Node-negative Group Research Articles

Short-term outcomes of 47 selective laparoscopic lymph node dissection for rectal cancer: A retrospective study.

This study aims to analyze the safety, feasibility, and short-term oncology outcomes of selective laparoscope lateral lymph node dissection (LLND) with total mesorectal excision surgery. Between December 2019 and May 2023, LLND with total mesorectal excision surgery was performed in 47 selected patients with advanced rectal cancer. Surgical complications and 2-year oncology survival outcomes were analyzed in the study. All 47 procedures were technically successful without converting conversion to open surgery. The mean operation time was 200.6 minutes (135-321 minutes), and the mean estimated blood loss was 92.9 mL (range 10-2000 mL). The most common postoperative complications were anastomotic (8.5%, n = 4), ileus (6.4%, n = 3), and chyle leakage (4.3%, n = 2). Lateral pelvic lymph node metastases were found in 19 (40.4%) patients. When divided into lateral pelvic lymph node positive and negative groups, there was no significant impact on overall survival (94.4% vs 100%, Log-rank P = .596) and local recurrence-free survival (LFRS) (76.7% vs 89.6%, Log-rank P = .210), except disease-free survival (DFS) (58.3% vs 90.2%, Log-rank P = .005). Subgroup analysis showed similar short-term survival outcomes between the pN+ group and the internal iliac metastasis group (Log-rank P of overall survival, LFRS, and DFS were all ˃.05). LRFS and DFS in the obturator or external iliac metastasis group were worse than those in the internal iliac metastasis group when the follow-up time was extended (Log-rank P of LFRS and DFS were .05 and .063). Selective laparoscopy LLND for rectal cancer is safety and feasibility, and its complications are manageable. Oncology survival outcomes for lateral pelvic lymph node metastases limited to the internal iliac are similar to the pN+ stage; therefore, it should be treated positively.

Prognostic Significance of EGFR, HER2, and c-Met Overexpression in Surgically Treated Patients with Adenocarcinoma of the Ampulla of Vater.

Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35-6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94-16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56-6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments.

Risk Factors for Lymph Node Metastasis in a Western Series of Patients with Distal Early Gastric Cancer.

Background: Assessment of potential lymph node metastasis is mandatory in the appropriate treatment of early gastric cancers. This study analysed factors associated with lymph node metastasis to identify differences between node-negative and node-positive patients and between T1a and T1b cancers. Methods: The clinicopathological features of 129 early gastric cancer patients who had undergone radical gastrectomy were analysed to identify predictive factors for lymph node metastasis. Results: Lymph node metastasis was detected in 76 (59.0%) patients. Node-positive patients were younger (58.1 ± 11.3 years) than those without metastasis (61.9 ± 9.6 years, p = 0.02). Greater tumour sizes were observed in patients with lymph node metastasis (3.6 ± 1.0 cm) compared to node-negative patients (1.9 ± 0.5 cm, p = 0.00001). Depressed form, ulceration, diffuse histological type, and undifferentiated lesions were more frequent in node-positive patients than in the node-negative group. Tumour size > 3.0 cm showed a correlation with lymph node metastasis in both T1a (p = 0.0001) and T1b (p = 0.006) cancer. The male sex (p = 0.006) had a significant correlation with lymph node metastasis in T1a cancer. Depressed appearance (p = 0.02), ulceration (p = 0.03), differentiation (p = 0.0001), diffuse type (p = 0.0002), and lower third location (p = 0.005) were associated with lymph node metastasis in T1b cancer. Conclusions: Tumour size > 3 cm, undifferentiated lesions, ulceration, diffuse type, lower third location, and submucosal invasion are risk factors for lymph node metastasis in early gastric cancer.

