Extent Of Lymph Node Metastasis Research Articles

Impact of surgical proximal and distal margins on the recurrence of resectable colon cancer: a single-center observational cohort study.

Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. Patients who had pT4 colon cancer with margins of more than 7cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. A resection margin of at least 7cm should be maintained for patients with pT4 colon cancer.

Characteristics and risk factors of cervical lymph node metastasis in cN0 papillary thyroid microcarcinoma of the isthmus.

The surgical resection range of papillary thyroid microcarcinoma of the isthmus (PTMCI) is controversial, and the guidelines do not fully guide the central lymph node dissection (CLND).We retrospectively studied the comparison of PTMCI (Group A, n = 65 cases) and non-PTMCI (Group B, n = 80 cases). Based on whether central lymph node metastasis (CLNM) was further detected, they were further divided into the PTMCI with CLNM (group C, n = 42 cases), the PTMCI without CLNM (group D, n = 23 cases), the non-PTMCI with CLNM (group E, n = 45 cases), the non-PTMCI without CLNM (group F, n = 35 cases). All patients underwent total thyroidectomy and CLND. The CLNM pathological examination was divided into right recurrent laryngeal nerve superficial lymph nodes (Right VI a), right recurrent laryngeal nerve deep lymph nodes (Right VI b), left VI area lymph nodes (Left VI), prelaryngeal lymph node, and pretracheal lymph node. The extent of lymph node metastasis and risk factors of PTMCI were analyzed by univariate and multivariate analysis. The ROC curve was used to calculate the maximum diameter of the tumor and the Youden index was calculated to analyze the impact of diameter on the risk factors for CLNM in PTMCI. To construct a prediction model of transfer risk of high risk factors by Nomogram, there were significant differences in prelaryngeal lymph nodes (p = 0.034) and pretracheal lymph nodes ( n = 0.035) between group A and group B, and the risk factors of lymph node metastasis were tumor invasion (p = 0.003), multifocality (p = 0.001), and the maximum tumor diameter≧6.5mm. PTMCI is more prone to metastasis of pretracheal lymph nodes and prelaryngeal lymph nodes, and the presence of tumor invasion, multifocality, and tumor diameter≧6.5mm are high risk factors for metastasis in PTMCI. According to the prediction model, with all risk factors the risk of cervical lymph node metastasis is up to 90%.

Suppression of NSUN2 enhances the sensitivity to chemosensitivity and inhibits proliferation by mediating cell apoptosis in gastric cancer

NSUN2 is a critical methyltransferase for adding m5C to RNA. Its upregulation promotes the growth and metastasis of several tumors including gastric cancer (GC). However, it is unclear if NSUN2 can improve the chemosensitivity of GC to treatment with therapeutic agents such as cisplatin (CDDP) and 5-fluorouracil (5-FU). Flow cytometry was used to measure the effects of knocked-down NSUN2 expression on GC cell apoptosis and cell cycle progression. Western blot analysis examined specific signaling pathways through which NSUN2 mediates control of responses underlying the GC tumorous phenotype. NSUN2 expression was upregulated in GC tissues and its levels of rises were related to the extent of lymph node metastasis and increases in Ki67 proliferative marker expression. NSUN2 shRNA transfection suppressed rises in ERK1/2 phosphorylation status and downregulated anti-apoptosis protein Bcl-2 and upregulated pro-apoptosis protein Bax. Overall, the results reveal that NSUN2 downregulation promotes the GC chemosensitivity to inverse modulation by chemotherapeutic agents of Bcl-2 and Bax expression levels and declines in ERK1/2-induced proliferation. Our results indicate that inhibition of NSUN2 activation may be an effective procedure to enhance the efficacy of chemotherapeutic agents used to clinically treat GC.

