Number Of Lymph Node Metastases Research Articles

The number of metastatic lymph nodes optimizes staging in patients aged 55 years or older with papillary thyroid cancer.

Current staging criteria for papillary thyroid cancer (PTC) do not include the number of metastatic lymph nodes (LNs), which is highly predictive of survival in multiple cancers. The LN metastasis burden is particularly relevant for older adults with thyroid cancer because of their poor prognosis. We examined a modified staging system for this population utilizing node number (Nn). Overall, 14,341 patients aged 55 years or older with stage I-IVB PTC were identified in the 2004-2015 Surveillance, Epidemiology and End Results database. Cox regression models were conducted to test the relationship between positive LN number and PTC-specific survival (PTCSS). Independent training/validation sets were used to derive and validate a new revised TNnM grouping. The 8th edition American Joint Committee on Cancer TNM staging system was compared with TNnM stage by calculating the 10-year PTCSS rates, Harrell's concordance index (C-index), and Akaike's information criterion (AIC). An increase in number of LN metastases was identified as an independent, negative prognostic factor for PTCSS in multivariate analysis. 10-year PTCSS for stage I-IVB based on the AJCC 8th edition TNM were 98.83%, 93.49%, 71.21%, 72.95%, and 58.52%, respectively, while 10-year PTCSS for the corresponding stage in the TNnM were 98.59%, 92.2%, 83.26%, 75.24%, and 56.73%, respectively. The revised TNnM stage was superior, with a higher C-index and a lower AIC in both the training and validation cohorts. The TNnM staging system for PTC patients ≥ 55 years could be associated with improved outcomes. External validation studies of this system are warranted.

Comparison of Lobectomy vs Total Thyroidectomy for Intermediate-Risk Papillary Thyroid Carcinoma With Lymph Node Metastasis

Surgical treatment of patients with papillary thyroid cancer (PTC) by either lobectomy or total thyroidectomy (TT) has long been a topic of debate, especially for patients with intermediate-risk PTC. To compare recurrence-free survival (RFS) for patients with PTC and lymph node metastasis after lobectomy vs TT. This retrospective cohort study included a review of patients with PTC treated from January 1, 2000, to December 31, 2017. Propensity score matching (PSM) was performed between patients treated with lobectomy and TT. This study involved a single institute in a cancer referral center. Enrolled were adult patients (aged 18-75 years) with unilateral PTC and ipsilateral clinical lateral neck metastasis (cN1b). Patients with the following characteristics were excluded: a lymph node yield less than 20, primary tumor size greater than 4 cm, gross extrathyroidal extension, metastatic lymph node size greater than 3 cm, and distant metastasis. Data analysis was performed from April 1 to April 30, 2022. Lobectomy and TT. The primary outcome was the association between extent of surgery and RFS, assessed using Cox proportional hazards regression models. A total of 946 patients with PTC (mean [SD] age, 37.0 [12.1] years, 630 female individuals [66.6%]) were analyzed. Lobectomy (624 [66.0%]) was negatively correlated with the frequencies of older age (≥65 years, 17 [2.7%]), female sex (393 [63.0%]), multifocality (132 [21.2%]), minor extrathyroidal extension (259 [41.5%]), number of metastatic lymph nodes (median [range], 9 [6-14] nodes), and radioactive iodine ablation (0). After PSM with treatment period and potential prognostic factors (age, sex, primary tumor size, multifocality, minor extrathyroidal extension, number of lymph node metastases and lymph node ratio), 265 pairs of patients were available for analysis. After a median (range) follow-up of 60 (9-150) months in the lobectomy group and 58 (8-161) months in the TT group, 21 (7.9%) and 17 (6.4%) structural recurrences were identified in the lobectomy and TT groups, respectively. Lobectomy was not associated with significantly compromised 5-year RFS rate (lobectomy, 92.3% vs TT, 93.7%; adjusted hazard ratio, 1.10; 95% CI, 0.58-2.11; P = .77). Power analysis indicated that the test had 90% power to detect a more than 4.9% RFS difference. No significant difference in RFS was observed between patients treated with TT and radioactive iodine ablation (n = 75) and their counterparts (adjusted hazard ratio, 0.59; 95% CI, 0.14-2.41; P = .46). Results of this cohort study suggest that patients with PTC and lymph node metastasis had a similar RFS after lobectomy vs those who had TT. If radioactive iodine ablation is not going to be performed, lobectomy may be an effective alternative option.

