promoting BC progress. Thus, we sought to investigate whether serum circulating HISLA was involved in dynamics underlying its applicability for the diagnosis and prognosis of BC. We assessed serum HISLA expression in 40 patients with BC and 20 healthy controls to investigate its roles in BC using quantitative real-time polymerase chain reaction (qRT-PCR). We also assessed measures of correlation of clinical and pathological parameters with prognoses of BC patients. Our findings suggested that serum HISLA expression in BC patients was significantly higher than in healthy controls. Furthermore, high expression of serum HISLA was positively associated with advanced stage lymph node metastasis. Expression of HISLA was reduced in postoperative BC patients' serum samples, compared with preoperative serum samples. Pearson correlation assessments indicated significant correlation between serum HISLA expression and the tissue sample HISLA expression in BC patients. Our findings suggested that serum HISLA may serve as newfound biomarker which could help to improve diagnoses and prognoses for BC-afflicted patients.