Lymph Node Isolated Tumor Cells in Patients With Endometrial Cancer

Isolated tumor cells (ITCs) are the histopathological finding of small clusters of cancer cells no greater than 0.2 mm in diameter in the regional lymph nodes. For endometrial cancer, the prognostic significance of ITCs is uncertain. To assess clinico-pathological characteristics and oncologic outcomes associated with ITCs in endometrial cancer. This retrospective cohort study using the National Cancer Database included patients with endometrial cancer who had primary hysterectomy and nodal evaluation from 2018 to 2020. Patients with microscopic and macroscopic nodal metastases and distant metastases were excluded. Data were analyzed from June to September 2023. Regional nodal status with ITCs (N0[i+] classification) or no nodal metastasis (N0 classification). (1) Clinical and tumor characteristics associated with ITCs, assessed with multivariable binary logistic regression model, and (2) overall survival (OS) associated with ITCs, evaluated by nonproportional hazard analysis with restricted mean survival time at 36 months. A total of 56 527 patients were included, with a median (IQR) age of 64 (57-70) years. The majority had T1a lesion (37 836 [66.9%]) and grade 1 or 2 endometrioid tumors (40 589 [71.8%]). ITCs were seen in 1462 cases (2.6%). In a multivariable analysis, ITCs were associated with higher T classification, larger tumor size, lymphovascular space invasion (LVSI), and malignant peritoneal cytology. Of those tumor factors, LVSI had the largest association with ITCs (7.9% vs 1.4%; adjusted odds ratio [aOR], 4.37; 95% CI, 3.87-4.93), followed by T1b classification (5.3% vs 1.3%; aOR, 2.62; 95% CI, 2.30-2.99). At the cohort level, 24-month OS rates were 94.3% (95% CI, 92.4%-95.7%) for the ITC group and 96.1% (95% CI, 95.9%-96.3%) for the node-negative group, and the between-group difference in expected mean OS time at 36 months was 0.35 (SE, 0.19) months, but it was not statistically significant (P = .06). There was a statistically significant difference in OS when the low-risk group (stage IA, grade 1-2 endometrioid tumors with no LVSI) was assessed per nodal status and adjuvant therapy use (P < .001): (1) among the cases treated with surgical therapy alone, 24-month OS rates were 95.9% (95% CI, 89.5%-98.5%) for the ITC group and 98.8% (95% CI, 98.6%-99.0%) for the node-negative group, and the between-group mean OS time difference at 36 months was 0.61 (SE, 0.43) months (P = .16); and (2) among the cases with ITCs, adjuvant therapy (radiotherapy alone, systemic chemotherapy alone, or both) was associated with improved survival compared with no adjuvant therapy (24-month OS rates, 100% vs 95.9%; between-group mean OS time difference at 36 months, 0.95 [SE, 0.43] months; P = .03). In this cohort study of patients with surgically staged endometrial cancer, the results of exploratory analysis suggested that presence of ITCs in the regional lymph node may be associated with OS in the low-risk group. While adjuvant therapy was associated with improved OS in the low-risk group with ITCs, careful interpretation is necessary given the favorable outcomes regardless of adjuvant therapy use. This hypothesis-generating observation in patients with low-risk endometrial cancer warrants further investigation, especially with prospective setting.

Lepidic-Type Lung Adenocarcinomas: Is It Safe to Observe for Growth Before Treating?

BackgroundLepidic-type adenocarcinomas (LPAs) can be multifocal, and treatment is often deferred until growth is observed. This study investigated the potential downside of that strategy by evaluating the relationship of nodal involvement with tumor size and survival. MethodsThe impact of tumor size on lymph node involvement and survival was evaluated for National Cancer Database patients who underwent surgery without induction therapy as primary treatment for cT1-3 N0 M0 histologically confirmed LPA from 2006 to 2019 by using logistic regression, Kaplan-Meier, and Cox analyses. ResultsPositive nodes occurred in 442 of 8286 patients (5.3%). The incidence of having positive nodes approximately doubled with each 1-cm increment increase in size. Patients with positive nodes were more likely to have larger tumors (27 mm vs 20 mm, P < .001) and clinical ≥T2 disease (40.7% vs 26.8%, P < .001) compared with node-negative patients. However, tumor size was the only significant independent predictor of having positive nodal disease in logistic regression analysis, and this association grew stronger with each incremental centimeter increase in size. Patients with positive nodes were more likely to undergo adjuvant radiotherapy (23.5% vs 1.1%, P < .001) and chemotherapy (72.9% vs 7.9%, P < .001), and expectedly, had worse survival compared with the node-negative group in univariate (5-year overall survival, 50.9% vs 81.1%, P < .001) and multivariable (hazard ratio, 2.56; 95% CI, 2.14-3.05; P < .001) analyses. ConclusionsNodal involvement is relatively uncommon in early-stage LPAs but steadily increases with tumor size and is associated with dramatically worse survival. These data can be used to inform treatment decisions when evaluating LPA patients.

Predictive Factor of Tumor Aggressiveness in Patients with Extrahepatic Cholangiocarcinoma Based on Diffusion-weighted MRI.

