Local recurrences in western low rectal cancer patients treated with or without lateral lymph node dissection after neoadjuvant (chemo)radiotherapy: An international multi-centre comparative study

BackgroundIn the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients.MethodsAn international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (≥5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group).ResultsLLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND- (p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent significant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups.ConclusionA LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution.     

低位直肠癌选择性侧方淋巴结清扫研究进展

盆腔侧方淋巴结(Lateral pelvic lymph node,LPLN)是低位直肠癌患者常见的局部转移部位,同时也是术后局部复发的主要部位,然而目前对于LPLN转移的治疗方案仍没有明确的定论.同时LPLN的转移应被看作是局部而不是全身,新辅助放化疗(Chemoradiotherapy,CRT)并不能替代手术清扫,...     

磁共振成像在进展期直肠癌淋巴结转移以及新辅助治疗后淋巴结再分期中的应用

术前新辅助放化疗是局部进展期直肠癌(cT3-4或cN+)综合治疗的重要组成部分.治疗前准确评估淋巴结状态以及新辅助治疗后的淋巴结再分期对临床医师的诊疗决策以及患者的预后评估有着重要意义.高分辨磁共振成像(high resolution magnetic resonance imaging,HR-MRI)、弥散加权磁共振...     

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer

BackgroundStandard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs.MethodsPubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed.ResultsSeven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3–15%) compared to LLND- (11–27%; RR = 0.40, 95%CI [0.25–0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61–78% vs. 46–79% for LLND-; RR = 0.72, 95%CI [0.51–1.02], p = 0.143), and neither was five-year OS (range 69–91% vs. 72–80%; RR = 0.72, 95%CI [0.45–1.14], p = 0.163).ConclusionIn rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.     

局部治疗在直肠癌盆腔侧方淋巴结转移中的作用北大核心CSCD

盆腔侧方淋巴结(LPLN)转移是直肠癌预后不佳因素, 在低位、T3-T4期、直肠系膜淋巴结阳性情况下更常见, 但无准确预测转移的因素。高分辨率MRI是目前诊断LPLN转移的首选手段, 但阈值选择仍不明确。局部进展期直肠癌的侧方淋巴结转移治疗模式在全球存在分歧, 欧美国家主张放化疗联合直肠全系膜切除术, 而日本推荐直肠全系膜切除术联合LPLN清扫。放疗与手术联合可取得很好的局控, 利用放疗前、后MRI的侧方淋巴结信息, 可筛选出高危患者进行强化治疗, 如放化疗后行LPLN清扫或LPLN区放疗推量。目前各种手段在治疗LPLN转移方面的作用仍缺乏高质量证据, 尚需更多的研究来改善治疗策略。     

Oncologic benefit of adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and curative surgery with selective lateral pelvic lymph node dissection: An international retrospective cohort study

IntroductionIntensive local treatment comprising total mesorectal excision (TME) with selective lateral pelvic lymph node dissection (LPND) after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) has received attention among clinicians treating rectal cancer. It remains unclear whether adjuvant chemotherapy (ACT) after intensive local treatment is beneficial for these patients. We evaluated the oncologic benefit of ACT for patients with LARC who received intensive local treatment.Materials and methodsThis international multicentre retrospective cohort study included 737 patients treated in Japan and Korea between 2010 and 2017. The effectiveness of ACT on recurrence-free survival (RFS) was evaluated using univariable and multivariable Cox proportional hazards models, with subgroup analyses to identify subpopulations potentially benefiting from ACT.ResultsThe median follow-up was 49 months; the 5-year RFS and local recurrence rates for the entire cohort were 72.1% and 4.9%, respectively; 514 patients (69.7%) received adjuvant chemotherapy, without an oncologic benefit (hazard ratio, 1.14; 95% confidence interval [CI]: 0.79–1.68) demonstrated in the multivariable Cox regression analysis. In subgroup analyses, the distributions of the 95% CI in patients aged ≥70 years and those with ypStage 0 tended to place a disproportionate emphasis that favoured the non-ACT treatment strategy.ConclusionDespite achieving good local control with intensive local treatment strategy, the effectiveness of ACT for the LARC patients with CRT followed by TME with selective LPND was not proved. Elderly patients and those with ypStage0 may not receive benefit from ACT after CRT and TME ± LPND.     

