Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types.Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN.ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78.ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.     

Development and validation of artificial intelligence models for preoperative prediction of inferior mesenteric artery lymph nodes metastasis in left colon and rectal cancer

BackgroundDissection of lymph nodes at the roots of the inferior mesenteric artery (IMAN) should be offered only to selected patients at a major risk of developing IMAN involvement. The aim of this study is to present the first artificial intelligence (AI) models to predict IMAN metastasis risk in the left colon and rectal cancer patients.MethodsA total of 2891 patients with descending colon including splenic flexure, sigmoid colon and rectal cancer undergoing major primary surgery and IMAN dissection were included as a study cohort, which was then split into a training set (67%) and a testing set (33%). Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) regression model. Seven AI algorithms, namely Support Vector Machine (SVM), Logistic Regression (LR), Extreme Gradient Boosting (XGB), Light Gradient Boosting (LGB), Decision Tree Classifier (DTC), Random Forest (RF) classifier, and Multilayer Perceptron (MLP), as well as traditional multivariate LR model were employed to construct predictive models. The optimal hyperparameters were determined with 5 fold cross-validation. The predictive performance of models and the expert surgeon was assessed and compared in the testing set independently.ResultsThe IMAN involvement incidence was 4.6%. The optimal set of features selected by LASSO included 10 characteristics: neoadjuvant treatment, age, synchronous liver metastasis, synchronous lung metastasis, signet ring adenocarcinoma, neural invasion, lymphovascular invasion, CA199, endoscopic obstruction, T stage evaluated by MRI. The most accurate model derived from MLP showed excellent prediction power with area under the receiver operating characteristic curve (AUROC) of 0.873 and produced 81.0% recognition sensitivity and 82.5% specificity in the testing set independently. In contrast, the judgment of IMAN metastasis by expert surgeon yield rather imprecise and unreliable results with a significantly lower AUROC of 0.509. Additionally, the proposed MLP had the highest net benefits and the largest reduction of unnecessary IMAN dissection without the cost of additional involved IMAN missed.ConclusionMLP model was able to maintain its prediction accuracy in the testing set better than other models and expert surgeons. Our MLP model could be used to help identify IMA nodal metastasis and to select candidates for individual IMAN dissection.     

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.     

Biopsia selectiva de ganglio centinela en cáncer de mama, ¿está justificada la espera al resultado intraoperatorio?

IntroductionIn our institution, the study of selective sentinel node biopsy (SLNB) is performed intraoperatively. The main objective of our study is to know the proportion of patients who benefits from the waiting of the results of SLNB.MethodsA retrospective analysis of patients operated on our center between January 1 st, 2018 and June 30, 2019 was carried out. We included women diagnosed with T1–T2 tumors, treated by lumpectomy and SLNB studied using OSNA method.ResultsOur study included 149 women. There were not statistically significant differences in terms of demographic data between the group treated with axillary lymph node dissection (ALND) and exclusively SLNB group. After analysis of SLN intraoperatively, there were performed 18 axillary lymphadenectomies. Only in six of these 18 cases, three or more sentinel nodes were founded. The location of the tumor, the presence of lymphovascular permeation and the total tumor load (TTL) showed statistically significant differences between groups. Only the TTL was established as the independent factor of the need for ALND.ConclusionsObtaining a deferred result of the SLNB allowed reducing the time of anesthesia and occupation of the operating room, since in a high percentage of cases an additional procedure is not performed.     

基于TCGA数据库挖掘甲状腺乳头状癌淋巴结转移相关的突变基因及其机制探讨北大核心

目的:挖掘并筛选与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)淋巴结转移相关的突变基因及其潜在的机制。方法:从TCGA数据库获得377例PTC患者的测序数据及完整的临床资料,并分为淋巴结转移组(LM,n=212)与无淋巴结转移组(NLM,n=165)。利用R语言(v3.6.2)对转移组特有的突变基因进行富集分析。采用String在线软件绘制蛋白互作网络,Cytoscape软件筛选网络中的核心基因。在UALCAN网站上验证基因表达量与淋巴结转移之间的关系。利用荧光实时定量PCR测定候选基因在细胞系中mRNA的表达量。结果:一共筛选出1197个仅在LM组发生突变的基因,它们主要富集在黏着连接、细胞黏附分子(cell adhesion molecules,CAMs)通路。CAMs通路的核心基因ITGB1与VCAN的表达量与淋巴结转移相关。与正常甲状腺细胞系相比,VCAN基因在PTC细胞系TPC-1和B-CPAP中mRNA的表达量较高,尤其是B-CPAP细胞系。结论:CAMs通路可能是PTC淋巴结转移相关机制之一,其中VCAN基因可能是潜在的分子标志物。     

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.     

