Site Of Lymph Node Metastasis Research Articles

Abstract 1388: Spatial transcriptome analysis of EMT trait and corresponding immune composition study in HNSCC

Abstract Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignant cancer worldwide. Conventional treatments for this type of cancer involve surgical resection, radiation therapy, and chemotherapy. However, in cases where the tumor recurs or metastasizes distantly, rendering surgical resection or radiation therapy impractical, the only viable option is the utilization of targeted drugs in conjunction with chemotherapy. Despite such interventions, the prognosis remains grim. Hence, the identification of genetic characteristics or biomarkers associated with easy metastasis or recurrence in the early stages of the tumor has become imperative for effective head and neck cancer treatment. The objective of this study is to analyze tumor specimens from the primary site and lymph node metastasis post-surgical resection in HNSCC patients. We employed the GeoMx Digital Spatial Profiler (DSP) for imaging-based digitized gene expression analysis. The DSP provides gene expression information at specific locations we selected, such as the primary tumor center core, primary tumor invasion borders, and lymph node metastasis specimens. The GeoMx DSP spatial analysis tool illustrates the cancer transcriptome atlas (CTA), encompassing the expression of 1825 genes related to cancer and immunity from the primary site to the metastatic site. We identified tissue-specific EMT gene expression patterns in paired tumor regions of interest (ROIs). ITGB1 emerged as the most significant co-expression marker in the primary outer tumor and metastatic tumor. Distinct EMT signature genes expressed in the HNSCC primary site and lymph node metastatic site were also discovered. Additionally, we conducted CTA profiling in correlated stroma ROIs. Through myeloid activity analysis in HNSCC paired samples, we identified distinct myeloid activation signatures in primary and metastatic site stroma cells. These results will provide crucial insights into head and neck cancer treatment strategies based on different tumor site characteristics. Citation Format: Chih-Hung Chung, Muh-Hwa Yang. Spatial transcriptome analysis of EMT trait and corresponding immune composition study in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1388.

Primary, Nonmidline, Extragonadal, Immature Teratoma of the Palm with Axillary Nodal Metastasis: A Rare Case Report and Review of Literature

AbstractPrimary, nonmidline, extragonadal germ cell tumors are rare. Numerous hypotheses have been proposed regarding their origin. There is lack of consensus regarding their appropriate management. We report a case of an immature teratoma arising of the left palm. A 36-year-old lady presented with a recurrent left palm swelling. Histopathological features with immunohistochemical evaluation were characteristic of an immature teratoma. Alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) were elevated. She received preoperative chemotherapy with bleomycin, etoposide, cisplatin (BEP) followed by wide excision of the palm lesion and reconstruction with free latissimus dorsi flap. Postoperatively, two more cycles of BEP were given. Eight months later, she presented with large left axillary mass which showed metastatic deposits of immature teratoma on trucut biopsy. AFP and LDH were mildly elevated. On staging fluorodeoxyglucose-positron emission tomography (FDG-PET), there were no distant metastases. She received two cycles of vinblastine, ifosfamide, and cisplatin (VeIP). Postchemotherapy FDG-PET showed good metabolic response; however, the mass remained morphologically stable. Complete resection of the axillary mass was achieved with resection of a segment of axillary vein and end-to-end reanastomosis. At 12 months of follow-up the patient is disease free. This is the first report of axillary metastases in immature teratoma of the upper extremity. Axilla is a possible site of lymph node metastases in extremity teratoma. Primary extragonadal germ cell tumor should be managed with complete surgical resection and chemotherapy.

Precise pattern of lymphatic spread of esophageal squamous cell carcinoma: results of 1074 patients with N1 disease.

