Origins of lymphatic and distant metastases in human colorectal cancer

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

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Mitochondrial DNA alteration in primary and metastatic colorectal cancer: Different frequency and association with selected clinicopathological and molecular markers

Tumor Biology ◽

10.1177/1010428317692246 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769224 ◽

Cited By ~ 4

Author(s):

Britta Kleist ◽

Thuja Meurer ◽

Micaela Poetsch

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Microsatellite Instability ◽

Metastatic Colorectal Cancer ◽

Lymph Node Metastases ◽

Primary Tumor ◽

Distant Metastases ◽

Primary Tumors ◽

Node Metastases ◽

Mitochondrial Microsatellite Instability

This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.

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A Head-to-Head Comparison of 68Ga-DOTA-FAPI-04 and 18F-FDG PET/MR in Patients with Nasopharyngeal Carcinoma: A Prospective Study

10.21203/rs.3.rs-252484/v1 ◽

2021 ◽

Author(s):

Chunxia Qin ◽

Fang Liu ◽

Jing Huang ◽

Weiwei Ruan ◽

Qingyao Liu ◽

...

Keyword(s):

Lymph Node ◽

Nasopharyngeal Carcinoma ◽

Lymph Nodes ◽

Skull Base ◽

Primary Tumor ◽

Fdg Pet ◽

Distant Metastases ◽

Tracer Uptake ◽

Visual Evaluation ◽

Primary Tumors

Abstract PurposeTo conduct a head-to-head comparison of the diagnostic ability of 68Ga-DOTA-FAPI-04 (68Ga-FAPI) and 18F-FDG PET/MR in nasopharyngeal carcinoma (NPC) patients.MethodsPatients diagnosed with NPC were prospectively enrolled. All patients underwent head-and-neck 68Ga-FAPI PET/MR and 18F-FDG PET/MR within one week. Primary tumor, lymph node numbers, and tracer uptake were compared by SUVmax and visual evaluation. The primary tumor volumes derived from 68Ga-FAPI, 18F-FDG PET, and MRI were also compared.ResultsFifteen patients were enrolled from June to August 2020. Both 68Ga-FAPI and 18F-FDG PET had 100% detection rate of the primary tumor. The 68Ga-FAPI SUVmax of primary tumors (13.87±5.13) was lower than that of 18F-FDG (17.73±6.84), but the difference was not significant (p=0.078). Compared with 18F-FDG, 68Ga-FAPI PET improved the delineation of skull-base invasion in eight out of eight patients and intracranial invasion in four out of four patients. When 25%SUVmax of 68Ga-FAPI or 20%SUVmax of 18F-FDG was utilized as a threshold for determining tumor volume, it was highly consistent with MRI. 18F-FDG PET detected much more positive lymph nodes than 68Ga-FAPI (100 vs 48). The SUVmax of 48 paired lymph nodes was significantly lower on 68Ga-FAPI than 18F-FDG (8.67±3.88 vs 11.79±6.17, p<0.001). Additionally, 68Ga-FAPI further detected four highly suspected small, distant metastases in three patients. Compared with 18F-FDG, 68Ga-FAPI changed overall staging in six of fifteen patients, with three patients being up-staged, and three down-staged.Conclusion68Ga-FAPI outperforms 18F-FDG in delineating the primary tumor and detecting suspected distant metastases, particularly in the evaluation of skull-base and intracranial invasion, suggesting 68Ga-FAPI hybrid PET/MR has the potential to serve as a single-step staging modality for patients with NPC. However, its value regarding lymph node and distant metastases evaluation needs further study.Trial registration: NCT04554719. Registered September 8, 2020 - retrospectively registered, http://clinicaltrails.gov/show/ NCT04554719

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Metastatic Spread of Stage I Melanoma of the Skin

Tumori Journal ◽

10.1177/030089168306900513 ◽

1983 ◽

Vol 69 (5) ◽

pp. 449-454 ◽

Cited By ~ 29

Author(s):

◽

Natale Cascinelli ◽

Ferdinando Preda ◽

Maurizio Vaglini ◽

Sergio Orefice ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Primary Tumor ◽

