Negative Nodes Research Articles

Presence of low volume metastases does not alter management in node-negative, early-stage cervical cancer patients who underwent postoperative adjuvant therapy: A retrospective cohort study

ObjectiveThis study sought to determine if patients with early stage cervical cancer who possessed intermediate-high risk factors (defined by Peters or Sedlis criteria) and had pathologically negative lymph nodes at the time of surgery had higher rates of low volume metastases (LVM) on retrospective ultrastaging. MethodsThis IRB-approved retrospective cohort study collected data via chart review on early stage, surgically-treated node-negative cervical cancer patients who underwent postoperative adjuvant therapy, treated at a single institution from January 2011 through June 2021. Nodal blocks were retrospectively ultrastaged per standard protocol. Descriptive statistics were performed for analysis. ResultsOver the 10-year study period, n = 20 patients met study inclusion criteria. Most patients were white with squamous cell histology, with a mean number of 25.15 (SD = 12) nodes examined on initial pathologic evaluation. 85 % (n = 17) patients were pathologic stage IB. 85 % of the cohort were recommended for adjuvant radiation, with the remaining 15 % for cisplatin-based chemoradiation. LVM in the form of micrometastasis was retrospectively identified in one patient (5 %) who had received whole pelvic radiation and recurred locally within the irradiated field. ConclusionsThis small retrospective series of surgically managed cervical cancer with intermediate-high risk tumor factors identified only 1 patient with LVM, representing 5% of the total population. The biologic importance of ITC and LVM remains unclear in cervical cancer, however this investigation highlights the low incidence even when all nodes are evaluated in a higher risk cohort. The presence of LVM would not have changed management decisions based on this retrospective analysis.

Selection of patients with malignant melanoma for pelvic lymph node dissection (PLND) using CT-PET

In melanoma patients with positive pelvic nodes, pelvic lymph node dissection (PLND) to achieve fully resected disease status facilitates adjuvant-dose systemic therapy and avoids higher treatment doses with greater toxicity. This study aimed to test the accuracy of prediction of nodal involvement of the 2010 joint BAPRAS/BAD guidance compared with Positron Emission Tomography (CT-PET). A retrospective review was undertaken of 26 melanoma patients undergoing PLND by a single surgeon between July 2012 and July 2020. The indications for performing PLND were in accordance with the 2010 guidance, but this was supplemented by CT-PET in 16/26 patients. Of the 26 patients undergoing PLND, 10 underwent surgery based upon the 2010 criteria alone and 16 underwent supplementary CT-PET. 17 patients had positive nodes on histology; of these, 13 had a positive CT-PET. Amongst node-negative patients, only one had a false positive CT-PET. CT-PET was 100% sensitive for pelvic nodal disease and 75% specific, with a positive predictive value for nodal involvement of 92%. Of the 10 patients who underwent PLND without CT-PET, only 4 had positive nodes while 6 patients had negative nodes. The 2010 guidelines remain broad and contributed to negative PLND in a third of our patients (9/26). Hence, the indications for performing PLND need to be revisited. Our series supports PET-CT as being 100% sensitive in the identification of pelvic nodal disease and 75% specific. We recommend that a positive PET-CT should be considered as the primary indication for PLND in melanoma patients.

A nomogram based on ultrasound radiomics for predicting the invasiveness of cN0 single papillary thyroid microcarcinoma.

