A prospective randomized controlled trial to assess the efficacy and safety of prophylactic central compartment lymph node dissection in papillary thyroid carcinoma.

BACKGROUND: The efficacy of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma remains controversial. We performed a randomized controlled trial to evaluate the efficacy and safety of prophylactic central compartment lymph node dissection in patients with papillary thyroid carcinoma. METHODS: In this parallel-group randomized controlled trial, we assessed 101 patients aged 20 to 70 years with small/noninvasive papillary thyroid carcinoma and no clinical metastases or history of cervical surgery/radiation exposure. Randomization ran from April 2015 to November 2017. Data were collected between April 2015 and October 2020. Of the 101 enrolled patients, 50 underwent total thyroidectomy (TTx group) and 51 underwent total thyroidectomy as well as prophylactic central compartment lymph node dissection (TTx+pCND group). Surgical completeness, local recurrence, successful ablation, postoperative complication, and papillary thyroid carcinoma upstaging were compared between the 2 groups. RESULTS: No patient showed structural recurrence after 46.6 ± 9.1 months of follow-up. Both groups had similar rates of surgical completeness and successful ablation. There was no difference in the incidence of complications. More patients were upstaged to pN1a in the TTx+pCND group compared to those in the TTx group (P < .05). CONCLUSIONS: Prophylactic central compartment lymph node dissection detected more lymph node metastases but did not affect recurrence. The 2 groups showed similar outcomes with regard to surgical completeness, successful ablation, and complications. In conclusion, for small/noninvasive papillary thyroid carcinoma without clinical evidence of lymph node metastases, prophylactic central compartment lymph node dissection may not be required if total thyroidectomy is planned.

Medullary thyroid cancer: What is the optimal management of the lateral neck in a node negative patient at index operation?

BACKGROUND: Medullary thyroid cancer is a neuroendocrine malignancy that can occur sporadically or as the result of genomic rearranged during transfection mutations. Medullary thyroid cancer has a higher rate of metastasis than well-differentiated thyroid cancer. Lateral neck dissection is often performed, and its prophylactic use is controversial. METHODS: Single-center, retrospective review (2000-2017) of patients undergoing primary surgical treatment for medullary thyroid cancer who had negative lateral neck imaging preoperatively. Demographics, genetic associations, clinical, and imaging findings were analyzed. Locoregional recurrence, overall recurrence, and overall survival were examined. RESULTS: A total of 110 patients were identified, of which 18 underwent prophylactic lateral neck dissection and 92 did not. Age, sex distribution, preoperative calcitonin levels, and follow-up were similar among groups. Overall recurrence was 20% for no prophylactic lateral neck dissection and 39% for prophylactic lateral neck dissection (P = .46). Most recurrences were locoregional recurrence, 7.6% for no prophylactic lateral neck dissection versus 22% for prophylactic lateral neck dissection (P = .08), half of it being to the lateral neck in both groups. A total of 7 patients from the no prophylactic lateral neck dissection group required treatment for recurrences versus 4 patients in prophylactic lateral neck dissection group (P = .57). Overall survival at 5 years was similar, 43% the no prophylactic lateral neck dissection group and 31% for prophylactic lateral neck dissection group (P = .52). CONCLUSION: Lateral neck dissection has no effect in decreasing locoregional or overall recurrences in medullary thyroid cancer and has no effect in overall survival when performed prophylactically at index surgical intervention.

A retrospective study on prophylactic regional lymphadenectomy versus nodal observation only in the management of dogs with stage I, completely resected, low-grade cutaneous mast cell tumors.

BACKGROUND: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). RESULTS: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. CONCLUSIONS: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.

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.

Independent Risk Factors of Postoperative Lymphatic Leakage in Patients with Gynecological Malignant Tumor: A Single-Center Retrospective Study.