Transhiatal lower mediastinal lymph node dissection for esophagogastric junction carcinoma by interconnecting four body cavities

BackgroundDue to the limited number of landmark structures, it is difficult to standardize the surgical procedures for advanced esophagogastric junction cancer such as Ivor Lewis esophagectomy that require transhiatal lower mediastinal lymph node dissection (TH-LMND). We demonstrate an easily reproducible procedure for TH-LMND, wherein four body cavities, namely, the abdominal cavity, infracardiac bursa (ICB), and left and right thoracic cavities are interconnected.MethodsFirst, the dissection between the right crus and the esophagus was used to connect the abdominal cavity to the ICB — a lower mediastinal cavity separated from the omental bursa during embryonic development [1,2]. Second, the right thoracic cavity was opened with the shortest distance by dissecting the cranial side of the ICB. The right pulmonary ligament was dissected from the right lung. Third, the dissection to the contralateral side while exposing the aorta and the pericardium connected the left and right thoracic cavities. Then, the left pulmonary ligament was dissected from the left lung. The dissected tissues, including the lymph nodes, were subsequently peeled from the esophagus.ResultsBetween April 2018 and August 2021, 14 patients underwent laparoscopic or robotic TH-LMND via the procedure above. The median time required to complete the dissection was 75 min. None of the procedures were converted to open surgery, and none of the patients experienced intraoperative complications such as pericardial injury, lung injury, or massive bleeding.ConclusionThe surgical concept of interconnecting four body cavities made the procedure more accessible and reproducible while achieving en bloc TH-LMND.     

Indocyanine green guidance for combined robotic pelvic and para-aortic sentinel node mapping in cervical cancer

BackgroundIndocyanine green (ICG) for pelvic sentinel lymph node (SLN) mapping is well established in endometrial cancer (Persson et al., 2019 Jul). However, the application for para-aortic SLNs is less reported; and the detection rate of para-aortic SLNs, mainly after cervical injection of ICG, varies between 14% and 71% (Rossi et al., 2013 Nov; Kim et al., 2020 Mar; Gallotta et al., 2019 Mar). One recent report differentiates between lower and upper para-aortic SLNs in endometrial cancer (Kim et al., 2020 Mar). Here we describe a technique using ICG for identifying pelvic SLNs, lower and upper para-aortic SLNs in cervical cancer.VideoA 46-year old female presented with high grade cervical dysplasia/carcinoma in situ on cervical smear. Cervical cone biopsy revealed a grade two squamous cell carcinoma (depth of invasion 6.8mm, width 20.8mm). Clinically she was staged as an early FIGO-stage IB2 cervical cancer. NMR revealed bilaterally enlarged iliac lymph nodes. Additional PET-CT revealed FDG-uptake in the enlarged pelvic lymph nodes. In view of the imaging findings a staging Robotic pelvic and para-aortic SLN procedure was planned, prior to select the primary treatment (radical hysterectomy or chemo-radiation). ICG was injected into the cervical stroma, and a robotic pelvic and para-aortic SLN dissection (using Firefly System ®, Intuitive Surgical Inc.) was initiated 15 minutes and 35 minutes, respectively, after cervical injection.ResultsThis video demonstrates the application of ICG for mapping bilateral primary pelvic SLNs, secondary and tertiary para-aortic SLNs in the lower and upper para-aortic region respectively, in cervical cancer. Pathology revealed one metastatic pelvic SLN on the left side, other four pelvic SLNs were negative; both the secondary/lower (n = 3) and tertiary/upper (n = 5) para-aortic SLNs were negative, as well as the non-SLNs (n = 8).ConclusionThe application of ICG for para-aortic SLN mapping should further be investigated and validated in staging surgically locally advanced cervical cancer and those with suspicious lymph nodes on imaging.     

Learning curve analysis for lateral pelvic lymph node dissection in rectal cancers – Outcomes improve with experience

IntroductionLateral pelvic lymph node dissection (LPLND) is a technically challenging procedure and its learning curve has not been analysed against an oncologically relevant outcome. The purpose of the study was to determine the learning curve for LPLND in rectal cancers using nodal retrieval as performance measure.MethodsConsecutive LPLND for rectal adenocarcinomas from a single institution were retrospectively analysed. Cumulative sum (CUSUM) control charts were used to detect difference in performance with respect to lymph node yield. Negative binomial regression was used to determine factors influencing nodal harvest using Incidence Risk Ratios (IRR). Separate CUSUM curves were generated for open and minimally invasive surgeries (MIS).ResultsOne-hundred and twenty patients were included and all received preoperative radiation. MIS was used in 53.3%. Median lymph node yield was 6 with 20% nodal positivity. Increasing experience (IRR – 1.196) and MIS (IRR – 1.586) were the only factors that influenced nodal harvest. CUSUM charts revealed that learning curve was achieved after the 83rd case overall and after the 19 operations in MIS. There was a 20% increase in nodal yield after every 30 MIS LPLND performed.ConclusionsLearning curve for LPLND is relatively long and only increasing experience and minimally invasive operations increased nodal yield.