Risk factors for lateral lymph node metastasis based on the molecular profiling of rectal cancer.

AIM: The association between molecular profiles and lateral lymph node metastasis (LLNM) in patients with rectal cancer remains unclear. Therefore, this study aimed to identify the molecular profiles of rectal cancer associated with LLNM. METHOD: We retrospectively examined patients who underwent rectal cancer surgery with lateral lymph node dissection without preoperative treatment and whose surgically resected specimens were evaluated using multiomics-based analyses from 2014 to 2019. We compared the clinical characteristics and molecular profiles of patients with pathological LLNM (pLLNM+) with those of patients without (pLLNM-) and identified risk factors for LLNM. RESULTS: We evaluated a total of 123 patients: 18 with and 105 without pLLNM. The accumulation of mutations in genes key for the development of colorectal cancer were similar between the groups, as was the tumour mutation burden. The distribution of consensus molecular subtypes (CMS) was significantly different between the groups (p = 0.0497). The pLLNM+ patients had a higher prevalance of CMS4 than the pLLNM- patients (77.8% vs. 51.4%). According to the multivariate analysis, the independent risk factors for LLNM were a short-axis diameter of the lateral lymph node of ≥6.0 mm and CMS4; furthermore, the presence of either or both had a sensitivity of 100% for the diagnosis of LLNM. CONCLUSION: Lateral lymph node size and CMS4 are useful predictors of LLNM. The combination of CMS classification and size criteria was remarkably sensitive for the diagnosis of LLNM.

Patterns of cervical lymph node involvement in mono-focal papillary thyroid carcinoma patients with different capsular status: A multi-center analysis.

OBJECTIVE: The characteristics of cervical lymph node involvement in papillary thyroid carcinoma (PTC) patients with different degree of capsular invasion remains unclear, especially for those with mono-focal lesion who have traditionally been considered as low neck metastasis risk subgroup. STUDY DESIGN: Retrospective cohort study. SETTING: Three academic teaching hospital. METHODS: A total of 1276 mono-focal PTC patients were retrospectively analyzed. RESULTS: Mono-focal PTC patients with extrathyroidal extension (ETE) showed significantly higher central lymph node metastasis (CLNM) rate than those without. For patients with no gross ETE (gETE), those with minimal ETE (mETE) also showed more commonly CLNM than those with encapsulated lesions. However, the lateral lymph node metastasis (LLNM) rates of patients with mETE and encapsulated tumors were comparable, both lower than that of patients with gETE. Age ≥40, male, and MTD ≥0.5 cm were identified as independent risk factors of CLNM for those with encapsulated tumors and were enrolled for creating a prediction model. In terms of LLNM, only MTD ≥1.0 cm was confirmed as independent risk factors of LLNM for patients with positive gETE. CONCLUSIONS: The presence and degree of ETE may have different effects on the risk of central and lateral lymph node metastasis. gETE demonstrates a strong correlation with both CLNM and LLNM while mETE is only associated with CLNM in mono-focal PTC patients. A comprehensive model is established in the aim of predicting neck involvement according to the capsular status and the corresponding stratified risk factors, which may aid clinical decision-making for the management of neck regions.

A nomogram for predicting lateral lymph node metastasis in cN0 unifocal papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for occult lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of lateral neck dissection (LND). The objective of this study was to develop a nomogram for predicting the probability of LLNM in patients with cN0 unifocal PTMC. METHODS: We conducted a retrospective analyzed a total of 4872 patients with cN0 unifocal PTMC who were treated at our center from January 2013 to June 2018. Logistic regression analysis was used to determine the risk factors for LLNM, and a nomogram was constructed based on these risk factors. RESULTS: The rate of LLNM was 3.2%. Tumors located in the upper lobe(odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.80-3.62; p < 0.001) and size greater than 7 mm (OR = 2.59, 95% CI 1.85-3.62; p < 0.001) had a significantly higher risk of LLNM compared to tumors in the lower or middle lobe and size less than or equal to 7 mm. Tumors with extrathyroidal extension (ETE) had a significantly higher risk of LLNM (OR = 1.41, 95% CI 1.01-1.99; p = 0.044). The presence of three or more central lymph node metastases (CLNMs) (OR = 5.84, 95% CI 3.83-8.93; p < 0.001) or one or two CLNMs (OR = 2.91, 95% CI 1.93-4.42; p < 0.001) also increased the risk of LLNM compared to having no CLNMs. A nomogram incorporating these risk factors was developed, and the receiver operating characteristic (ROC) curve demonstrated an area under the curve (AUC) of 0.777, indicating a high degree of predictive accuracy. CONCLUSION: Tumor location in the upper lobe, greater than 7 mm in size, ETE, and CLNMs, especially three or more, were independent risk factors for LLNM in cN0 unifocal PTMC. The nomogram based on these factors exhibited favorable predictive value and consistency.

