Ex Vivo Stimulation of Tumor-Draining Lymph Node Cells from Lung Cancer Patients:A Potential Resource for Adoptive Immunotherapy

To find a feasible method for the stimulation of tumor-draining lymph node （TDLN） cells in preparation for use in the clinic, the CTL activity of TDLN cells induced by different stimuli （IL-2 alone, IL-2 ＋ autologous tumor antigen （atAg）, IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg） was measured by maximal LDH enzyme release. The mechanisms were explored by the observation of morphology and the detection of CD83^＋ TDLN cells. The expansion of TDLN cells by IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg was significantly higher than that by IL-2 alone or IL-2 ＋ atAg （p 〈 0.01）. Antitumor CTL activity of TDLN cells induced by IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg was significantly higher than those of other groups. The number of CD83^＋ cells within the TDLN population treated with IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg was significantly elevated. The method of stimulating TDLN cells by IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg was better than the stimulation with IL-2 or IL-2 ＋ atAg. TDLN cells induced by IL-2 ＋ GM-CSF ＋ IL-4 ＋ atAg produced more dendritic cells （DCs）. In our study, we established a system that T cells and DCs were stimulated together ex vivo, which was easy to conduct and produce promising results. It provided a new method for improving TDLN cell antitumor activity which might be used in the clinical cancer therapy. Cellular ＆ Molecular Immunology. 2008;5（4）：307-313.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy

The advent of sentinel lymph-node technique has led to a shift in lymph-node staging,due to the emergence of new entities namely micrometastases(p N1mi) and isolated tumor cells [p N0(i+)].The prognostic significance of this low positivity in axillary lymph nodes is currently debated,as is,therefore its management.This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting,discussing the locoregional treatment in p N0(i+) and p N1 mi patients(completion axillary dissection,axillary irradiation with or without regional nodes irradiation,or observation),according to systemic treatment,with the goal to help physicians in their daily practice.

Radiomics-based predictive risk score: A scoring system for preoperatively predicting risk of lymph node metastasis in patients with resectable non-small cell lung cancer

Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical usefulness.Results: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features.Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.

Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P【0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P 【0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.

Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma:A systematic review and meta-analysis

BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM To evaluate risk factors for LNM in T1 ESCC.METHODS We searched Embase,PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC.Included studies were divided into LNM and non-LNM groups.We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features.Odds ratio(OR),mean differences and 95%confidence interval(CI)were assessed using a fixed-effects or randomeffects model.RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria.After excluding studies with heterogeneity based on influence analysis,tumor size(OR=1.93,95%CI=1.49-2.50,P<0.001),tumor location(OR=1.46,95%CI=1.17-1.82,P<0.001),macroscopic type(OR=3.17,95%CI=2.33-4.31,P<0.001),T1 substage(OR=6.28,95%CI=4.93-8.00,P<0.001),differentiation(OR=2.11,95%CI=1.64-2.72,P<0.001)and lymphovascular invasion(OR=5.86,95%CI=4.60-7.48,P<0.001)were found to be significantly associated with LNM.Conversely,sex,age and infiltrative growth pattern were not identified as risk factors for LNM.CONCLUSION A tumor size>2 cm,lower location,nonflat macroscopic type,T1b stage,poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.

A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Superficial esophageal squamous cell carcinoma(SESCC)is defined as carcinoma with mucosal or submucosal invasion,regardless of regional lymph node metastasis(LNM).The lymph node status is not only a key factor to determine the training strategy,but also the most important prognostic factor in esophageal cancer.In this study,we establish a clinical nomogram for predicting LNM in patients with SESCC.A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018.A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation.Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed(concordance index[C-index],0.860;95%confidence interval[CI],0.825-0.894)through internal validation.The external validation cohort presented good discrimination(C-index,0.916;95%CI,0.860-0.971).This model may facilitate the prediction of LNM in patients with SESCCs.