Extrahepatic cholangiocarcinoma (EHCC), an exceedingly malignant neoplasm, often eludes early detection, culminating in a dire prognosis. Accurate cancer staging systems and pathological differentiation are designed to guide adjuvant interventions and predict postoperative prognoses. This study sought to investigate the predictive capacity of DW-MRI in discerning T stages, lymph node metastasis, and pathological differentiation grades in patients with EHCC. Eighty-five patients were pathologically diagnosed with EHCC and underwent abdominal MRI within two weeks before surgery at our hospital from Aug 2011 to Aug 2021. Tumor axial maximum area (AMA) and apparent diffusion coefficient (ADC) values for diverse T stages, N stages, and differentiation grades were retrospectively analyzed. The Mann-Whitney U test displayed significantly higher lesion AMA values (P =0.006) and lower tumor ADC values (P = 0.001) in the nodepositive group (median ADC and AMA value: 1.220×10-3 mm2/s, 82.231 mm2) than in the node-negative group (median ADC and AMA value: 1.316×10-3 mm2/s, 51.174 mm2). A tumor ADC value<1.249×10-3 mm2/s from the receiver operating characteristic curve (AUC=0.725, P=0.001) exhibited the capability to predict node-positive EHCC with a sensitivity of 64.29%, and specificity of 73.68%. Furthermore, a progressive decrease in the degree of EHCC differentiation was associated with a reduction in the tumor ADC value (P=0.000). The N stage and differentiation of EHCC can be evaluated non-invasively using diffusion-weighted MRI.

Prediction of axillary lymph node metastasis using tumor volume to breast volume ratio: retrospective cohort study.

Tumour size appear to be a risk factor of axillary lymph node metastasis in breast cancer. Recent evidence shows that higher the T staging is associated with higher rate of axillary lymph node metastasis. However, no studies shows that in the same T staging or tumour size but different breast size or breast volume the incidence of axillary lymph node metastasis differ or not . This Study aimed to investigate the association between tumour to breast ratio in breast cancer as a predictive factor of axillary lymph node metastasis. This study included 200 consecutive patients diagnosed with breast cancer between January 2012 to march 2022. The authors retrospectively reviewed medical data pathologic report and Ultrasonography and mammography of breast. Tumour diameter reported in pathologic report was used to calculate tumour volume using formula for ellipse. Breast volume was calculate using formula referencing from study of Jack W. Rostas et all by formula Breast Volume=1/3׶×Radius2ccview×Heightccview by measuring from mammography of patient. Tumour volume to breast volume ratio was calculated and analyzed. Of 200 patient included in this study, 84 patient (42%) was in lymph node positive group and 116 patient (58%) was in lymph node-negative group. Median for tumour and breast volume ratio in node positive group was higher [median 0.0093 (interquartile range=0.0047-0.023)] than in node-negative group [median 0.0065 (interquartile range (0.0028-0.0199)]. P=0.0414 receiver operating characteristic curve for tumour to breast ratio showed AUC of 0.7389 (95% CI 0.67993-0.82335) Which seems to be a significance as predictive factors for Axillary lymph node metastasis. Higher tumour volume to breast volume ratio tends to be a significance predictive factors for axillary lymph node metastasis in breast cancer patients.

Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

Axillary Downstaging and the Impact of Clinical Axillary Status on Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis.

Background: Lymph node downstaging and the achievement of total-pCR (ypT0/is ypN0) after neoadjuvant therapy are of great importance in HER-2 positive breast cancer. We aim to provide an overall review of neoadjuvant regimens for lymph node downstaging and to indirectly compare the total-pCR by various neoadjuvant regimens with network meta-analysis in HER2-positive patients according to their clinical lymph node status. Methods: Five English databases were searched comprehensively and systematically for relevant RCTs and case-control studies. The data extracted from the included studies were analyzed with the use of Review Manager 5.3 or STATA 15.0 software. Results: A total of 1508 published manuscripts were identified, and 17 studies including 4747 patients were finally included in our analysis. The network meta-analysis of total-pCR showed that dual-target therapy is significantly better than single-target therapy in clinically node-positive patients, and carboplatin performed significantly better than anthracycline in single-target condition. Lapatinib performed poorly in clinically node-positive patients. However, lapatinib in combination with trastuzumab was ranked at the top in the clinically node-negative group, and pertuzumab showed dissatisfied performance in contrast to the primacy of pertuzumab in clinically node-positive groups. Conclusion: In summary, different lymph node statuses led to the diverse first choice of neoadjuvant regimen. We highly recommended TCbHP as the first choice for the neoadjuvant treatment in clinically node-positive HER-2 positive breast cancer. Since lapatinib with trastuzumab ranked top in the clinically node-negative group, we looked forward to discovering the potential value of TKI in clinically node-negative patients, which needs further analysis in the future.

