scholarly journals Lymphatic metastases have more diverse roots than distant metastases

2019 ◽  
Author(s):  
Johannes G. Reiter ◽  
Shriya Nagpal ◽  
Kamila Naxerova

AbstractBoth lymphatic and distant metastases arise through cancer cell migration and colonization of ectopic sites. Nonetheless, the two metastasis types are associated with significantly different clinical outcomes, suggesting that distinct biological mechanisms may drive their formation. Here we show fundamental differences in the seeding patterns of lymphatic and distant metastases. Analyzing the reconstructed phylogenies of human colorectal cancers, we find that distant metastases typically are monophyletic, originating from one common ancestor. Lymphatic metastases, in contrast, are almost exclusively polyphyletic and can be seeded from many primary tumor regions. We develop a rigorous mathematical framework for quantifying the phylogenetic diversity of metastases while accounting for differential lesion sampling among patients. Our results indicate that a smaller fraction of primary tumor cells gives rise to distant metastases than lymphatic metastases. Thus, the two metastasis types exhibit profoundly distinct phylogenetic traits, indicating that different evolutionary mechanisms may drive their formation and influence their clinical behavior.

Author(s):  
Shoshana Zhang ◽  
Kristan Schiele ◽  
Clay J. Cockerell ◽  
Roopal Bhatt

mBio ◽  
2021 ◽  
Author(s):  
Tao Li ◽  
Yi-Zhou Gao ◽  
Jia Xu ◽  
Shu-Ting Zhang ◽  
Yuan Guo ◽  
...  

Because anthropogenic nitroaromatic compounds have entered the biosphere relatively recently, exploration of the recently evolved catabolic pathways can provide clues for adaptive evolutionary mechanisms in bacteria. The concept that nitroarene dioxygenases shared a common ancestor with naphthalene dioxygenase is well established.


Author(s):  
Feng-Yuan Liu ◽  
Ting-Wen Sheng ◽  
Jing-Ren Tseng ◽  
Kai-Jie Yu ◽  
Ke-Hong Tsui ◽  
...  

Objectives: To investigate whether PET/CT or PET/MRI is more appropriate for imaging prostate cancer, in terms of for primary tumor detection, local staging and recurrence, as well as lymph nodes and distant metastases. Methods: A systematic literature search was conducted on Embase, PubMed/MEDLINE, and the Cochrane Library database. Studies evaluating the diagnostic performance of PET/CT vs PET/MRI in prostate cancer patients were emphasized. Results: We reviewed 57 original research articles during the period 2016—2021: 14 articles regarding the radiotracer PSMA; 18 articles regarding the primary tumor detection, local tumor staging, managing local recurrence; 17 articles for managing lymph node metastases; and eight articles for managing bone and other distant metastases. PSMA PET could be complementary to mpMRI for primary prostate cancer localization and is particularly valuable for PI-RADS three lesions. PET/MRI is better than PET/CT in local tumor staging due to its specific benefit in predicting extracapsular extension in MRI-occult prostate cancer patients. PET/MRI is likely superior as compared with PET/CT in detecting local recurrence, and have slightly higher detection rates than PET/CT in lymph node recurrence. PET/CT and PET/MRI seem to have equivalent performance in detecting distant bony or visceral metastases. Conclusion: In conclusion, PET/MRI is suitable for local and regional disease, either primary staging or restaging whereas PET/CT is valuable for managing distant bony or visceral metastasis. Advances in knowledge: We reviewed the emerging applications of PET/MRI and PET/CT in clinical aspects. Readers will gain an objective overview on the strength and shortfalls of PET/MRI or PET/CT in the management of prostate cancer.


1988 ◽  
Vol 6 (7) ◽  
pp. 1107-1117 ◽  
Author(s):  
B Fowble ◽  
R Gray ◽  
K Gilchrist ◽  
R L Goodman ◽  
S Taylor ◽  
...  