BACKGROUND We aimed this investigation to screen and analyze the risk factors of postoperative lymphatic leakage of gynecological malignant tumors that contribute to the treatment of the diseases. MATERIAL AND METHODS According to the occurrence of lymphatic leakage after an operation, 655 patients with pelvic lymph node and/or abdominal para-aortic lymph node dissection for gynecological malignant tumor were retrospectively analyzed and divided into a case group and a control group. Univariate and multivariate logistic regression analysis were used to screen the effective independent risk factors and establish a clinical prediction model. The differentiation and calibration of the clinical prediction model were evaluated, and we performed internal and external validation of the model with 207 cases. RESULTS The surgeons, the number of removed lymph nodes, the field and range of lymph nodes to be removed, the method of drainage, and postoperative infection are the independent risk factors of lymphatic leakage after lymph node dissection for gynecological malignant tumors. The area under the ROC curve of the clinical prediction model was 0.839 (P<0.001), the calibration Hosmer-Lemeshow test shows χ²=4.381, P=0.821. Through 10-fold cross-validation, the average correct rate of the prediction model was 0.899, the area under the ROC curve of the external verification group was 0.741, and the calibration Hosmer-Lemeshow test showed χ²=12.728, P=0.122. CONCLUSIONS The new logistic prediction model showed a good degree of differentiation and calibration in both the modeling and verification groups, and it can be used for early warning of the occurrence of lymphatic leakage after lymph node dissection.

LncRNA EPB41L4A-AS2 represses Nasopharyngeal Carcinoma Metastasis by binding to YBX1 in the Nucleus and Sponging MiR-107 in the Cytoplasm.

Nasopharyngeal carcinoma (NPC) is known for its potential to progress to the lymph nodes and distant metastases at an early stage. As an important regulator in tumorigenesis biological processes, the functions of lncRNA in NPC tumor development remain largely unclear. In this research, the expression of EPB41L4A-AS2 in NPC tissues and cells was analyzed via real-time quantitative polymerase chain reaction (qRT-PCR). CCK8, colony formation, and EDU experiments were used to determine the viability of NPC cells. Transwell and wound healing assays were performed to test NPC cell migration and invasion. RNA pull-down and mass spectrometry analysis were used to identify potential binding proteins. Then, a popliteal lymph node metastasis model was established to test NPC metastasis. EPB41L4A-AS2 is repressed by transforming growth factor-beta, which is downregulated in NPC cells and tissue. It is associated with the presence of distant metastasis and adverse outcomes. The univariate and multivariate survival assays confirmed that EPB41L4A-AS2 expression was an independent predictor of progression-free survival (PFS) in patients with NPC. Biological analyses showed that overexpression of EPB41L4A-AS2 reduced the metastasis and invasion of NPC in vitro and in vivo, but had no significant effect on cell proliferation. Mechanistically, in the nucleus we identified that EPB41L4A-AS2 relies on binding to YBX1 to reduce the stability of Snail mRNA to enhance the expression of E-cadherin and reverse the progression of epithelial-to-mesenchymal transition (EMT). In the cytoplasm, we found that EPB41L4A-AS2 blocked the invasion and migration of NPC cells by promoting LATS2 expression via sponging miR-107. In a whole, the findings of this study help to further understand the metastasis mechanism of NPC and could help in the prevention and treatment of NPC metastasis.

Transcriptional super-enhancers control cancer stemness and metastasis genes in squamous cell carcinoma.

Cancer stem cells (CSCs) play a critical role in invasive growth and metastasis of human head and neck squamous cell carcinoma (HNSCC). Although significant progress has been made in understanding the self-renewal and pro-tumorigenic potentials of CSCs, a key challenge remains on how to eliminate CSCs and halt metastasis effectively. Here we show that super-enhancers (SEs) play a critical role in the transcription of cancer stemness genes as well as pro-metastatic genes, thereby controlling their tumorigenic potential and metastasis. Mechanistically, we find that bromodomain-containing protein 4 (BRD4) recruits Mediators and NF-κB p65 to form SEs at cancer stemness genes such as TP63, MET and FOSL1, in addition to oncogenic transcripts. In vivo lineage tracing reveals that disrupting SEs by BET inhibitors potently inhibited CSC self-renewal and eliminated CSCs in addition to elimination of proliferating non-stem tumor cells in a mouse model of HNSCC. Moreover, disrupting SEs also inhibits the invasive growth and lymph node metastasis of human CSCs isolated from human HNSCC. Taken together, our results suggest that targeting SEs may serve as an effective therapy for HNSCC by eliminating CSCs.