Up to 15.3% of papillary thyroid microcarcinoma (PTMC) patients with negative clinical lymph node metastasis (cN0) were confirmed to have pathological lymph node metastasis in level VI. Conventional ultrasound (US) focuses on the characteristics of tumor capsule and the periphery to determine whether the tumor has invasive growth. However, due to its small size, the typical features of invasiveness shown by conventional 2-dimensional (2D) US are not well visualized. US-based radiomics makes use of artificial intelligence and big data to build a model that can help improving diagnostic accuracy and providing prognostic implication of the disease. We hope to establish and assess the value of a nomogram based on US radiomics combined with independent risk factors in predicting the invasiveness of a single PTMC without clinical lymph node metastasis (cN0). A total of 317 patients with cN0 single PTMC who underwent US examination and operation were included in this retrospective cohort study. Patients were randomly divided into training and testing set in the ratio of 8:2. The US images of all patients were segmented, and the radiomics features were extracted. In the training dataset, the US with features of minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were selected and radiomics signatures were then established according to their respective weighting coefficients. Univariate and multivariate logistic regression analyses were employed to generate the risk factors of possible invasive PTMC. The nomogram is then made by combining high risk factors and the radiomics signature. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and its clinical application value was assessed by decision curve analysis (DCA). The testing dataset was used to validate the model. In the model, seven radiomics features were selected to establish the radiomics signature. A nomogram was made by incorporating clinically independent risk factors and the radiomics signature. Both the ROC curve and calibration curve showed good prediction efficiency. The area under the curve (AUC), accuracy, sensitivity, and specificity of the nomogram in the training data were 0.76 [95% confidence interval (CI): 0.71-0.82], 0.811, 0.914, and 0.727, respectively whereas the results of the testing dataset were 0.71 (95% CI: 0.58-0.84), 0.841, 0.533, and 0.868. As such, the efficacy of the nomogram in predicting the invasiveness of PTMC was subsequently validated by the DCA. Nomogram based on thyroid US radiomics has an excellent predictive value of the potential invasiveness of a single PTMC without clinical lymph node metastasis. With these promising results, it can potentially be the imaging marker used in daily clinical practice.

The Role of Nonmetastatic Lymph Nodes in the Survival of Colorectal Cancer: A Systematic Review.

In this review, we aim to provide an overview of literature on lymph node (LN) histomorphological features and their relationship with the prognosis in colorectal cancer (CRC). Lymph nodes play a crucial role in the treatment and prognosis of CRC. The presence of LN metastases considerably worsens the prognosis in CRC patients. Literature has shown that the total number of LNs and the number negative LNs (LNnegs) has prognostic value in CRC patients. In esophageal carcinoma, LN size seems to be surrogate of the host antitumor response and a potentially clinically useful new prognostic biomarker for (y)pN0 esophageal carcinoma. A comprehensive search was performed in Pubmed, Embase, Medline, CINAHL, and the Cochrane library in March 2021. The PRISMA guidelines were followed. Only studies focusing on histomorphological features and LN size and their relation to overall survival were selected. A total of 9 unique articles met all inclusion criteria and were therefore included in this systematic review. Six of these studies investigated HMF (eg, paracortical hyperplasia, germinal center predominance, and sinus histiocytosis) and 4 studies LNneg size and their relationship with overall survival. The presence of paracortical hyperplasia and an increased number of large LNnegs is related to a more favorable prognosis in CRC. The results of this systematic review seem to support the hypothesis that there is a relationship between the host antitumor response reflected in different histomorphological reaction patterns visible in LNnegs and LNneg size related to survival in CRC patients.

Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes.Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated.Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types.Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

Invasive Solid Papillary Carcinoma of breast in an elderly male: a rare entity in an uncommon gender - case report and review of literature

Abstract Introduction/Objective Male breast cancers (MBC) account for less than 1% of all breast cancers. Papillary cancers constitute less than 3% of MBCs. Solid papillary carcinoma (SPC) is a rare subtype of papillary cancer with a solid growth pattern associated with fibrovascular cores. SPC is an indolent disease that typically presents in a post- menopausal woman as a central breast mass. Neuroendocrine differentiation, ER/PR positive status and Her-2 neu negative status are characteristic. SPC can be in situ or have invasive components. SPC is a rare entity in men and so far, approximately less than 40 cases of SPC in men have been discussed in literature. Here, we report a rare case of SPC with multiple invasive foci in an elderly male. Methods/Case Report An 84-year-old white male presented with a painless mass in his left breast. Excision biopsy revealed Solid Papillary Carcinoma. He subsequently underwent a Left Modified Radical Mastectomy with Left Sentinel Lymph Node Excision. The final histopathology report showed a background of SPC with multiple invasive foci with largest focus measuring 2 mm. Margins were negative and lymph nodes were negative for malignancy. The tumor was ER and PR positive, Her-2 neu negative and had a Ki-67 proliferation index of 42%. Negative IHC staining for Cytokeratin AE1/AE3 confirmed the absence of metastatic epithelial cells in the examined lymph nodes. Results (if a Case Study enter NA) N/A Conclusion SPC is an uncommon subtype among the papillary lesions of breast. Furthermore, only a few cases of SPC have been reported in men. Despite its rarity, it has a good prognosis and lymph node positivity, distant metastasis and local recurrence are uncommon. However, there is limited data about SPC with invasive components which may behave like other invasive breast lesions leaving management a dilemma for clinicians. We believe this case will add to the scarce existing literature about invasive SPC in men.