The route of lymphatic spread in esophageal cancer remains unclear. The present study aimed to determine the pattern of lymphatic metastasis in its early stages. The data were reviewed of 1074 patients who underwent curative esophagectomy for thoracic esophageal squamous cell carcinoma and metastasis in 1-2 lymph nodes between January 2015 and December 2021. The frequencies of lymph node metastasis were analyzed by the anatomic sites and regions involved. Of the 1074 patients, 668 patients (62.2%) with one positive lymph node and 406 (37.8%) with two positive lymph nodes. Paracardial lymph nodes were the most frequently involved nodes (35.1%), followed by right thoracic recurrent nerve nodes (24.0%), middle thoracic paraesophageal nodes (14.7%), left thoracic recurrent nerve nodes (10.4%), subcarinal nodes (8.0%), lower thoracic paraesophageal nodes (7.8%), and upper thoracic paraesophageal nodes (5.7%). The frequency of lymph node metastasis in other sites was less than 3%. The majority of lymph node metastases occurred in the longitudinal direction to the perigastric (36.5%) and bilateral recurrent nerve regions (33.4%) and in the transverse direction to the paraesophageal region (27.7%). As the tumor location changed from the upper to the lower thoracic esophagus, the frequencies of lymph node metastasis decreased in the bilateral recurrent nerve region but increased in the perigastric region. Bilateral recurrent nerve nodes, paraesophageal lymph nodes, and perigastric nodes were the most common sites of early lymph node metastasis. Esophageal squamous cell carcinoma involves more longitudinal than transverse lymph node metastases.

A nomogram incorporating Ki67 to predict survival of acral melanoma

BackgroundThe proliferation marker Ki67 is associated with the progression and prognosis of melanoma. However, its prognostic impact on acral melanoma (AM) remains unclear.MethodsA total of 314 AM patients were enrolled from a cohort of 5758 patients with melanoma at Peking University Cancer Hospital between 2006 and 2018. The patients were divided into Ki67 high- and low-expressing groups using a cut-off value of 30%. The associations between Ki67 and clinicopathologic characteristics as well as survival were analyzed. Cox proportional regression analysis was used to establish a nomogram to predict the survival probabilities of AM.ResultsAmong 314 patients, the Ki67-high group (Ki67 ≥ 30%) included 49.4% of patients at diagnosis. Patients in the Ki67-high group had lower median melanoma-specific survival (MSS) than those in the Ki67-low group (60.7 months vs. not reached, p < 0.001). In multivariate analyses, Ki67, lymph node metastasis and primary site were independent prognostic factors for MSS. The nomogram showed that Ki67 had the fourth greatest impact on survival, following Breslow thickness, lymph node metastasis and primary site. The C-index of the nomogram was 0.765 and 0.758 in the training and validation cohort, respectively. Area under the curve values were both near 0.8 in the training and validation cohorts. Net reclassification improvement and integrated discrimination improvement demonstrated that the predictive nomogram performed better than the traditional AJCC staging system.ConclusionKi67 expression is an independent prognostic factor for MSS in AM. A predictive model incorporating Ki67 and clinical factors was constructed to predict the prognosis of AM.

Risk Factors and Sampling Range Evaluation of Lymph node Metastasis for Non-small Cell Lung Cancer with Diameter ≤2 cm

