Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

Sawabata, Noriyoshi; Funaki, Soichiro; Hyakutake, Takeru; Shintani, Yasushi; Fujiwara, Ayako; Okumura, Meinoshin

doi:10.1007/s00595-016-1318-4

Cited by 49 publications

(48 citation statements)

References 19 publications

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“…These results suggest that a tumor biopsy of a lung cancer lesion has the potential to dislodge tumor cells into the peripheral circulating blood, as can occur with a surgical procedure. [12][13][14][15] Initially, tumor cell dislodgement to the peripheral circulating blood by surgical manipulation was demonstrated using a cytological technique, but the sensitivity was very low. [17] Later, polymerase chain reaction [18,19] and flow-cytometry [20] methods were introduced to improve sensitivity and specificity, but results were not predictable.…”

Section: Discussionmentioning

confidence: 99%

“…[16,25] Recently, CTC dislodgement during surgery for lung cancer was proven by detecting CTCs in the peripheral circulating blood using a size selection method, and the presence of cluster CTC has been an indicator of early recurrence among surgical lung cancer patients. [13] A CTC assessment during FFB procedures needs a method that can extract CTCs from the peripheral blood sensitively, and for this reason we chose the sensitive method of micropore membrane size selection. This let us that the FFB procedure causes CTCs dislodgement into the circulating blood, with distinguishing cluster CTC that may be a crucial indicator of tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15] Above all, detecting cluster circulating tumor cell (CTC) is speculated the best a strong predictor of early recurrence. [13] FBB also manipulates the area of lung cancer during biopsy; thus, CTCs might be dislodged from the lesion to the circulating blood as the same manner as surgical manipulation. For that reason we assessed the status of CTC before and after FFB biopsy to diagnose lung cancer.…”

Section: Introductionmentioning

confidence: 99%

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Lung cancer biopsy dislodges tumor cells into circulating blood

Sawabata¹,

Kitamura²,

Nitta³

et al. 2017

JCMT

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Aim:A "seed" of lung cancer metastasis is circulating tumor cells (CTCs), which may be dislodged from a tumor during biopsy. This possibility was assessed among patients who underwent lung tumor biopsy using flexible fiber-topic bronchoscopy (FFB). Methods: The study involved six patients with non-small cell lung cancer who underwent FFB biopsy to diagnose a lesion pathologically (5 males and 1 female, median age 63 years, 6 adenocarcinomas, of 4 clinical-stage IA, 1 stage IB, and 1 stage IIIA), CTCs were extracted from the peripheral vein blood at pre-FFB and at post-FFB using a size selection method. Results: No tumor cell was detected at pre-and post-FFB was in three cases (50%); no tumor cells were detected pre-FFB while CTCs were detected at post-FFB in two cases (33.3%); and CTCs were detected at pre-FFB with numerous CTCs detected at post-FFB in one case (17.7%). In addition, similar tendencies were observed in each analysis of singlecell and clustered-cell categories. Conclusion: These results suggest that a FFB biopsy of lung cancer may potentially dislodge CTCs from a tumor into the circulating peripheral blood. Key words:Lung cancer, biopsy, circulating tumor cells ABSTRACTArticle history:

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lung cancer biopsy dislodges tumor cells into circulating blood

Sawabata¹,

Kitamura²,

Nitta³

et al. 2017

JCMT

Self Cite

View full text Add to dashboard Cite

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“…In addition to TGF-β, many chemical substances that play a role in immune signaling may inhibit the proliferation of cancer cells. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumor cells (CTCs) [5,6]. High CTC levels are associated with an unfavorable prognosis in many cancers.…”

Section: Introductionmentioning

confidence: 99%

“…The "original" cancer cells may be able to inhibit the growth of other cancer cells; removal or killing of the original cancer cells may allow other non-detected cancer cells to grow. Researchers are investigating the use of auxiliary drugs combined with surgery or radiotherapy to reduce the risk of recurrence or tumor metastasis [6].…”