Regional Lymph Node ◽

Distant Metastases ◽

Stage I ◽

Regional Lymph Nodes ◽

Prognostic Criteria ◽

Regional Node ◽

Node Metastases

1164 patients with stage I melanoma of the skin who were submitted to wide excision only of the primary tumor were studied to evaluate the rates of regional lymph node and distant metastases. Of these, 516 (44.3%) had a recurrence of the disease which was at regional lymph nodes in 264 (22.7%), at distant sites in 91 (7.8%), and simultaneously at regional lymph nodes and distant sites in 161 (13.8%). Most of the patients had a relapse within 5 years: regional node metastases were most frequently observed during the first 3 years, and distant metastases appeared later. The ratio regional:distant metastases was not different (P > 0.05) when subgroups of patients were considered according to prognostic criteria (sex, site of origin, levels, thickness, ulceration). Sex, levels, thickness and ulceration were found to be significantly related with the frequency of recurrences (regional and distant). It is concluded that the prognostic criteria considered do not predict whether the tumor will metastasize to regional nodes or to distant sites.

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Systematic assessment of intra- and peri-metastatic tumor budding in patients with stage IV colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.626 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 626-626

Author(s):

Annika Blank ◽

Sandra Burren ◽

Inti Zlobec ◽

Heather Dawson ◽

Alessandro Lugli

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Tumor Progression ◽

Primary Tumor ◽

Stage Iv ◽

Distant Metastases ◽

Metastatic Tumor ◽

University Hospital ◽

Tumor Budding ◽

Primary Tumors

626 Background: Tumor budding is a strong independent prognostic factor in primary colorectal cancer (CRC). The prognosis of stage IV CRC is still poor and there is need for biomarkers to facilitate the clinical management. Data on tumor budding in colorectal cancer distant metastases (CRDM) are still missing. Therefore, the aim of this study was to analyze its role in tumor progression. Methods: 73 stage IV CRC with clinico-pathological data were retrieved from a cohort of 331 CRC patients, surgically treated between 2002 and 2013 at the University Hospital of Bern. Tumor budding was visualized immunohistochemically by pan-cytokeratin staining. Tumor budding was defined as intra- and peri-tumoral budding in the primary tumor (ITB = buds in the tumor center; PTB = buds at the tumor margin), intra- and perinodal budding (INB and PNB) and intra- and peri-metastatic tumor budding (IMB and PMB). Overall tumor budding was defined as tumor buds independent of the center and margin (OTB, ONB, OMB). The tumor bud count was assessed by calculating the mean number of tumor buds in 10 high power fields. For survival analysis a cut off of 10 tumor buds was applied to subdivide the tumors with low and high numbers of tumor buds. Results: In lymph nodes and CRDM, the tumor bud count was lower compared to primary tumors (PNB: 13; INB: 18; ONB: 21 vs PMB: 10; IMB: 21; OMB: 22 vs PTB: 23; ITB: 24; OTB: 33). For PTB/PNB and OTB/ONB, there were significant differences between primary tumor and lymph node metastasis (PTB/PNB: p < 0.001; OTB/ONB: 0.008) and primary tumor and distant metastases (PTB/PMB: p < 0.001; OTB/OMB: 0.007). The presence of PMB was predicted by INB, PNB and V1 (p = 0.032, p = 0.001 and p = 0.003). A trend towards a worse prognosis in patients with a high OMB number was observed. Conclusions: Tumor budding is present in lymph node and distant metastases of CRC, but its number is lower compared to the corresponding primary tumor. As tumor budding in local and distant metastases seems to be a predictor of tumor progression, these novel data should be considered as a basis for further analysis in large and multicentric clinical trials.

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Primary Tumor Site, Size, Patients Age and Axillary Lymph Nodes in Breast Cancers

Tumori Journal ◽

10.1177/030089168607200306 ◽

1986 ◽

Vol 72 (3) ◽

pp. 259-265 ◽

Cited By ~ 5

Author(s):

Salvatore Toma ◽

Stefano Bonassi ◽

Riccardo Puntoni ◽

Guido Nicolò

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Primary Tumor ◽

Lymph Node Involvement ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Breast Cancers ◽

Primary Tumor Site ◽

Primary Tumors ◽

Node Involvement

This study considers the correlations between some characteristics of the primary tumor and level of lymph node involvement in 185 primary breast cancers. The average number of lymph nodes was higher in N + women than in N— women. Primary tumors with a diameter of more than 4 cm yielded the highest mean number of lymph nodes (17.5). The risk of developing lymph node metastases was fourfold in tumors with a diameter greater than 2 cm when compared to those with a diameter less than or equal to 2 cm. The most commonly metastasized lymph node level, in both large and small tumors, was the first; however, one-fifth of the patients had simultaneous lymph node metastasis in all three axillary levels. Although the left breast was the most affected (58.9 %), there was no evidence of a different risk of metastasis between the two breasts; 34.1 % of the tumors were multifocal. Lymph node involvement was higher in women under 50 years of age with a primary tumor larger than 2 cm.