Lateral pelvic lymph node dissection in the management of locally advanced low rectal cancer: Summary of the current evidence

Lateral pelvic lymph nodes (LPLN) are a major site for local recurrence following curative resection for low locally advanced rectal cancer. Ongoing advances in imaging techniques have improved predicting LPLN metastasis (LPLNM) during pre-operative staging. However, there is ongoing debate on optimal management of this subgroup of patients with variation between guidance of different societies. In Japan, LPLNM is considered as local disease and addressed by lateral pelvic node dissection (LPLND) in addition to total mesorectal excision (TME). However, in the west, LPLNM is considered as metastatic disease and those patients are offered neoadjuvant chemoradiotherapy (nCRT) followed by TME surgery. The potential surgical risks and morbidity associated with LPLND as well as the uncertainty of the oncological outcome have raised the concern that patients with locally advanced low rectal cancer with LPLNM could be over or under-treated.A comprehensive review of literature was performed, summarizing the current evidence on available modalities for predicting LPLNM, the role of LPLND in the management of advanced low rectal cancer and the available surgical approaches with their impact on surgical and oncological outcomes.LPLND is associated with increased operative time, blood loss and post-operative morbidity. The potential benefits for local disease control and survival still awaits high quality studies. There has been increasing number of reports of the use minimally invasive approaches in LPLND in an attempt to reduce post-operative complications.There is need for high quality evidence to define the role of LPLND in management of patients with advanced low rectal cancer.     

Predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis (clinical stage II/III): The analysis of data from the clinical trial (JCOG0212)

BackgroundMesorectal excision (ME) is the standard surgical procedure for lower rectal cancer. However, in Japan, total or tumor-specific ME with lateral pelvic lymph node dissection (LLND) is the standard surgical procedure for patients with clinical stages II or III lower rectal cancer, because lateral pelvic lymph node metastasis occasionally occurs in these patients. The aim of study was to elucidate the predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis.MethodsData form the clinical trial (JCOG0212) was analyzed. The JCOG0212 was a randomized controlled trial to confirm the non-inferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection for clinical stage II/III patients who don't have clinical lateral pelvic lymph node metastasis in terms of relapse free survival. This study was conducted at a multitude of institution33 major hospitals in Japan. Among the 351 patients who underwent lateral lymph node dissection in the JCOG0212 study, 328 patients were included in this study. Associations between pathological lateral pelvic lymph node metastasis and preoperative and postoperative factors were investigated. The preoperative factors were age, sex, clinical stage, tumor location, distance from anal verge, tumor size, and short-axis diameter of lateral pelvic lymph node on computed tomography and the postoperative factors were pathological T, pathological N, and histological grade.ResultsAmong the 328 patients, 24 (7.3%) had pathological lateral pelvic lymph node metastasis. In multivariable analysis of the preoperative factors, patient age (p = 0.067), tumor location (p = 0.025), and short-axis diameter of lateral pelvic lymph node (p = 0.002) were significantly associated with pathological lateral pelvic lymph node metastasis.ConclusionsPatient age, tumor location, and short-axis diameter of lateral pelvic lymph node were predictive factors of pathological lateral pelvic lymph node metastasis.     