Identification and validation of DNA methylation markers to predict axillary lymph node metastasis of breast cancer.

Axillary lymph node metastasis (ALNM) is one of the most important prognostic factors for breast cancer patients, and DNA methylation is involved in ALNM of breast cancer. However, the methylation profile of breast cancer ALNM remains unknown. Breast cancer tissues were collected from patients with and without ALNM. We investigated the genome-wide DNA methylation profile in breast cancer with and without ALNM using reduced representation bisulfite sequencing (RRBS). Then, differentially methylated regions (DMRs) were verified by targeted bisulfite sequencing. A total of 21491 DMRs were identified between the lymph node positive group and negative group. Compared to the LN-negative breast cancer, LN-positive breast cancer had 10,920 hypermethylated DMRs and 10,571 hypomethylated DMRs. Then, 10 DMRs in the gene promoter region were detected by targeted bisulfite sequencing, these gene included HOXA5, PTOV1-AS1, RHOF, PAX6, GSTP1, RASGRF2, AKR1B1, BNIP3, CRMP1, ING5. Compared with negative lymph node, the promoter methylation levels of RASGRF2, AKR1B1 and CRMP1 increased in positive lymph node, while the promoter methylation level of RHOF decreased in positive lymph node. In addition, Cancer Genome Atlas (TCGA) data showed that RASGRF2, AKR1B1 and CRMP1 were low expressed in breast Cancer tissues, while RHOF was high expressed in breast Cancer tissues. Furthermore, in addition to highly methylated AKR1B1, RASGRF2 and CRMP1 gene promoters, BNIP3, GSTP1, HOXA5 and PAX6 gene promoters were also methylated in ER-positive and HER2-negative breast cancer with ALNM. When compared to negative lymph node breast cancer, the positive lymph node breast cancer has a differential methylation status. Promoter methylation of RASGRF2, AKR1B1, CRMP1 and RHOF in lymph node positive breast cancer tissues was significantly different from that in lymph node negative breast cancer tissues. AKR1B1, RASGRF2, CRMP1, BNIP3, GSTP1, HOXA5 and PAX6 genes were methylated in ER-positive and HER2-negative breast cancer with ALNM. The study provides an important biological base for understanding breast cancer with ALNM and developing therapeutic targets for breast cancer with ALNM.

Predictability of lymph node involvement in uterus-confined endometrioid endometrial cancer by tumour size, pattern and location measured with transvaginal ultrasonography: can we save time?

We aimed to investigate whether transvaginal ultrasonography (TVUSG)-measured tumour size, pattern and location were significant predictors for lymph node metastasis in the uterus-confined endometrioid endometrial cancer (EEC) patients. A total of 213 patients with EEC were recruited and 73 of them were considered eligible and were analysed according to lymph node involvement. Tumour size, pattern and location measured by transvaginal ultrasound were recorded. Thereafter, patients were distributed according to their lymph node involvement and were compared with respect to these parameters. The patients’ median age was 56 (27–80). Mean of the resected lymph nodes was 29.68 and 33.5 in lymph-node-negative and positive patients, respectively (p=.525). Tumour diameter was measured >2 cm on transvaginal ultrasound in 28 (48.3%) and 13 (86.7%) cases of the lymph node-negative and positive arms, respectively (p=.008). Transvaginal ultrasound revealed that 18 (31.0%) tumours in lymph node-negative and two (13.3%) in the node positive patients had polypoid pattern (p=.171). Seventeen (54.8%) tumours of the lymph node-negative group and three (42.9%) of the node positive group were determined in the lower uterine segment (p=.250). While tumour diameter measured with TVUSG was predictable for lymph node involvement in the uterus-confined EEC, its pattern and location were not. Impact Statement What is already known on this subject? In clinically early-stage endometrioid endometrial cancer (EEC), it has been recognised for decades that selective lymphadenectomy is a more acceptable strategy than the systematic lymphadenectomy, owing to the low rate of lymph node metastases in the patients. Preoperative imaging, frozen section and recently accepted lymph node concept are the prominent methods in designating appropriate candidates for lymphadenectomy. The measurement of tumour diameter or size obtained intraoperatively by frozen section assessment is one of the parameters used in MAYO criteria for selective lymphadenectomy in endometrial cancer patients. What do the results of this study add? In our study, tumour diameter measured with transvaginal ultrasonography was predictable for lymph node involvement in the uterus-confined EEC. What are the implications of these findings for clinical practice and/or further research? Transvaginal ultrasonography-measured tumour diameter can be considered in deciding to proceed with pelvic lymphadenectomy while waiting for the frozen section result. It should be remembered that this approach could be considered only in clinics using MAYO criteria for selective lymphadenectomy, and it needs to be confirmed with more prospective studies.

