The role of adjuvant radiotherapy in locally advanced T4 mandible squamous cell carcinoma in the N0 patient: a single centre experience.

In locally advanced oral squamous cell carcinoma (OSCC), namely that showing invasion of the mandible, demonstrating no high-risk (e.g. extranodal extension, positive margin) or intermediate-risk histopathological features (e.g. perineural invasion, lymphovascular invasion), the additional benefit of postoperative radiotherapy (PORT) currently remains uncertain. A retrospective review covering the period between January 1, 2010 and December 31, 2019 was conducted to identify patients from a single UK centre with locally advanced invasive mandibular OSCC defined as pT4a, with no nodal or distant metastasis (N0 M0). The primary outcome was to determine the disease-free survival and overall survival rates in the surgery + PORT group, in comparison to the surgery only group. Twenty-eight eligible patients were identified, with 13 patients in the surgery + PORT group and 15 patients in the surgery only group. A single patient in the surgery + PORT group developed disease recurrence and subsequently died (1/13) (median follow-up 5.24 years, range 2.13-10.71 years). No patient in the surgery only group developed disease recurrence or died (0/15) (median follow-up 5.13 years, range 1.37-10.93 years). It may be reasonable to consider omitting PORT in pT4a pN0 M0 OSCC of the mandible in patients who demonstrate no high- or intermediate-risk histopathological features, following multidisciplinary team discussion.

Spontaneous regression of advanced-stage oropharyngeal squamous cell carcinoma.

BACKGROUND: Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour proven by microscopic examination in the absence of any substantial treatment. This paper presents the case of an older woman whose advanced-stage tonsillar squamous cell carcinoma was noted to have spontaneously regressed at seven months. CASE REPORT: A 66-year-old woman presented with a 4-month history of dysphagia and odynophagia in September 2020. An exophytic tumour was seen on the right tonsil; this was diagnosed radiologically and histologically as a squamous cell carcinoma of the tonsils, with tumour-node-metastasis staging of T4aN0M0. The patient received best supportive care. Seven months later, the oropharyngeal lesion had disappeared, with no treatment. Subsequent computed tomography imaging showed radiological resolution of the previously noted right-sided oropharyngeal lesion. CONCLUSION: Several mechanisms of spontaneous regression are discussed. Further studies should review this case in conjunction with other reports of spontaneous tumour regressions, to elucidate underlying mechanisms.

Rapidly progressive hearing loss occurring over weeks: review of differential diagnoses.

BACKGROUND: Sudden hearing loss, or progressive hearing loss occurring over months to years, are well-established presentations. However, little is described in the medical literature on how to approach patients presenting with a rapidly progressive hearing loss occurring over weeks. This study aimed to evaluate the clinical significance of patients presenting with rapidly progressive hearing loss. METHODS: A case of rapidly progressive hearing loss occurring over 12 weeks is presented. A PubMed literature review was performed to determine the evidence-based differential diagnoses for rapidly progressive hearing loss. RESULTS: Fifteen causes were identified for rapidly progressive hearing loss: intracranial aetiologies (meningioma, lymphoma, metastatic deposit, cavernous angioma, meningitis, superficial siderosis); paraneoplastic syndrome (small cell lung carcinoma, thymoma); inflammatory or autoimmune disorders (autoimmune inner-ear disease, sarcoidosis, vasculitis, Sjögren's syndrome); infective disorders (syphilis, human immunodeficiency virus); and medication-induced causes. CONCLUSION: Rapidly progressive hearing loss should be considered a 'red flag' symptom that warrants urgent action. Most causes are systemic or sinister in nature, and the patient's hearing loss can potentially be reversed.

Schwannoma of the sinonasal tract: case report with review of the literature.

Schwannomas of the sinonasal tract are rare, accounting for <4% of head and neck schwannomas. We report the case of a 61-year-old male who presented with unilateral nasal symptoms. Examination and imaging revealed a unilateral polyp at the level of the middle turbinate, with an initial biopsy suggestive of an inflammatory polyp. Due to the persistence of the patient's symptoms and his polyp despite medical therapy, endoscopic nasal polypectomy was performed. The histology surprisingly showed a schwannoma. No further interventions were carried out, and the patient remains disease-free 6 months postoperatively. A review of the literature comprising 60 cases is included. An optimal clinical approach to the investigation and management of schwannomas of the sinonasal tract is subsequently discussed.

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience.

