Identification of stemness-related glycosylation changes in head and neck squamous cell carcinoma.

BACKGROUND: Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors. METHODS: Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed. RESULTS: Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential. CONCLUSIONS: A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified.

MRI Findings in Acute Tonsillar Infections.

BACKGROUND AND PURPOSE: Previous literature is vague on the prevalence and exact nature of abscesses in tonsillar infections, ranging from intratonsillar and peritonsillar collections to deep extension involving the parapharyngeal and retropharyngeal spaces. MR imaging has excellent diagnostic accuracy in detecting neck infections and can potentially clarify this issue. We sought to characterize the spectrum of MR imaging findings regarding tonsillar infections. MATERIALS AND METHODS: We conducted a retrospective cohort study of emergency neck MR imaging scans of patients with tonsillar infections. Imaging data were assessed in terms of signs of infection and the location of abscesses and were compared with clinical findings, final diagnoses, and surgical findings as reference standards. RESULTS: The study included 132 patients with tonsillar infection. Of these, 110 patients (83%) had ≥1 abscess (99 unilateral, 11 bilateral; average volume, 3.2 mL). Most abscesses were peritonsillar, and we found no evidence of intratonsillar abscess. Imaging showed evidence of parapharyngeal and retropharyngeal extension in 36% and 10% of patients, respectively. MR imaging had a high positive predictive value for both abscesses (0.98) and deep extension (0.86). Patients with large abscesses and widespread edema patterns had a more severe course of illness. CONCLUSIONS: Emergency neck MR imaging can accurately describe the extent and nature of abscess formation in tonsillar infections.

Impact of deep learning-determined smoking status on mortality of cancer patients: never too late to quit.

BACKGROUND: Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm. MATERIALS AND METHODS: This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms. RESULTS: The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models. CONCLUSIONS: Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.

Effect of coronavirus disease 2019 on recurrences and follow up of head and neck squamous cell carcinoma.

OBJECTIVE: This prospective study aimed to evaluate possible diagnostic delays in head and neck squamous cell carcinoma recurrences due to the changed follow-up protocol during the coronavirus disease 2019 pandemic. METHODS: The follow-up appointments of head and neck squamous cell carcinoma patients treated more than one year prior to the pandemic were changed to telephone appointments in order to reduce physical visits to the hospital. All contacts, reasons for contact and recurrent cancers were recorded. RESULTS: There were 17 recurrences during a seven-month study period among 178 patients treated in the previous year (10 per cent); 14 of these recurrences occurred in patients whose treatment had ended less than one year previously and 3 occurred more than one year after treatment had ended. There was no delay in diagnoses of recurrent tumours or treatment despite reduced visits because of the coronavirus disease 2019 pandemic. CONCLUSION: According to our analyses, no delay was caused in the diagnoses of recurrent diseases. Follow up by telephone or telemedicine can be considered as part of the follow-up protocol one year after the treatment of head and neck squamous cell carcinoma when necessary.

Critical review of the follow-up protocol for head and neck cancer patients.

OBJECTIVE: Head and neck cancer follow-up length, interval and content are controversial. Therefore, this study aimed to evaluate the efficacy of the follow-up protocol after curative treatment in head and neck cancer patients. METHOD: Clinical data of 456 patients with new malignancy of the head and neck from a tertiary care centre district from 1999 to 2008 were analysed. Time from treatment, symptoms and second-line treatment outcomes of patients with recurrent disease were evaluated. RESULTS: A total of 94 (22 per cent) patients relapsed during the 5-year follow-up period; 90 per cent of recurrences were found within 3 years. Fifty-six per cent of the patients had subjective symptoms indicating a recurrence of the tumour. All recurrent tumours found during routine follow-up visits without symptoms were found within 34 months after completion of treatment. CONCLUSION: Routine follow up after three years is questionable; recurrent disease beyond this point was detected in only 2 per cent of patients. In this study, all late tumour recurrences had symptoms of the disease. Easy access to extra follow-up visits when symptoms occur could cover the need for late follow up.

Determinants of re-operation for bleeding in head and neck cancer surgery.

OBJECTIVE: Post-operative bleeding in the head and neck area is potentially fatal. This 'real world' study sought to assess factors that increase the risk of re-operation for post-operative bleeding in head and neck cancer surgery. METHODS: A total of 456 patients underwent surgery for head and neck cancer (591 operations). The primary endpoint was re-operation for bleeding. RESULTS: The rate of re-operation for bleeding was 5 per cent of all operations. Re-operation for bleeding was an independent risk factor for 30-day mortality (odds ratio = 5.27, p = 0.014). Risk factors for re-operation because of bleeding included excessive (more than 4000 ml) fluid administration (over 24 hours) (p < 0.001), heavy alcohol consumption (p = 0.014), pre-operative oncological treatment (p = 0.017), advanced disease stage (p = 0.020) and higher tumour (T) classification (p = 0.034). Operations with more excessive bleeding (700 ml or more) were associated with an increased risk (p = 0.001) of re-operation for post-operative bleeding. Moreover, the risk of re-operation was significantly higher in patients undergoing microvascular surgery compared to those who had no oncological treatment pre-operatively (18 vs 6 per cent, p = 0.001). CONCLUSION: The 30-day mortality risk increased over 5-fold in patients undergoing re-operation for bleeding.

Incidence and predictors of 30-day cardiovascular complications in patients undergoing head and neck cancer surgery.