Significance of the Number and the Location of Metastatic Lymph Nodes in Locally Recurrent or Persistent Cervical Cancer Patients Treated with Salvage Hysterectomy plus Lymphadenectomy.

We retrospectively investigated the significance of metastatic lymph nodes in patients with locally recurrent or persistent cervical cancer in a previously irradiated field and subsequently had salvage hysterectomy. Clinical data were obtained from a chart review, and the prognostic impact of the presence, number (1–2 versus ≥3), and location (pelvic versus pelvic plus para-aortic) of lymph node metastasis was investigated by comparing recurrence and survival. In total, 50 patients were included in this study, of which 21 (42.0%) showed pathological evidence of lymph node metastasis (node-positive group). Both the univariate and multivariate analyses showed that lymph node metastasis was an independent prognostic factor for postoperative recurrence (hazard ratio (HR) 5.36; 95% CI 1.41–6.66; p = 0.0020). The predominant sites of recurrence after salvage surgery were the visceral organs and lymph nodes in the node-negative and node-positive groups, respectively. Patients with ≥3 node metastases showed similar survival to those with 1–2 node metastases. Patients with pelvic node metastasis showed similar survival to those with pelvic and para-aortic node metastases. The presence, not number or location, of lymph node metastasis was an independent poor prognostic factor for post-operative recurrence in patients who developed locally recurrent or persistent cervical cancer treated with salvage hysterectomy plus lymphadenectomy.

Occurrence of No.12 lymph node micrometastasis in gastric cancer and its effect on clinicopathological parameters and prognosis*

Abstract Objective This study aimed to investigate the occurrence of No.12 lymph node micrometastasis in patients with gastric cancer and its relationship with clinicopathological parameters and prognosis. Methods A cohort of 160 gastric cancer patients who underwent gastrectomy and lymph node dissection were selected as the research subjects. The immunohistochemical method was used to detect the micrometastasis of No.12 lymph node sections with negative routine pathological detection. At the same time, the clinical data of patients were collected and followed up to analyze the clinical significance of No.12 lymph node micrometastasis. Results A total of 370 No.12 lymph nodes were detected in 160 surgical specimens. Among 160 patients, 27 patients were found to be positive for No.12 lymph nodes during routine pathological examination, with a positive rate of 16.8%. A total of 308 lymph nodes from 133 patients with negative routine pathological examinations were stained by immunohistochemistry. A total of 17 lymph nodes from 10 patients were found to be positive. The results showed that 37 of the 160 patients had No.12 lymph node metastasis, and the positive rate was 23.1%, which was 6.3% higher than that of routine pathological examination. Logistic multivariate analyses showed that the depth of invasion, lymph node metastasis in other groups, and clinical stage were independent risk factors for No.12 lymph node metastasis. The average follow-up time was 79.3 months, and the overall median survival time was 47.9 months. The survival time of the No.12 lymph node-negative group was 67.3 ± 2.5 Â months, the median survival time was 73.2 months; the survival time of the No.12 lymph node-positive group was (28.4 ± 5.4) months, and the median survival time was 31.3 months. The survival time of the No.12 lymph node-negative group was significantly longer than that of the positive group (χ2 = 12.75, P = 0.000). Conclusion No.12 lymph node micrometastasis is a signal affecting the prognosis of patients with gastric cancer. Standardized dissection of No.12 lymph nodes is recommended for patients with gastric cancer who can undergo radical resection.

Selective Neck Dissection for Node-Positive Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study

Introduction Selective neck dissection in clinically node-negative neck is considered the standard of care for oral squamous cell carcinomas (SCCs). Controversy still prevails in node-positive disease regarding the extent of neck dissection. In our part of the world, comprehensive neck dissection is mostly considered to be the minimal optimal treatment for palpable neck disease. Objective To compare regional control and disease-specific survival between clinically node-positive and node-negative patients undergoing selective neck dissection for oral SCC. Methods This was a retrospective cohort study conducted in the department of ENT, Head and Neck surgery at a tertiary care hospital. All patients with biopsy-proven oral and lip SCC, with or without nodal disease, who underwent selective neck dissection between April 2006 and July 2015 were included in the study. Results During the study period, 111 patients with oral SCC underwent selective neck dissection, of whom 71 (62%) were clinically node-negative and 40 (38%) patients had clinically positive nodes in the neck. The mean follow-up was 16.62 months (standard deviation [SD]: 17.03). The overall regional control rates were 95 versus 96% for clinical negative versus positive nodes, respectively ( p = 0.589). The disease-specific survival was 84.5% in the node negative group versus 82.5% in the node-positive group ( p = 0.703). Conclusion Selective neck dissection in node-positive neck oral SCC has similar regional control rates when compared with node-negative neck SCC. The difference in disease-specific survival between the two groups is also not significant.

