Prophylactic Lateral Lymph Node Dissection Research Articles

The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study.

The purpose of this study was to evaluate the benefits of prophylactic lymph node dissection in medullary thyroid carcinoma (MTC) patients without radiographically lateral neck metastases. Retrospective cohort study. Tianjin Medical University Cancer Institute and Hospital. Patients who underwent primary surgery for MTC between 2011 and 2019 and without structural disease of the lateral neck preoperatively. Locoregional recurrence, disease-free survival (DFS), and overall survival (OS) were examined. The patients were divided into two groups: the central lymph node dissection (CLND) only group and the prophylactic lateral lymph node dissection (PLND) group, which included CLND and ipsilateral lateral lymph node dissection (LLND). A total of 89 patients were included: 71 patients in the CLND group and 18 patients in the PLND group. Although there were no significant differences in age, gender, multifocality, capsule invasion or TNM stage between the two groups, the tumour size and preoperative median calcitonin levels were different. The recurrence rate was 4.2% for the CLND group and 5.6% for the PLND group (p > 0.05). DFS among the CLND and PLND groups was 95.4% and 94.4%, and OS among the groups was 100% and 94.1% (p > 0.05) at 5 years. The biochemical cure rates were similar. PLND in the absence of structural disease of the lateral neck preoperatively is not associated with improved survival in patients with sporadic MTC.

Scope of prophylactic lymph node dissection in the surgical treatment of differentiated thyroid cancer. Recommendations of the AFCE (Association francophone de chirurgie endocrinienne) with the SFE (Société française d’endocrinologie) and the SFMN (Société française de médecine nucléaire)

Prophylactic lymph node dissection is considered only for papillary cancers. It is not indicated for vesicular cancers or oncocytic cancers, nor should it entail a secondary surgical intervention in the event of an incidental discovery of papillary cancer on a thyroidectomy specimen. Prophylactic lymph node dissection means a cervical lymph node dissection in the absence of any pre- or intraoperative evidence (biological, cytological, histological, clinical or ultrasound) of lymph node metastases. There is currently no evidence in the literature that prophylactic central dissection improves overall survival, which is similar for N0 and NX patients. Yet although prophylactic lymph node dissection is not justified by overall survival, it does seem to reduce the risk of locoregional recurrence in the case of micro-N1, and it allows occult metastases to be detected and a tumour to be reclassified. This enables patients at risk of recurrence to be more surely identified and therapeutic strategy and follow-up adapted accordingly. Prophylactic homolateral central lymph node dissection is warranted for papillary cancers with largest ultrasound diameter 4cm and above and/or with intraoperative macroscopic evidence of perithyroid tissue invasion. The benefits and risks of lymph node dissection must be assessed and discussed on a case-by-case basis. Only a central lymph node dissection homolateral to the tumour is recommended, except for bilateral or isthmic cancers, for which a prophylactic bilateral central lymph node dissection may be considered. This bilateral lymph node dissection incurs an increased risk of complications (parathyroids, recurrent laryngeal nerve). Prophylactic lateral lymph node dissection is not recommended.

Extent of cervical lymph node dissection: Recommendations from the Francophone Association for Endocrine Surgery, the French Society of Endocrinology and the French Society of Nuclear Medicine

When metastatic ipsilateral central lymph nodes from thyroid cancer are identified pre- or intraoperatively (cN1a), ipsilateral central lymph node dissection should be performed concomitantly with thyroidectomy. When the patient is N1a on one side, contralateral prophylactic central lymph node dissection can also be considered. Prophylactic ipsilateral lymph dissection is not recommended. Ipsilateral compartment lymph node dissection is recommended in the corresponding sector for treatment of thyroid cancer with lymph node involvement (cN1b). Lymph node dissection can be limited to sectors III and IV when one of these sectors (or both) is involved and ultrasound does not demonstrate involvement of the other lateral sectors. Associated prophylactic lymph node dissection of sectors IIA and IIB is not recommended, while lymph node dissection of sector V (and exceptionally sector I) is indicated only when metastatic lymph nodes are proven. Prophylactic lymph node dissection of sector VB can be considered when positive lymph nodes are identified in sectors II, III and IV. When isolated metastatic lateral lymph nodes are identified (cN1b), prophylactic central (sector VI) lymph node dissection is recommended on the same side as the lateral compartment in addition to ipsilateral lateral lymph node compartment dissection. The level of evidence is insufficient to recommend prophylactic lateral lymph node dissection on the contralateral side for unilateral cN1b tumors. This type of lymph node dissection can be discussed for tumors that are at high risk of recurrence, bilateral tumors, in case of ipsilateral lateral lymph nodes > 3cm or in presence of > 4 metastatic lymph nodes in the central compartment.