Incidence and predictors of peri-operative or post-operative cardiovascular complications in head and neck cancer surgery remain poorly elucidated. In this retrospective study, we investigated the rate and pre-operative risk factors for cardiovascular and cerebrovascular complications. This study included all patients (n = 456) operated for head and neck cancer between 1999 and 2008. Patients' medical records were reviewed and the adjudication of endpoints was performed by adjudication committee. The 30-day incidence of cardiovascular and cerebrovascular complications was 7.2 %. Cardiac mortality at 30 days was 1.0 %. Univariate predictors of MACCE (major adverse cardiac and cerebrovascular events) at the 30-day follow-up were history of myocardial infarction (OR 4.56, 95 % CI 1.73-11.97, p = 0.002); history of heart failure (OR 4.14, 95 % CI 1.32-13.02, p = 0.015); pre-existing coronary artery disease (OR 3.98, 95 % CI 1.75-9.06, p = 0.001); prior aspirin medication (OR 3.73, 95 % CI 1.81-7.71, p < 0.001); prior betablocker medication (OR 3.67, 95 % CI 1.79-7.51, p < 0.001); hypertension (OR 2.55, 95 % CI 1.25-5.19, p = 0.010); and increasing age (OR 1.08, 95 % CI 1.05-1.12, p < 0.001). In a multivariate model, independent predictors of MACCE were pre-existing coronary artery disease (OR 2.45, 95 % CI 1.03-5.80, p = 0.042) and increasing age (OR 1.08, 95 % CI 1.04-1.11, p < 0.001). Patients having surgery for head and neck cancer are at high (>5 %) risk of developing vascular complications. Prior coronary artery disease and increasing age are independent risk factors for MACCE.

Effects of epithelial and neutrophil CXCR2 on innate immunity and resistance to kidney infection.

The murine chemokine receptor 2 (mCXCR2) controls resistance to urinary tract infection. We have previously shown that mCXCR2 knockout mice develop severe acute pyelonephritis and renal tissue damage with sub-epithelial neutrophil entrapment. In this study we examined the relative importance of neutrophil- and epithelial-specific mCXCR2 expression for bacterial clearance in bone marrow chimeric mice infected with uropathogenic Escherichia coli. Mice expressing mCXCR2 on their neutrophils responded rapidly to experimental urinary tract infection, clearing the infection from the kidneys. Mice lacking epithelial mCXCR2, however, showed delayed exit of neutrophils from the tissues. Mice lacking neutrophil mCXCR2 and mice with no mCXCR2 had no neutrophil recruitment and bacterial clearance. Mice expressing mCXCR2 only in their epithelial cells had a transient epithelial chemokine response; however, neutrophil recruitment was inhibited and bacteria grew without constraint. Our study shows that the expression of mCXCR2 on hematopoietic cells was crucial for bacterial clearance, while its expression on non-bone marrow-derived cells influenced the neutrophil response. These results emphasize the importance of mCXCR2 for the innate defense against urinary tract infection.

Expansion of CD56Bright natural killer cells in the peripheral blood of multiple sclerosis patients treated with interferon-beta.

We studied how interferon-beta (IFN-beta) treatment of relapsing-remitting multiple sclerosis (MS) affects subgroups of natural killer cells (NK cells). Following IFN-beta treatment, there was an expansion of CD56(Bright) NK-cells in the peripheral blood of MS patients, while at the same time the proportion of CD56(Dim) cells was diminished. In a control group, the proportion of CD56(Bright) NK-cells was significantly higher in secondary lymphoid tissues compared to the peripheral blood of the same individual. Our findings confirm that CD56(Bright) NK-cells preferably locate within the secondary lymphoid tissues, where they may interact with T cells and thereby contribute to the control of the disease activity in MS.

HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium.

Continuous lymphocyte recirculation between blood and lymphoid tissues forms a basis for the function of the immune system. Lymphocyte entrance from the blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphatics have remained virtually unknown. In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement in binding of lymphocytes to lymphatic vessels. We also show that the binding requires L-selectin, and L-selectin and MR form a receptor-ligand pair. On the other hand, L-selectin binds to peripheral lymph node addressins (PNAds) on high endothelial venules (HEVs) that are sites where lymphocytes enter the lymphatic organs. Interestingly, MR is absent from HEVs and PNAds from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct ligand molecules to mediate binding at sites of lymphocyte entrance and exit within lymph nodes. Taken together, interaction between L-selectin and MR is the first molecularly defined mechanism mediating lymphocyte binding to lymphatic endothelium.

Vascular adhesion protein 1 mediates binding of immunotherapeutic effector cells to tumor endothelium.

Tumor-infiltrating lymphocytes (TIL) can be used as an immunotherapeutic tool to treat cancer. Success of this therapy depends on the homing and killing capacity of in vitro-activated and -expanded TIL. Vascular adhesion protein 1 (VAP-1) is an endothelial molecule that mediates binding of lymphocytes to vessels of inflamed tissue. Here, we studied whether VAP-1 is involved in binding of TIL, lymphokine-activated killer (LAK) cells, and NK cells to vasculature of the cancer tissue. We demonstrated that VAP-1 is expressed on the endothelium of cancer vasculature. The intensity and number of positive vessels varied greatly between the individual specimens, but it did not correlate with the histological grade of the cancer. Using an in vitro adhesion assay we showed that VAP-1 mediates adhesion of TIL, LAK, and NK cells to cancer vasculature. Treatment of the tumor sections with anti-VAP-1 Abs diminished the number of adhesive cells by 60%. When binding of different effector cell types was compared, it was evident that different cancer tissues supported the adhesion of TIL to a variable extent and LAK cells were more adhesive than TIL and NK cells to tumor vasculature. These data suggest that VAP-1 is an important interplayer in the antitumor response. Thus, by up-regulating the expression of VAP-1 in tumor vasculature, it can be possible to improve the effectiveness of TIL therapy.