直肠癌新辅助治疗后淋巴结转移相关因素分析

背景与目的：新辅助治疗（放疗或放化疗）可使直肠癌的浸润深度和淋巴结转移状况都发生改变,而淋巴结转移情况对直肠癌的新辅助治疗方案的选择及后继治疗方案的选择有重要参考作用。本研究的目的是通过回顾性分析了解直肠癌新辅助治疗后影响淋巴结转移的相关因素。方法：收集2003年8月至2008年2月接受新辅助治疗及TME手术的中低位直肠癌病例93例,建立数据库。选择年龄、性别、肿瘤距肛缘距离、组织类型、新辅助治疗后T分期（ypT分期）、放疗前血清癌胚抗原（careinoembryonic antigen．CEA）水平和CA19—9水平、放疗后血清CEA水平和CA19—9水平、放射剂量、接受含奥沙利铂方案的同期化疗与否、放射治疗与手术的时间间距等12项临床病理指标及治疗参数,用单因素分析和多因素分析的方法研究各因素对93例行新辅助治疗的直肠癌患者淋巴结转移情况的影响。结果：单因素分析显示．放疗后血清CEA水平、放射剂量、放射治疗与手术的时间间距、接受含奥沙利铂方案的同期化疗以及ypT分期是新辅助治疗后淋巴结转移情况（ypN分期）的相关因素。有序反应变量Logistic回归模型多因素分析显示,接受同期含奥沙利铂方案化疗及术后T分期是淋巴结转移的独立影响因素,相关系数分别为-0．481和0．503。结论：直肠癌新辅助治疗后ypT分期仍与ypN分期相关,ypT0-1患者淋巴结转移率低。含奥沙利铂的同期化疗可显著降低淋巴结转移的风险。有改善预后的潜在优势。     

直肠癌病理特征与淋巴结转移的关系

目的探讨大肠癌的组织学分型、浸润与淋巴结转移的关系。方法回顾性研究167例大肠癌根治标本中具有淋巴结转移的84例病理资料。结果未分化癌最常发生淋巴结转移(16／16)，其它依次为低分化腺癌(13／17)、粘液腺癌(12／20)、中分化腺癌(44／89)及高分化腺癌(2／21)。其中肠管全层浸润115例，侵犯深肌层8例，浅肌层10例。另外还发现，淋巴结的阳性率与术中切除淋巴结的数量有关。结论大肠癌的淋巴结转移与组织学分型、肿瘤细胞的分化程度、浸润的范围及切除的淋巴结数量具有密切关系。     

Predictive factors for early distant metastasis after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

BACKGROUNDDistant relapse is the leading cause of cancer-related death in locally advanced rectal cancer. Neoadjuvant chemoradiation (NACRT) followed by surgery inevitably delays delivery of systemic treatment. Some patients show early distant metastasis before systemic treatment.AIMTo identify the most effective treatments. We investigated prognostic factors for distant metastasis, especially early distant metastasis, using the standard treatment paradigm to identify the most effective treatments according to recurrence risk.METHODSFrom January 2015 through December 2019, rectal cancer patients who underwent NACRT for having clinical T 3-4 or clinical N 1-2 disease according to the 8^th American Joint Committee on Cancer staging system were included. Radiotherapy was delivered to the whole pelvis with concomitant chemotherapy. Patients received surgery 6-8 wk after completion of NACRT. Adjuvant chemotherapy was administered at the physician’s discretion. RESULTSA total of 127 patients received NACRT. Ninety-three patients (73.2%) underwent surgery. The R0 resection rate was 89.2% in all patients. Pathologic tumor and node downstaging rates were 41.9% and 76.3%. Half the patients (n = 69) received adjuvant chemotherapy after surgery. The 3-year distant metastasis-free survival (DMFS) and overall survival (OS) rates were 81.7% and 83.5%. On univariate analyses, poorly differentiated tumors, > 5 cm, involvement of mesorectal fascia (MRF), or presence of extramural involvement (EMVI) were associated with worse DMFS and OS. Five patients showed distant metastasis at their first evaluation after NACRT. Patients with early distant metastasis were more likely to have poorly differentiated tumor (P = 0.025), tumors with involved MRF (P = 0.002), and EMVI (P = 0.012) than those who did not. CONCLUSIONEMVI, the involvement of MRF, and poor histologic grade were associated with early distant metastasis. In order to control distant metastasis and improve treatment outcome, selective use of neoadjuvant treatment according to individualized risk factors is necessary. Future studies are required to determine effective treatment strategies for patients at high risk for distant metastasis.     