More early-stage non-small cell lung cancer (NSCLC) are diagnosed in time and treated surgically, but systematic lymph node dissection can not bring enough survival benefits for them, and even increase the probability of postoperative complications. This study aims to analyze the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes for NSCLC with diameter ≤2 cm, so as to provide reference for surgery. We collected 1051 patients with pulmonary nodule diameter ≤2 cm who were treated by pulmonary lobectomy with lymph node sampling/dissection in Department of Thoracic Surgery of the First Affiliated Hospital with Nanjing Medical University from December 2009 to December 2019. SPSS 26.0 statistical software was used for statistical analysis, to explore the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes. 95 of 1051 (9.04%) patients presented lymph node metastasis. Male, pathological non-adenocarcinoma, 1 cm<tumor diameter≤2 cm, spread through air spaces (STAS), visceral pleural invasion (VPI), vascular invasion, low differentiation of adenocarcinoma, and micropapillary or solid adenocarcinoma subtype were the risk factors for lymph node metastasis (P<0.01). Male, 1 cm<tumor diameter≤2 cm, STAS, VPI and vascular invasion were independent risk factors for lymph node metastasis (P<0.05). Lymph node metastasis of #2R, #4R, #9 appeared in upper and middle lobe of right lung (P<0.05), and #7 appeared in right lower lobe (P<0.05). Lymph node metastasis of #5 and #6 in the left upper lobe was more common (P<0.05), while metastasis of #7 and #9 had no significant difference (P>0.05). Lymph nodes in group N1 were significantly correlated with lymph node metastasis in groups #2R, #4R, #5, #6, #7 and #9 (P<0.01). Lobe-specific lymph node dissection (LSND) can be performed for early-stage NSCLC. Male, pathological non-adenocarcinoma, 1 cm<tumor diameter≤2 cm, STAS, VPI, vascular invasion, low differentiation of adenocarcinoma, and micropapillary or solid adenocarcinoma subtype would increase the risk of lymph node metastasis.

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells.

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 μM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 μM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.

Efficacy of adjuvant therapy in patients (pts) with AJCC v8 stage IIIA cutaneous melanoma.

9518 Background: Pts with resected AJCC v8 stage IIIA melanoma have been under-represented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted and immunotherapy in this population is unclear. Methods: In this multicenter, retrospective study, pts with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab (PD1), BRAF/MEK-targeted therapy dabrafenib + trametinib (TT), or no adjuvant treatment (OBS) were included. Recurrence free survival (RFS), distant metastasis free survival (DMFS), and toxicity rates were examined. Results: 613 pts from 34 centers across Australia, Europe and USA were included. The median follow-up was 2.6 yrs (IQR, 1.6-3.4 yrs). Pt characteristics and follow-up were similar across the cohorts (Table). Completion rates of 12-month PD1 and TT therapy were 57.0% and 69.2% respectively. 1-yr RFS was 93.3% (95% CI, 90.3-96.4) in PD1, 100% in TT and 91.3% (95% CI, 88.1-94.7) in OBS cohorts. 2-yr RFS was 79.3% (95% CI, 74.1-84.8) for PD1, 100% for TT and 84.3% (95% CI, 79.9-89.0) in OBS cohorts. 2-yr DMFS was 88.4% (95% CI, 84.3-92.8) in PD1, 100% in TT and 91.1% (95% CI, 87.7-94.7) in OBS cohorts. Risk of recurrence was associated with higher breslow thickness (HR 1.73, 95% CI 1.36-2.20), higher mitotic rate (HR 1.07, 95% CI 1.02-1.12) and neck as the site of nodal metastases (HR 2.71, 95% CI 1.45-5.06) in the overall cohort (p&lt;0.05). Neck nodal metastases were associated with higher risk of recurrence in OBS cohort (HR 3.82, 95% CI 1.91-7.66; p&lt;0.05) but not in the PD1 cohort. Rates of ≥ Grade 3 toxicities were 10.9% with PD1 and 20.0% with TT; discontinuation due to toxicity occurred in 25.0% and 30.0%, respectively. No new safety signals were observed. Rates of unresolved toxicity at last follow-up were 26.9% in PD1 and 7.7% in TT cohorts. Conclusions: In this large international study, adjuvant PD1 or TT did not significantly improve RFS or DMFS compared to OBS in pts with resected stage IIIA melanoma. Prognosis in stage IIIA melanoma is favourable and outcomes after adjuvant therapy in this population needs further study in prospective randomised trials. [Table: see text]