Lymph Node Examination and Patterns of Nodal Metastasis Among Patients with Left- Versus Right-Sided Intrahepatic Cholangiocarcinoma After Major Curative-Intent Resection.

We sought to investigate whether the unique lateral patterns of lymphatic drainage impacted lymphadenectomy (LND), lymph node metastasis (LNM), and long-term survival of patients after curative hemi-hepatectomy for left- versus right-sided intrahepatic cholangiocarcinoma (ICC). Data on patients who underwent curative hemi-hepatectomy for left- or right-sided ICC were collected from 15 high-volume centers worldwide, as well as from the Surveillance, Epidemiology, and End Results (SEER) registry. Primary outcomes included overall survival (OS) and disease-free survival (DFS). Among 697 patients identified from the multi-institutional database, patients who underwent hemi-hepatectomy for left-sided ICC (n = 363, 52.1%) were more likely to have an increased number of LND versus patients with right-sided ICC (n = 334, 47.9%) (median, left 5 versus right 3, p = 0.012), although the frequency (left 66.4% versus right 63.8%, p = 0.469) and station (beyond station no. 12, left 25.3% versus right 21.1%, p = 0.293) were similar. Consequently, left-sided ICC was associated with higher incidence of LNM (left 33.3% versus right 25.7%, p = 0.036), whereas the station and number of LNM were not different (both p > 0.1). There was no difference in OS (median, left 34.9 versus right 29.6 months, p = 0.130) or DFS (median, left 14.5 versus right 15.2 months, p = 0.771) among patients who underwent hemi-hepatectomy for left- versus right-sided ICC, which were also verified in the SEER dataset. LNM beyond station no. 12 was associated with even worse long-term survival versus LNM within station no. 12 among patients with either left- or right-sided ICC after curative-intent resection (all p < 0.05). The unique lateral patterns of lymphatic drainage were closely related to utilization of LND, as well as LNM of left- versus right-sided ICC.

Influence of Obesity Parameters on Different Regional Patterns of Lymph Node Metastasis in Papillary Thyroid Cancer.

Obesity increases risk of thyroid cancer. However, the association between obesity and the progression of papillary thyroid cancer (PTC) remains controversial. This retrospective study aimed to explore the relationship between obesity and regional patterns of lymph node metastasis (LNM) in PTC. We retrospectively reviewed data from 1015 patients with PTC. We calculated obese parameters, such as body mass index (BMI), body fat percentage (BFP), and body surface area (BSA). Logistic regression models were used to assess associations between obese parameters and the rate of lymph node metastasis (LNM), number of LNM, pattern of LNM, and lymph node ratio (LNR). Higher BMI was not associated with different regional patterns of LNM in PTC. In men with PTC, high BFP was an independent predictor of total LNM, central lymph node metastasis (CLNM), total lateral lymph node metastasis (LLNM), multiple lateral lymph node metastasis, and simultaneous metastasis in lateral compartment. In addition, male patients with high BFP had higher central LNR and higher number of CLNM. For women, high BSA was an independent predictor of LLNM and level IV metastasis. Female patients with high BSA had higher number of CLNM. BFP and BSA, possibly influenced by gender, were positively associated with the number and risk of LNM in different regions of PTC patients. However, BMI was not the predictor for aggressiveness of PTC in terms of LNM. Clinical decision-making for regional LNM in PTC patients should consider the factor of obesity.

Association of lymph node metastases, grade and extent of mesenteric lymph node dissection in locoregional small intestinal neuroendocrine tumors with recurrence-free survival.