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Metastases to the regional lymph nodes, lymph node recurrence, and distant metastases in nonadvanced papillary thyroid carcinoma

Surgery Today ◽

10.1007/bf00311254 ◽

1995 ◽

Vol 25 (4) ◽

pp. 324-328 ◽

Cited By ~ 34

Author(s):

Kiminori Sugino ◽

Yoshio Kure ◽

Hiroyuki Iwasaki ◽

Osamu Ozaki ◽

Takashi Mimura ◽

...

Keyword(s):

Lymph Node ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Lymph Nodes ◽

Distant Metastases ◽

Papillary Thyroid ◽

Regional Lymph Nodes ◽

Lymph Node Recurrence

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The decreased platelet-to-lymphocyte ratio could predict a good prognosis in patients with oligometastatic colorectal cancer: a single-center cohort retrospective study

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02406-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiaojuan Huang ◽

Jin Cui ◽

Xiaohui Li ◽

Chao Liu ◽

Jujie Sun ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Nodes ◽

Primary Tumor ◽

Tumor Resection ◽

Good Prognosis ◽

Primary Tumor Resection ◽

Platelet To Lymphocyte Ratio ◽

Regional Lymph Nodes ◽

Lymphocyte Ratio ◽

N Stage

Abstract Background Inflammation markers have an important effect on tumor proliferation, invasion, and metastasis. Oligometastatic disease (OMD) is an intermediate state between widespread metastases and locally confined disease, where curative strategies may be effective for some patients. We aimed to explore the predictive value of inflammatory markers in patients with oligometastatic colorectal cancer (OMCC) and build a nomogram to predict the prognosis of these patients. Methods Two hundred nine patients with OMCC were retrospectively collected in this study. The Kaplan-Meier survival curves and Cox regression analysis were used to estimate overall survival (OS) and progression-free survival (PFS). A multivariate Cox analysis model was utilized to establish the nomogram. The concordance index (C-index), calibration curve, and receiver operating characteristics (ROC) were established to verify the validity and accuracy of the prediction model. Results According to the multivariate analysis, decreased platelet-to-lymphocyte ratio (PLR) might independently improve OS in patients with OMCC (HR = 2.396, 95% CI 1.391–4.126, P = 0.002). Metastases of extra-regional lymph nodes indicated poor OS (HR = 2.472, 95% CI 1.247–4.903, P = 0.010). While the patients with early N stage had better OS (HR = 4.602, 95% CI 2.055–10.305, P = 0.001) and PFS (HR = 2.100, 95% CI 1.364–3.231, P = 0.007). Primary tumor resection (HR = 0.367, 95% CI 0.148–0.908, P = 0.030) and lower fibrinogen (HR = 2.254, 95% CI 1.246–4.078, P = 0.007) could significantly prolong the OS in patients with OMCC. PLR, metastases of extra-regional lymph nodes, N stage, primary tumor resection, and fibrinogen were used to make up the nomogram. The C-index and area under the curve (AUC) of the ROC in nomogram were 0.721 and 0.772 respectively for OS, showed good consistency between predictive probability of OS and actual survival. Conclusions Decreased PLR could predict a good prognosis in patients with OMCC. The nomogram including inflammatory factors and clinicopathological markers was credible and accurate to predict survivals in patients with OMCC.