OR32-03 mRNA Expression Based Tumor Behavior Prediction Models In Thyroid Nodules

Abstract Disclosure: A. Golding: None. G. Correa: None. E. Valenzuela Sheker: None. R. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Liu: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. G.C. Kennedy: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. D. Bimston: None. The 2015 ATA thyroid cancer risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as lymph node metastases. The objectives of this study were to evaluate the prevalence of invasion and lymph node metastases in a cohort enriched with thyroid malignancies and provide a risk signature with a high negative predictive value ruling out these tumor features. Histopathology reports from Afirma Genomic Sequencing Classifier (GSC) algorithm training and from thyroid cancer patients managed at an integrative endocrine surgery community care practice (total 697 and ∼50% from each) were reviewed for invasion and metastases. An integer from 0-3 was assigned based on the extent of invasion (ranging from none to extensive extra-thyroidal) or extent of lymph node metastases (ranging from none to lateral node metastases). To develop predictive signatures for invasion/metastases, over 400 literature-derived expression-based signatures were evaluated; they cover a broad spectrum of molecular processes, including cancer hallmarks such as endothelial to mesenchymal transition, tumor microenvironment, immune-oncology, metabolism, and treatment sensitivity. Further, acknowledging that multiple complex molecular processes are associated with invasion/metastases, over 200 machine-learning (ML) models were trained within the repeated and nested cross-validation (CV) framework. They utilized these literature-derived signatures as well as differentially expressed genes between high and low risk of invasion/metastases as the basic building blocks. The application of top performing signatures among Bethesda (B) V/VI nodules as well as indeterminate thyroid nodules (ITN - BIII/IV) that are GSC-suspicious, showed that 40-50% of these lesions were marked as low risk for invasion/metastases. With a starting prevalence of 10.0% of high-level invasion (scored 2 or 3), 41.3% of the cohort is ruled out for clinically relevant invasion with a negative predictive value (NPV) of 97.6%. With a starting prevalence of 11.3% of high-level metastases (scored 2 or 3), 49.8% of the cohort is ruled out for clinically relevant metastases with an NPV of 98.6%. The rule-out capability represents more than 4-fold or 7-fold reduction in high-level invasion/metastases from the baseline prevalence, respectively. Expression-based signatures that confidently rule out tumor invasion and metastasis may help personalize the surgical approach for individuals. This may reduce excess surgery and overtreatment, optimizing the initial response to therapy and decreasing the rates of surgical complications and post-operative hypothyroidism. Presentation: Sunday, June 18, 2023

Lymph node involvement is rare in mucinous cystic neoplasms of the pancreas: Role of minimally invasive surgery.

Mucinous cystic neoplasm (MCN) is a premalignant cystic tumor of the pancreas. Resection of MCN in the distal pancreas is a standard treatment; however, at present, there is no consensus on the necessity or extent of lymph node dissection, and minimally invasive pancreatectomy is commonly the preferred surgical technique. Thus, the present study aimed to assess the efficacy of minimally invasive surgery and the extent of lymph node metastasis as factors in determining an appropriate surgical treatment for MCN. The present study retrospectively analyzed 21 consecutive patients who underwent distal pancreatectomy (DP) for MCN under general anesthesia at Chiba University Hospital (Chiba, Japan) between April 2011 and July 2019. All 21 patients were female. DP with a splenectomy was performed in all the patients. A total of 14 patients underwent laparoscopic DP (LDP). No lymph node metastasis was found in any of the patients. The minimally invasive surgery group had lower operative blood loss and a shorter hospital stay than the open surgery group. There was no significant difference in the number of dissected lymph nodes between the open surgery group and the minimally invasive surgery group. Preoperative findings of malignancy in MCN included solid components on enhanced CT and endoscopic ultrasonography, high carbohydrate antigen 19-9 values and large tumor size. In conclusion, DP with spleen preservation, which is minimally invasive, may be preferentially considered as a surgical technique for MCN without malignant findings because lymph node metastases are rare in MCN and were not observed in the present study.

The influence of the extent of lymph node metastasis on the prognosis for patients with intrahepatic cholangiocarcinoma.

Reports showed that some of intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM) may also gain survival benefit undergone resection. However, the effect of the extent of LNM on prognosis and surgical indication is barely discussed. From September 1994 to November 2018, primary ICC patients undergone initial curable surgery were enrolled. Based on the extent of LNM, we divided these patients into 4 groups, including patients with no LNM (group N0), LNM to hepatoduodenal ligament or common hepatic artery (region A, group A), LNM to gastrohepatic lymph nodes for left liver ICC and periduodenal and peripancreatic lymph node for right liver ICC (region B, group B), or LNM beyond these regions (region C, group C). Multivariable Cox regression analysis was performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in all groups. A total of 133 patients were enrolled. There were 56, 21, 17, and 39 patients in groups N0, A, B, and C, respectively. There was significant difference between groups N0 and C in RFS (P < 0.001) and OS (P = 0.002). When we compared group N0 + A + B with group C, we also found that RFS (P < 0.001) and OS (P = 0.007) were significantly different. In multivariable analysis, the extent of LNM was an independent risk factor for RFS (P < 0.050). ICC patients with the LNM to regions A and B could still achieve good prognosis with resection. Surgery should be carefully considered when LNM to region C.