We aimed to assess the prognostic impact of tumor- and patient-related parameters in patients with stage I-III small intestinal neuroendocrine tumors (SI-NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I-III SI-NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI-NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well-differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki-67: 2%, range 1%-50%). One-hundred and sixty-three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0-63), whereas the median number of positive LNs was 2 (0-43). After a mean ± SD follow-up of 54.1 ± 64.1months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5-285.1) months. The 5- and 10-year recurrence-free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN-positive and LN-negative patients (log-rank, p=.380 and .198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n=125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI]=107.4 [0-229.6] vs. 73.7 [35.3-112.1]months; log-rank, p=.048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)]=46.9 [36.4-57.3] vs. 120.7 [82.7-158.8]months; log-rank, p=.001). In multivariable Cox-regression RFS analysis in stage IIIb patients, the Ki-67 proliferation index (hazard ratio=1.08, 95% CI=1.035-1.131; p < .0001) and the number of LN metastases (hazard ratio=1.06, 95% CI=1.001-1.125; p=.047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI-NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki-67 proliferation index and the LN metastases count were independent predictors of RFS.

The prognostic role of metastatic lymph node ratio in colon cancer: a retrospective cohort study on 241 patients in a single center.

The detection of nodal status is based on examination of lymph nodes (LN) after the tumor surgical resection and the current guidelines recommend examining at least 12 regional LN. An inadequate number of examined LN may lead to a lower N stage or to a false-negative nodal disease. To overcome these issues, many authors proposed to consider the metastatic lymph node ratio (mLNR). MLNR is the ratio of the number of metastatic LN to the number of examined LN. Two hundred forty-one colon cancer (CC) specimens from patients who had undergone surgical resection between January 2010 and December 2015 at the General Surgery Unit of Parma University Hospital were analyzed. mLNR, which is defined as the ratio of the number of positive LN to the number of examined LN, was calculated in CCs with LN metastasis. In this study we focused on the following mLRN cutoffs: <0.15, 0.15-0.3 and >3 and we evaluated the prognostic implication of mLNRs. Regarding the impact of examined LN on involved LN in CC, our results showed that the number of involved LN increased with the increasing number of examined LN (P=0.03). We found a significant correlation between OS and RFS rate of patients with CCs and mLNR. Patients with mLNR<0.15 were associated with better OS and RFS rate whereas patients with mLNR>0.3 were associated with worse OS and RFS rate. OS rate for patients with a mLNR<0.15 was 95.24% (89-100%) at 1 year, 83.27% (72.7-95.4%) at 3 years and 68.07% (55.1-84.1%) at 5 years whereas patients with a mLNR>0.3 had an OS rate of 51.7% (34.6-77.3%) at 1 year, 36.55% (20.08-64.3%) at 3 years and 31.33% (16.5-59.4%) at 5 years. RFS rate for patients with a mLNR<0.15 was 100% (100-100%) at 1 year, 92.2% (84-100%) at 3 years and 85.2% (73.8-98.31%) at 5 years whereas patients with a mLNR>0.3 had a RFS of 63.2% (42.8-93.58%) at 1 year and 54.2% (33.1-88.93%) at 3 and 5 years. The prognostic value of pN stage could be more accurate if we consider both the number of LN metastasis and harvested LN. This can be achieved by using the mLNR that can be a useful tool in daily practice to predict the prognosis of patients who undergone surgery for CC.

Prognostic and clinicopathological significance of transcription factor c-Jun in hypopharyngeal squamous cell carcinoma: a 3-year follow-up retrospective study.

PurposeTo investigate the expression and prognostic value of c-Jun in hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA retrospective study was performed on a cohort of 99 HPSCC patients. The expression of c-Jun and phosphorylated-c-Jun (p-c-Jun) was evaluated via immunohistochemistry (IHC) staining. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier method and multivariate Cox regression analysis.ResultsThe high expression of c-Jun and p-c-Jun in HPSCC accounted for 60.61% and 16.16%, respectively. High expression of c-Jun was closely associated with cT stage (p = 0.0401), tumor size (p = 0.0276), number of lymph node metastases (p = 0.0205) and pathological differentiation (p = 0.0108). The expression of c-Junhigh (p = 0.0043), p-c-Junhigh (p = 0.0376) and c-Junhigh/p-c-Junhigh were closely associated with poor OS. The Cox proportional multivariate hazard model revealed that lymphovascular invasion and c-Jun expression were independent influencing factors of OS in HPSCC patients.ConclusionOur findings suggest that c-Jun is a reliable prognostic factors in HPSCC patients.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

The analysis of risk factors for accidental parathyroid resection during thyroid surgery: a retrospective analysis of 1775 patients.