Development and validation of prognostic nomogram based on log odds of positive lymph nodes for patients with gastric signet ring cell carcinoma

Objective: Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma(SRC), for individualized prediction of overall survival(OS) rate and cancer-specific survival(CSS).Methods: We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results(SEER) database, and then randomly partitioned them into a training cohort and a validation cohort.Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index(C-index), receiver operating characteristics(ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement(IDI), net reclassification improvement(NRI) and decision curve analysis(DCA) were used to assess clinical utility of our nomogram models.Results: Six independent predicted indicators, age, race, log odds of positive lymph nodes(LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer(AJCC) 8 th edition tumor-node-metastasis(TNM) staging system(0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.Conclusions: The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8 th edition TNM staging system alone.

Lymph node ratio-based staging system for esophageal squamous cell carcinoma

AIM: To analyze a modified staging system utilizing lymph node ratio(LNR) in patients with esophageal squamous cell carcinoma(ESCC).METHODS: Clinical data of 2011 patients with ESCC who underwent surgical resection alone between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College were reviewed. The LNR, or node ratio(Nr) was defined as the ratio of metastatic LNs ompared to the total number of resected LNs. Overall survival between groups was compared with the log-rank test. The cutoff point of LNR was established by grouping patients with 10% increment in Nr, and then combining the neighborhood survival curves using the log-rank test. A new TNr M staging system, was constructed by replacing the American Joint Committee on Cancer(AJCC) N categories with the Nr categories in the new TNM staging system. The time-dependent receiver operating characteristic curves were used to evaluate the predictive performance of the seventh edition AJCC staging system and the TNr M staging system.RESULTS: The median number of resected LNs was 12(range: 4-44), and 25% and 75% interquartilerangeswere8 and 16. Patients were classified into four Nr categories with distinctive survival differences(Nr0: LNR = 0; Nr1: 0% < LNR ≤ 10%; Nr2: 10% < LNR ≤ 20%; and Nr3: LNR > 20%). From N categories to Nr categories, 557 patients changed their LN stage. The median survival time(MST) for the four Nr categories(Nr0-Nr3) was 155.0 mo, 39.0 mo, 28.0 mo, and 19.0 mo, respectively, and the 5-year overall survival was 61.1%, 41.1%, 33.0%, and 22.9%, respectively(P < 0.001). Overall survival was significantly different for the AJCC N categories when patients were subgrouped into 15 or more vs fewer than 15 examined nodes, except for the N3 category(P = 0.292). However, overall survival was similar when the patients in all four Nr categories were subgrouped into 15 or more vs fewer than 15 nodes. Using the time-dependent receiver operating characteristic, we found that the Nr category and TNr M stage had higher accuracy in predicting survival than the AJCC N category and TNM stage. CONCLUSION: A staging system based on LNR may have better prognostic stratification of patients with ESCC than the current TNM system, especially for those undergoing limited lymphadenectomy.

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival

AIM: To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC).

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma:A real-world retrospective cohort study

BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.

Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases

AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.RESULTS: The systematic literature review yielded eight descriptions(n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven(64.7%) patients had limited disease(LD) and six(35.3%) had extensive disease(ED) at presentation. Chemotherapy(n = 6, 35.3%) or surgery(n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12(70.6%) of the patients. Median(interquartile range) progression free survival and overall survival was 15(7-42) mo and 22(12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.

Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma

BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.

