• cancer marker
• head and neck squamous cell carcinoma
• lymp node
• meastasis
• occult metastasis
• regional metastasis

• Humans
• Squamous Cell Carcinoma of Head and Neck/genetics
• Squamous Cell Carcinoma of Head and Neck/pathology
• Squamous Cell Carcinoma of Head and Neck/metabolism
• Squamous Cell Carcinoma of Head and Neck/virology
• Lymphatic Metastasis/genetics
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Head and Neck Neoplasms/pathology
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/metabolism
• Lymph Nodes/pathology

The formation of distant metastases often determines the fate of patients with head and neck squamous cell carcinoma (HNSCC). The expression of cell adhesion molecules (CAMs) and their ligands of the leukocyte adhesion cascade has been associated with metastatic competence in several malignant entities. In this study, human HNSCC cell lines were analyzed in vitro and in a spontaneous metastatic xenograft model. Immunohistochemical analyses of several CAMs were performed on xenograft tumors and tissue microarrays (TMA) from 453 patients with head and neck squamous cell carcinomas with full histo-pathological and clinical follow-up data. UTSCC 24A and 24B cells bind to E-selectin in vitro, show E-selectin dependent binding to human umbilical vein endothelial cells (HUVECs), and express sLeX. All HNSCC cells engrafted into severe combined immunodeficient (SCID) mice, and UTSCC 24A cells formed sporadically spontaneous lung metastases. The expression of CAMs varied between the cell lines, but a correlation between tumor growth and metastatic potential did not exist. None of the CAMS or their ligands could be identified to be of prognostic relevance in the TMA study. The in vitro results indicate that E-selectin and sLeX are involved in the adhesion of HNSCC cells to endothelium. However, specific prognostic markers chosen from the leukocyte adhesion cascade for HNSCC were not identified.

• SCID mouse
• cell adhesion molecules
• head and neck squamous cell carcinoma
• metastasis
• selectin
• xenograft model

• Cytokeratin 19
• biomarker
• disseminated tumor cells
• neoplasm diagnosis
• neoplasm prognosis

• cf DNA
• circulating cancer stem cells
• circulating tumour cells
• ctDNA
• radiotherapy

The prognostic impact of circulating tumor cells (CTC) on disease recurrence, progression and survivals in patients with head and neck squamous cell carcinoma (HNSCC) has not been adequately described. The objective of this study was to determine the impacts of the presence of CTC on loco-regional recurrence and survival of HNSCC patients by conducting a systematic review and meta-analysis.

A comprehensive search for articles published between 1990 and 2016 was conducted and data from these studies were extracted, using the MEDLINE, Cochrane Library, and EMBASE databases. The main outcomes were overall survival (OS) and recurrence-free survival (RFS) of HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. The quality of the studies, heterogeneity and publication bias were assessed with the appropriate statistical methods.

Six eligible studies with 429 patients were identified. The presence of CTC was significantly associated shorter RFS (HR = 4.88 [95%CI: 1.93–12.35], P < 0.001). However, it could not predict patients’ OS (HR = 1.92 [95%CI: 0.93–3.96], P = 0.078). The following analyses using univariable values of each study also made the similar results (HR = 1.70 [95%CI: 0.83–3.45] for OS, HR = 3.79 [95%CI: 2.02–7.13] for RFS). Heterogeneity and publication bias were not significant, except one enrolled study.

The presence of CTC is not a significant prognostic indicator for OS of patients with HNSCC, although it could reflect the outcomes of loco-regional disease.

Many studies have assessed the clinical use of circulating tumor cells (CTCs) in head and neck cancer, but the clinicopathological and prognostic significance of CTCs is still unclear.

Two authors systematically searched the studies independently with keywords in PubMed, MEDLINE, EMBASE, Science Citation Index Expanded and Cochrane Library (from inception to February 2017). The estimated hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. All analyses were performed by STATA 12.0.

A total of 17 studies were included in this meta-analysis. Positive CTCs were significantly associated with poor overall survival (HR =2.80, 95% CI: 1.34–5.86), disease-free survival (HR =3.86, 95% CI: 2.03–7.36) and progression-free survival (HR =3.31, 95% CI: 1.71–6.42). CTC-positive patients tend to have higher recurrence (RR =2.13, 95% CI: 1.26–3.59) and regional lymph node metastasis (RR =1.18, 95% CI: 1.02–1.36) rate and a more advanced tumor stage (RR =1.16, 95% CI: 1.03–1.32).

Our meta-analysis has confirmed the significant prognostic value of CTCs in head and neck cancer patients. The presence of CTCs could be used as a monitoring tool for tumor status of head and neck cancer, especially for the early detection of the tumor recurrence and progression, advanced disease and the node metastasis.

• circulating tumor cells
• clinicopathological characteristics
• head and neck cancer
• meta-analysis
• prognostic

• Cancer immunology
• Cancer signaling
• Dormancy
• Dormancy models
• Latency
• Metastasis
• Microenvironment
• Minimal residual disease

• Animals
• Humans
• Neoplasm, Residual/pathology
• Neoplasms/pathology
• Tumor Microenvironment

• R01 CA109182 NCI NIH HHS
• R03 CA191430 NCI NIH HHS

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma (OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool to determine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

• Circulating tumour cells
• Disseminated tumour cells
• Oral squamous cell carcinoma
• Head and neck squamous cell carcinoma
• Bone marrow
• Peripheral blood
• Micrometastasis
• Minimal residual disease
• Epithelial-mesenchymal transition

Perioperative visual loss (POVL) is an uncommon, but devastating complication that remains primarily associated with spine and cardiac surgery. The incidence and mechanisms of visual loss after surgery remain difficult to determine. According to the American Society of Anesthesiologists Postoperative Visual Loss Registry, the most common causes of POVL in spine procedures are the two different forms of ischemic optic neuropathy: anterior ischemic optic neuropathy and posterior ischemic optic neuropathy, accounting for 89% of the cases. Retinal ischemia, cortical blindness, and posterior reversible encephalopathy are also observed, but in a small minority of cases. A recent multicenter case control study has identified risk factors associated with ischemic optic neuropathy for patients undergoing prone spinal fusion surgery. These include obesity, male sex, Wilson frame use, longer anesthetic duration, greater estimated blood loss, and decreased percent colloid administration. These risk factors are thought to contribute to the elevation of venous pressure and interstitial edema, resulting in damage to the optic nerve by compression of the vessels that feed the optic nerve, venous infarction or direct mechanical compression. This review will expand on these findings as well as the recently updated American Society of Anesthesiologists practice advisory on POVL. There are no effective treatment options for POVL and the diagnosis is often irreversible, so efforts must focus on prevention and risk factor modification. The role of crystalloids versus colloids and the use of α-2 agonists to decrease intraocular pressure during prone spine surgery will also be discussed as a potential preventative strategy.

• Perioperative visual loss
• Ischemic optic neuropathy
• Central retinal artery occlusion
• Cortical blindness
• Posterior reversible encephalopathy
• Spine surgery
• Prone positioning

Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients’ blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are found on the surface of circulating cells from the primary tumour. In mice, MICs have been isolated from CTCs using such markers, which have then been transplanted into xenograft model to show whether they give rise to metastasis in different organs. Considering these findings, in this review we have attempted to summarize the studies connected with MICs and their gene expression profiles that are responsible for metastasis in renal cancer.

• Circulating tumour cells
• metastasis-initiating cells
• renal cell carcinoma
• tumour-initiating cells.