A population-based analysis of clinical features and lymph node dissection in head and neck malignant neurogenic tumors.

BACKGROUND: The influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors. METHODS: Data of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group. RESULTS: In total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0-91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0-336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79-0.85) and 69.0% (95% CI, 0.64-0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients. CONCLUSIONS: In head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.

Prophylactic Central Neck Dissection in Papillary Thyroid Carcinoma: All Risks, No Reward.

BACKGROUND: Central neck dissection (CND) remains a controversial intervention for papillary thyroid carcinoma (PTC) patients with clinically negative nodes (cN0) in the central compartment. Proponents state that CND in cN0 patients prevents locoregional recurrence, while opponents deem that the risks of complications outweigh any potential benefit. Thus, there remains conflicting results amongst studies assessing oncologic and surgical outcomes in cN0 PTC patients who undergo CND. To provide clarity to this controversy, we sought to evaluate the efficacy, safety, and oncologic impact of CND in cN0 PTC patients at our institution. MATERIALS AND METHODS: Six hundred and ninety-five patients with PTC who underwent thyroidectomy at our institution between 1998 and 2018 were identified using an institutional cancer registry and supplemental electronic medical record queries. Patients were stratified by whether or not they underwent CND; identified as CND(+) or CND(-), respectively. Patients were also stratified by whether or not they received adjuvant radioactive iodine (RAI) therapy. Patient demographics, pathologic results, as well as surgical and oncologic outcomes were reviewed. Standard statistical analyses were performed using ANOVA and/or t-test and chi-squared tests as appropriate. RESULTS: Among the 695 patients with PTC, 492 (70.8%) had clinically and radiographically node negative disease (cN0). The mean age was 50 ± 1 years old and 368 (74.8%) were female. Of those with cN0 PTC, 61 patients (12.4%) underwent CND. CND(+) patients were found to have higher preoperative thyroid stimulating hormone (TSH) values, 2.8 ± 0.8 versus 1.5 ± 0.2 mU/L (P = 0.028) compared to CND(-) patients. CND did not significantly decrease disease recurrence, development of distant metastatic disease (P = 0.105) or persistence of disease (P = 0.069) at time of mean follow-up of 38 ± 3 months compared to CND(-) patients. However, surgical morbidity rates were significantly higher in CND(+) patients; including transient hypocalcemia (36.1% versus 14.4%; P < 0.001), transient recurrent laryngeal nerve (RLN) injury (19.7% vers us 7.0%; P < 0.001), and permanent RLN injury (3.3% versus 0.7%; P < 0.001). CONCLUSIONS: The majority of patients at our institution with cN0 PTC did not undergo CND. This data suggests that CND was not associated with improvements in oncologic outcomes during the short-term follow-up period and led to increased postoperative morbidity. Therefore, we conclude that CND should not be routinely performed for patients with cN0 PTC.

F-18 FDG PET-CT for response evaluation in head and neck malignancy: Experience from a tertiary level hospital in south India.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck cancers. There has been no established qualitative system of interpretation for therapy response assessment using PET-CT for HNSCC. AIM: To assess response evaluation of nodal status in post-treatment PET-CT scans in HNSCC using a 5-point Likert scale (Deauville score [DS]). METHODS AND RESULTS: Retro-prospective analysis was performed of the nodal status of pre and post-RT PET-CT in patients diagnosed with HNSCC (n = 43) from May 2013 to March 2018. All eligible patients underwent a pre-RT PET-CT scan before the start of RT. Another post-RT PET-CT scan was performed 12 weeks after the completion of RT. The median time from completion of radiotherapy (RT) to post-RT PET-CT was 92 days; 80% of the patients had their post-RT PET-CT scan between 77 and 147 days after therapy. Of 43 patients (M/33, F/10, age range 18 to 80 years (median 54 years) selected for the study, good concordance was noted between DS and clinical response in these patients. The change in SUV from pre-RT PET to post-RT PET was analyzed using a paired t-test. The P-value was found to be statistically significant while comparing pre and post-RT SUVmax levels showing that RT had significantly reduced the SUVmax levels of the nodes in DS 2-3 groups whereas the number of patients was too small to allow a reliable calculation in DS 4-5 groups. It was found that 36/39 patients with DS 1-3 had no nodal recurrence showing a high NPV of 92.3%. Of the four patients with DS 4-5, all had active disease showing PPV of 100%. Applying Fisher's exact test, the P-value was found to be .004. CONCLUSION: DS seems to satisfy the requirements for a simple qualitative method of interpreting PET scans and for identifying patients requiring neck dissection. Consensus regarding qualitative assessment would facilitate standardization of PET reporting in clinical practice and enable comparative multicentric studies.