Comparison of indocyanine green-near-infrared fluorescence guided and traditional mediastinal lymphadenectomy during radical esophagectomy: A randomized controlled trial

BackgroundThe extent of lymph node dissection during radical esophagectomy remains a controversial topic. Thus, this study mainly aimed to explore the location of sentinel lymph nodes in esophageal squamous cell carcinoma and the application value of the indocyanine green–near-infrared fluorescence system in lymphadenectomy. MethodsThis randomized controlled clinical trial (ClinicalTrials.gov, NCT04615806) included 42 participants without neoadjuvant therapy who were lymph node negative based on positron emission tomography/computed tomography findings. Traditional esophagectomy with indocyanine green–near-infrared fluorescence imaging was performed after injecting 0.5 mL indocyanine green (1.25 mg/mL) into the esophageal submucosa in the 4 peritumoral quadrants. The primary endpoint was to determine the location of the sentinel lymph node in esophageal squamous cell carcinoma based on postoperative pathologic reports. ResultsA total of 40 patients, with 20 in each group, were included in the final analysis. In the indocyanine green group, indocyanine green–near-infrared fluorescence imaging was successful in all subjects. Seven cases (cases 2, 3, 9, 11, 17, 18, and 20) in the indocyanine green group exhibited lymph node metastases, all of which were near-infrared positive. The detection rate, positive predictive value, negative predictive value, sensitivity, and specificity were 100% (20 of 20 cases), 8.7% (13/150), 100% (265/265), 100% (13/13), and 65.9% (265/402), respectively. All near-infrared–negative lymph nodes were nonmetastatic lymph nodes. In addition, the number of mediastinal lymph nodes resected in the indocyanine green group was significantly higher than in the non–indocyanine green group. ConclusionIndocyanine green–near-infrared might be an important and promising technique in predicting sentinel lymph nodes of esophageal squamous cell carcinoma and could significantly improve the detection rate of lymph nodes of esophageal squamous cell carcinoma.

The feasibility of level Ib-sparing intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma and high-risk factors classified based on the International Guideline

Background and PurposeTo examine the feasibility of level Ib-sparing intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) who had high-risk factors classified based on the International Guideline (IG). Materials and MethodsWe evaluated 961 non-metastatic NPC cases based on IG recommendations for prophylactic Ib irradiation. Four high-risk factors were used to categorise patients into three cohorts: A, B, and C. Propensity score matching was used to balance baseline characteristics in Cohort C, resulting in a matched Cohort C. Recurrence rates at level Ib and regional relapse-free survival (RRFS) rates were evaluated. ResultsAmong patients with negative Ib lymph nodes (LNs), 18, 54, 420, and 444 exhibited involvement of structures that drain to level Ib as the first echelon (FES), involvement of the submandibular gland (SMG), level II LNs with radiologic extranodal extension (rENE), and level II nodes with a maximal axial diameter (MAD) ≥ 2 cm, respectively. The recurrence rate was highest in Cohort A (11.1 %). Cohort B had no level Ib recurrence. In matched Cohort C, recurrence rates were low in both groups (Ib-sparing group: 0.6 % vs. Ib-covering group: 0.6 %, P > 0.999). No significant differences were observed in 5-year RRFS rates between the two groups in cohort A (p = 0.208), cohort B (p = 0.905), and matched cohort C (p = 0.423). ConclusionsLevel Ib-sparing IMRT could be performed safely for NPC patients with level II LNs who had rENE and/or MAD ≥ 2 cm. Further research should determine the necessity of level Ib prophylactic irradiation for patients with FES or SMG involvement.

The role of radiotherapy in the management of squamous cell cancer of the penis.