A prediction model incorporating the BRAFV600E protein status for determining the risk of cervical lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis

Background and objectivesCervical lateral lymph node metastasis (LLNM) is a predictor of poor prognosis for papillary thyroid carcinoma (PTC) patients. However, the risk factors for LLNM remain unclear. The purpose of the study was to examine the risk factors for LLNM and construct a prediction model.MethodsWith Ethics Committee approval, a total of 1198 PTC patients were retrospectively included in our study. Univariate and multivariate analyses were performed to explore the relationship between clinicopathological characteristics and LLNM. A nomogram for predicting LLNM in PTC patients with central lymph node metastasis (CLNM) was constructed and validated.ResultsThe negative BRAF^V600E protein expression was significantly correlated with positive LLNM status in PTC patients. In PTC patients with CLNM, the number of metastatic central lymph nodes (LNN) ≥ 3 and the ratio of metastatic central lymph nodes (LNR) ≥ 0.565 were found to be significantly associated with positive LLNM status. The nomogram for predicting LLNM risk in PTC patients with CLNM incorporated four risk factors: tumor size, the BRAF^V600E protein expression, LNN and LNR. The prediction model showed excellent discrimination, with a C-index of 0.714.ConclusionsThe negative BRAF^V600E protein expression was more likely to lead to LLNM. LNN ≥3 and LNR ≥0.565 were associated with LLNM risk in PTC patients with CLNM. Our nomogram might assist clinicians in developing individual suitable follow-up strategies for PTC patients with CLNM.     

远端胃癌淋巴结转移规律及临床意义*

目的：探讨远端胃癌各组淋巴结转移的特点,指导远端胃癌根治手术中淋巴结清扫的范围。方法：回顾性分析2010年2 月至2014年9 月天津医科大学肿瘤医院远端胃癌患者773 例接受D 2（D 2 +）胃次全切除术的临床病理资料,分析其淋巴结转移特点。结果：773 例远端胃癌患者术后病理证实淋巴结转移为423 例（54.72%）,各组淋巴结中发生转移的患者所占比例由高至低依次为NO.6、NO.3、NO.4sb 、NO.5 组淋巴结。N 1 淋巴结转移率由高至低依次为NO.3、NO.6、NO.5、NO.4d 组淋巴结;N 2 淋巴结转移率由高至低依次为NO.8a 、NO.7、NO.1 组淋巴结。50.68% 的患者出现NO.8a 组淋巴结跳跃性转移。结论：远端胃癌根治性手术应注意NO.8a 淋巴结转移的可能性,必要时应适当扩大淋巴结的清扫范围。     

Lateral lymph node dissection in rectal cancer: State of the art review

Half of the local regional recurrences from rectal cancer are nowadays located in the lateral compartments, most likely due to lateral lymph node (LLN) metastases. There is evidence that a lateral lymph node dissection (LLND) can lower the lateral local recurrence rate. An LLND without neoadjuvant (chemo)radiotherapy in patients with or without suspected LLN metastases has been the standard of care in the East, while Western surgeons believed LLN metastases to be cured by neoadjuvant treatment and total mesorectal excision (TME) only. An LLND in patients without enlarged LLNs might result in overtreatment with low rates of pathological LLNs, but in patients with enlarged LLNs who are treated with (C)RT and TME only, the risk of a lateral local recurrence significantly increases to 20%. Certain Eastern and Western centers are increasingly performing a selective LLND after neoadjuvant treatment in the presence of suspicious LLNs due to new scientific insights, but (inter)national consensus on the indication and surgical approach of LLND is lacking. An LLND is an anatomically challenging procedure with intraoperative risks such as bleeding and postoperative morbidity. It is therefore essential to carefully select the patients who will benefit from this procedure and where possible to perform the LLND in a minimally invasive manner to limit these risks. This review gives an overview of the current evidence of the assessment of LLNs, the indications for LLND, the surgical technique, pitfalls in performing this procedure and the future studies are discussed, aiming to contribute to more (inter)national consensus.