Construction and Validation of a Prediction Model for Identifying Clinical Risk Factors of Lateral Lymph Node Metastasis in Medullary Thyroid Carcinoma.

PurposeMedullary thyroid carcinoma (MTC) is a rare but highly invasive malignancy, especially in terms of cervical lymph node metastasis. However, the role of prophylactic lateral lymph node dissection (LLND) is still controversial. We hereby aim to explore the risk factors of lateral lymph node metastasis (LLNM) in patients with MTC to guide clinical practice.Patients and MethodsThe clinicopathological characteristics of patients with MTC from the Surveillance, Epidemiology, and End Results (SEER) Program and the Second Affiliated Hospital of Chongqing Medical University were reviewed and analyzed. Univariate and multivariate logistics regression analyses were used to screen the risk factors of LLNM in patients with MTC.ResultsFour variables, including male gender, multifocality, extrathyroidal invasion (EI), and large tumor size (all p < 0.05), were identified as potential independent factors of LLNM in patients with MTC. Based on these results, an individualized prediction model was subsequently developed with a satisfied C-index of 0.798, supported by both internal and external validation with a C-index of 0.816 and 0.896, respectively. We also performed the decision curve analysis (DCA) and calibration curve, which indicated a remarkable agreement in our model for predicting the risk of LLNM.ConclusionWe determined that various clinical characteristics, male gender, multifocality, EI, and large tumor size, were significantly associated with LLNM in patients with MTC. Thus, a validated prediction model utilizing readily available variables was successfully established to help clinicians make individualized clinical decisions on MTC management, especially regarding whether the LLND is necessary for patients with clinical negative lateral lymph node involvement and the frequency of follow-up without LLND.

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

BackgroundThe 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.MethodsData 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.ResultsSignificantly 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.ConclusionsIn 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.

The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway

Background: Preoperative predictors for the need of prophylactic lymph node dissection in the lateral neck have been studied in patients with medullary thyroid carcinoma (MTC). Objectives: To evaluate the ability of serum calcitonin to predict the extent of surgery needed in the lateral neck. Methods: This retrospective population-based cohort study includes data from 94 of 139 patients with MTC surgically treated in Norway from 2003 to 2016. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway, and grouped according to calcitonin levels. In 58 patients without distant metastases or disease progression to the next tumor level (NPNL), data were compared in prognostic groups (N0-NPNL), (N1a-NPNL), and (N1b-NPNL). Results: At calcitonin levels ≤500, 501–1,000, and >1,000 pmol/L, metastatic lymph nodes in the lateral neck were found in 16, 50, and 71% of the patients, respectively. In the prognostic groups, 19% of N0-NPNL patients had calcitonin >500 pmol/L and 17% of N1b-NPNL patients had calcitonin ≤500 pmol/L. In multivariate analysis, factors predicting biochemical cure and calcitonin level ≤500 pmol/L were no metastatic lymph nodes in the lateral neck (p = 0.030) and tumor diameter ≤20 mm (p < 0.001), respectively. Factors related to metastatic lymph nodes in the lateral neck were extrathyroidal extension (p = 0.007) and no biochemical cure (p = 0.028). Conclusions: Basal calcitonin cannot predict the need for prophylactic lateral lymph node dissection in patients with MTC. Further prospective, randomized studies are warranted.

