The effect of matrices on the gene expression profile of patient-derived head and neck carcinoma cells for in vitro therapy testing.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with a 5-year mortality rate of ~ 50%. New in vitro methods are needed for testing patients' cancer cell response to anti-cancer treatments. We aimed to investigate how the gene expression of fresh carcinoma tissue samples and freshly digested single cancer cells change after short-term cell culturing on plastic, Matrigel or Myogel. Additionally, we studied the effect of these changes on the cancer cells' response to anti-cancer treatments. MATERIALS/METHODS: Fresh tissue samples from HNSCC patients were obtained perioperatively and single cells were enzymatically isolated and cultured on either plastic, Matrigel or Myogel. We treated the cultured cells with cisplatin, cetuximab, and irradiation; and performed cell viability measurement. RNA was isolated from fresh tissue samples, freshly isolated single cells and cultured cells, and RNA sequencing transcriptome profiling and gene set enrichment analysis were performed. RESULTS: Cancer cells obtained from fresh tissue samples changed their gene expression regardless of the culturing conditions, which may be due to the enzymatic digestion of the tissue. Myogel was more effective than Matrigel at supporting the upregulation of pathways related to cancer cell proliferation and invasion. The impacts of anti-cancer treatments varied between culturing conditions. CONCLUSIONS: Our study showed the challenge of in vitro cancer drug testing using enzymatic cell digestion. The upregulation of many targeted pathways in the cultured cells may partially explain the common clinical failure of the targeted cancer drugs that pass the in vitro testing.

Handgrip Strength Predicts Poorly the Surgical Outcome or Length of Hospitalization in Patients With Surgically Operated Oral Cancer.

BACKGROUND/AIM: Handgrip strength has been used to evaluate the potential of elderly patients to survive different medical conditions or procedures, or to predict the nutritional status and length of hospitalization. The aim of this study was to evaluate the use of handgrip strength as a predictor of the length of hospitalization and need for prolonged intensive care in patients with oral malignancies requiring surgical resection and simultaneous primary reconstruction with microvascular free flap. PATIENTS AND METHODS: This is a retrospective study of 37 head and neck carcinoma patients operated between 2012 and 2014 who had undergone a handgrip force test. The microvascular free flaps used were: radial forearm flap (n=23), anterolateral thigh flap (n=10), and iliac crest free flap (n=4). RESULTS: Average stay at the hospital was 13.3 days after the operation and there was a 2.9-days need for intensive care. Handgrip strength did not predict susceptibility to complications, duration of hospitalization, or 12-month survival in the study population. CONCLUSION: Other anamnestic and medical factors and not handgrip strength should be considered when evaluating operability of the patient or their individual risks for microvascular reconstruction.

The combined anterolateral thigh-Partial iliac crest minihybrid free flap for mandibular reconstruction.

BACKGROUND AND AIMS: Tumors of the oral cavity often require extensive resections leading to significant hard and soft tissue defects. Microvascular free flaps, consisting of both hard and soft tissue, are often required in reconstructions. Hybrid flaps, composed of two different joint free flaps, offer potential alternatives for head and neck reconstruction. This report presents our results with a modified hybrid ALT/DCIA, that is, minihybrid free flap (MH-flap) composed of the anterolateral thigh (ALT) and a partial inner lamina iliac crest only (partial DCIA) for reconstruction of the mandibular region. PATIENTS AND METHODS: Eight patients underwent oral cancer reconstruction of the mandible with the MH-flap. The MH-flap was harvested sparing the outer crest and lamina of crista, and its pedicle was combined to the distal pedicle of ALT. Clinical data and postoperative complications were analyzed. RESULTS: The mean length of the osseous graft was 64 mm (range 54-78 mm). None of the patients had complications requiring surgical intervention. No donor site complications were observed. The overall survival rate was 100%. The mean length of follow-up was 16 months (range 7-30 months). CONCLUSIONS: According to our results, the ALT-partial DCIA MH-flap has postoperative outcomes comparable to those of the fibular flap. The flap is a good option with excellent bone properties for reconstruction of limited mandibular defects not suitable for fibular or scapular reconstruction.

Preoperative C-reactive protein to albumin ratio and oral health in oral squamous cell carcinoma patients.