The distribution pattern of pelvic lymph nodal metastases in cervical cancer

PurposeDepiction of pelvic lymph node metastasis (LNM) sites among patients with cervical cancer facilitates accurate determination of the extent of dissection and radiotherapy regimens.MethodsA retrospective study of 1182 cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection between 2008 and 2018 was performed. The number of removed pelvic lymph nodes and metastasis status in different anatomical regions was analyzed. The prognostic difference of patients with lymph node involvement stratified by various factors was analyzed by Kaplan–Meier method.Results The median number of pelvic lymph nodes detected was 22, mainly from obturator (29.54%) and inguinal (21.14%) sites. Metastatic pelvic lymph nodes were found in 192 patients, with obturator accounting for the highest percentage (42.86%). The patients with lymph node involvement in single site had better prognosis that those in multiple sites. The overall- (P = 0.021) (OS) and progression-free (P < 0.001) survival (PFS) curves of patients with inguinal lymph node metastases were worse compared to those with obturator site. There was no difference in the OS and PFS among patients with 2 and more than 2 lymph nodes involvement.ConclusionAn explicit map of LNM in patients with cervical cancer was presented in this study. Obturator lymph nodes tended to be involved. The prognosis of patients with inguinal lymph node involvement was poor in contrast to that with obturator LNM. In patients with inguinal lymph node metastases, clinical staging needs to be reconsidered and extended radiotherapy to the inguinal region needs to be strengthened.

Central node dissection in papillary thyroid carcinoma in the era of near-infrared fluorescence.

The most common site of lymph node metastases in papillary thyroid carcinoma is the central compartment of the neck (level VI). In many patients, nodal metastases in this area are not clinically apparent, neither on preoperative imaging nor during surgery. Prophylactic surgical clearance of the level VI in the absence of clinically suspicious lymph nodes (cN0) is still under debate. It has been suggested to reduce local recurrence and improve disease-specific survival. Moreover, it helps to accurately diagnose the lymph node involvement and provides important staging information useful for tailoring of the radioactive iodine regimen and estimating the risk of recurrence. Yet, many studies have shown no benefit to the long-term outcome. Arguments against the prophylactic central lymph node dissection (CLND) cite minimal oncologic benefit and concomitant higher operative morbidity, with hypoparathyroidism being the most common complication. Recently, near-infrared fluorescence imaging has emerged as a novel tool to identify and preserve parathyroid glands during thyroid surgery. We provide an overview of the current scientific landscape of fluorescence imaging in thyroid surgery, of the controversies around the prophylactic CLND, and of fluorescence imaging applications in CLND. To date, only three studies evaluated fluorescence imaging in patients undergoing thyroidectomy and prophylactic or therapeutic CLND for thyroid cancer. The results suggest that fluorescence imaging has the potential to minimise the risk of hypoparathyroidism associated with CLND, while allowing to exploit all its potential benefits. With further development, fluorescence imaging techniques might shift the paradigm to recommend more frequently prophylactic CLND.

Anatomical site and size of sentinel lymph node metastasis predicted additional axillary tumour burden and breast cancer survival.

Sentinel lymph node (SLN) biopsy is the current standard assessment for tumour burden in axillary lymph node (ALN). However, not all SLN+ patients have ALN metastasis. The prognostic implication of SLN features is not clear. We aimed to evaluate predictive factors for ALN metastasis and the clinical value of SLN features. A total of 228 SLN+ and 228 SLN- (with matched year and grade) cases were included. Clinicopathological features in SLN, ALN and primary tumours, treatment data and survival data were analysed according to ALN status and outcome. Except for larger tumour size and the presence of LVI (both P< 0.001), no significant differences were found in SLN- and SLN+ cases. Only 31.8% of SLN+ cases with ALN dissection had ALN metastasis. The presence of macrometastases (MaM), extranodal extension (ENE), deeper level of tumour invasion in SLN and more SLN+ nodes were associated with ALN metastasis (P≤ 0.025). Moreover, isolated tumour cells (ITC) and level of tumour invasion in SLN were independent adverse prognostic features for disease-free survival and breast cancer-specific survival, respectively. Interestingly, cases with ITC located in the subcapsular region have better survival than those in cortex (OS: χ2 = 4.046, P= 0.044). Our study identified features in SLN, i.e. the level of tumour invasion at SLN and tumour size in SLN as useful predictors for both ALN metastasis and breast cancer outcome. The presence of ITC, particularly those with a deeper invasion in SLN, portended a worse prognosis. Proper attention should be taken for their management.

Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma.

Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites. METHODS AND RESULTS: The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H-scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1-dominant (SCLC-A), NEUROD1-dominant (SCLC-N), ASCL1/NEUROD1 double-negative with POU2F3 expression (SCLC-P), and negative for all three markers (SCLC-I). In whole slides, 40 SCLC-A (52%), 20 SCLC-N (26%), 15 SCLC-P (20%), and two SCLC-I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P=0.0047; NEUROD1, P=0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens. CONCLUSION: The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.

Relationship between prognostic impact of N3 lymph node metastasis at the root of the feeding artery and location of colon cancer

To determine whether N3 nodal involvement predicts outcomes and whether its prognostic implications vary with tumor location in patients with Stage III colon cancer (CC). We defined N3 as lymph node metastases near the bases of the major feeding arteries. We retrospectively examined recurrence rates and patterns by tumor location and sites of lymph node metastases in 57 patients with N3 CC who had undergone curative resections between January 2000 and March 2019. Survival analysis was performed to compare the prognoses of patients with and without N3 lymph node metastasis. Most N3 patients had large tumors (T ≥ 3); five had T2 disease. Recurrence occurred quickly in one patient with T2N3M0 disease. Multivariate survival analysis demonstrated that N3 lymph node metastasis is an independent predictor of poor prognosis in Stage III CC patients (P < 0.001). Categorizing N3 patients according to UICC-TNM staging system does not stratify risk of recurrence (P = 0.970). To investigate the impact of tumor location on recurrence risk, we classified N3 CC into two subtypes according to tumor location: metastasis at the base of the superior mesenteric artery in right-sided CC and inferior mesenteric artery in left-sided CC. The former was found to have a statistically significant poorer prognosis than the latter (P = 0.091). N3 is a robust prognostic marker in CC patients. Recurrence risk varies by tumor location. N3 right-sided CCs with lymph node metastasis at the base of the superior mesenteric artery have poorer prognoses than do N3 left-sided CCs.

Relationship between postoperative nodal skip metastasis of mid-thoracic esophageal squamous cell carcinoma and patient prognosis and its value in guiding postoperative adjuvant treatment.

To evaluate the predictive role of nodal skip metastasis (NSM) in the prognosis of lymph node-positive mid-thoracic esophageal squamous cell carcinoma, and to evaluate the significance of postoperative adjuvant treatment in patients with different sites of metastatic nodes. A retrospective analysis was performed on clinical data of 321 lymph node-positive mid-thoracic esophageal squamous cell carcinoma patients who underwent surgery in the Fourth Hospital of Hebei Medical University. Based on the site and condition of lymph node metastasis by postoperative pathology, the patients were divided into two groups: NSM group and non-NSM (NNSM) group. The propensity score matching (PSM) method was employed to match the two groups. The prognostic factors of patients before and after PSM as well as the effect of different adjuvant treatment modes on the prognosis of patients before and after PSM were analyzed. SPSS 29.0 statistical software was used for analysis. PSM in a 1 : 1 matching ratio was performed, 103 patients were assigned to NSM group and NNSM group respectively. Significant differences were found in the 3- and 5-year OS and DFS between the two groups before PSM, the 3- and 5-year OS also showed a significant difference after PSM (P < 0.05). Multivariate analysis illustrated that gender, postoperative adjuvant treatment mode, N stage and lymph node metastasis were independent risk factors for OS and DFS after PSM (P < 0.05); for NSM patients, postoperative adjuvant chemotherapy and radiotherapy significantly prolonged OS and DFS before and after PSM (P < 0.05). But no significant difference was found in OS and DFS for NNSM patients after PSM (P > 0.05). Postoperative NSM is a good prognostic factor for patients with mid-thoracic esophageal squamous cell carcinoma, postoperative adjuvant chemoradiotherapy was recommended for those group, thereby gaining survival benefits.