The present study discussed the effects of accidental parathyroid resection on hypoparathyroidism and investigated the risk factors associated with accidental parathyroid resection. Clinical data from patients who have undergone thyroidectomy at a university hospital in the period from November 2018 and October 2020 were entered into the database and analyzed. Risk factors for accidental parathyroid resection were recorded. A total of 1775 cases were included in this study. The analysis showed that lymph-node dissection (p < 0.001), T staging (p = 0.037), and treatment group (p < 0.001) were independent risk factors for accidental parathyroid resection. Different treatment groups were important risk factors for accidental parathyroid resection. There were significant differences between the professional and non-professional groups in the following aspects: accidental parathyroid resection (p < 0.001), Scope (p < 0.001), T stage (p = 0.009), N stage (p < 0.001), range of lymph-node dissection (p < 0.001), number of lymph nodes dissected in central area (p < 0.001), and number of lymph-node metastases in the central region (p < 0.001). The causes of accidental parathyroid resection are multifactorial. The predictors for accidental parathyroid resection include lymph-node dissection in the central region, T staging, as well as the operating surgeons' experience.

Correlation analysis of clock genes and MEN2 medullary thyroid carcinoma

Objective: To investigate the correlation between CLOCK and BMAL1 genes and MEN2 medullary thyroid carcinoma (MTC). Methods: Thirteen cases with MEN2 MTC and thirteen cases with non-MEN2 MTC were selected who were treated in the Yantai Yuhuangding Hospital between January 2013 and September 2021. Clinical indicators such as blood calcitonin level, tumor diameter and metastatic lymph node of patients were collected. The expression differences of CLOCK and BMAL1 between MEN2 MTC and para-carcinoma tissue as well as between MEN2 MTC and non-MEN2 MTC were detected by immunohistochemistry and qPCR. The correlation between lymph node metastasis and CLOCK or BMAL1 expression was analyzed. Protein-protein interaction (PPI) network analysis combined with qPCR and correlation analysis was used to explore the expression regulation relationship between RET and circadian clock genes. The rhythm disorder of MEN2 cells was verified by lipopolysaccharide cell stimulation experiment after dexamethasone rhythm synchronization. Results: MEN2 MTC exhibited typical RET gene mutation. The mean blood calcitonin level, the tumor diameter and the number of metastatic lymph nodes of patients with MEN2 MTC were higher than those of patients with non-MEN2 MTC (t value was 2.76, 2.53, 2.26, all P<0.05). Immunohistochemical results showed that the expression levels of CLOCK and BMAL1 in MEN2 MTC were higher than those in non-MEN2 MTC, while negatively expressed in para-cancerous thyroid follicle. qPCR displayed that the expression of CLOCK gene in cancer tissues was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.68 and 2.86, all P<0.05); the expression of BMAL1 gene in MEN2 MTC was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.21 and 2.35, all P<0.05). Correlation analysis showed that the expression levels of CLOCK and BMAL1 genes were positively correlated with the number of lymph node metastases in patients with MEN2 MTC (r=0.65, P<0.001; r=0.52, P=0.005). PPI network analysis indicated that the expression of CLOCK gene was positively correlated with the abnormal expression of RET gene (r=0.96, P<0.001). With lipopolysaccharide to stimulate cultured cells in vitro after dexamethasone rhythm synchronization, the expressions of CLOCK and BMAL1 in MEN2 MTC cells (0.47±0.22 and 2.60±1.48) at 12 hours of synchronization were significantly lower than those in para-cancerous tissues (1.70±1.62 and 8.23±2.52), the difference was statistically significant(t=5.04, P=0.007; t=3.34, P=0.029). Conclusion: CLOCK and BMAL1 are correlated with the occurrence and development of MEN2 MTC, and may be potential targets for the development of new therapeutic strategies for MEN2 MTC.

Superiority of metastatic lymph node ratio over number of node metastases and TNM/AJCC N classification in predicting cancer-specific survival in medullary thyroid cancer.