Abstract P4-07-22: Evaluation of human epididymis protein 4 serum and tissue expression in ductal carcinoma in situ of the breast

Abstract Background: Human epididymis protein 4 (HE4), also known as WFDC2, is a member of whey acidic protein (WAP) family with a presumptive role in natural immunity. HE4 expression has been increased in many cancer types, particularly in gynecologic and pulmonary cancers. HE4 has been identified as an important serum biomarker in the diagnosis and monitoring of epithelial ovarian cancer. Recent researches have demonstrated that HE4 levels in serum and tissues are elevated in patients with breast cancer and HE4 is thought be involved in breast cancer progression. In contrast, expression of HE4 in ductal carcinoma in situ (DCIS) has not been well characterized yet. The present work was undertaken to evaluate serum and tissue levels of HE4 in DCIS and their correlations with clinicopathological features of DCIS. Materials and methods: Preoperative serum HE4 levels in 59 DCIS patients was analyzed using the ARCHITECT assay. Tissue microarray containing DCIS and adjacent normal tissues from the same cohort were tested for HE4 mRNA and protein by RNAscope in situ hybridization (ISH) and immunohistochemistry analysis, respectively. Tissue microarray containing only DCS tissues from 41 patients were also tested for HE4 mRNA and protein. To validate prognostic potential of HE4 in breast cancer patients, the BreastMark database was used. Results: HE4 levels in 59 DCIS patients ranged from 23.5 to 86.3 pmol/L (mean ± SD: 39.4 ± 11.9). Based on the cutoff level, there were no abnormal cases for HE4. Serum HE4 levels did not differ according to clinicopathological parameters except for menopause status. RNAscope ISH and immunohistochemistry confirmed an increase in HE4 in DCIS tissues compared with their corresponding normal tissues. Spearman’s correlation analyses revealed no significant correlation between serum and tissue levels of HE4. Among 100 DCIS tissues, there was a positive correlation between HE4 mRNA ISH scores and HE4 immunohistochemical staining scores (r = 0.771, P &amp;lt; 0.001). High mRNA and protein expression of HE4 were observed in 25 of 99 (25.3%) and 34 of 99 (34.3%) cases, respectively. High mRNA HE4 expression was significantly associated with low stromal tumor infiltrating lymphocyte (TIL) density scores, ER positivity, HER2 negativity, and HR+/HER2- subtype. High protein HE4 expression was also significantly associated with absence of comedo-type necrosis, low stromal TIL density scores, ER positivity, HER2 negativity, and HR+/HER2- subtype. HE4 mRNA and protein expression did not correlate with recurrence of DCIS. In breast cancer patients, high HE4 expression was significantly associated with good survival in the overall group (HR = 0.838, P = 0.003, n = 2,652) and lymph node negative group (HR = 0.791, P = 0.029, n = 1,183). Conclusions: Our study revealed that serum HE4 is not elevated in patients with DCIS. High expression of HE4 mRNA and protein in DCIS tissues are associated with good clinicopathological characteristics, which warrant. further investigations. Citation Format: Ji Shin Leee, Nah Ihm Kim, Min Ho Park. Evaluation of human epididymis protein 4 serum and tissue expression in ductal carcinoma in situ of the breast [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-22.