To review the evidence for radiotherapy in the management of primary penile cancer, either as brachytherapy or external beam radiation, and the role of external beam radiotherapy in node positive penile cancer. English language literature was reviewed for the past 3 decades. As penile cancer is uncommon in developed nations, high quality evidence to guide management is limited. Single institution reports often span decades during which time staging systems and treatments have evolved, reducing their relevance to current practice. Successful clinical trials require collaboration not only among disciplines but also among multiple institutions and nations. Radiotherapy is a definitive organ-preserving option for T1-T2 penile cancers. Interstitial brachytherapy is associated with penile preservation in 85% of men at 5years, maintained in 70% by 10years. Results of external radiotherapy are not quite as promising but nonetheless 60% of men will have an intact penis at 5years. Inguino-pelvic external radiotherapy has been reported to increase overall survival when delivered as adjuvant treatment for men with pN3 groin but pN0 pelvic nodes, and improve disease specific survival for those with involved pelvic nodes. InPACT (ECOG-ACRIN_8134) is investigating the role of inguino-pelvic chemo-radiotherapy for men with pN3 inguinal nodes but imaging negative pelvic nodes. Radiotherapy has a well-defined role to play in treatment of squamous cell cancers of other sites, such as vulva, anal canal, uterine cervix and head and neck malignancies. Emerging data support the incorporation of radiotherapy into treatment paradigms for penile cancer.

Comparison of perioperative and histopathologic outcomes among neoadjuvant treatment strategies for locoregional gastric cancer.

The National Cancer Database queried patients who received NAC or NCRT followed by resection for T2-T4 and/or node-positive gastric cancer (2006-2018). Logistic and Poisson regression assessed perioperative (30-day readmission, 30- and 90-day mortality, length of stay [LOS]) and histopathologic outcomes (pathologic complete response [PCR], margin status, and negative pathologic lymph nodes [ypN0]). Kaplan-Meier methods and Cox regression assessed overall survival (OS). Of 9831 patients, 4221 (42.9%) received NAC and 5610 (57.1%) NCRT. There were no differences in perioperative outcomes, apart from patients treated with NCRT exhibiting increased LOS (incidence rate ratio 1.09, 95% confidence interval [CI] 1.03-1.16). Patients who received NCRT were more likely to achieve PCR, margin-negative resection, and ypN0 (all p < 0.05). Median OS was 36.8 months for NAC and 33.6 months for NCRT (p < 0.001). NCRT independently predicted worse OS (vs.NAC, hazard ratio 1.10, 95%CI 1.03-1.18). NCRT was associated with better histologic tumor response although NAC was associated with improved OS. Better understanding prognostication through histologic assessment following neoadjuvant therapy is needed.

Aquaporin 1, Aquaporin 8, and Aquaporin 9 Expressions in Malignant Melanoma: A Possible Correlation with Prognosis and Clinical Outcome.

Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.

Positive predictive value of axillary lymph node cortical thickness and nodal, clinical, and tumor characteristics in newly diagnosed breast cancer patients.

Axillary lymph nodes (LNs) with cortical thickness > 3mm have a higher likelihood of malignancy. To examine the positive predictive value (PPV) of axillary LN cortical thickness in newly diagnosed breast cancer patients, and nodal, clinical, and tumor characteristics associated with axillary LN metastasis. Retrospective review of axillary LN fine needle aspirations (FNAs) performed 1/1/2018-12/31/2019 included 135 axillary FNAs in 134 patients who underwent axillary surgery. Patient demographics, clinical characteristics, histopathology, and imaging features were obtained from medical records. Hypothesis testing was performed to identify predictors of axillary LN metastasis. Cytology was positive in 72/135 (53.3%), negative in 61/135 (45.2%), and non-diagnostic in 2/135 (1.5%). At surgery, histopathology was positive in 84 (62.2%) and negative in 51 (37.8%). LN cortices were thicker in metastatic compared to negative nodes (p < 0.0001). PPV of axillary LNs with cortical thickness ≥ 3mm, ≥ 3.5mm, ≥ 4mm and, ≥ 4.25mm was 0.62 [95% CI 0.53, 0.70], 0.63 [0.54, 0.72], 0.67 [0.57, 0.76] , and 0.74 [0.64, 0.83], respectively. At multivariable analysis, abnormal hilum (OR = 3.44, p = 0.016) and diffuse cortical thickening (OR = 2.86, p = 0.038) were associated with nodal metastasis. In newly diagnosed breast cancer patients, increasing axillary LN cortical thickness, abnormal fatty hilum, and diffuse cortical thickening are associated with nodal metastasis. PPV of axillary LN cortical thickness ≥ 3mm and ≥ 3.5mm is similar but increases for cortical thickness ≥ 4mm. FNA of axillary LNs with cortex < 4mm may be unnecessary for some patients undergoing sentinel LN biopsy.