1827P - Surgery for lymph node metastases of sporadic medullary thyroid carcinoma

Background: Medullary thyroid carcinoma (MTC) arises from malignant proliferation and differentiation of C cells, approximately 2% of all thyroid malignancies. Calcitonin (CT) and carcinoembryonic antigen (CEA) secreted by C cells are the main secretory product and serves as a marker for the diagnosis of this disease. It is also used in the follow-up of MTC patients after thyroidectomy for the identification of relapse or progression of disease. Compared with other thyroid cancers, MTC has unique biological characteristics and is insensitive to radiotherapy, chemotherapy and iodine therapy. Surgical intervention is currently the only effective, curative treatment for medullary thyroid cancer. The 2015 American Thyroid Association recommended total thyroidectomy and different range of lymph node dissection, but controversy remains surrounding the indication for prophylactic lateral lymph node dissection. This study was performed to analyze the risk factors for cervical lymph node metastases and predict the indication for prophylactic lateral neck dissection in patients with sporadic medullary thyroid carcinoma (SMTC). Methods: The aims of this study were to analyze the risk factors of cervical lymph node metastases, and also to predict the indication of prophylactic lateral neck dissection in SMTC patients. Results: Metastases rates in central and lateral compartment were 46.2% (30/65) and 40.0% (26/65), respectively. Univariate analyses showed the incidence of cervical lymph node metastases was significantly higher in patients with tumor size >1cm, tumor multifocality and thyroid capsule invasion. Multivariate analyses revealed that only thyroid capsule invasion was an independent predictive factor for central compartment metastases (p < 0.001, OR = 11.080) and lateral neck metastases (p < 0.001, OR = 9.067). Moreover, the possibility of central compartment metastases was higher when preoperative value of serum carcinoembryonic antigen (CEA) was above 30 ng/mL (60% vs 34.3%, χ2=4.298, P = 0.038). Conclusions: The medullary thyroid carcinoma has a high incidence of cervical lymph node metastases. Prophylactic lateral node dissection is necessary in patients with thyroid capsule invasion or with high value of serum carcinoembryonic antigen (CEA). Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Clinicopathological features for predicting central and lateral lymph node metastasis in papillary thyroid microcarcinoma: Analysis of 66 cases that underwent central and lateral lymph node dissection

Currently the surgical approach for papillary thyroid microcarcinoma (PTMC), particularly the range of lymph node dissection, remains controversial. The present study aims to evaluate the risk factors for central and lateral lymph node metastasis (CLNM and LLNM) for appropriate clinical decision of neck lymph node dissection in PTMC. A total of 66 cases of PTMC that underwent unilateral or bilateral lobectomy plus prophylactic cervical lymph node dissection were collected for clinicopathological evaluation, including age, gender, tumor size, subtypes, extrathyroidal invasion, multifocality, calcifications, loss of cellular polarity/cohesiveness (LOP/C) in the invasive front, CLNM and LLNM, and retrospectively analysis. Univariate analysis revealed that LOP/C was significantly associated with CLNM (P=0.001) and LLNM (P<0.0001). The male gender was a risk factor of CLNM (P=0.04), while the age <45 years, tumor size >0.5 cm and multifocality were high-risk factors of LLNM (P=0.022, 0.044 and 0.005, respectively). Multivariable analysis revealed that LOP/C was significantly associated with CLNM [P=0.007, odds ratio (OR)=7.765, 95% confidence interval (CI)=1.773–33.996] and LLNM [P=0.029, OR=5.717, 95% CI=1.190–27.470]. Both multivariable analysis and χ2 test revealed that CLNM was another important high-risk factor of LLNM (P=0.021, OR=5.444, 95% CI=1.290–22.969, χ2=17.867, P<0.001). The present study revealed that prophylactic central lymph node dissection is essential for PTMC surgery and that prophylactic lateral lymph node dissection is recommend for patients with LOP/C and CLNM, which can be performed by intraoperative frozen section pathological examination. This must be considered discreetly in the case of patients with age <45 years, tumor size >0.5 cm and multifocal lesions.

Risk prediction and clinical model building for lymph node metastasis in papillary thyroid microcarcinoma.