The Effect of Tumor Characteristics and Location on the Extent of Lymph Node Metastases of Head and Neck Cutaneous Squamous Cell Carcinoma.

BackgroundThe extent of a neck dissection for patients with metastasis of cutaneous squamous cell carcinoma of the head and neck (HNcSCC) is still subject to debate and clear guidelines are lacking. Tumor characteristics like size, differentiation and tumor location are known risk factors for lymph node metastasis (LNM). There is some evidence that, depending on tumor location, LNM follows a specific pattern. This study aims to identify which tumor characteristics can predict the pattern and extent of LNM.MethodIn this cohort study 80 patients were included, who underwent a primary neck dissection for LNM of HNcSCC between 2003 and 2018 at the University Medical Center Groningen, the Netherlands. Retrospective data was collected for primary tumor characteristics and LNM and included surgical and follow-up data. Influence of tumor characteristics on the extent of LNM was analyzed using non-parametric tests. Logistic regression analysis were used to identify a metastasis pattern based on the primary tumor location.ResultsOnly primary tumor location was associated with the pattern of LNM. HNcSCC of the ear metastasized to level II (OR = 2.6) and the parotid gland (OR = 3.6). Cutaneous lip carcinoma metastasized to ipsilateral and contralateral level I (OR = 5.3). Posterior scalp tumors showed a metastasis pattern to level II (OR = 5.6); level III (OR = 11.2), level IV (OR = 4.7) and the parotid gland (OR = 10.8). Ear canal tumors showed a low risk of LNM for all levels. The extent of LNM was not related to age or any tumor characteristics i.e. tumor diameter, infiltration depth, differentiation grade, perineural growth and vascular invasion.ConclusionPrimary tumor location determines the LNM pattern. Whereas known unfavorable tumor characteristics did not relate to the extent of LNM. Location guided limited neck dissection combined with parotidectomy will treat most patients adequately.

Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis.

The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis.

Correlation between imaging and histopathology in head and neck oncology – A retrospective study

Introduction: Tumour size, depth of invasion, type and extent of nodal metastasis are some of the key prognostic indicators in operable head and neck cancers. Initial Imaging with USS of neck and FNAC or core biopsy has been established to have a high sensitivity and specificity. In addition, CT neck and thorax and MRI scan of the primary tumour are recommended as part of staging scans. Information from this work up guides the MDT and patients towards a tailored management plan. We aimed to compare preoperative imaging work up and TNM staging with post-operative histopathology. Methods: We retrospectively reviewed 48 patients who underwent resection and selective neck dissection from January 2020 to August 2021, assessing their initial work up and its adherence to current guidelines. We also evaluated its correlation to final histopathology. Results: 100% compliance was noted with USS and FNAC, 94% compliance with CT and MRI and 96% had incisional biopsy. USS showed a 80 % specificity and a 55% sensitivity. CT had a specificity of 62.5% and sensitivity of 75%. MRI specificity was 58.8% and sensitivity 73.6%. Conclusions: Our results compare favourably to other published data on imaging correlation to histopathology in head and neck oncology. Time lapse between preoperative work-up and surgical resection during COVID pandemic may have led to advanced disease that is not evident on preoperative staging scans. Newer modalities including real time imaging and in-vivo surgical margin assessment remain to be explored. Introduction: Tumour size, depth of invasion, type and extent of nodal metastasis are some of the key prognostic indicators in operable head and neck cancers. Initial Imaging with USS of neck and FNAC or core biopsy has been established to have a high sensitivity and specificity. In addition, CT neck and thorax and MRI scan of the primary tumour are recommended as part of staging scans. Information from this work up guides the MDT and patients towards a tailored management plan. We aimed to compare preoperative imaging work up and TNM staging with post-operative histopathology. Methods: We retrospectively reviewed 48 patients who underwent resection and selective neck dissection from January 2020 to August 2021, assessing their initial work up and its adherence to current guidelines. We also evaluated its correlation to final histopathology. Results: 100% compliance was noted with USS and FNAC, 94% compliance with CT and MRI and 96% had incisional biopsy. USS showed a 80 % specificity and a 55% sensitivity. CT had a specificity of 62.5% and sensitivity of 75%. MRI specificity was 58.8% and sensitivity 73.6%. Conclusions: Our results compare favourably to other published data on imaging correlation to histopathology in head and neck oncology. Time lapse between preoperative work-up and surgical resection during COVID pandemic may have led to advanced disease that is not evident on preoperative staging scans. Newer modalities including real time imaging and in-vivo surgical margin assessment remain to be explored.

