The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Current laboratory models of lymphatic metastasis generally require either genetically modified animals or are technically challenging. Herein, we have developed a robust protocol for the induction of intralymphatic metastasis in wild-type mice with reproducible outcomes. To determine an optimal injection quantity and timeline for tumorigenesis, C57Bl/6 mice were injected directly into the mesenteric lymph duct (MLD) with varying numbers of syngeneic murine colon cancer cells (MC38) or gastric cancer cells (YTN16) expressing GFP/luciferase and monitored over 2-4 weeks. Tumor growth was tracked via whole-animal in vivo bioluminescence imaging (IVIS). Our data indicate that the injection of tumor cells into the MLD is a viable model for lymphatic metastasis as necropsies revealed large tumor burdens and metastasis in regional lymph nodes. This protocol enables a closer study of the role of lymphatics in cancer metastasis and opens a window for the development of novel approaches for treatment of metastatic diseases.
OBJECTIVE - To determine if there is a critical depth of invasion that predicts micrometastasis in early oral tongue cancer.
METHODS - Retrospective series identifying patients undergoing primary surgical resection of T1 or T2 oral tongue cancer who elected against neck treatment between 2000 and 2015. Cox proportional-hazard model compared the relative hazard and cumulative incidence of recurrence to depth of invasion. The model used a 2 parameter quadratic effect for depth that was chosen based on Akaike's information criterion.
RESULTS - Ninety-three patients were identified with T1 or T2 oral tongue squamous cell carcinoma and clinically N0 neck undergoing glossectomy without elective neck treatment. 61% were male and median age was 60 years. Median follow up was 45 months, and 76 patients had at least two years of follow up. Thirty-six of 76 patients recurred (47.4%), with 15 recurring in the oral cavity (19.7%) and 21 developing nodal metastasis (27.6%). Cox proportional-hazards quadratic polynomial showed increasing hazard of recurrence with depth of invasion and the cumulative incidence increased sharply within the range of data from 2 to 6 mm depth of invasion.
CONCLUSIONS - Depth of invasion is significantly associated with nodal metastasis and has been added to the 8th AJCC staging guidelines. Variable depths of invasion have been associated with regional metastasis; however, there is likely not a critical depth that predicts neck recurrence due to progressive hazards and cumulative risk of occult metastasis. The risk of regional metastasis is likely much greater than previously believed and increases progressively with increasing depth.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.
The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.
Copyright © 2018 by the National Comprehensive Cancer Network.
BACKGROUND - Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.
METHODS - A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late.
RESULTS - With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence.
CONCLUSIONS - Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.
BACKGROUND - A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting."
OBJECTIVE - This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma.
DESIGN - This is a retrospective case control study.
SETTINGS - The National Cancer Database 2006 to 2014 was used to identify patients for this study.
PATIENTS - Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative.
MAIN OUTCOME MEASURES - The main outcome was nodal disease. The secondary outcome was overall survival.
RESULTS - A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002).
LIMITATIONS - This study was limited by the lack of clinical detail in the database and the inability to assess recurrence.
CONCLUSIONS - Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for "watchful waiting" strategies. See Video Abstract at http://links.lww.com/DCR/A458.
BACKGROUND - The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.
METHODS - Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.
RESULTS - In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort.
CONCLUSION - Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.
Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Mesenteric tumor deposits (MTDs) are not included in the American Joint Committee on Cancer (AJCC) staging system for midgut small intestinal neuroendocrine tumors (NETs). We examined the prognostic significance of MTDs associated with midgut NETs. Hematoxylin and eosin slides from 132 resected jejunal/ileal NETs were reviewed for AJCC tumor stage, lymph node (LN) metastasis, MTDs, and hepatic metastases. MTDs were defined as discrete irregular mesenteric tumor nodules discontinuous from the primary tumor. Clinical or pathologic evidence of metastases and survival data were abstracted from electronic medical records. The cohort included 72 male and 60 female patients with a median age of 60 years. LN metastasis, MTDs, and liver metastasis were present in 80%, 68%, and 58% of patients, respectively. Female sex and presence of MTDs were independent predictors of liver metastasis. The odds ratio for hepatic metastasis in the presence of MTDs was 16.68 (95% confidence interval [CI], 4.66-59.73) and 0.81 (95% CI, 0.20-3.26) for LN metastasis. Age, MTDs, and hepatic metastasis were associated with disease-specific survival (DSS) in univariate analysis. Primary tumor histologic grade, pT3/T4 stage, and LN metastasis were not associated with DSS. Multivariate analysis of liver metastasis-free survival stratified by tumor grade showed that MTDs were associated with adverse outcomes. The hazard ratio for MTDs was 4.58 (95% CI, 1.89-11.11), compared with 0.98 (95% CI, 0.47-2.05) for LN metastasis. MTDs, but not LN metastasis, in midgut NETs are a strong predictor for hepatic metastasis and are associated with poor DSS.
BACKGROUND - Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas.
OBJECTIVE - We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior.
METHODS - We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed.
RESULTS - There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01).
CONCLUSIONS - IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.
Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
BACKGROUND - We previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared with patients with KRAS wild-type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer.
METHODS - We reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6-year time period. We evaluated the associations among KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient dataset.
RESULTS - Among 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p = 0.99), smoking status (p = 0.33), or when comparing specific amino acid substitutions (p = 0.20). In our dataset, patients with KRAS codon 13 mutant tumors (n = 53) had shorter overall survival compared with patients with codon 12 mutant tumors (n = 624) (1.1 versus 1.3 years, respectively; p = 0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex, and smoking status (hazard ratio: 1.52, 95% confidence interval: 1.11-2.08; p = 0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 versus 1.1 years, respectively; p = 0.41).
CONCLUSIONS - Among individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are no apparent differences in outcome based on KRAS mutation subtype.