PURPOSE: Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective study to assess the benefit/risk profile of routine laparoscopic examination for occult IH (RLEOH) with a synchronous repair in patients receiving PD catheter placement. METHODS: 432 patients were enrolled in this study. Patients with an internal hernia sac at all sizes were deemed to have occult IH. We retrospectively reviewed data including demographic characteristics and operative details. We also measured incidence rates of symptomatic IH, metachronous IH repair, and catheter survival over a follow-up period after starting PD. RESULTS: These patients were classified into the RLEOH group (n = 365) and the non-RLEOH group (n = 67). The RLEOH group was subdivided into occult IH with a synchronous repair (n = 17; the subgroup A), no occult IH (n = 339; the subgroup B), and occult IH without a synchronous repair (n = 9; the subgroup C). The incidence rates of symptomatic IH developed after staring PD in subgroups A, B, and C were 0, 5.6, and 22.2%, respectively, whereas that in the non-RLEOH group was 13.4%. The RLEOH group had a reduced hazard ratio for metachronous IH repair compared with the non-RLEOH group (HR = 0.426; 95% CI 0.195-0.930, p = 0.032). None of our patients suffered from herniorrhaphy-related complications. CONCLUSION: RLEOH with a synchronous repair during PD catheter insertion confers clinical benefits in reducing the risk of developing IH after starting PD and the need for a metachronous repair. This is a safe and reasonable approach.

Evaluation of CpG-ODN-adjuvanted polyanhydride-based intranasal influenza nanovaccine in pigs.

Influenza results in significant economic loss in the swine industry each year. A broadly protective swine influenza vaccine would have the dual benefit of protecting pigs from influenza A viruses (IAVs) and limiting their possible zoonotic transmission to humans. In this study, we developed polyanhydride nanoparticles-based swine influenza vaccine (KAg + CpG-nanovaccine) co-encapsulating inacticated/killed soluble antigen (KAg) and Toll-like receptor (TLR)-9 agonist (CpG-ODN). The immunogenicity and protective efficacy of KAg + CpG-nanovaccine was compared with KAg vaccine containing five-times greater quantity of antigens following heterologous virus challenge. Prime-boost intranasally delivered KAg + CpG-nanovaccine induced significantly higher levels of cross-reactive antigen-specific IgA antibody responses in the nasal cavity, greater lymphoproliferative response in peripheral blood mononuclear cells (PBMCs), and higher IFN-γ secretion during antigen-induced recall responses of PBMCs and tracheobronchial lymph nodes cells compared to those immunized with KAg alone. Importantly, KAg + CpG-nanovaccine provided better protective efficacy through a significant reduction in influenza-induced fever, 16-fold reduction of nasal virus shedding and 80-fold reduction in lung virus titers compared to those immunized with soluble KAg. Our results indicated that CpG-ODN-adjuvanted polyanhydride nanovaccine can induce higher mucosal antibody and cellular immune responses in pigs; and provide better protection as compared with intranasally delivered soluble KAg.

Assessing Vascularity of Osseous Spinal Metastases with Dual-Energy CT-DSA: A Pilot Study Compared with Catheter Angiography.

BACKGROUND AND PURPOSE: Spine debulking surgery in patients with hypervascular spinal metastasis is associated with massive intraoperative blood loss, but currently, the vascularity of tumor is determined by invasive conventional angiography or dynamic contrast MR imaging. We aimed to investigate the usefulness of noninvasive dual-energy CT-DSA, comparing it with conventional angiography in evaluating the vascularity of spinal metastasis. MATERIALS AND METHODS: We conducted a retrospective study from January to December 2018. A total of 15 patients with spinal metastasis undergoing dual-energy CT, conventional DSA, and subsequent debulking surgery were included. CT-DSA images were produced after rigid-body registration and subtraction between CT phases. Qualitative and quantitative assessments of tumor vascularity were conducted. Correlations between CT-DSA and conventional DSA results were evaluated using the Spearman coefficient. The mean enhancement in the estimated tumor volume and surgical blood loss was compared between hypervascular and nonhypervascular groups using the Wilcoxon rank sum test. RESULTS: The CT-DSA and DSA results were strongly correlated, with ρ = 0.87 (P < .001). The DSA and the quantitative enhancement index also showed a strong correlation with ρ = 0.83 (P < .001). Wilcoxon rank sum testing between hypervascular and nonhypervascular CT-DSA groups showed a difference in enhancement indices (P = .0003). The blood loss between the hypervascular and nonhypervascular groups was nonsignificant (P = .09). CONCLUSIONS: Dual-energy CT-DSA correlates well with conventional DSA in assessing the vascularity of spinal metastasis. It may serve as a noninvasive preoperative evaluation option before debulking surgery.

Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Incidence of idiopathic pulmonary fibrosis in Korea based on the 2011 ATS/ERS/JRS/ALAT statement.

OBJECTIVE: To estimate the annual incidence rate of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) in Korea. DESIGN: A retrospective cohort design using the Korean Health Insurance Review and Assessment Service (HIRA) database spanned the period from January 2008 to December 2012. Patients with ILD and IPF were identified based on the International Classification of Disease-10 (ICD-10) diagnosis and procedure codes. Definition 1 is code J84 (ILD); Definition 2 is code J84 plus high-resolution computed tomography (HRCT), bronchoalveolar lavage (BAL) or lung biopsy; Definition 3 is code J84.1 (ILD with fibrosis); Definition 4 is code J84.1 and HRCT, BAL or lung biopsy; and Definition 5 is code J84.1A (IPF), and was specifically implemented for IPF. RESULTS: The incidence rates of ILD per 100,000 population based on Definitions 1-5 were respectively 48.5, 32.2, 16.2, 11.4 and 1.7. CONCLUSION: The incidence of ILD with fibrosis was approximately 23% of overall ILD incidence. IPF incidence was approximately 10% of the incidence of ILD with fibrosis. Based on the new ATS/ERS/JRS/ALAT statement published in 2011, the incidence rate of IPF was 1.7/100,000.

Alcohol consumption and persistent infection of high-risk human papillomavirus.

Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002-2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32-4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17-4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01-3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35-9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10-6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06-7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

A case of prolonged fever and a diagnosis obscured by an opaque sinus.

Prolonged fever in patients can be a diagnostic challenge. Clinicians generally consider infectious diseases, malignant diseases and collagen vascular diseases as possible causes of pyrexia of unknown origin (PUO). Even after extensive evaluation as many as 15 percent of patients with prolonged fever may remain undiagnosed. This case report describes subacute thyroiditis as a cause of prolonged fever and documents how that diagnosis was finally made after 40 days of fever.

Transection of the obturator nerve by an electrosurgical instrument and its immediate repair during laparoscopic pelvic lymphadenectomy: a case report.

Obturator nerve injury seldom occurs in gynecologic surgery. However, gynecologic oncologic surgery, including pelvic lymph node dissection, increases the risk of this type of injury. Microsurgical techniques are usually performed for the repair of the nerve injury. Herein the authors report a case of obturator nerve injury caused by an electrosurgical instrument during laparoscopic pelvic lymphadenectomy, and its prompt repair by laparoscopic procedure in a 44-year-old patient with cervical cancer.

14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death.

14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.

CT angiography findings in carotid blowout syndrome and its role as a predictor of 1-year survival.

BACKGROUND AND PURPOSE: Carotid blowout is a serious late complication of prior treatment of advanced head and neck cancer. We evaluate the efficacy of CTA in the diagnosis of impending carotid blowout syndrome in patients with head and neck cancer, and its capability to predict clinical outcome. MATERIALS AND METHODS: The clinical data of 29 patients with impending carotid blowout who underwent CTA were collected and analyzed. Imaging signs included tissue necrosis, exposed artery, viable perivascular tumor, pseudoaneurysm, and contrast extravasation. DSA was obtained in 20 patients. One-year outcomes were compared based on management. RESULTS: The most common CTA finding was necrosis (94%), followed by exposed artery (73%), viable tumor (67%), pseudoaneurysm (58%), and contrast extravasation (30%). Exposed artery, pseudoaneurysm, and contrast extravasation were the 3 CTA findings related to outcomes. All of the pseudoaneurysm and contrast extravasation cases were associated with an exposed artery. An exposed artery was the most important prognostic predictor and could not be diagnosed on DSA. Patients without the 3 findings on CTA (group 1) had the best survival rate at 1-year follow-up, followed by patients with the 3 findings treated immediately by permanent artery occlusion (group 2). Patients with the 3 findings who had no immediate treatment (group 3) had the worst outcomes (P < .001 in group 1 vs group 3 and group 2 vs group 3; P = .056 group 1 vs group 2). CONCLUSIONS: CTA, with its ability to diagnose an exposed artery compared with DSA, may offer important management and prognostic information in patients with impending carotid blowout.