The Clinical Utility of Preoperative Thyroglobulin for Surgical Decision Making in Thyroid Disease

Serum thyroglobulin (Tg) levels are used to monitor for differentiated thyroid cancer (DTC) recurrence and have been correlated with posttreatment disease burden. The clinical significance of Tg in the preoperative setting to predict the risk of DTC is unclear. Our aim is to examine the clinical utility of preoperative Tg levels in those undergoing thyroidectomies for DTC or benign disease. From a prospectively collected database, we identified 385 patients who underwent thyroidectomy from 01/14 to 12/19 and had preoperative Tg levels available. Preoperative Tg levels were compared by preoperative indication for surgery, Bethesda category of biopsied nodules, presence of DTC on surgical pathology, and number of metastatic lymph nodes. There was no difference in mean preoperative Tg level when comparing indication for surgery (P=0.2) or Bethesda classification (P=0.4). Mean preoperative Tg levels were lower in patients with DTC (238 ± 77) compared to without DTC (532 ± 97) on final pathology (P=0.02). Among 188 DTC patients who had lymph nodes removed, there was no significant correlation between the preoperative Tg level and number of positive lymph nodes on final pathology (P=0.4). Preoperative serum Tg levels were lower in patients with DTC compared to those with benign disease on final pathology and did not correlate with extent of lymph node metastasis in patients with DTC. We found that serum Tg levels obtained in the preoperative setting do not predict DTC or lymph node metastasis and, therefore, do not inform the extent of surgery for differentiated thyroid cancer.

Regional lymph nodes and hematogenous metastasis of cancer

Aim. Morphological study of the microvasculature of regional lymph nodes in relation to the cancer of the lymph nodes as possible additional or alternative metastasis pathways. Methods. The lymph nodes of 150 cancer patients (1263 nodes in total), regional to cancer of various localization, were studied. Histological sections staining with hematoxylin and eosin by Van-Giesons method, pyronine by Brachets method, toluidine blue and picro-Mallory were prepared. An immunohistochemical study was performed using monoclonal antibodies to pan-cytokeratins, CD31, type IV collagen, CD3, CD20, and CD68. The area of metastases to the lymph nodes was determined by using a morphometric grid and used to identify the four study groups. In addition, the immunomorphological reactions of the lymph nodes were taken into account in each group. Results. It was identified that the microvasculature of the lymph nodes can be involved in the metastatic process along with the lymphatic pathways. At the same time, there is a decrease in vascular wall function and violation of the rheological properties of blood, accompanied by the deposition of intra- and extravascular fibrin. Hematogenous metastasis is largely influenced by the state of lymph node sinuses, in which blood is found, and in some observations by the expression of CD31 (a marker of blood endothelium). Hematogenous dissemination of cancer often begins after the appearance of lymph node metastases. The greater the anatomical extent of lymph node metastases, the more often tumor cells are present in the blood vessels. In addition, an isolated lesion of the microvasculature with the presence of tumor cells in the extranodal vessels without metastases in the lymph node itself was revealed. It was observed that the invasion of tumor cells into the microvasculature depended on the immunomorphological reactions of the lymph nodes. Conclusion. The microvasculature of regional lymph nodes can be both an additional and an alternative lymphogenous metastasis pathway of cancer; at the same time, vascular invasion is accompanied by microcirculation disorders and depends on the volume of metastases and the immunomorphological reactions of the lymph nodes.

Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer.

To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram. PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60Hz]; 0.975 vs. 0.904, P = 0.060 [90Hz], respectively). MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors and Reference Markers of Treatment Options for Locally Advanced Squamous Cell Carcinoma Located in the Middle and Upper Esophagus.

BackgroundVarious inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed.MethodsNLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival.ResultsNLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045).ConclusionLow pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Preoperative Serum Calcitonin and Its Correlation with Extent of Lymph Node Metastasis in Medullary Thyroid Carcinoma.

Simple SummarySurgery is the only curative treatment for medullary thyroid carcinoma (MTC), but the initial surgical extent is still controversial. We examined whether the preoperative serum calcitonin level reflects the extent of lymph node metastasis (LNM), and therefore might be used to predict the optimal initial surgical extent for MTC. Furthermore, positive and negative likelihood ratios for preoperative serum calcitonin were calculated for calcitonin concentration categories, revealing that serum calcitonin levels can be of diagnostic value and might be applicable to surgical decision-making.The optimal initial surgical extent for medullary thyroid carcinoma (MTC) remains controversial. Previous studies on serum calcitonin are limited to reporting the calcitonin threshold according to anatomical disease burden. Here, we evaluated whether preoperative calcitonin levels can be used to predict optimal surgical extent. We retrospectively reviewed the 170 patients with MTC at a tertiary Korean hospital from 1994 to 2019. We extracted data on preoperative calcitonin level, primary tumor size and the number and location of lymph node metastases (LNMs). To evaluate disease extent, we divided the patients into five groups: no LNM, central LNM, ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis. We calculated the positive and negative likelihood ratios (LRs) for multiple categories of preoperative calcitonin levels. Preoperative calcitonin level positively correlated with primary tumor size (rho = 0.744, p < 0.001) and LNM number (rho = 0.537, p < 0.001). Preoperative calcitonin thresholds of 20, 200, and 500 pg/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. The negative LRs were 0.1 at a preoperative calcitonin cut-off of 100 pg/mL in the central LNM, 0.18 at a cut-off of 300 pg/mL in the ipsilateral lateral LNM, and 0 at a cut-off of 300 pg/mL in the contralateral lateral LNM. The preoperative calcitonin level correlates with disease extent and has diagnostic value for predicting LNM extent. Our results suggest that the preoperative calcitonin level can be used to determine optimal initial surgical extent.

A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol

BackgroundSince the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8–2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC.MethodsThis two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA–IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5–6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial.DiscussionIn unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated.Trial registrationclinicaltrials.gov (NCT03308552, November 1, 2017).

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.

Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Cancer Stem Cells-Role in Oral Squamous Carcinoma - A Review of Literature

The cancer stem cells (CSC) are responsible for the growth of cancerous tumours. The renewal of cancer stem cells is considered synonymous with that of normal cells. The cancer cells are considered a progeny of specific and designated stem cells. The identification of these cancer stem cells has proven to be more difficult than anticipated due to the specific niches they are present in, within the tumour. Oral squamous carcinoma is the Sixth most common cancer constituting up to 2–4% of all malignancies worldwide and with poor prognosis. Tumour size and extent of lymph node metastasis are the most important predictors. The CSC works on the mechanism of bulk tumour cell formation and treatment resistance. But there are increased studies under this topic as it has been found that specifically targeting these cells can curb cancer. This review compiles information about the role of CSC in oral squamous cell carcinomas, the applications of CSC, and their use in the development of novel treatment options for oral cancer.

57% decline in Rhode Island invasive breast cancer mortality between 1987 and 2017: mammography predominates in preventing mortality.