Nomogram Model Based on Iodine Nutrition and Clinical Characteristics of Papillary Thyroid Carcinoma to Predict Lateral Lymph Node Metastasis.

OBJECTIVE: Preoperative evaluation of lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) has been one of the major clinical challenges. This study aims to develop and validate iodine nutrition-related nomogram models to predict lateral cervical lymph node metastasis in patients with PTC. METHODS: This is a retrospective study. Urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured in 187 LLNM patients and 289 non-LLNM (NLLNM) patients. All patients were randomized 3:1 into the training cohort (n = 355) and the validation cohort (n = 121). Using logistic regression analysis, we analyzed the influence of iodine nutrition-related factors and clinicopathological characteristics on LLNM in PTC patients. Lasso regression method was used to screen risk factors and construct a nomogram for predicting LLNM. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training and validation cohorts. RESULTS: Gender, SIC, smoking history, drinking history, family history of PTC, multifocality, bilateral or unilateral tumors, TSH, Tg, and tumor size were included in the nomogram model predicting LLNM, with an area under the curve (AUC) of .795. The nomogram model showed good calibration and clinical benefit in both the training and validation cohorts. CONCLUSION: The nomogram model based on iodine nutrition and other clinicopathological features is effective for predicting the lateral lymph node metastasis in PTC patients.

Risk factors for recurrent disease in small papillary thyroid cancers - a Swedish register-based study.

AIMS: To study the correlation between clinicopathological risk factors and the risk for intervention-requiring cancer recurrence in patients with small papillary thyroid cancers (sPTCs). MATERIALS AND METHODS: Records for 397 patients with sPTC (T1 ≤ 20mm) were obtained from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) between 2010 and 2016. Follow-up time was at least 5 years. Data regarding intervention-requiring cancer recurrence were obtained from patient medical records and analysed regarding lymph node (LN) status (N0, N1a and N1b) and recurrence. RESULTS: Age was significantly lower in the N1a and N1b groups compared to N0 (45 vs. 40.5 vs. 49 years, respectively; p = 0.002). Tumour size was smaller in the N1a group compared to N1b group (9 vs. 11.8 mm; p <0.01). The mean number of metastatic LNs at initial surgery was higher in the N1b compared to N1a group (6.6 vs. 3; p = 0.001), and in the recurrent compared to the non-recurrent group (7 versus 3.9; p <0.01). The recurrence rate was higher in the N1b group than the N1a and N0 groups (25% vs. 2.4% vs. 1.4%, respectively; p = 0.001). CONCLUSIONS: Lymph node stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. The management of patients with sPTC should include thorough lymph node mapping for optimal treatment and individual risk stratification.

Predicting papillary thyroid carcinoma cervical lymph node metastases: an algorithm using the American College of Radiology Thyroid Imaging, Reporting and Data System.