Label-guided graph contrastive learning for semi-supervised node classification

Semi-supervised node classification is a task of predicting the labels of unlabeled nodes using limited labeled nodes and numerous unlabeled nodes. Recently, Graph Neural Networks (GNNs) have achieved remarkable success in this task. However, GNNs typically have shallow architectures and only consider labeled nodes and their low-order neighbors during training. As a result, the supervision signals from the massive unlabeled nodes remain underutilized. To address this limitation, graph contrastive learning has been applied in semi-supervised node classification, which pulls together positive nodes and pushes away negative nodes in the embedding space. Nevertheless, existing node-level contrastive learning methods usually sample the same node from two augmented views as positive nodes and all different nodes as negative nodes. Consequently, many semantically similar nodes are not sampled as positive nodes but are mistakenly sampled as negative nodes. To tackle this issue, we propose a novel Label-guided Graph Contrastive Learning (LGGCL) training algorithm for semi-supervised node classification. Specifically, we first propose a Label-guided Graph Contrastive Learning framework as the basis of LGGCL training algorithm. Then we incorporate a self-checking mechanism based on deep clustering to ensure the authenticity of the sampled positive nodes. Moreover, we design a reweighting strategy based on the probability distribution of the anchor node to enhance the effect of hard negative nodes. Finally, experimental results on various graph benchmarks demonstrate the superiority of our LGGCL.

Prognostic value of 18F-FDG PET in uterine cervical cancer patients with stage IIICr allocated by imaging

The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB–IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications. The prognostic performance of pretreatment 18F-FDG PET and CT for assessing lymph node metastasis was evaluated by two experienced readers. The PET and CT findings were correlated with the risk of progression-free survival (PFS) and overall survival (OS). Kaplan–Meier survival curves showed that PFS was significantly worse in patients with positive lymph nodes on 18F-FDG PET than in those patients with negative lymph nodes on 18F-FDG PET (p = 0.003), whereas there was no significant difference in PFS between patients with lymph nodes sized ≥ 1 cm and those sized < 1 cm (p = 0.140). Univariate analysis showed that positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006), whereas lymph node size was not significantly associated with poor PFS (p = 0.145). In multivariate analysis, positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006) and was an independent prognostic factor for PFS. 18F-FDG PET offers high prognostic value for patients with stage IIICr allocated by imaging compared with CT, suggesting that 18F-FDG PET might be useful in clinical staging decisions and thus promote optimal diagnostic and therapeutic strategies.

CT Texture Analysis and Node-RADS CT Score of Lymph Nodes in Patients With Perihilar Cholangiocarcinoma.

Texture analysis can provide quantitative imaging markers from computed tomography (CT) images. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of CT texture analysis and the Node-RADS classification to categorize and stage lymph nodes in patients with perihilar cholangiocarcinoma. Overall, 25 patients (n=9 females, 36%) with a mean age of 72.4±8.1 years were included. All patients were surgically resected and the lymph nodes were histopathologically analyzed. CT-texture analysis was performed with the Mazda package. All investigated lymph nodes were scored in accordance with the Node-RADS classification. Regarding lymph node discrimination (N- versus N+), Node-RADS classification achieved an area under the curve (AUC) of 0.86 resulting in a sensitivity of 78% and a specificity of 86%. Multiple investigated texture features were different between negative and positive lymph nodes. The "S(0,1)SumVarnc" achieved the best AUC of 0.75 resulting in a sensitivity of 0.91 and a specificity of 0.67. Correlation analysis showed various statistically significant associations between CT texture features and Node-RADS score. Several CT texture features and the Node-RADS score derived from preoperative staging CT were associated with the malignancy of the hilar lymph nodes and might aid for preoperative staging. This could change surgical treatment planning in hilar cholangiocarcinoma.