Primary site and regional lymph nodeinvolvement are independent prognosticfactors for early？stage extranodal nasal？typenatural killer/T cell lymphoma

Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Log odds of positive lymph nodes is a better prognostic factor for oesophageal signet ring cell carcinoma than N stage

BACKGROUND Signet ring cell carcinoma is a rare type of oesophageal cancer,and we hypothesized that log odds of positive lymph nodes(LODDS)is a better prognostic factor for oesophageal signet ring cell carcinoma.AIM To explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors,log odds of positive LODDS and N stage.METHODS A total of 259 cases of oesophageal signet ring cell carcinoma after oesophagectomy were obtained from the Surveillance,Epidemiology,and End Results database between 2006 and 2016.The prognostic value of LODDS and N stage for oesophageal signet ring cell carcinoma was evaluated by univariate and multivariate analyses.The Akaike information criterion and Harrell’s C-index were used to assess the value of two prediction models based on lymph nodes.External validation was performed to further confirm the conclusion.RESULTS The 5-year cancer-specific survival(CSS)and 5-year overall survival(OS)rates of all the cases were 41.3%and 27.0%,respectively.The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared(OS:46.162,CSS:41.178)than N stage(OS:36.215,CSS:31.583).Univariate analyses showed that insurance,race,T stage,M stage,TNM stage,radiation therapy,N stage,and LODDS were potential prognostic factors for OS(P<0.1).The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection(P<0.05),while N stage was not considered to be a significant prognostic factor(P=0.122).Model 2(LODDS)had a higher degree of discrimination and fit than Model 1(N stage)(LODDS vs N stage,Harell’s C-index 0.673 vs 0.656,P<0.001;Akaike information criterion 1688.824 vs 1697.519,P<0.001).The results of external validation were consistent with those in the study cohort.CONCLUSION LODDS is a superior prognostic factor to N stage for patients with oesophageal signet ring cell carcinoma after oesophagectomy.

Maximum standardized uptake value on PET/CT in preoperative assessment of lymph node metastasis from thoracic esophageal squamous cell carcinoma

The presence of lymph node metastasis is an important prognostic factor for patients with esophageal cancer.Accurate assessment of lymph nodes in thoracic esophageal carcinoma is essential for selecting appropriate treatment and forecasting disease progression.Positron emission tomography combined with computed tomography(PET/CT)is becoming an important tool in the workup of esophageal carcinoma.Here,we evaluated the effectiveness of the maximum standardized uptake value(SUVmax)in assessing lymph node metastasis in esophageal squamous cell carcinoma(ESCC)prior to surgery.Fifty-nine surgical patients with pathologically confirmed thoracic ESCC were retrospectively studied.These patients underwent radical esophagectomy with pathologic evaluation of lymph nodes.They all had18F-FDG PET/CT scans in their preoperative staging procedures.None had a prior history of cancer.The pathologic status and PET/CT SUVmax of lymph nodes were collected to calculate the receiver operating characteristic(ROC)curve and to determine the best cutoff value of the PET/CT SUVmax to distinguish benign from malignant lymph nodes.Lymph node data from 27 others were used for the validation.A total of 323 lymph nodes including 39 metastatic lymph nodes were evaluated in the training cohort,and 117lymph nodes including 32 metastatic lymph nodes were evaluated in the validation cohort.The cutoff point of the SUVmax for lymph nodes was 4.1,as calculated by ROC curve(sensitivity,80%;specificity,92%;accuracy,90%).When this cutoff value was applied to the validation cohort,a sensitivity,a specificity,and an accuracy of 81%,88%,and 86%,respectively,were obtained.These results suggest that the SUVmax of lymph nodes predicts malignancy.Indeed,when an SUVmax of 4.1 was used instead of 2.5,FDG-PET/CT was more accurate in assessing nodal metastasis.

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin:the impact of chemoradiotherapy

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge.We report here our experience in treating these patients with chemoradiotherapy as a curative approach.Data from 40 patients were reviewed.In total,20(50%) patients underwent excisional biopsy.All patients underwent radiotherapy,which was delivered to both sides of the neck and pharyngeal mucosa(extensive field),and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2.The clinical stage of the cervical nodes at presentation was N1 in 25%,N2 in 60%,and N3 in 15%.Most patients(75%) developed at least grade 3 mucositis.Eight patients(20%) had grade 3 xerostomia and 18 patients(45%) required esophageal dilation for stricture.The 5-year overall survival(OS) rate of all patients was 67.5%.The 5-year OS rates of patients with N1,N2,and N3 lesions were 100%,67%,and 41%,respectively(P = 0.046).The 5-year progression-free survival rate was 62.5%.In multivariate analysis,only N stage significantly affected OS(P = 0.022).Emergence of the occult primary was very limited(1 patient only).Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor.Because the survival of patients with unknown primary is comparable to that of patients with known primary,an attempt at cure should always be made.