Abstract P3-21-01: A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction

Abstract Background The rate of Nipple Areolar Complex (NAC) sparing mastectomy with implant reconstruction is rapidly increasing as the Korean National Health Insurance reimbursed reconstructive surgery for breast cancer patients from 2015. However, only a few reports about oncologic safety have been reported in the absence of large-scale data. We have analyzed the oncologic outcomes of all consecutive breast cancer patients who had NAC sparing mastectomy with immediate implant reconstruction. Methods We used the data from prospectively collected clinical data of patients who underwent immediate implant reconstruction after NAC sparing mastectomy at the National Cancer Center between January 2012 and December 2017. Demographics, clinicopathological characteristics and the follow-up results were analyzed. The statistical analysis was done to infer relations between risk factors and oncologic outcomes such as death, distant metastasis or locoregional recurrence. Results: A total of 538 breasts was analyzed in 486 patients. The mean age of the patients was 44.6 years. The mean BMI was 22.48 kg/m2. The number of bilateral cases was 52 (10.7%) and 135 patients (27.8%) had multiple tumors. Median follow-up was 4.5 years. Molecular subtypes were 373 HR(+)/HER2(-) (69.3%), 31 HR(+)/HER2(+) (5.8%), 76 HR(-)/HER2(+) (14.1%) and 35 HR(-)/HER2(-) (6.5%). Chemotherapy was performed in a total of 212 (43.6%) patients, of which 68 (32.1%) were neoadjuvant and 144 (67.9%) were adjuvant purposes. Trastuzumab was administered to 53 (10.9%) of patients whose tumor size are larger than 1cm under guideline of reimbursement. Postoperative radiotherapy was performed in 131 patients (26.9%). Distant metastasis occurred in 20 patients (3.7%), and seven (1.4%) died. Locoregional recurrence occurred in 43 cases (8.0%) of 538 breasts, including 14 nipples (2.6%) and 12 subareolar lesions (2.2%). Analyzing risk factors related to locoregional recurrence, HR(-)/HER2(+) type showed the highest incidence of 11/76 (14.7%) among four subtypes. The incidence was statistically significantly lower in the group that received postmastectomy radiotherapy than in the group that did not. (6/131 (4.6%) vs 37/355 (10.4%), p=0.001). The node negative group who did not have postmastectomy radiotherapy (31/377 (8.2%)) showed a numerically higher incidence than the node positive group (8/121 (6.6%)). Conclusion Our results showed that NAC sparing mastectomy with immediate implant reconstruction had similar oncologic outcome in terms of overall survival or distant metastasis, however the locoregional recurrence was rather high. Even this is remediable problems we would admit that NAC sparing mastectomy is a bit different from traditional mastectomy. In case that we inevitably apply this operation to relatively young women with multifocal breast cancer, careful consideration would be needed. In addition, identifying risk factors of locoregional recurrence and tailored post-operative radiation therapy are expected to improve the disease-free survival of breast cancer. Citation Format: Ji Young You, Eun-Gyeong Lee, Soo Jin Park, Byeong Nam Kim, Seeyoun Lee, Eun Sook Lee, So-Youn Jung, Youngmi Kwon, Yun Ju Kim, Chan Wha Lee, Tae Hyun Kim. A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-21-01.

The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma.

Simple SummaryThis study investigated the immunohistochemical expression of 14 biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma, comparing 53 node-negative (Group A) and 48 node-positive (Group B) patients. Our results show a significantly higher p16 expression (surrogate of HPV-related tumors) in the vulvar samples of non-metastatic patients. In Group B, PD-L1 positivity and high EGFR expression were found in the vast majority of vulvar and/or nodal specimens. VEGF showed strong/moderate-diffuse expression in almost 14% of all vulvar samples. A mutated p53 and over-expressed PD-L1 showed a significant association with nodal metastasis. Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs, especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.

Determinants of prognosis in patients with oral squamous cell carcinoma metastasizing to a single cervical lymph node

ObjectivesMetastasis in a single lymph node without adverse tumour factors and perineural invasion has been assigned to a lower risk category by the ASCO recommendations of 2019. We analyzed patients with a single positive node with a view to identifying high risk features and their impact on prognosis within this subgroup. Materials and MethodsThe study retrospectively analyzed 707 patients with OSCC. Descriptive statistics were used to compare distribution of clinicopathologic risk features between 323 N0 and 121 single node positive (Ns) patients. The Ns group was further analyzed for the impact of clinicopathologic factors on disease free (DFS) and overall survival (OS) using univariate and multivariate models. ResultsThe Ns group exhibited greater depth of invasion compared to the N0 group and significantly higher proportion of lymphovascular invasion (LVI), perineural invasion (PNI) and poorly differentiated tumors. Within the Ns group, primary tumor localised to the gingivobuccal subsite (HR 2.55, 1.18–5.52 95%CI, p = 0.02) and PNI (HR 2.55, 1.14–5.62, 95%CI p = 0.02) exhibited poor DFS. PNI also contributed to poor OS (HR 2.86, 1.27–6.47 95%CI, p = 0.01). Uninvolved margins (HR 0.46, 0.22–0.96 95%CI, p = 0.04) and chemoradiation (HR 0.18,0.05–0.68 95% CI, p = 0.01) improved OS. ConclusionSignificant differences are noted in the prevalence of pathologic risk factors between the single node positive and node negative groups. Within the single node positive group, tumour factors like the gingivobuccal subsite, PNI and margin positivity impacted survival. Among nodal factors, deposit size of 12 mm or more and presence of ENE are pointers to poor prognosis. These patients would benefit from adjuvant treatment.