The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central/lateral lymph node dissection, remains controversial. This study investigated the clinicopathologic factors predictive of lymph node metastasis (LNM) in patients diagnosed with PTMC. Multivariate logistic regression analysis was used for PTMC patients identified from the Surveillance, Epidemiology, and End Results database who were treated by surgery between 2002 and 2012, to determine the association of clinicopathologic factors with LNM. According to the results, a total of 31,017 patients met the inclusion criteria of the study. Final histology confirmed 2,135 (6.9%) cases of N1a disease and 1,684 cases (5.4%) of N1b disease. Our multivariate logistic regression analysis identified variables associated with both central LNM and lateral lymph node metastasis (LLNM), including a younger age (<45 years), male sex, non-Hispanic white and other race, classical papillary histology, larger tumor size, multifocality, and extrathyroidal extension; distant metastasis was also significantly associated with LLNM. The significant predictors identified from multivariable logistic regression were integrated into a statistical model that showed that extrathyroidal extension had maximum weight in the predictive role for LNM. LLNM was validated to be a significant risk factor for cancer-specific death in Cox regression analyses, whereas central LNM failed to predict a worse cancer-specific survival according to our data. Therefore, we suggested that central lymph node dissection could be performed in certain patients with risk factors. Given the prevalence of LLNM in PTMC, a thorough inspection of the lateral compartment is recommended in PTMC patients with risk factors for precise staging; from the viewpoint of a radical treatment for tumors, prophylactic lateral lymph node dissection that aims to remove the occult lateral lymph nodes may be an option for PTMC with risk factors. Multicenter studies with long-term follow-up are recommended to better understand the risk factors and surgical management for cervical nodes in PTMC.

Lateral Lymph Node Dissection for Lower Rectal Cancer

The mainstay of surgical therapy for rectal cancer is colectomy (including lesions) with lymph node dissection. The lymphatic spread of rectal cancer can proceed in two directions: medially toward the origin of the inferior mesenteric artery or laterally toward the pelvis aslong the internal iliac artery. To prevent postoperative recurrence, lymph nodes situated along these two axes should be adequately dissected, leaving no residual cancer cells. In Japan, the standard procedure for advanced lower rectal cancer is mesorectal excision and lateral lymph node dissection with autonomic nerve preservation. In Europe and North America, lateral lymph node dissection used to be performed, but it led to increased blood loss, complications, and dysfunction, with no improvement in survival. Lateral lymph node dissection is thus no longer performed. Instead, multidisciplinary therapy combining mesorectal excision with preoperative chemoradiotherapy is now the standard treatment for advanced rectal cancer. Although lateral lymph node dissection decreases the rate of local recurrence similar to preoperative chemoradiotherapy, whether it contributes to improved survival remains unclear. In addition, it is unlikely that prophylactic lateral lymph node dissection is required in all patients with rectal cancer. Definition of the indications for lateral lymph node dissection is thus an important concern.

Lateral cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging‐guided and prophylactic removal of the lateral compartment

Papillary thyroid cancer (PTC) is a common endocrine cancer and frequently presents with lymph node (LN) metastases. The frequency of LN metastases in the lateral compartment and their surgical removal are poorly defined. There are no prospective randomised controlled trials addressing an eventual outcome difference relating to the extent of the initial surgical approach. The aim of this study was to define the extent of lateral LN involvement and the role of imaging in identification of these metastatic LN. A systematic review of studies of patients with PTC undergoing either prophylactic or therapeutic lymphadenectomy of the lateral cervical compartment. Studies involving imaging modalities in the detection of lateral cervical LNs in PTC were also analysed. Systematic review on the frequency of lateral LN metastases and their detection using various imaging tools identified 19 studies containing data on 5587 patients undergoing prophylactic or imaging-guided removal of the lateral compartment. Imaging-guided surgery retrieved cancerous lateral LNs in 446/3178 or 14% of eligible patients, whilst prophylactic lateral neck dissection yielded histopathological proof of cancer in 1177/204 or 57·5% of patients. The frequency of lateral compartment metastases increased with T stage. The sensitivity of ultrasound and CT was poor as low as 27% when accurately calculated. Metastatic cervical LNs were found in more than half of patients when prophylactic lateral LN dissection was performed. Use of conventional imaging for the selection of the surgical approach to the lateral cervical compartment may commonly identify stage N1a instead of N1b and thus lead to false stage assignment as stage III rather than stage IV, concealing the severe prognostic implications of this stage progression in individual patients.