BACKGROUND: The C-reactive protein to albumin (CRP/alb) ratio can predict early survival of a hospitalized patient. We evaluated factors that influence the preoperative CRP/alb ratio in oral squamous cell carcinoma (OSCC) patients and in particular clarified the role of oral health to this ratio. MATERIALS AND METHODS: Data from surgically treated OSCC patients were collected retrospectively. The outcome variables were preoperative CRP/alb ratio, CRP level, and alb level. The studied predictors were total number of teeth, periodontal stability, marginal bone loss, tumour stage, T-class, lymph node status, and site. The statistical significance of age, sex, comorbidity combination of age and disease history (Charlson Comorbidity Index [CCI]), smoking, and alcohol history for outcome variables were evaluated. Patient 3-month mortality and occurrence of postoperative infections were recorded. RESULTS: A total of 159 patients were included in the study. The early mortality was 3.8%. CRP/alb was higher in these patients than in those who survived. The only independent variables for CRP/alb changes were CCI and heavy alcohol use. The CRP/alb ratio was significantly lower in non-heavy alcohol users (odds ratio [OR] 0.114, 95% confidence interval [CI] 0.024-0.541; adjusted p = 0.006) than in other patients. Patients with CCI 0-1 were more likely to have a lower CRP/alb ratio than patients with CCI ≥ 5 (OR 0.033, 95% CI 0.004-0.284; adjusted p = 0.002). In addition, high CRP/alb ratio associated with postoperative infections (p = 0.026). CONCLUSIONS: The CRP/alb ratio was high in OSCC patients with combined comorbities of age and disease history and in patients with heavy alcohol use. Oral health or tumour-related variables did not independently affect the CRP/alb ratio. The CRP/alb ratio appears suitable for prediction of OSCC patient early survival.

Challenges in diagnosing head and neck cancer in primary health care.

BACKGROUND: Early diagnosis of head and neck cancer (HNC) will improve patient outcomes. The low incidence of HNC renders its detection challenging for a general practitioner (GP) in primary health care (PHC). PATIENTS AND METHODS: To examine these challenges, our cohort consisted of all patients visiting PHC centres in the City of Helsinki in 2016. We chose 57 ICD-10 codes representing a sign or symptom resulting from a possible HNC and compared data for all new HNC patients. RESULTS: A total of 242,211 patients (499,542 appointments) visited PHC centres, 11,896 (5%) of whom presented with a sign or symptom possibly caused by HNC. Altogether, 111 new HNCs were diagnosed within the Helsinki area, of which 40 (36%) were referred from PHC. The median delay from the initial PHC visit to the referral to specialist care was 5 days, whereby 88% of patients were referred within one month. CONCLUSIONS: Despite the low incidence of HNC and the large number of patients presenting with HNC-related symptoms, GPs working in PHC sort out potential HNC patients from the general patient group in most cases remarkably effectively. KEY MESSAGES For every head and neck cancer (HNC) patient encountered in the primary health care, a general practitioner (GP) will meet approximately 6000 other patients, 100 of whom exhibit a sign or a symptom potentially caused by a HNC. Despite the low incidence of HNC, GPs referred patients to specialist care effectively, limiting the median delay from the initial appointment to referral to only 5 days.

Perioperative Dexamethasone Is Associated With Higher Short-Term Mortality in Reconstructive Head and Neck Cancer Surgery.

PURPOSE: Studies of the effects of perioperative dexamethasone (DEX) during oncologic surgery are scarce. The first aim of the present study was to clarify whether perioperative DEX affects the short-term mortality in patients with head and neck cancer (HNC). The second aim was to analyze the causes of death and predictors affecting long-term mortality. PATIENTS AND METHODS: The present prospective, double-blind randomized, controlled study included patients with HNC who had undergone microvascular reconstruction from 2008 through 2013. The patients were randomized into 2 groups: the receipt of perioperative DEX for 3 days (study group) or no DEX (control group). The patients' data and cause of death were registered until the end of 2017. The primary cause of death was used in the analyses. RESULTS: A total of 93 patients were included in the present study: 51 in the DEX group (study group) and 42 in the NON-DEX group (control group). Altogether 38 patients died during a median follow-up period of 5.3 years. During the first year, more deaths had occurred in the DEX group than in the NON-DEX group: at 1 month, 4% versus 0%; at 6 months, 14% versus 0%; and at 12 months, 22% versus 5% (P = .043). The overall survival rate for all patients was 59%. HNC was the primary cause of death for most of the patients who died. On univariate analysis, the deceased patients had more advanced disease (higher T classification, P = .002; higher stage, P = .008), a greater need for a gastrostoma (P = .002), more often received postoperative chemotherapy (P = .005), and more often had locoregional (P = .025) or distal (P < .001) metastases. In the multivariate Cox model, the most important long-term predictors of death were the presence of distant metastases (P < .001), a Charlson comorbidity index (CCI) of 5 to 9 (P < .001), and the use of perioperative DEX (P = .004). CONCLUSIONS: The use of perioperative DEX was associated with higher short-term mortality after reconstructive HNC surgery. The most important long-term predictors of death were the receipt of DEX, the presence of distant metastases, and a CCI of 5 to 9. These findings do not encourage the routine use of perioperative DEX for these patients.