Metastatic clear cell renal cell carcinoma in isolated retroperitoneal lymph node without evidence of primary tumor in kidneys: A case report

BACKGROUND Retroperitoneal lymph node dissection(RPLND)plays a diagnostic,therapeutic,and prognostic role in myriad urologic malignancies,including testicular carcinoma,renal cell carcinoma(RCC),and upper urinary tract urothelial carcinoma.RCC represents 2%of all cancers with approximately 25%of patients presenting with advanced disease.Clear cell RCC(CCRCC)is the most common RCC,accounting for 75%-80%of all RCC.CASE SUMMARY A 71-year-old man presented with a history of benign prostatic hypertrophy.He was asymptomatic without any hematuria,pain,or other urinary symptoms.A computed tomography(CT)scan of the abdomen and pelvis showed a 1.8 cm left retroperitoneal lymph node.There was no evidence of renal pathology.A core biopsy was performed of the left para-aortic lymph node.Although the primary tumor site was unknown,the morphological and immunohistochemical features were most consistent with CCRCC.A RPLND was performed which revealed a single mass 5.5 cm in greatest dimension with extensive necrosis.The retroperitoneal lymph node was most compatible with CCRCC.A nephrectomy was not conducted as a renal mass had not been detected on any prior imaging studies.The patient did not receive any type of adjuvant therapy.The patient underwent surveillance with serial CT scans with contrast of the chest,abdomen,and pelvis for the next 5 years,all of which demonstrated no recurrent or metastatic disease and no evidence of retroperitoneal adenopathy.CONCLUSION Our unique case emphasizes the therapeutic role of metastasectomy in metastatic CCRCC even in the absence of primary tumor in the kidneys.

Unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection in Stage II non-seminomatous germ cell tumor:A tertiary care experience

Objective Post-chemotherapy retroperitoneal lymph node dissection(PC-RPLND)represents an integral component of the management of patients with non-seminomatous germ cell tumor(NSGCT).Modified templates have been proposed to minimize the surgical morbidity of the procedure.Moreover,the implementation of robotic surgery in this setting has been explored.We report our experience with unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection(PC-rRPLND)for clinical Stages IIA and IIB NSGCTs.Methods A retrospective single institution review was performed including 33 patients undergoing PC-rRPLND for Stages IIA and IIB NSGCTs between January 2015 and February 2019.Following orchiectomy,patients were scheduled for chemotherapy with three cycles of bleomycin-etoposide-cisplatin.Patients with a residual tumor of<5 cm and an ipsilateral metastatic disease on pre-and post-chemotherapy CT scans were eligible for a unilateral template in absence of rising tumor markers.Descriptive statistics were provided for demographics,clinical characteristics,intraoperative and postoperative parameters.Perioperative,oncological,and functional outcomes were recorded.Results Overall,7(21.2%)patients exhibited necrosis or fibrosis;14(42.4%)had mature teratoma;and 12(36.4%)had viable tumor at final histology.The median lymph node size at surgery was 25(interquartile range[IQR]21-36)mm.Median operative time was 180(IQR 165-215)min and no major postoperative complications were observed.Anterograde ejaculation was preserved in 75.8%of patients.Median follow-up was 26(IQR 19-30)months and a total of three recurrences were recorded.Conclusion PC-rRPLND is a reliable and technically reproducible procedure with safe oncological outcomes and acceptable postoperative ejaculatory function in well selected patients with NSGCTs.

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,