Risks and benefits of additional surgery for early gastric cancer in the upper third of the stomach meeting non-curative resection criteria after endoscopic submucosal dissection

BackgroundAdditional surgery is recommended after non-curative endoscopic submucosal dissection for early gastric cancer. However, it is not easy to recommend for tumors located in the upper third of the stomach, because it would be a total or proximal gastrectomy. This study aimed to evaluate the actual risks and benefits of additional gastrectomy for upper third tumors.MethodsWe reviewed the clinicopathological data of patients who underwent total or proximal gastrectomy for early gastric cancer in the upper third of the stomach between March 2002 and January 2021. The incidence of lymph node metastasis and postoperative complications were calculated, and risk factors for lymph node metastasis were identified using logistic regression analysis. Survival rates were analyzed using the Kaplan–Meier method and log-rank test.ResultsA total of 523 patients underwent total or proximal gastrectomy for early gastric cancer; 379 of them had tumors meeting the non-curative resection criteria for endoscopic submucosal dissection. The overall lymph node metastasis rate was 9.5%, and lymphovascular invasion was the only significant risk factor for lymph node metastasis (p < 0.001). The most common sites of lymph node metastasis were stations 1, 3, and 7, with their rates being 3.2%, 3.7%, and 3.2%, respectively. Overall and severe (Clavien–Dindo grade III or higher) postoperative complication rates were 21.1% and 14.0%, respectively, while postoperative mortality was 0.5% (2/379). The 5-year overall survival rates for patients with and without lymph node metastasis were 96.1% and 81.1%, respectively (p = 0.076).ConclusionsBefore planning an additional gastrectomy after non-curative endoscopic resection for the upper third tumor, we should consider both the benefit of the 9.5% curability for lymph node metastasis and the risks of the 21% postoperative complications and 0.5% mortality.

Pattern and prognostic value of lymph node metastasis in sinonasal mucosal melanoma.

To analyze the pattern of lymph node (LN) metastasis and its effect on prognosis in sinonasal mucosal melanoma (SNMM). This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) Program data. Survival outcomes were analyzed using the Kaplan-Meier method. Factors were compared between groups using log-rank test and Fisher's exact test, and prognostic factors were screened using the Cox proportional hazards model. Propensity score matching (PSM) was conducted to examine the treatment differences after accounting for sex, age, race, T stage, N stage, and M stage. Level I (57.1%) and level II (53.6%) nodes were the most common sites of lymph node metastasis, followed by level III (17.9%) and IV (17.9%) nodes. T stage, M stage, and tumor size were associated with LN metastasis. The 5-year overall survival rates for patients without and with LN metastasis were 35.2% and 5.3%, respectively. Level I and II lymph nodes may be the sentinel nodes of SNMM, Advanced T stage and increasing tumor size could promote LN metastasis. LN metastasis may promote distant metastasis and remains an important prognostic factor for patients with SNMM.

Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma

ObjectiveLittle is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis. MethodsAll patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors. ResultsOf 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)—in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)—was associated with increased risk of recurrence. ConclusionsOne-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Progression-free survival, PFS, depending on the site of lymph-node metastases in patients after salvage lymph node dissection, sLAD, in lymph node only recurrent prostate cancer.