Controversy exists regarding proportional contributions of mammographic screening versus systemic therapy to declining disease-specific mortality of female invasive breast cancer (IBC) in the United States. Understanding relative contributions may help address allocation of medical resources. A 31-year (1987-2017) review of Rhode Island (RI) Cancer Registry data of female IBC was carried out in a state with high rates of mammographic screening. Over 31years in RI, statistically significant improvements occurred at initial diagnosis of IBC: mean and median maximum cancer diameters decreased by 21% and 30% respectively. Despite 1997 introduction of more accurate sentinel lymph node biopsy, the proportion of patients with axillary lymph node metastases (LNM) decreased by 27%. Extent of LNM also decreased as patients with over three node metastases decreased 67%. By 2017, 53% of all patients with LNM had only one. Poorly differentiated cancers decreased 50%. Disease-specific mortality decreased 57%. Improvements in initial presentation of IBC are consistent with most having progressive growth, from cellular origin to palpable mass, the currently accepted biological model. Breast cancers identified earlier at initial diagnosis through screening mammography are characterized by smaller size, fewer axillary LNMs, better grade differentiation, and decreased mortality. Statistical analysis from these improved diagnostic parameters indicate that the majority of mortality decline from invasive breast cancer in RI can be attributed to earlier detection. Thus, mammography predominates in preventing mortality.

Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma.

Lymphovascular invasion (LVI) is an established adverse prognostic factor in many cancers, however, there are few studies assessing its significance in papillary thyroid carcinoma (PTC). We aimed to determine if LVI is an independent prognostic factor in PTC. We conducted a single institution retrospective analysis of 610 patients with PTC treated between 1987 and 2016. LVI was defined as the presence or absence of cancer cells in blood vessels and/or lymphatics on histopathology. Multivariate Cox regression analysis was used to evaluate the association between LVI and recurrence-free survival (RFS). The study cohort included 481 (78.9%) females and 129 (21.1%) males, with a median age of 47.6 years and median follow-up of 3.4 years. LVI was present in 56 (9.2%) patients and was associated with nodal metastases (P < 0.001), extrathyroidal extension (P < 0.001), extranodal extension (P < 0.001), multifocality (P = 0.018) and microscopic positive margins (P < 0.001). On univariate analysis, LVI was associated with reduced RFS (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.3-4.3; P = 0.007). However, after adjusting for nodal stage (pN0, pN1a, pN1b) there was no association between LVI and RFS (HR 1.3; 95% CI 0.7-2.5; P = 0.398). Similar results were obtained in full multivariate models adjusting for additional prognostic factors (HR 1.2; 95% CI 0.6-2.4; P = 0.627). LVI is strongly associated with other adverse prognostic factors in PTC, particularly the presence and extent of nodal metastases. However, after adjusting for these, LVI is not an independent predictor of recurrence.

Topographic lymph node staging system shows prognostic superiority compared to the 8th edition of AJCC TNM in gastric cancer. A western monocentric experience

IntroductionThe current Tumor Node Metastasis staging system (TNM) for gastric cancer classifies the extent of lymph node metastasis based upon the number of lymph nodes involved. Choi et al. have recently proposed a new anatomical classification based upon the regionality of the involved nodes. This new classification seems to have a better predictive prognostic value than the traditional one. We investigated the prognostic role of the new anatomical based classification, reviewing our institutional gastric cancer database. MethodsWe performed a retrospective chart review of 329 patients who underwent gastrectomy at our Institution from 2003 to 2017. We excluded from data analysis any patient with distant metastases at the time of first diagnosis and or surgery, pathology other than adenocarcinoma, lymphadenectomy less than D2, impossibility to identify location of lymph nodes (LNs) on pathological report and neoadjuvant chemotherapy. The extent of D2 lymphadenectomy was defined according to Japanese Gastric Cancer Association criteria. LN metastasis were reclassified into three topographic groups (lesser, greater curvature, and extraperigastric nodes) and staged according to Choi. The new N stage was combined with the current pT according to the 8th edition of TNM and a new hybrid TNM stage was established. All patients were followed up until June 2019. The prognostic performance of the new stage and of the current anatomical numeric based system (TNM) was analyzed and assessed by the C-index, AIC and likelihood ratio χ2 value. ResultsIn predicting both Overall Survival (OS) and Disease free Survival (DFS) the new N stage and the new TNM staging system had the highest C-index and likelihood ratio χ2 value and the lowest Akaike Information Criterion (AIC), showing a better accuracy and displaying a better prognostic performance. ConclusionsOur study is the first from the Western world to compare the new hybrid classification, based on the anatomical location of metastatic nodes, to the 8th of American Joint Committee on Cancer (AJCC) TNM staging system. Our findings on a small, monocentric sample suggest that hybrid topographic lymph node staging system is more accurate than TNM.