In medullary thyroid cancer (MTC), it is unclear which nodal classification system, metastatic lymph node ratio (MLNR), number of node metastases, or TNM/AJCC N classification, predicts cancer-specific survival best. Kaplan-Maier analysis of cancer-specific survival after operation at a tertiary center. Included were 505 MTC patients. The spread of the survival curves was greatest after stratification by MLNR (in 0.20 increments), followed by number of node metastases (in 10-node and 20-node increments) and TNM/AJCC classification (N0, N1a, N1b). After collapsing overlapping survival curves, all adjacent curves (MLNRs ≤0.20 vs. 0.21-0.60 vs. >0.60; 0 vs. 1-20 vs. >20 node metastases; and TNM/AJCC N classification N0/N1a vs. N1b) significantly differed between each other. In MTC, MLNR, reflecting intensity of lymphatic spread, predicts cancer-specific survival better than number of node metastases or TNM/AJCC N classification. The applicability of these findings to patients with limited neck dissection requires more research.

Sublobar resection without staging and lymphadenectomy for ≤2 cm Non-Small Cell Lung Cancer is no adequate therapy

ObjectiveSublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with ≤2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors ≤2 cm at our institution. MethodsNodal upstaging, lymphangiosis- (L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method. Results747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with ≤2 cm tumors. The mean tumor size was 1.4 cm ± 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 ± 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 ± 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p < 0.001). Upstaged patients showed significantly worse 3- (upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates. Conclusion16.5% of patients with ≤2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis

Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Relapse and disease-specific mortality after a diagnosis of BC. The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

Prognostic Significance of Size, Location, and Number of Lymph Node Metastases in Endometrial Carcinoma.

Regional lymph node metastasis is a well-established negative predictive prognostic factor in endometrial carcinomas. Recently, our approach to the pathologic evaluation of lymph nodes in endometrial carcinomas has changed, mainly due to the utilization of immunohistochemical stains in the assessment of sentinel lymph nodes, which may result in the identification of previously unrecognized disease [particularly isolated tumor cells (ITCs)] on hematoxylin and eosin stained slides. However, the clinical significance of this finding is not entirely clear. Following the experience in other organs systems such as breast, the Eight Edition of the American Joint Committee on Cancer's Cancer Staging Manual has recommended utilizing the N0(i+) terminology for this finding, without impact in the final tumor stage. We performed a comparative retrospective multi-institutional survival analysis of 247 patients with endometrial carcinoma with regional lymph node metastasis of various sizes identified in nonsentinel lymphadenectomy, demonstrating that the cumulative survival of patients with isolated tumor cells in regional lymph nodes is not statistically different from patient with negative lymph nodes, and is statistically different from those with lymph nodes showing micrometastasis or larger metastatic deposits. In addition, we evaluated the prognostic implications of the number of involved regional lymph nodes, demonstrating a worsening prognosis as the number of involved lymph nodes increases from none to one, and from one to more than one. Our data suggests that regional lymph nodes with isolated tumor cells in patients with endometrial carcinoma should likely be considered, for staging purposes, as negative lymph nodes, simply indicating their presence with the (i+) terminology.

Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy.

To investigate the protein expression levels of cyclin-dependent kinase subunit 2 (CKS2) and the cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significance. A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumour, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analysed the clinical significance of the expression of the two factors. (1) The positivity rates for CKS2 in benign gastric tumour tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, that is, 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumour diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=.625, P=.000). (3) The median follow-up time of 126 patients was 46.5months, and the overall survival (OS) rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the OS rate for patients in the CKS2 (+) group was significantly worse and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse OS (30.1% vs 60.5%, χ2 =15.67, P=.000). (4) The OS rates of CKS2 (+) CD47 (+) group, CKS2 (+) CD47 (-) group, CKS2 (-) CD47 (+) group, and CKS2 (-) CD47 (-) group were 20.0% (13/65), 58.3% (7/12), 57.1% (8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2 (+) CD47 (+) group was significantly poor. High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1–3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry

AimPostmastectomy radiotherapy (PMRT) is the standard treatment for locally advanced breast cancer. However, the effectiveness of PMRT in patients with pT1-2 and N1 tumours remains controversial. Therefore, this study aimed to determine the prognostic impact of PMRT in patients with breast cancer and with pT1-2 and 1–3 lymph node metastases. MethodsUsing data from the Japanese National Clinical Database from 2004 to 2012, we evaluated the association of PMRT with locoregional recurrence (LRR), any recurrence, and mortality. We enrolled patients who had undergone mastectomy and axillary node dissection and were diagnosed with pT1-2 and N1. We compared clinicopathological factors and prognosis between patients who received (PMRT group) and those who did not receive (No-PMRT group) PMRT. ResultsAmong 8914 patients enrolled, 492 patients belonged to the PMRT group and 8422 to the No-PMRT group. The median observation time was 6.3 years. There was no significant difference in the incidences of LRR (4.0% versus 5.0%, P = 0.61), recurrence (13.8% versus 11.8%, P = 0.23) and breast cancer death (6.0% versus 4.3%, P = 0.08) at 5 years between the groups. Multivariable analysis revealed that LRR was significantly associated with tumour size, number of node metastases and triple-negative subtype but not with PMRT. ConclusionsThe LRR rate in the No-PMRT group was 5.0% at 5 years among patients with T1-2 and N1. PMRT did not significantly influence LRR in patients with T1-2 and N1. However, PMRT administration should be tailored considering the individual risks of tumour size, 3 node metastases and triple-negative subtype.

Prognostic Characteristics of Immune-Related Genes and the Related Regulatory Axis in Patients With Stage N+M0 Breast Cancer.

Breast cancer (BRCA) has the highest incidence rate among female tumours. The function of the immune system affects treatment efficacy and prognosis in patients with BRCA. However, the exact role of immune-related genes (IRGs) in stage N+M0 BRCA is unknown. We constructed a predictive risk scoring model with five IRGs (CDH1, FGFR3, INHBA, S100B, and SCG2) based on the clinical, mutation, and RNA sequencing data of individuals with stage N+M0 BRCA sourced from The Cancer Genome Atlas. Results from the Shandong Cancer Hospital and Institute validation cohort suggested that regardless of clinical stage, tumour size, or the number of lymph node metastases, this model was able to reliably discriminate low-risk patients from high-risk ones and assess the prognosis of patients with stage N+M0 BRCA, and low-risk patients could benefit more from immunotherapy than high-risk patients. In addition, significant inter-group variations in immunocyte infiltration and the tumour microenvironment were observed. Moreover, risk score and age were found to be independent factors in multivariate COX regression analysis, which influenced the outcome of patients with stage N+M0 BRCA. Based on the above findings, we plotted a prognostic nomogram. Finally, we constructed a lncRNA KCNQ1OT1-LINC00665-TUG1/miR-9-5p/CDH1 regulatory axis of the ceRNA network to explore the mechanism of BRCA progression. In summary, we conducted a systemic and extensive bioinformatics investigation and established an IRG-based prognostic scoring model. Finally, we constructed a ceRNA regulatory axis that might play a significant role in BRCA development. More research is required to confirm this result. Scoring system-based patient grouping can help predict the outcome of patients with stage N+M0 BRCA more effectively and determine their sensitivity to immunotherapies, which will aid the development of personalised therapeutic strategies and inspire the research and development of novel medications.

A Nomogram to Predict Nodal Response after Induction Chemotherapy for Hypopharyngeal Carcinoma.

For hypopharyngeal carcinoma, metastatic neck nodes with a low response to induction chemotherapy (ICT) should not be managed with concomitant chemoradiotherapy (CCRT), and the prediction of chemosensitivity before ICT could prevent adverse events from occurring during chemotherapy. In this study, we developed a nomogram to predict the regional response to ICT. A total of 153 hypopharyngeal carcinoma patients with regional metastasis treated with ICT in our institution from January 2010 to September 2020 were retrospectively studied. According to ICT response evaluated by RECIST 1.1, patients were divided into chemo-insensitive (PR < 70%/SD/PD) (group 1) and chemosensitive (CR/PR ≥ 70%) (group 2) groups. Patients' clinical, image, and hematologic data before ICT were collected. The nomogram was built based on multivariate analysis and stepwise logistic regression and was evaluated from the aspects of discrimination and calibration. A nomogram based on five critical predictors, namely, tumor differentiation degree, T classification, metastatic lymph node size, number of lymph node metastases, and cervical nodal necrosis, was developed. The areas under the curve (AUC) values were 0.76 and 0.70 after adjusting the results using bootstrap methods. The calibration curve showed relatively good agreement between the predicted and observed probabilities. Our nomogram yielded good accuracy in predicting the regional ICT response and will be a useful tool to assist clinicians in decision making. 4 Laryngoscope, 133:849-855, 2023.