Controlling lymph node micrometastases by neoadjuvant chemotherapy affects the prognosis in advanced esophageal squamous cell carcinoma.

PURPOSE: The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. RESULTS: One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. CONCLUSION: In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.

A DNA nanodevice-based vaccine for cancer immunotherapy.

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA 'locking strands' outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge.

Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer.

OBJECTIVE: Main controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades. METHODS: All consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed. RESULTS: The rate of lymphadenectomy was reduced from 78% in 2001-2012 to 53% in 2013-2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010-2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37-0.65] in 2001-2009 compared to 0.61 [0.45-0.83] in 2010-2019, p = 0.04 and 0.51 [0.39-0.68] to 0.71 [0.60-0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged. CONCLUSIONS: Our study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients.

Prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B.

There is no evidence-based guidance on the extent of prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B (MEN 2B), a newly emerging entity in the molecular era. In this investigation of MEN 2B children who inherited the M918T RET germline mutation from a phenotypically affected MEN 2B parent, 6 MEN 2B children (4 girls and 2 boys) from 5 MEN 2B parents (4 mothers and 1 father) were identified. None of the 6 second-generation MEN 2B children who had preoperative calcitonin serum levels between 2 and 105 pg/mL and underwent prophylactic total thyroidectomy before the age of 4 years after receiving a positive RET gene test harbored node metastases. There was no recurrent laryngeal nerve palsy or postoperative hypoparathyroidism. Within the limitations of this study, total thyroidectomy alone is adequate therapy for second-generation MEN 2B children aged 1-4 years old with preoperative calcitonin serum levels ≤100 pg/mL.

Can laparoscopic spleen-preserving splenic hilar lymph node dissection replace prophylactic splenectomy for proximal advanced gastric cancers that invade the greater curvature?

BACKGROUND AND OBJECTIVES: Proximal advanced gastric cancer that invades the greater curvature is often treated by prophylactic splenectomy because of a risk for metastasis to the splenic hilar lymph node (station No.10). We evaluated whether laparoscopic spleen-preserving splenic hilar dissection (SPSHD) could be a better approach. METHODS: We reviewed records of patients with proximal gastric cancer who underwent total gastrectomy with No.10 dissection between 2012 and 2018 using our in-house database set. We divided patients by whether they had received SPSHD or splenectomy, first to compare surgical outcomes, and subsequently to analyze survival outcomes among patients with tumors invading the greater curvature. RESULTS: Of 145 patients enrolled in this study, 82 had SPSHDs and 63 had splenectomies. All SPSHDs were laparoscopic; 80% of splenectomies were laparotomic. Morbidity ≥ grade III was seen in 8.5% of the SPSHD group and 11.1% of the splenectomy group. The median number of retrieved No. 10 nodes was three in each group. In multivariable analysis, SPSHD was not an independent prognostic factor among patients whose tumors invaded the greater curvature (n = 73). Among propensity-matched cohorts (n = 25 each), 5-year relapse-free survival rates were 77.6% in the SPSHD group and 49.9% in the splenectomy group. CONCLUSION: Laparoscopic SPSHD can potentially replace prophylactic splenectomy.

Platelet-Rich Plasma (PRP) in Breast Cancer Patients: An Application Analysis of 163 Sentinel Lymph Node Biopsies.