BACKGROUND: It is important to predict lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) preoperatively; however, the relationship between the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) score and cervical LNM remains unclear. PURPOSE: To evaluate the association between the ACR TI-RADS score and cervical LNM in patients with PTC. MATERIAL AND METHODS: This retrospective study consisted of 474 patients with 548 PTCs. Cervical LNM including central LNM (CLNM) and lateral LNM (LLNM) were confirmed by pathology. Univariate and multivariate analyses were performed to investigate the risk factors of CLNM and LLNM. RESULTS: Multivariate logistic regression analyses indicated that younger age and multifocality were risk factors for CLNM in PTCs with TR5. In addition, younger age, larger tumor size, and Hashimoto's thyroiditis (HT) were risk factors for LLNM in PTCs ≥ 10 mm with TR5. In PTCs with TR4, ACR TI-RADS scores 5-6 conferred risks for LNM. In PTCs ≥ 10 mm with TR5, ACR TI-RADS scores ≥9 were risk factors for LLNM. CONCLUSION: A higher ACR TI-RADS score is a predictor for cervical LNM in PTCs with TR4 and PTCs ≥ 10 mm with TR5.

Construction of prediction models for determining the risk of lateral lymph node metastasis in patients with thyroid papillary carcinoma based on gender stratification.

BACKGROUND: Lateral lymph node metastasis (LLNM) is associated with poor prognosis in patients with papillary thyroid cancer (PTC). The purpose of this study was to determine the risk factors for LLNM and establish prediction models that could individually assessed the risk of LLNM. METHODS: A total of 619 PTC patients were retrospectively analyzed in our study. Univariate and multivariate analysis were performed for male and female patients, respectively, to assess relationships between clinicopathological features and LLNM. By integrating independent predictors selected by binary logistic regression modeling, preoperative and postoperative nomograms were developed to estimate the risk of LLNM. RESULTS: LLNM was detected in 80 of 216 male patients. Of 403 female patients, 114 had LLNM. The preoperative nomogram of male patients included three clinical variables: the number of foci, tuner size, and echogenic foci. In addition to the above three variables, the postoperative nomogram of male patients included extrathyroidal extension (ETE) detected in surgery, central lymph node metastasis (CLNM) and high-volume CLNM. The preoperative nomogram of female patients included the following variables: age, chronic lymphocytic thyroiditis (CLT), BRAF V600E, the number of foci, tumor size and echogenic foci. Variables such as CLT, BRAF V600E, the number of foci, tumor size, ETE detected in surgery, CLNM, high-volume CLNM and central lymph node ratio were included in the postoperative nomogram. Above Nomograms show good discrimination. CONCLUSIONS: Considering the difference in the incidence rate of LLNM between men and women, a separate prediction system should be established for patients of different genders. These nomograms are helpful in promoting the risk stratification of PTC treatment decision-making and postoperative management.

Laparoscopic Extraperitoneal Approach for Lateral Pelvic Node Dissection in Rectal Cancer: Techniques and Short-Term Outcomes.

BACKGROUND: Lateral pelvic lymph node dissection has been performed selectively in rectal cancer cases; however, it involves highly skilled techniques because of the complex adjacent anatomical structures. MATERIALS AND METHODS: Laparoscopic EP-LPND was performed in Korea University Anam Hospital from June 2018, and short-term surgical outcomes were analyzed from June to December 2018. Among the patients with histologically diagnosed rectal adenocarcinoma, patients who were suspected Lateral pelvic lymph node metastasis at magnetic resonance imaging were selected for this procedure. RESULTS: Seven patients underwent laparoscopic extraperitoneal approach for lateral pelvic lymph node dissection in the study period. The mean number of retrieved lymph node was 4.57, and metastatic lymph nodes were identified in 3 patients (42.8%). All of the lymph nodes with suspected metastasis preoperatively were removed in postoperative images. There was no immediate postoperative complication beyond the moderate grade associated with lateral pelvic lymph node dissection. The median follow-up was 9 months, and there were no local recurrence nor complications related to sexual and voiding functions. CONCLUSIONS: The laparoscopic extraperitoneal approach might be an efficient way to perform lateral pelvic lymph node dissection using the same principles as the conventional method without violation of the peritoneum.