SSLpheno: a self-supervised learning approach for gene-phenotype association prediction using protein-protein interactions and gene ontology data.

Medical genomics faces significant challenges in interpreting disease phenotype and genetic heterogeneity. Despite the establishment of standardized disease phenotype databases, computational methods for predicting gene-phenotype associations still suffer from imbalanced category distribution and a lack of labeled data in small categories. To address the problem of labeled-data scarcity, we propose a self-supervised learning strategy for gene-phenotype association prediction, called SSLpheno. Our approach utilizes an attributed network that integrates protein-protein interactions and gene ontology data. We apply a Laplacian-based filter to ensure feature smoothness and use self-supervised training to optimize node feature representation. Specifically, we calculate the cosine similarity of feature vectors and select positive and negative sample nodes for reconstruction training labels. We employ a deep neural network for multi-label classification of phenotypes in the downstream task. Our experimental results demonstrate that SSLpheno outperforms state-of-the-art methods, especially in categories with fewer annotations. Moreover, our case studies illustrate the potential of SSLpheno as an effective prescreening tool for gene-phenotype association identification. https://github.com/bixuehua/SSLpheno.

Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children's Oncology Group Studies AREN03B2 and AREN0532.

The prognostic impact of positive lymph nodes (LN+) and/or singular loss of heterozygosity (LOH) of 1p or 16q were assessed in children with stage III favorable histology Wilms tumor (FHWT) enrolled on AREN0532 or AREN03B2 alone. A total of 635 stage III FHWT vincristine/dactinomycin/doxorubicin (DD4A)-treated patients met inclusion criteria. Event-free survival (EFS) and overall survival are reported overall and by LN sampling, LN status, LOH 1p, LOH 16q, and a combination of LN status and singular LOH. Patients with unknown or positive combined LOH of 1p and 16q status and AREN03B2-only patients with unknown outcomes or treatment other than DD4A were excluded. EFS did not differ by study, supporting pooling. Lack of LN sampling (hazard ratio [HR],2.12; p=.0037), LN positivity (HR,2.78; p=.0002), LOH 1p (HR,2.18; p=.0067), and LOH 16q (HR,1.72; p=.042) were associated with worse EFS. Compared with patients with both LN- and LOH-, those with negative nodes but positive LOH 1p or 16q and those with LN+but LOH- for 1p or 16q had significantly worse EFS (HR,3.05 and 3.57, respectively). Patients positive for both LN and LOH had the worst EFS (HR,6.33; overall group factor, p<.0001). Findings confirm LN+status as an adverse prognostic factor amplified by presence of singular LOH 1p or 16q, supporting study of intensified therapy for patients with LN+ in combination with singular LOH in a prospective clinical trial.

Concordance between Axillary Ultrasound and Sentinel Biopsy in Clinically Node-Negative Early Breast Cancer

Objective: To determine the sensitivity of axillary ultrasound in detecting axillary nodal metastasis in clinically and radiologically uninvolved axillary nodes in early carcinoma breast by comparing with sentinel node biopsy histopathology on frozen section. Study Design: Comparative cross-sectional study Place and Duration of Study: Breast Clinic, CMH, Rawalpindi Pakistan, from Aug 2020 to May 2021. Methodology: Patients included in the study presented with breast cancer lesions with clinically impalpable axillary lymph nodes aged 18-75. Patients with clinically impalpable nodes underwent an ultrasound of the axilla; if suspicious nodes were found, the patient had subsequent axillary node dissection. Sentinel node biopsy (SLNB) was performed on axillary ultrasound in all patients with no suspicious or benign-looking nodes. Histopathological reporting was taken as standard. Lymph nodal status on axillary ultrasound, SLN biopsy and axillary lymph node clearance were documented and analyzed. Results: Twenty-nine patients were included who had benign-looking lymph nodes on axillary ultrasound and underwent sentinel lymph node biopsy. The mean age of the patients was 54.03 ± 7.94. Out of 29 patients, 24(82.8%) patients had negative Sentinel lymph node biopsy, and 5(17.2%) had positive Sentinel lymph node biopsy, who then underwent axillary lymph node dissection. Conclusion: Sentinel lymph node biopsy is the gold standard to determine axillary lymph nodes involved in early carcinoma breast, which seem benign on pre-operative axillary ultrasound.