Clinicopathological characteristics and prognostic factors of 130 patients with Krukenberg tumors of gastric origin.

e16023 Background: Krukenberg tumors of gastric origin have a poor prognosis. Their clinicopathologic characteristics are rarely reported and they lack optimal clinical management. There is an urgent need to explore new strategies to improve patient survival and quality of life. Methods: The clinicopathological characteristics, treatments and survival data were collected and analyzed from 130 patients with Krukenberg tumors of gastric cancer. Results: The median age of the patients was 41 years. A total of 63.1% of patients had synchronous ovarian metastasis, 70.8% had bilateral ovarian metastasis, 68.5% had peritoneum metastasis, and 98.4% had pathologically poorly differentiated adenocarcinoma. The positive rate of HER-2 was 1.8%. Only one patient showed dMMR. The follow-up rate was 90.8%. The median OS from the diagnosis of ovarian metastasis was 13.0 months. Univariate analysis showed that the significant survival factors included menstrual status, size of the gastric lesion and ovarian metastasis, number of lymph node metastases, interval time to ovarian metastasis, resection of gastric foci, peritoneal metastasis, oophorectomy, chemotherapy after ovarian metastasis, 2-drug regimen chemotherapy, albumin, serum CA-125 level, platelet count, D-dimer, fibrinogen, pretreatment high FAR, PLR and SII. Further multivariable analysis found that albumin, peritoneal metastasis and oophorectomy were independent prognostic factors. Conclusions: Patients of gastric cancer with Krukenberg tumors had some unique clinical characteristics. Active improvement of hypoalbuminemia, treatment of hypercoagulability, management of peritoneal metastasis, timely oophorectomy and chemotherapy can improve the patients’ prognosis. This suggests that we should focus on the nutritional status and coagulation function of patients with Krukenberg tumors in our clinical work.

Intratumor heterogeneity of positive lymph nodes provide a promising prognostic stratification factor for stage III colorectal cancer.

e15554 Background: Stage III colorectal cancer (CRC) is defined as patients with regional positive lymph nodes (pLN) but without distant metastasis, including stage IIIA, IIIB, IIIC. The prognosis of patients with stage III CRC varies dramatically, with 5-year survival rates ranging from 80 percent to 30 percent form stage IIIA to IIIC CRC, that does not exactly to be fully explained by the difference in the number of pLN. Therefore, other prognostic indicators need to be identified to improve and personalize prognosis prediction for patients with stage III CRC. Intratumor heterogeneity (ITH) widely exists between primary and metastatic lesions of CRC, however, there have been few studies focused on ITH of pLN. Therefore, this study aims to explore whether ITH of pLN could serve as a novel prognostic stratification factor for stage III CRC. Methods: We retrospectively analyzed the Poly-G genotype to reconstruct high-confidence phylogenetic trees for 20 CRC patients using 317 accurately scraped biopsy (134 primary tumors, 66 lymph node metastases and 37 normal samples). Root diversity score (RDS) index was used to reflect ITH of pLN. The association among Poly-G mutation rates, RDS index and clinical pathological data was analyzed. The area under the receiver operating characteristic (ROC) curves were calculated and the cut-off valve was confirmed. Results: Poly-G mutations accumulate in the occurrence and development of CRC. Poly-G mutation rate was correlated with tumor grade, N stage and microsatellite state (all P &lt; 0.05), and had a certain correlation trend with age (P = 0.066). The results of multivariate Cox regression analysis showed that ITH of pLN was an independent risk factor for recurrence and metastasis which lead to a poor progression free survival (PFS). The area under the curve (AUC) was 76%, and the cut-off valve of RDS index was 0.25. We also found ITH of pLN was not associated with substages of stage III CRC, which indicated that ITH of pLN and the number of metastases are two different dimensions. Conclusions: ITH of pLN may provide a promising prognostic stratification factor for the patients with stage III CRC. A higher ITH of pLN indicates that subclones with distant metastasis potential might more likely to exist in the primary tumors, which lead to a poor PFS including recurrence and distant metastasis. In addition, ITH of pLN is not related to the number of lymph node metastases in stage III CRC, suggesting that ITH of pLN is promising to serve as a supplementary strategy of TNM staging for patients with Stage III CRC.