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

Impact of the viability assessment of lateral lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) without lateral lymph node (LLN) dissection is widely performed for lower advanced rectal cancer. However, it is unclear whether residual cancer cells in the LLNs undergo apoptosis, disappear, or regrow if unresected. METHODS: Overall, 293 consecutive patients with T3/4 rectal cancer who underwent CRT followed by radical surgery between September 2003 and December 2018 were retrospectively reviewed. We assessed apoptosis of the residual primary tumor, mesorectum lymph nodes (MLN), and LLN using M30 cytoDEATH immunostaining and evaluated the degree of apoptosis. The difference in the prognosis of the lateral lymph node metastasis positive (LLNM +) and lateral lymph node metastasis negative (LLNM-) groups was assessed. RESULTS: There were 31 patients (10.6%) who were diagnosed with a complete response by hematoxylin and eosin (HE) staining. The residual cancer cells showed complete apoptosis in the primary lesion in 28 patients, in the metastatic MLN in only two patients, and in the metastatic LLN in one patient. The LLNM + group had a significantly poorer distant recurrence, recurrence-free survival, and overall survival than the LLNM- group. CONCLUSION: The majority of the residual cancer tissue in LNs observed by HE staining was found to be non-apoptotic. If LLN metastasis is suspected on pretreatment imaging, performing LLN dissection together with TME should be considered.

Nomograms based on sonographic and clinicopathological characteristics to predict lateral lymph node metastasis in classic papillary thyroid carcinoma.

BACKGROUND: Lateral lymph node metastasis (LLNM) has been considered a risk factor of recurrence in papillary thyroid cancer (PTC). Preoperative detecting LLNM accurately is difficult. Solitary lateral lymph node metastasis is a special type of LLNM. We aimed to develop nomograms for predicting LLNM and multiple lateral lymph node metastasis (MLLNM). METHODS: We retrospectively retrieved 528 classic PTC patients that underwent surgery between March 2019 and May 2020. Sonographic and clinicopathological features were collected. Risk factors of LLNM and MLLNM were determined by univariate and multivariate analysis. Nomograms for predicting LLNM and MLLNM were developed. RESULTS: LLNM was independently associated with tumor size, the number of foci, location, margin, central lymph node metastasis, and lymph node ratio. Independent predictors of MLLNM were age, margin, and the number of metastatic lymph nodes in central compartment. By using above variables, we constructed nomograms for predicting LLNM and MLLNM, with area under curves of 0.864 and 0.748, respectively. CONCLUSION: Through these accurate and easy-to-use nomograms, we can detect the risk of residual LLNM postoperatively for classic PTC patients who did not receive lateral neck dissection and provide an individualized plan for postoperative management of classic PTC patients.

The middle rectal artery detected by contrast-enhanced magnetic resonance imaging predicts lateral lymph node metastasis in lower rectal cancer.

PURPOSE: Lateral lymph node (LLN) metastasis is one of the leading causes of local recurrence in patients with lower rectal cancer. Unfortunately, no diagnostic biomarkers are currently available that can predict LLN metastasis preoperatively. Accordingly, we investigated the relationship between the middle rectal artery (MRA) identified by contrast-enhanced magnetic resonance imaging (ceMRI) and LLN metastases. METHODS: Data from 102 patients with lower rectal cancer who underwent surgery, and were evaluated by preoperative ceMRI, between 2008 and 2016 were reviewed retrospectively. Two expert radiologists evaluated the MRA findings. The diagnostic performance of MRA for LLN metastasis was evaluated by a multivariate analysis with conventional clinicopathological factors. RESULTS: The MRA was detected in 67 patients (65.7%), including 32 (31.4%) with bilateral MRA and 35 (34.3%) with unilateral MRA. The tumor size, presence of the MRA, and clinical LLN status were significantly correlated with LLN metastasis. A multivariate analysis demonstrated that the presence of MRA (P = 0.045) and clinical LLN status (P = 0.001) were independent predictive factors for LLN metastasis. Furthermore, the sensitivity and negative predictive value of MRA for LLN metastasis were 95% and 97.1%, respectively. CONCLUSION: We successfully demonstrated that MRAs could be clearly detected by ceMRI, and the presence of MRA robustly predicted LLN metastasis in patients with lower rectal cancer, highlighting its clinical significance in the selection of more appropriate treatment strategies. TRIAL REGISTRATION: Trial registration number: retrospectively registered 2126 Trial registration date of registration: August 23, 2019.