Section: Introductionmentioning

confidence: 99%

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma Through PEBP1

Huang

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hepatocellular carcinoma (HCC) is a major threat to human health. The condition carries a high risk of death; 45% of new cases occur in China. Surgical resection is the first choice for treatment of HCC, but 30.9% of patients experience recurrence within 6 months after the operation. To improve patient survival, we must determine how to reduce the probability of recurrence and metastasis and elucidate the underlying mechanism of disease. We therefore studied the effect of somatostatin octapeptide (octreotide) on the invasion and metastasis of HCC. Methods: The migration and invasion cytological tests were used to detect the effect of octreotide on liver cancer cells (SK-Hep-1 and HepG2). PEBP1 RNAi was used to knockdown expression. Invasion and metastasis were measured with transwell migration and wound-healing assays. Western blotting was used to detect changes in levels of PEBP1 and invasion pathway proteins after octreotide treatment. The effect of octreotide was studied in vivo by establishing a pulmonary metastasis model using SK-Hep-1 cells in nude mice. In-vivo bioluminescence imaging and hematoxylin and eosin staining of lung tissue were used to verify the results. Results: Increasing concentrations of octreotide were progressively more effective in halting the invasion and metastasis of liver cancer cells. Octreotide may upregulate PEBP1, TIMP-2, and E-cadherin while downregulating MMP-2 and Twist to inhibit cell invasion and metastasis. And downregulation of PEBP1 would also change the expression of MMP-2, TIMP-2 and Twist. The in-vivo experiments showed no cancer cell metastasis in 4 of the 6 mice in the octreotide-treatment group, while all of the mice in the control group displayed pulmonary metastasis of human HCC cells. And the survival period of the mice in the octreotide-treatment group was significantly prolonged. Conclusions: Octreotide may weaken invasion and metastasis through the upregulation of PEBP1. Octreotide may reduce the risk of recurrence and metastasis after surgery for liver cancer.

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Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non–Small Cell Lung Cancer

et al. 2019

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IMPORTANCEIt is important to develop a surgical technique to reduce dissemination of tumor cells into the blood during surgery.OBJECTIVE To compare the outcomes of different sequences of vessel ligation during surgery on the dissemination of tumor cells and survival in patients with non-small cell lung cancer. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, randomized clinical trial was conducted from December 2016 to March 2018 with patients with non-small cell lung cancer who received thoracoscopic lobectomy in West China Hospital, Daping Hospital, and Sichuan Cancer Hospital. To further compare survival outcomes of the 2 procedures, we reviewed the Western China Lung Cancer database (2005-2017) using the same inclusion criteria.INTERVENTIONS Vein-first procedure vs artery-first procedure. MAIN OUTCOMES AND MEASURESChanges in folate receptor-positive circulating tumor cells (FR + CTCs) after surgery and 5-year overall, disease-free, and lung cancer-specific survival.RESULTS A total of 86 individuals were randomized; 22 patients (25.6%) were younger and 64 (74.4%) older than 60 years. Of these, 78 patients were analyzed. After surgery, an incremental change in FR + CTCs was observed in 26 of 40 patients (65.0%) in the artery-first group and 12 of 38 (31.6%) in the vein-first group (P = .003) (median change, 0.73 [interquartile range (IQR), −0.86 to 1.58] FU per 3 mL vs −0.50 [IQR, −2.53 to 0.79] FU per 3 mL; P = .006). Multivariate analysis confirmed that the artery-first procedure was a risk factor for FR + CTC increase during surgery (hazard ratio [HR], 4.03 [95% CI,]; P = .005). The propensity-matched analysis included 420 patients (210 with vein-first procedures and 210 with artery-first procedures). The vein-first group had significantly better outcomes than the artery-first group for 5-year overall survival (73.6% [95% CI, 64.4%-82.8%] vs 57.6% [95% CI, 48.4%-66.8%]; P = .002), disease-free survival (63.6% [95% CI, 55.4%-73.8%] vs 48.4% [95% CI, 40.0%-56.8%]; P = .001), and lung cancer-specific survival (76.4% [95% CI, 67.6%-85.2%] vs 59.9% [95% CI, 50.5%-69.3%]; P = .002). Multivariate analyses revealed that the artery-first procedure was a prognostic factor of poorer 5-year overall survival (HR, 1.65 [95% CI, 1.07-2.56]; P = .03), disease-free survival (HR, 1.43 [95% CI, 1.01-2.04]; P = .05) and lung cancer-specific survival (HR = 1.65 [95% CI, 1.04-2.61]; P = .03). CONCLUSIONS AND RELEVANCELigating effluent veins first during surgery may reduce tumor cell dissemination and improve survival outcomes in patients with non-small cell lung cancer.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03436329

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Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

Abstract: CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

Cited by 49 publications

References 19 publications

Lung cancer biopsy dislodges tumor cells into circulating blood

Lung cancer biopsy dislodges tumor cells into circulating blood

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma Through PEBP1

Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non–Small Cell Lung Cancer

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