INTRODUCTION: Literature shows platelet-rich plasma (PRP) to improve overall outcomes in orthopedics, dermatology, ophthalmology, gynecology, and plastic surgery. Data on oncological patients is very limited. Only one publication is available on PRP in breast cancer patients. This work evaluated PRP in sentinel node biopsy procedures for breast cancer patients in terms of complication rates and oncological short-term follow-up. METHODS: The evaluated PRP was ACP®, i.e., autologous conditioned plasma by Arthrex®. Between 2015 and 2018, 163 patients were offered to receive an ACP®/PRP injection in their lymph node biopsy site. Recruitment resulted in an approximate one-to-one ratio for analysis. Endpoints were major (revision) and minor (seroma, hematoma, and infection) complications rates as well as distant metastases, local recurrence, and overall survival. Median follow-up was 30 months. RESULTS: Complication rates and oncological follow-up showed PRP to be applicable to use in a sentinel node biopsy scenario in breast cancer patients. There were 0 revisions in the ACP®/PRP group and 1.2% revisions in the control group (not significant). Oncological follow-up showed zero (0) distant metastases and local recurrences as well as a 100% 30-month overall survival. CONCLUSIONS: This is the first analysis of ACP®/PRP used in breast cancer patients in a sentinel node biopsy setting worldwide. PRP does not seem to increase rates of local recurrence within this 30-month follow-up time frame. Also, trend towards decreasing complication rates could be shown.

Anlotinib suppresses lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma through a process potentially involving VEGFR-3 signaling.

Objective: Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer. However, few anti-lymphangiogenic drugs have been approved for clinical use to date. Therefore, new therapies to block lymphangiogenesis are urgently required. Methods: Immunohistochemistry, immunofluorescence, Western blot, migration assays, and lymphangiogenesis and lymphatic metastasis assays were used. Results: Anlotinib, a receptor tyrosine kinase inhibitor, suppressed the rate of new metastatic lesions (31.82% in the placebo arm and 18.18% in the anlotinib arm) in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study. D2-40+-lymphatic vessel density was strongly correlated with disease stage, metastasis, and poor prognosis in 144 Chinese patients with lung adenocarcinoma. In mice bearing A549EGFP tumors, tumor lymphatic vessel density, tumor cell migration to lymph nodes, and the number of distant metastatic lesions were lower in the anlotinib group than in the controls. Anlotinib inhibited the growth and migration of human lymphatic endothelial cells (hLECs) and lymphangiogenesis in vitro and in vivo. Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3 (VEGFR-3). Conclusions: Anlotinib inhibits lymphangiogenesis and lymphatic metastasis, probably through inactivating VEGFR-3 phosphorylation. The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma. (Trial registration: ALTER0303; NCT02388919; March 17, 2015.).

ATIP3 deficiency facilitates intracellular accumulation of paclitaxel to reduce cancer cell migration and lymph node metastasis in breast cancer patients.

Taxane-based chemotherapy is frequently used in neoadjuvant treatment of breast cancer patients to reduce tumor growth and lymph node metastasis. However, few patients benefit from chemotherapy and predictive biomarkers of chemoresistance are needed. The microtubule-associated protein ATIP3 has recently been identified as a predictive biomarker whose low levels in breast tumors are associated with increased sensitivity to chemotherapy. In this study, we investigated whether ATIP3 deficiency may impact the effects of paclitaxel on cancer cell migration and lymph node metastasis. Expression levels of ATIP3 were analyzed in a cohort of 133 breast cancer patients and classified according to lymph node positivity following neoadjuvant chemotherapy. Results showed that low ATIP3 levels are associated with reduced axillary lymph node metastasis. At the functional level, ATIP3 depletion increases cell migration, front-rear polarity and microtubule dynamics at the plus ends, but paradoxically sensitizes cancer cells to the inhibitory effects of paclitaxel on these processes. ATIP3 silencing concomitantly increases the incorporation of fluorescent derivative of Taxol along the microtubule lattice. Together our results support a model in which alterations of microtubule plus ends dynamics in ATIP3-deficient cells may favor intracellular accumulation of paclitaxel, thereby accounting for increased breast tumor sensitivity to chemotherapy.

Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion.

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis. RESULTS: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.