The prognostic value of the histological shape of tumor negative sentinel nodes in breast cancer.

Sentinel lymph node (SLN) metastasis is an important predictor of prognosis in breast cancer (BC) patients, guiding treatment decisions. However, patients with the same BC subtype and tumor negative SLN (SLNneg) can have different survival outcomes. We hypothesized that the host anti-tumor immune reaction in SLNneg is important and results in morphometrically measurable changes in SLN size or shape which are related to patient prognosis. Surface area, circumference, long axis and short axis were histologically measured in 694 SLNneg from 356 cases of invasive BC and 67 ductal carcinoma in situ cases. The area occupied by fat was categorized as less or more than 50%. The long to short axis (L/S) ratio was calculated. The relationship between SLNneg morphometries and clinicopathological variables like tumor-infiltrating lymphocytes (TILs) within the primary tumor, as well as prognosis at 10 years follow up were analyzed. The mean SLNneg surface area was 78.7mm2, circumference 40.3mm, long axis 13.1mm, short axis 8.2mm and L/S ratio 1.7. Larger surface area, long axis and short axis, including age >55 years were associated with higher body mass index (BMI) and SLN fat over 50% (p<0.003). In invasive BC, a high SLNneg L/S ratio (≥1.9) was related to poorer disease-free (HR=1.805, 95%CI 1.182-2.755, p=0.006) and overall (HR=2.389, 95%CI 1.481-3.851, p<0.001) survival. A low SLNneg L/S ratio (<1.9) was associated with high TILs in the primary BC (≥10%) (p=0.005). However a high TIL count was not of prognostic relevance. This is the first study to suggest that morphometric characteristics of axillary SLNneg, like L/S ratio, could be used to predict prognosis in patients with SLNneg invasive BC of all subtypes. The association between low L/S ratio and high TILs suggest that SLN shape is related to immunological functioning of the SLN and could be used in addition to TIL evaluation. Regarding the dubious role of TILs in hormone receptor positive breast cancer, SLNneg morphometry to gain information about host immune status could especially be of benefit in this subtype. Further studies are warranted to better understand the underlying biological mechanisms.

Sentinel lymph node biopsy in patients with breast cancer. Experience in implementing at the regional level. Priority issues

Background. Despite the fact that sentinel lymph node biopsy (SLNB) in breast cancer patients has become a routine diagnostic procedure, it is still of great interest to researchers, since the priority issues of choosing methodology, equipment, technology, and stages of use are still being discussed. Although all obstacles to this technique implementation into routine clinical practice have been eliminated, SLNB in locally advanced breast cancer is still rarely used. We describe the experience of implementing SLNB in Nizhny Novgorod Regional Clinical Oncology Dispensary. We also discuss organizational, tactical, and practical approaches aimed to minimize the number of errors in technical terms, as well as to choose a multidisciplinary approach to the development of regulations for the examination and treatment of patients with locally advanced breast cancer.Aim. To assess the efficacy of SLNB implementation for patients with locally advanced breast cancer at the regional level.Materials and methods. This study included 500 patients with invasive (T1–2) breast cancer with clinically negative sentinel lymph nodes of all immunohistochemical subtypes that had undergone SLNB and histological examination. Sentinel lymph nodes were visualized using the radioisotope colloid 99mTc-Nanotop. We present the implementation algorithm for this procedure into routine clinical practice and evaluate short-term results.Results. A total of 500 patients have undergone SLNB. The first 30 cases were considered pilot cases, where all patients positive for sentinel lymph nodes additionally underwent standard axillary lymph node dissection. We observed a 100 % concordance of histological results. Then the surgery was routinely performed for all patients from this category. The assessment of short-term surgical outcomes demonstrated significant improvement of the postoperative period, reduced frequency of postoperative complications (persistent seroma of the axillary area to 2.85 %), reduced length of hospital stay (by 52.7 %) and improved functional and aesthetic results in the majority (&gt;62 %) of patients.Conclusion. Our algorithm of SLNB use in patients with breast cancer in routine clinical practice at the regional level allows for rapid method implementation, reduced length of hospital stay, better functional and aesthetic results, and lower incidence of persistent seroma of the axillary area.