Long-term quality of life after surgery of head and neck cancer with microvascular reconstruction: a prospective study with 4.9-years follow-up.

PURPOSE: The aim of this study was to evaluate the long-term health-related quality of life (HRQoL) of head and neck cancer patients with microvascular surgery. Surgical treatment causes great changes in patient HRQoL. Studies focusing on long-term HRQoL after microvascular reconstruction for head and neck cancer patients are scarce. METHODS: We conducted a prospective study of 93 patients with head and neck cancer and microvascular reconstruction in Helsinki University Hospital Finland. HRQoL was measured using the 15D instrument at baseline and after a mean 4.9-years follow up. Results were compared with those of an age-standardized general population. RESULTS: Of the 93 patients, 61 (66%) were alive after follow-up; of these, 42 (69%) answered the follow-up questionnaire. The median time between surgery and HRQoL assessment was 4.9 years (range 3.7-7.8 years). The mean 15D score of all patients (n = 42) at the 4.9-years follow up was statistically significantly (p = 0.010) and clinically importantly lower than at baseline. The dimensions of "speech" and "usual activities" were significantly impaired at the end of follow up. There was a significant difference at the 4.9-years follow-up in the mean 15D score between patients and the general population (p = 0.014). After follow up, patients were significantly (p < 0.05) worse off on the dimensions of "speech," "eating," and "usual activities." CONCLUSIONS: Long-term HRQoL was significantly reduced in the whole patient cohort. Speech and usual activities were the most affected dimensions in head and neck cancer patients with microvascular reconstruction at the end of the 4.9-years follow up.

More Harm Than Benefit of Perioperative Dexamethasone on Recovery Following Reconstructive Head and Neck Cancer Surgery: A Prospective Double-Blind Randomized Trial.

PURPOSE: Prospective studies on the effect of dexamethasone after microvascular reconstructive head and neck surgery are sparse despite the widespread use of dexamethasone in this setting. The aim of this study was to clarify whether perioperative use of dexamethasone would improve the quality and speed of recovery. The authors hypothesized that dexamethasone would enhance recovery and diminish pain and nausea. MATERIALS AND METHODS: Ninety-three patients with oropharyngeal cancer and microvascular reconstruction were included in this prospective double-blinded randomized controlled trial. Patients in the study group (n = 51) received dexamethasone 60 mg over 3 perioperative days; 42 patients did not receive dexamethasone and served as controls. Patient rehabilitation, postoperative opioid and insulin consumption, postoperative nausea and vomiting (PONV), and C-reactive protein (CRP), leukocyte, and lactate levels were recorded. RESULTS: There was significantly less pain in the study group (P = .030) and the total oxycodone dose for 5 days postoperatively was lower (P = .040). Dexamethasone did not significantly lessen PONV for 5 days postoperatively (P > .05). There were no differences between groups in intensive care unit or hospital stay or in other clinical measures of recovery. Patients receiving dexamethasone required significantly more insulin compared with patients in the control group (P < .001). Lactate and leukocyte levels were significantly higher (P < .001) and CRP levels were significantly lower in the study group. CONCLUSION: The only benefit of perioperative dexamethasone use was lower total oxycodone dose; however, the disadvantages were greater. Because dexamethasone can have adverse effects on the postoperative course, routine use of dexamethasone as a pain or nausea medication during reconstructive head and neck cancer surgery is not recommended.