131 Background: To analyze the influence of anatomic site in patients with lymph node only recurrent disease in 68Ga-PSMA-PET. Methods: We retrospectively analyzed PFS after salvage lymph node dissection in 98 patients. Patients were stratified to Group 1 advanced (retroperitoneal) (=9), Group 2 atypical (pararectal, presacral)(n=5), Group 3 typical (A iliaca externa, interna, Fossa obturator, A iliaca communis) (n=74) and Group 4 multifocal (combination of all groups)(n=10) recurrence. There were no statistically significant differences in the four patient groups in preoperative clinical parameters. Results: The most obvious PSA reduction after sLAD could have been demonstrated in patients with atypically located lymph node metastases (3.6ng/ml to 0.25ng/ml) although this did not reach statistic significance. Patients in the advanced group showed stable PSA values (3,55ng/ml to 3.26ng/ml). Significant results are seen in Group3 (2,52ng/ml to 1,7ng/ml)(p=0.01). Even patients with multifocal disease had a significant decrease in PSA (3.24ng/ml to 1.41ng/ml). 6- and 12 months PFS for Group 1-4 was 41.7% and 13.9%, 60% and 40%, 52.7% and 25.7% and 60% and 40% respectively. Conclusions: SLAD is an individual treatment approach for patients with lymph node only recurrent disease after radical prostatectomy and or radiotherapy. In our preliminary results we could not demonstrate a significant difference in early oncologic results in the four patient groups. Nevertheless, there might be an influence by patient numbers in the different groups so that a validation in a larger cohort is recommended.

The Site of Lymph Node Metastasis: A Significant Prognostic Factor in Pancreatic Ductal Adenocarcinoma.

While the presence and number of metastatic lymph nodes (LNs) are important prognostic factors for pancreatic ductal adenocarcinoma (PDAC), there is no recommendation to specify metastatic regional LN localization in the current staging system. The aim of this study was to evaluate the prognostic effect of regional metastatic LN localizations in PDAC. Metastatic sites of 101 consecutive PDAC patients who underwent pancreaticoduodenectomy were classified as peripancreatic, perigastric, hepatica communis, hepatoduodenal, and superior mesenteric artery. The frequency of metastasis in each region and the association between the presence of metastasis in each site and overall and disease-free survival were statistically analyzed. Eighty cases (79.2%) had peripancreatic, 7 (6.9%) had perigastric, 6 (5.9%) had hepatica communis, 7 (6.9%) had hepatoduodenal, and 4 (4%) had superior mesenteric artery LN metastasis. The overall and disease-free survival values were significantly shorter in patients with hepatoduodenal LN metastasis (log rank; p= 0.001, p=0.017, respectively). The presence of metastatic superior mesenteric artery LN was significantly associated with shorter disease-free survival in univariate analysis (p=0.017). Hepatoduodenal LN metastasis was an independent predictor of mortality (p=0.005) in multivariate analysis. The presence of hepatoduodenal LN metastasis is an independent poor prognostic factor for mortality. The presence of metastatic LN in the superior mesenteric artery region was significantly associated with shorter disease-free survival time, although not an independent predictor. We conclude that the metastatic regional LN sites, especially the hepatoduodenal region, have an impact on the prognosis, and should be included in synoptic pathology reports.

B7-1 and programmed cell death-ligand 1 in primary and lymph node metastasis lesions of non-small cell lung carcinoma.

BackgroundProgrammed cell death ligand 1 (PD‐L1) status has been reported to be different between metastatic and primary lesions in some cases. Therefore, the interaction between carcinoma and immune cells could influence their expression in the tumor microenvironment. PD‐L1 is known to bind not only to Programmed cell death 1 (PD‐1) but also to B7‐1 (CD80). In this study, we examined the interaction between lung carcinoma cell lines and peripheral blood mononuclear cells (PBMCs) in vitro. We then examined the significance of B7‐1 expression non‐small cell lung cancer (NSCLC) microenvironment.MethodsThe interaction of lung carcinoma cell lines and PBMC through the soluble factors was analyzed using a co‐culture system. The changes in expression of immune checkpoint‐related factors in PBMC were examined by PD‐1/PD‐L1 Checkpoint Pathway qPCR Array Kit. B7‐1 expression in NSCLC tissues was examined by immunohistochemistry.ResultsB7‐1 was upregulated following the co‐culture with the lung carcinoma cell lines. B7‐1 expression in NSCLC tissues was significantly higher in smokers and squamous cell carcinomas and was significantly positively correlated with PD‐L1 status in primary cancer. However, B7‐1 and PD‐1 were not correlated between primary and metastatic diseases in the same patients.ConclusionPD‐1 inhibitors inhibited PD‐1/PD‐L1 binding but not PD‐L1/B7‐1 binding. These results demonstrated that the intratumoral ratio of B7‐1 positive T cells in NSCLC tissue could be involved in the therapeutic efficacy of PD‐L1 inhibitors. This study focused on lymph node metastasis but other sites of distant metastases should be explored by further analysis.