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.

INTRODUCTION: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. METHODS: Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70. RESULTS: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. CONCLUSIONS: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.

Diagnostic value of CA125 as a predictor of recurrence in advanced ovarian cancer.

PURPOSE: The aim of this study was to establish the guidelines for detecting early recurrences of advanced epithelial ovarian cancer by use of the CA-125 level. MATERIALS AND METHODS: Eighty-five of the patients who met the inclusion criteria were enrolled in this study. The authors examined 25 incremental changes of CA125 from one to 25 IU/ml, and compared the CA-125 value with other prognostic factors. Increases in the CA-125 level from the nadir level were expressed as CA-125- increments. RESULTS: Among the 25 increments, a CA-125-8 (eight IU/ml) was selected as the predictor that was the most efficient and time-effective. CA-125-8 had a sensitivity of 91.5%, a specificity of 84.6%, a positive predictive value of 93.1%, a negative predictive value of 81.5%, an efficiency of 89.4%. and a median lead-time of 68.5 days (p <0.0001). CONCLUSION: The authors suggest the incremented CA-125-8 as a predictor of recurrent advanced ovarian cancer.

Bisphosphonate treatment may reduce osteoporosis risk in female cancer patients with morphine use: a population-based nested case-control study.

UNLABELLED: Chronic use of morphine is a risk factor for endocrinopathy and osteoporosis. Bisphosphonates accentuated the protective effect to develop osteoporosis in female patients with malignancy with morphine treatment. INTRODUCTION: This study investigates the risk of osteoporosis associated with morphine use by comparing the incidence of osteoporosis in female cancer patients treated with and without morphine. METHODS: A population-based nested case-control retrospective analysis was performed using the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. A malignancy cohort of 12,467 female patients without a history of osteoporosis during 1998-2010, and then 639 patients who subsequently developed osteoporosis as the osteoporosis group, were evaluated. Control-group patients were selected from the malignancy cohort without osteoporosis and frequency matched to each osteoporosis case 2:1 for age, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age. RESULTS: Female cancer patients who received morphine had a 10% lower risk of developing osteoporosis than non-morphine users, but this risk reduction was not significant. For patients treated with bisphosphonates, the morphine group had significantly lower odds in developing osteoporosis than the non-morphine group. CONCLUSION: Morphine treatment is not associated with the incidence of osteoporosis, and bisphosphonates accentuated the protective effect of morphine in the development of osteoporosis in female patients with malignancy in Taiwan.

Association of KIR genes and HLA-C alleles with HPV-related uterine cervical disease in Korean women.

This study investigated whether killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles, receptors and ligands of natural killer cells are associated with the development of human papillomavirus (HPV)-related cervical disease in Korean women. Blood samples from 132 women with HPV-related cervical disease and 159 women without HPV infection were collected for genotyping of KIR genes and HLA-C alleles. Although no relationship was found between KIR genes and HPV-related cervical disease, a significant relationship was found between HLA-C alleles as ligands of KIR and HPV-related cervical disease. Women with HPV-related cervical disease were found to be significantly more likely to carry HLA-C*0303, particularly those with HPV 16 or 18 infection, and less likely to carry HLA-C*01 compared to women without HPV infection. HLA-C*0303 was found to confer susceptibility to HPV-related cervical disease, whereas HLA-C*01 was found to confer a protective effect against HPV-related cervical disease.

Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers.

14-3-3 proteins are involved in several cellular processes, including the G1/S and G2/M cell cycle transitions. However, their roles during mitosis are not well understood. Here, we showed that depletion of 14-3-3η, a 14-3-3 protein isoform, enhanced mitotic cell death, resulting in sensitization to microtubule inhibitors and inhibition of aneuploidy formation. The enhanced mitotic cell death by depletion of 14-3-3η appeared to be both caspase-dependent and independent. Furthermore, enhanced mitotic cell death and a reduction in aneuploidy following 14-3-3η depletion were independent of the mitotic checkpoint, which is thought to be the primary signaling event in the regulation of the cell death induced by microtubule inhibitors. When 14-3-3η depletion was combined with microtubule inhibitors in HCT116 and U87MG cells, it sensitized both cancer cell lines to microtubule inhibitors. These results collectively suggest that 14-3-3η may be required for mitotic progression and may be considered as a novel anti-cancer strategy in combination with microtubule inhibitors.