Effective dissection for rectal cancer with lateral lymph node metastasis based on prognostic factors and recurrence type.

PURPOSE: There are no reports showing the significance and effective range of dissection for patients with lateral lymph node metastasis (LLNM). This study aimed to investigate the indications for lateral lymph node dissection (LLND) in patients with LLNM based on prognostic factors and recurrence types. METHODS: We reviewed 379 patients with advanced rectal cancer who were treated with total mesorectal excision plus LLND. We analyzed background factors and survival times of patients who had LLNM to determine prognostic factors and recurrence types. RESULTS: Pathological LLNM occurred in 44 (11.6%). Among patients with LLNM, the predictors of poor prognoses, according to univariate analysis, were > 3 node metastases, the presence of node metastasis on both sides, and spreading beyond the internal iliac lymph nodes. Moreover, LLNM beyond the internal iliac region was found to be an independent prognostic risk factor. Twenty-eight of the 44 patients with lateral lymph node metastasis (64%) relapsed, 22 of whom had distant metastases and 11 of whom experienced local recurrences. Among the latter group, nine (20%) and two (5%) had recurrences in the central and lateral pelvis, respectively. CONCLUSION: The therapeutic benefit of resection was high, especially in patients with ≤ 3 positive lateral lymph nodes, one-sided bilateral lymph node areas, and positive nodes localized near the internal iliac artery.

Is prophylactic lateral lymph node dissection needed for lower rectal cancer? A single-center retrospective study.

BACKGROUND: The effectiveness of prophylactic lateral lymph node dissection (LLND) in treating patients with lower rectal cancer remains controversial and has not been clearly established. Therefore, we aimed to retrospectively analyze the survival impact of prophylactic LLND in patients with lower rectal cancer. METHODS: Data of 301 patients with lower rectal cancer (tumor's lower edge on the anal side of the peritoneal reflexion) with clinical T3 disease and negative preoperative lateral lymph node metastasis, who underwent radical resection (R0) at our hospital between April 2007 and March 2017, were included in this study. Patients who received preoperative chemotherapy or radiotherapy were excluded. The relapse-free survival (RFS) and overall survival (OS) rates were compared between the dissection (prophylactic LLND, n = 37) and non-dissection (no prophylactic LLND, n = 264) groups. RESULTS: Significantly fewer men and younger patients were noted in the dissection group than in the non-dissection group. Post-surgery 3- and 5-year RFS rates were 69.6% and 66.8% in the dissection group and 75.1% and 72.5% in the non-dissection group, respectively (5-year post-surgery RFS, p = 0.58). In the dissection and non-dissection groups, the 5-year OS rates were 86.5% and 79.7%, respectively (p = 0.29), and the 5-year cancer-specific survival rates were 88.9% and 86.0%, respectively (p = 0.29), with no significant differences. Lateral lymph node recurrence was observed in one (2.7%) and 10 patients (3.8%) in the dissection and non-dissection groups, respectively, and there was no significant difference between the groups. CONCLUSIONS: In this study, the effectiveness of prophylactic LLND was limited in patients with > T3 lower rectal cancer with no evidence of preoperative lymph node metastasis. Prophylactic LLND may not be necessary if there is no preoperative lymph node metastasis, even if the invasion depth is T3 or higher.

What is the impact of systemic chemotherapy for lateral lymph nodes in patients with locally advanced low rectal cancer?