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Injection of Carbon Nanoparticles for Lymph Node Detection After Laparoscopic Colorectal Cancer Surgery

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18667 ◽

2021 ◽

Vol 21 (2) ◽

pp. 886-894

Author(s):

Donghua Wang ◽

Manyu Chen ◽

Long Lv ◽

Yu Chen ◽

Kui Tian

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Nodes ◽

Treatment Plan ◽

Regional Lymph Nodes ◽

Colorectal Cancer Surgery ◽

Lymphatic Gland ◽

Node Metastasis

Colorectal cancer is the third most common cause of cancer-related death in the world because of its poor prognosis and many related complications. In clinical practice, lymph node metastasis is an important index to evaluate the recurrence and survival rate of patients with rectal cancer, it also the main method to determine the treatment plan of patients with rectal cancer. Nano carbon tracer can guide surgeons to clear regional lymph nodes accurately, improve the number of lymph nodes detected, and then improve the accuracy of pathological staging of rectal cancer. It has an important clinical significance in the removal of lymph nodes of middle and low rectal cancer, and provides an important basis for the development of postoperative adjuvant treatment plan. The purpose of this study is to explore the application value of this method in improving the detection rate of lymph nodes in laparoscopic colorectal cancer. According to the research results, the total number of lymphatic gland, the number of small lymphatic gland, the rate of lymph node metastasis, the number of black stained lymphatic gland and the number of lymphatic gland confirmed by pathology in the two groups were better than those in the traditional surgical treatment, which had better application value in the radical operation of colorectal cancer.

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A Giant Verrucous Carcinoma of the Penis Presenting with Urinary Sepsis and Angina

Case Reports in Medicine ◽

10.1155/2014/207026 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Michael Nomikos ◽

Paschalis Barmpoutis ◽

Eleni Papakonstantinou ◽

Zacharias Chousianitis ◽

Prodromos Ouzounoglou ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Histological Examination ◽

Verrucous Carcinoma ◽

Corpus Cavernosum ◽

Distant Metastases ◽

Ct Scans ◽

Regional Lymph Nodes ◽

Genital Region ◽

Urinary Sepsis

Penile verrucous carcinoma also known as Buschke-Löwenstein tumor in the genital region is an uncommon variant of penile carcinoma exhibiting slow, expansive growth. We present a case of a 63-year-old male who presented with a giant purulent penile mass causing urinary sepsis and angina. Regional lymph nodes were clinically negative and staging with CT scans of thorax and abdomen did not show any signs of lymph node or distant metastases. After resuscitation, radical penectomy was performed and a perineal urethrostomy was created. Histological examination revealed a Buschke-Löwenstein tumor of the penis with no invasion of corpus cavernosum and urethra.

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Breast Cancer: Primary Tumor Characteristics Related to Lymph Node Involvement

Tumori Journal ◽

10.1177/030089168106700104 ◽

1981 ◽

Vol 67 (1) ◽

pp. 19-26 ◽

Cited By ~ 4

Author(s):

Alessandro Rasponi ◽

Alberto Costa ◽

Rosaria Bufalino ◽

Alberto Morabito ◽

Maurizio Nava ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Primary Tumor ◽

Lymph Node Involvement ◽

Maximum Diameter ◽

Histologic Type ◽

Regional Lymph Nodes ◽

The Status ◽

Node Involvement ◽

Node Metastases

From November 1st 1977 to August 31st 1978, 842 consecutive patients with operable breast cancer were observed at the National Cancer Institute of Milan. Characteristics of the primary tumor and the status of regional lymph nodes were evaluated at clinical and postsurgical examination: it was found that qualitative characteristics of the primary were properly defined by clinicians, who usually overestimated maximum diameter of the primary. The status of regional lymph nodes is not reliable at clinical examination: 34.5 % of clinically uninvolved nodes were found to contain metastatic growth at histologic examination. Age of patients, maximum diameter of the primary, histologic type and quadrant of origin of the primary tumor were significantly related to the frequency of regional node metastases. Multifactorial analysis showed that the last three factors were independent variables, while age, which is significant by itself, loses importance when adjusted by at least one of the other three factors. Frequency of extension of node metastases beyond the lymph node capsule was found to be related to the number of involved nodes: maximum diameter, histologic type and site of origin are significantly related to the frequency of extracapsular invasion. This study confirms that the evaluation of the status of regional lymph nodes is not reliable at clinical examination and indicates that characteristics of the primary may be useful in predicting regional lymph node involvement. The direct correlation between the number of involved nodes and the frequency of infiltration beyond the capsule suggests that prognosis of patients with positive nodes depends more on this factor than on the number of involved nodes.

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