Characteristics of lymph node (No.5 and No.6) metastasis and significance of lymph node dissection in Siewert type II esophagogastric junction adenocarcinoma (AEG): No.5 and No.6 lymph node metastases of AEG and clearance.

Background:To analyze the characteristics, related risk factors, and prognosis of lymph node metastasis (Number [No.] 5 and No.6) in the group of adenocarcinoma of esophagogastric junction (AEG).Methods:The patients with Siewert II AEG who underwent total gastrectomy and D2 lymph node dissection from September 2015 to December 2018 in Lanzhou University Second Hospital were enrolled in this study. The pathological features of the postoperative specimens were analyzed (sex, age, maximum diameter, location, depth of invasion, degree of differentiation, neurological and vascular invasion, etc), and the lymph node metastasis rate of No.5, No.6 groups were calculated. The analysis was performed by IBM SPSS statistical software. The risk factors associated with lymph node metastasis in No.5 and No.6 groups were analyzed. Survival analysis was performed by Kaplan-M method, and survival rate was estimated, Log-rank test was used for comparison, and the difference was statistically significant at P < .05.Results:There were 142 cases of Siewert type II AEG with the positive rate of No.5 lymph nodes being 10.81% (8/74), and the positive rate of No.6 lymph nodes was 8.33% (11/132). No.5 and No.6 lymph nodes metastasis were not associated with gender, age, tumor maximum diameter, location (cardiac left/cardiac right) (P > .05), and were associated with invasion depth, differentiation degree, nerve and vascular invasion (P < .05). In the No.5 lymph node-positive group, the 3-year Overall Survival (OS) was 25.0%, and the No.5 lymph node-negative group had a 5-year OS of 57.8%, which was statistically different (P < .05). The 3-year OS was 18.2% in No.6 node-positive group and 53.8% in No.6 node-negative group, and the difference was statistically significant (P < .05).Conclusion:For Siewert type II AEG, the lymph node metastasis rate was higher in No.5 and No.6 groups when the tumor invaded all layers of gastric wall and was poorly differentiated complicated with vascular nerve invasion, and the lymph node metastasis rate was lower at 3 years, which may be more appropriate for total gastrectomy +D2 lymph node dissection.

Epithelial-mesenchymal plasticity and lymph node metastases in invasive breast carcinoma of no special type

Background: Breast cancer is the commonest cancer among women with distant metastases being the leading cause of mortality. Epithelial-mesenchymal plasticity (EMP) is a proposed mechanism involved in establishment of metastasis. E-cadherin and vimentin can be used as epithelial and mesenchymal markers, respectively, to identify EMP. Aims: To compare E-cadherin and vimentin expressions between node-negative and node-positive invasive breast carcinoma–no special type (IBC-NST) and their lymph node metastases. Methods: Forty node negative tumours and 44 axillary node positive tumours of IBC-NST with their metastatic lymph nodes were retrieved from patients who had undergone mastectomy at the Teaching Hospital, Peradeniya. Samples were subjected to dual immunohistochemical staining with anti-E-cadherin and anti-vimentin primary antibodies. Any cytoplasmic staining for vimentin and 70% or more of membranous staining for E-cadherin were taken as positive and cells counted in 10 high power fields. Intensity of staining was graded as high=3, moderate=2, low=1 and absent=0 by comparing with internal controls. Percentage of positive cells was multiplied by the intensity to obtain the immuno-score (IS) for both protein expressions. IS was compared using independent and paired t-test. Results and conclusions: A lower E-cadherin (p=0.001) and higher vimentin (p=0.008) expression was seen in node positive group compared to node negative group. A higher E-cadherin (p<0.001) and lower vimentin (p<0.001) expression was seen in lymph nodes compared to the corresponding primary tumours. A significant loss of epithelial properties and acquisition of mesenchymal properties in the node positive group indicates epithelial to mesenchymal transition of tumour cells, contributing to metastasis. In the lymph nodes, higher E-cadherin and lower vimentin expression suggests a reverse mechanism, i.e., mesenchymal to epithelial transition. These Results are suggestive of epithelial-mesenchymal plasticity of tumour cells in establishment of metastasis in IBC-NST.