PURPOSE: Systemic chemotherapy (SC) before surgery is a potential treatment to improve survival in patients with advanced rectal cancer. However, the impact of SC on lateral lymph nodes (LLNs) remains unclear. METHODS: A total of 78 patients with stage II/III low rectal cancer, who received 3-month oxaliplatin-based SC followed by LLN dissection (LLND) in principle, were analysed retrospectively. "Total lateral lymph node metastases (tLLNMs)" was defined as having either pathological LLNMs (pLLNMs) or lateral local recurrences (LLRs). Patients with the maximum short-axis size of LLNs ≥ 7 mm were classified into the swollen group (n = 21). RESULTS: In the total cohort, tLLNMs included 6 pLLNMs (7.7%) and 2 LLRs (2.6%). In the non-swollen group, no patients had pLLNMs, but one had LLR (1.8%). In the swollen group, pLLNMs and LLRs were detected in 6 (28.6%) and 1 (4.8%), respectively. The swollen group was an independent risk factor for tLLNMs (P < 0.001), leading to the significantly worse 5-year relapse-free survival (RFS) of 52.4% than the others. CONCLUSION: For patients without swollen LLNs, SC could allow for omission both of lateral irradiation and LLND. For patients with swollen LLNs, the lateral local control was favourable after SC and LLND without chemoradiotherapy (CRT); however, oxaliplatin-based SC might be insufficient to improve survival, requiring more intensive chemotherapy. CRT should be indicated according to the other risk factors of central local recurrence, although the swollen LLNs should be removed.

Rectal neuroendocrine tumor developing lateral lymph node metastasis after curative resection: a case report.

BACKGROUND: Among gastrointestinal neuroendocrine tumors (NETs), rectal NETs account for about one-third of all tumors. Despite the occasional observation of lateral lymph node metastasis in patients with rectal NETs, lateral lymph node recurrence is rare. We present a rare case of lateral lymph node recurrence after curative resection of a rectal NET. CASE PRESENTATION: A 55-year-old man presented with fecal occult blood and colonoscopy revealed a mass in the distal rectum. Systematic computed tomography scan showed no evidence of regional lymph node or distant metastasis. The patient underwent laparoscopic intersphincteric resection and D2 lymph node dissection with diverting stoma. Diverting stoma closure was performed 6 months after the initial operation. Pathological diagnosis was NET of the rectum, grade 2, T1b, N0, Stage I without lymphovascular invasion. At 54 months after the surgery, recurrence in a left lateral lymph node was suspected and lymph node dissection was performed. The pathological diagnosis of the specimen was consistent with lateral lymph node metastasis of a recurrent rectal NET. To our best knowledge, there are no case reports in English of lateral lymph node recurrence after curative resection of a rectal NET, grade 2, T1b, N0, Stage I without lymphovascular invasion. CONCLUSION: Considering that patients with lateral lymph node metastasis have worse survival than those without metastasis in rectal cancer, if complete resection of the tumor can be achieved for lateral lymph node recurrence, surgery may be an important option in the strategy to treat this condition.

Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice.

BACKGROUND: Cervical lymph node metastases are very common in papillary thyroid cancer (PTC), and typically spread in a predictable stepwise fashion in clinical practice. However, lateral lymph node metastasis (LLNM) without central lymph node metastasis (CLNM) as skip metastasis is not rare in PTC. The aim of this study was to investigate the incidence, risk factors and pattern of skip metastasis in PTC. METHODS: A total of 271 patients with PTC and suspicious LLN diagnosed by pre-operation examinations who underwent total thyroidectomy and central lymph node dissection plus lateral lymph node dissection between January 2008 and December 2011 were enrolled in this study. Clinicopathological features were collected, and the pattern of cervical lymph node metastasis and skip metastasis were analyzed. RESULTS: The LLNM rate was 74.9% (203/271, diagnosed by postoperative pathology examination) and significantly associated with extrathyroid extension (ETE), primary tumor located at the upper pole, and CLNM (p < 0.05). The skip metastasis rate was 14.8% (30/203) and was more frequently found in microcarcinoma patients, especially when the primary tumor size was ≤0.5 cm (p = 0.001 OR = 12.9). However, skip metastasis was unrelated to the remaining factors examined. CONCLUSION: Small cancers with a pre-operation diagnosis of LLNM are more likely to have skip metastases, especially when the primary tumor size is less than 0.5 cm in diameter; however, this type of metastasis appears to develop in a random fashion. Thus, additional research is needed to identify potential predictive factors, such as a primary tumor located at the upper pole.

Lateral lymph node metastasis in papillary thyroid microcarcinoma: a study of 5241 follow-up patients.