Risk factors for isolated local-regional (LR) recurrence following mastectomy for breast cancer were analyzed in a review of 627 women entered into Eastern Cooperative Oncology Group (ECOG) adjuvant chemotherapy trials between 1978 and 1982. Premenopausal patients were randomized to cyclophosphamide, methotrexate, and fluorouracil (5-FU) (CMF), cyclophosphamide, methotrexate, 5-FU, and prednisone (CMFP), or cyclophosphamide, methotrexate, 5-FU, prednisone, and tamoxifen (CMFPT). Postmenopausal patients were randomized to observation, CMFP, or CMFPT. Median follow-up time was 4.5 years. At 3 years, 225 patients relapsed and in 70 (31% of failures, 11% of all patients) the initial site was LR without distant metastases. In a multivariate analysis, the risk of an isolated LR recurrence significantly correlated with the number of positive axillary nodes, the primary tumor size, the presence of tumor necrosis, and the number of axillary nodes examined. Factors that significantly discriminated between an isolated LR recurrence and distant metastasis were the number of positive nodes and primary tumor size. Patients with four to seven positive nodes or tumor size greater than or equal to 5 cm had a chance of developing an isolated LR recurrence almost equal to the risk of distant metastases. These findings suggest a potential for improved survival in this subset of patients with the addition of postmastectomy radiation to chemotherapy, and continue to emphasize the presence of a group of patients at high risk for isolated LR recurrence despite adjuvant chemotherapy.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 625
Author(s):  
Hosu Kim ◽  
So Young Park ◽  
Jun-Ho Choe ◽  
Jee Soo Kim ◽  
Soo Yeon Hahn ◽  
...  

Lymph node metastasis (LNM) in differentiated thyroid cancer (DTC) is usually detected with preoperative ultrasonography; however, this has limited sensitivity for small metastases, and there is currently no predictive biomarker that can help to inform the extent of surgery required. We evaluated whether preoperative serum thyroglobulin levels can predict tumor burden and extent. We retrospectively reviewed the clinical records of 4029 DTC cases diagnosed and treated at a Samsung Medical Center between 1994 and 2016. We reviewed primary tumor size, number and location of LNM, and presence of distant metastases to reveal relationships between tumor burden and extent and preoperative serum thyroglobulin levels. We found a linear association between increasing preoperative thyroglobulin levels, the size of the primary tumor, and the number of LNM (r = 0.34, p < 0.001, r = 0.20, p < 0.001, respectively). Tumor extent also increased with each decile of increasing preoperative thyroglobulin level (r = 0.18, p < 0.001). Preoperative thyroglobulin levels of 13.15 ng/mL, 30.05 ng/mL, and 62.9 ng/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. Our results suggest that preoperative measurement of serum thyroglobulin may help to predict LNM and help to tailor surgery.


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2246
Author(s):  
Marina Tsoli ◽  
Maria-Eleni Spei ◽  
Göran Wallin ◽  
Gregory Kaltsas ◽  
Kosmas Daskalakis

The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle–Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53–1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24–3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.


2005 ◽  
Vol 12 (4) ◽  
pp. 1083-1092 ◽  
Author(s):  
Francesco Panzuto ◽  
Silvia Nasoni ◽  
Massimo Falconi ◽  
Vito Domenico Corleto ◽  
Gabriele Capurso ◽  
...  

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan–Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for ≤ 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P<0.0001), Ki67 (53.5% for > 2% vs 90.1% for ≤ 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for ≤ 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 141-141
Author(s):  
T. Osako ◽  
R. Nishimura ◽  
Y. Okumura ◽  
R. Tashima ◽  
Y. Toyozumi ◽  
...  

141 Background: The purpose of this study was to investigate factors for survival after locoregional recurrence in patients who underwent mastectomy or breast-conserving therapy (BCT) for primary breast cancer in our hospital. Methods: Out of 3,332 patients operated on from 1989 to 2008, 50 patients had chest wall recurrences after mastectomy (CWR), 40 patients had regional nodal recurrences (RNR), and 24 patients had ipsilateral breast tumor recurrences (IBTR) from 1997 to 2008. To investigate the prognostic factors for survival after locoregional recurrence, we conducted uni- and multivariate analyses of these cases. Results: The median follow-up time was 49.2 months. The 5-year survivals after recurrence of the patients with CWR, RNR and IBRT were 52%, 28%, and 68%, respectively. And the 10-year survivals were 15%, 0%, and 62%, respectively. Furthermore, the 5-year distant metastasis-free survivals were 24%, 13%, and 59%, respectively. In a multivariate analysis of the patients with CWR, type of recurrent nodules (diffuse/single, RR 21.0, p= 0.001), pT (T3 or 4 /T1, RR 11.4, p=0.01), pN (N3/N0, RR 15.5, p= 0.03), Ki67 of primary tumor (>50%/<20%, RR6.7, p=0.02) and ER of the primary tumor (+ / -, RR 2.6, p = 0.02) were independent prognostic factors. In a multivariate analysis of RNR, the method of first line salvage therapy (local /local + systemic, RR 16.1, p = 0.01) was only an independent prognostic factor. In the cases of IBTR, there were no independent prognostic factors for survival after recurrence. Conclusions: Although CWR developed distant metastases within 5 years, the survival depended upon the several biological factors. RNR developed distant metastases within a few years and provided poor prognosis. These suggested that RNR would be the first appearance of systemic metastasis not local disease. In contrast, IBTR provided better prognosis and a salvage treatment cured about 60% of the patients.


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