Lysine Demethylase 6B Regulates Prostate Cancer Cell Proliferation by Controlling c-MYC Expression.

Elevated expression of lysine demethylase 6A (KDM6A) and lysine demethylase 6B (KDM6B) has been reported in prostate cancer (PCa). However, the mechanism underlying the specific role of KDM6A/B in PCa is still fragmentary. Here, we report novel KDM6A/B downstream targets involved in controlling PCa cell proliferation. KDM6A and KDM6B mRNAs were higher in prostate adenocarcinoma, lymph node metastatic site (LNCaP) but not in prostate adenocarcinoma, bone metastatic site (PC3) and prostate adenocarcinoma, brain metastatic site (DU145) cells. Higher KDM6A mRNA was confirmed at the protein level. A metastasis associated gene focused oligonucleotide array was performed to identify KDM6A/B dependent genes in LNCaP cells treated with a KDM6 family selective inhibitor, ethyl-3-(6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-ylamino)propanoate (GSK-J4). This identified five genes [V-myc myelocytomatosis viral oncogene homolog (avian) (c-MYC), neurofibromin 2 (merlin) (NF2), C-terminal binding protein 1 (CTBP1), EPH receptor B2 (EPHB2), and plasminogen activator urokinase receptor (PLAUR)] that were decreased more than 50% by GSK-J4, and c-MYC was the most downregulated gene. Array data were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), which detected a reduction in c-MYC steady state mRNA and prespliced mRNA, indicative of transcriptional repression of c-MYC gene expression. Furthermore, c-MYC protein was also decreased by GSK-J4. Importantly, GSK-J4 reduced mRNA and protein levels of c-MYC target gene, cyclinD1 (CCND1). Silencing of KDM6A/B with small interfering RNA (siRNA) confirmed that expression of both c-MYC and CCND1 are dependent on KDM6B. Phosphorylated retinoblastoma (pRb), a marker of G1 to S-phase transition, was decreased by GSK-J4 and KDM6B silencing. GSK-J4 treatment resulted in a decrease in cell proliferation and cell number, detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay and conventional cell counting, respectively. Consequently, we conclude that KDM6B controlling c-MYC, CCND1, and pRb contribute regulation of PCa cell proliferation, which represents KDM6B as a promising epigenetic target for the treatment of advanced PCa. SIGNIFICANCE STATEMENT: Lysine demethylase 6A (KDM6A) and 6B (KDM6B) were upregulated in prostate cancer (PCa). We reported novel KDM6A/B downstream targets controlling proliferation. Amongst 84 metastasis associated genes, V-myc myelocytomatosis viral oncogene homolog (avian) (c-MYC) was the most inhibited gene by KDM6 inhibitor, ethyl-3-(6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-ylamino)propanoate (GSK-J4). This was accompanied by decreased c-MYC targets, cyclinD1 (CCND1) and phosphorylated retinoblastoma (pRb), which were KDM6B dependent. GSK-J4 decreased proliferation and cell counting. We conclude that KDM6B controlling c-MYC, CCND1, and pRb contribute regulation of PCa proliferation.