PURPOSE: To investigate the impact of lateral lymph node metastasis in papillary thyroid microcarcinoma (PTMC). METHODS: 5241 PTMC patients with follow-up information were enrolled in the current study. These patients underwent primary surgery in our situation from January 1997 to December 2016. Additionally, a validation cohort consisting of 274 PTMC patients who underwent primary surgery between January 2020 and December 2021 was also included. Univariable and multivariate logistic analyses were conducted to identify the association between clinicopathologic features and lateral lymph node metastasis (LLNM). Kaplan-Meier survival curve analysis was used to calculate the disease-free survival (DFS) rate. The fitting curve was generated to identify the quantitative relationship between central lymph node metastases (CLNM) and LLNM. RESULTS: Of 5241 PTMC patients, cervical lymph node metastasis was detected in 1494 (28.5%) cases, including 1364 (26.0%) with CLNM only and 130 (2.5%) with LLNM. With a median follow-up time of 60 months (interquartile range [IQR], 44-81), recurrence was detected in 114 patients (2.2%). Multivariate Cox regression analyses showed that LNM was the only independent risk factor for recurrence, with HR values of 3.03 in CLNM and 11.14 in LLNM, respectively. Tumor diameter >0.5 cm (hazard ratio [HR]:1.80), multifocality (HR:2.59), bilaterality (HR:2.13), extrathyroidal invasion (HR:2.13), and CLNM (HR:5.11) were independent risk factors for LLNM. The prevalence of LLNM escalated significantly with increasing number of lymph node involvement in CLNM when stratified by the number of metastatic lymph nodes and trend was observed similarly in the validation cohort. The fitting curve showed that the incidence of LLNM could be as high as 20.7% when the number of CLNM ≥ 5. CONCLUSIONS: By analyzing a large database with follow-up information, our study provides evidence that LLNM is significantly correlated with tumor recurrence in patients with PTMC. Tumor size (>0.5 cm), multifocality, bilaterality, extrathyroidal extension (ETE) and CLNM are independent risk factors for LLNM.

The role of the tumor microenvironment in papillary thyroid microcarcinoma nodal metastasis.

The genetic alterations currently identified in papillary thyroid microcarcinomas (PTMCs) are insufficient for distinguishing tumors with aggressive features. We aimed to identify candidate markers associated with lateral lymph node metastasis (LLNM, N1sb disease) in patients with PTMC using transcriptomic analysis. RNA sequencing was performed on 26 matched tumor and normal thyroid tissue samples (N0, n = 14; N1b, n = 12), followed by functional enrichment analyses of differentially expressed genes (DEGs). EcoTyper was used to explore the distinct tumor microenvironment (TME). We identified 631 DEGs (213 upregulated and 418 downregulated) between N1b and N0 PTMCs. The most significantly upregulated genes in N1b were associated with tumorigenesis, adhesion, migration, and invasion. DEGs were mainly enriched in the pathways of idiopathic pulmonary fibrosis, TME, wound healing, and inhibition of matrix metalloproteases. We predicted the activation of these pathways in N1b PTMCs. N1b PTMCs had a unique TME with abundant fibroblasts and epithelial cells, associated with an increased risk of disease progression. Fibroblast marker genes, including POSTN, MMP11, TNFAIP6,and FN1, and epithelial cell marker genes, including NOX4, MFAP2, TGFVBI,and TNC, were selected. POSTN and FN1, fibroblast cell-specific genes, and NOX4 and TNC, epithelial cell-specific genes, were promising biomarkers for predicting LLNM development and recurrence in patients with PTMC. We delineated the cellular ecotypes within the TME of patients with N1b PTMC and revealed potential markers for predicting LLNM and the prognosis of PTMC. These findings provide valuable insights into the contributions of cancer-associated fibroblasts and epithelial cells to PTMC progression and metastasis.

Efficacy of lateral lymph node dissection for local control of rectal cancer: A multicenter study.

Background: This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods: We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (-) groups, respectively. Propensity score-matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results: In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3-year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (-) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3-year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (-) groups, respectively. Conclusion: LLND would lead to comparable local control in the pLLNM (+) and (-) groups if the clinicopathological characteristics except for LLNM are similar.