Inguinal Hernia Repair but No Hernia Present: A Nationwide Cohort Study.

INTRODUCTION: Groin hernia repair can relieve pain from conditions other than groin hernias, such as "sports groin." The aim of this study was to assess the nationwide frequency of surgically treated sports groins and identify conditions found during groin hernia surgery with no hernia present. MATERIALS AND METHODS: In this nationwide cohort study, we included patients with no hernia found during groin hernia repair. Patients were identified in the nationwide Danish Hernia Database. Outcomes were assessed from medical and surgical records. Medical history, preoperative examinations, and operative details were extracted. RESULTS: Data from 259 patients were included. Of these, 152 (58%) were considered to have a sports groin. A weak posterior inguinal wall was identified in 41 sports groins, a wide profound inguinal ring in 10, and no specific anatomic pathology was described in the remaining patients with a sports groin. A lipoma was found in addition to a sports groin in 60 patients. Findings in patients without a sports groin were predominantly lipomas, and less frequent findings were a cyst and hydrocele. CONCLUSIONS: More than half of the patients were assessed to have a sports groin. Frequent findings that co-existed with a sports groin were weak posterior inguinal wall and/or lipoma.

DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are often diagnosed in advanced stages. In search of new diagnostic tools, focus has shifted towards the biological properties of the HNSCC, and the number of different biomarkers under investigation is rapidly growing. OBJECTIVES: The objective was to review the current literature regarding aberrantly methylated DNA found in peripheral blood plasma or serum in patients with HNSCC and to evaluate the diagnostic accuracy of these changes. METHODS: The inclusion criteria were clinical studies involving patients with verified HNSCC that reported findings of aberrantly methylated DNA in peripheral blood serum or plasma. We systematically searched PubMed, OVID Embase and Cochrane Library. In addition to the search, we performed forward and backward chaining in references and Web of Science. The protocol was registered in PROSPERO: CRD42019135406. Two authors independently extracted data. The quality and the risk of bias of the included studies were assessed by the QUADAS-2 tool. RESULTS: A total of 1,743 studies were found eligible for screening, while ultimately seven studies were included. All studies were found to have methodological weaknesses, mainly concerning patient selection bias. The best individual marker of HNSCC was Septin 9 in plasma with a sensitivity of 57% and a specificity of 95%. CONCLUSIONS: None of the aberrantly methylated genes found in the retrieved studies are applicable as single diagnostic markers for HNSCC and the best gene-panels still lack diagnostic accuracy. Future studies may benefit from newer sequencing techniques but validation studies with well-designed cohorts are also needed in the process of developing epigenetic based diagnostic tests for HNSCC.

First-line treatment of pelvic organ prolapse and discontinuation of pessary treatment.

INTRODUCTION: The primary objective of this study was to investigate the percentages of women choosing watchful waiting, pessary use or surgery as first-line treatment of pelvic organ prolapse (POP). Second, the rate and cause of discontinuation of pessary use were investigated. METHODS: A retrospective chart review was conducted on 794 patients referred with POP at a Danish tertiary center for urogynecology at Aalborg University Hospital between 1 January 2014 and 31 December 2015. The following data were registered: age, BMI, previous use of a pessary, total number of births, vaginal births, cesarean sections, previous hysterectomy, prolapse surgery and incontinence surgery, smoking, menopause, sexual status and POP-Q stage in the three vaginal compartments. Pessary treatments were evaluated after 3 months. Additional visits, reason for discontinuation and secondary treatment were noted. RESULTS: First-line treatment was surgery in 50%, watchful waiting in 33% and pessary use in 17% of patients. Characteristics associated with choosing surgery instead of a pessary were age < 65 years, previous prolapse surgery, prolapse in the anterior or posterior compartment, and POP-Q stage > 2. Characteristics associated with choosing watchful waiting instead of a pessary were age < 65 years and prolapse in the posterior compartment. A total of 33% discontinued pessary treatment within the first 3 months. Discontinuation was associated with age < 65 years, previous hysterectomy and pelvic surgery, and additional visits. Expulsion of the pessary and pain/discomfort were the main causes of discontinuation. CONCLUSION: This study showed that 50% of patients referred with POP were treated with conservative treatment (watchful waiting and pessary) and thus more women could probably be treated in primary care.

Oral mucosa tissue gene expression profiling before, during, and after radiation therapy for tonsil squamous cell carcinoma.

BACKGROUND: Radiation-therapy (RT) induces mucositis, a clinically challenging condition with limited prophylactic interventions and no predictive tests. In this pilot study, we applied global gene-expression analysis on serial human oral mucosa tissue and blood cells from patients with tonsil squamous cell cancer (TSCC) to identify genes involved in mucositis pathogenesis. METHODS AND FINDINGS: Eight patients with TSCC each provided consecutive buccal biopsies and blood cells before, after 7 days of RT treatment, and 20 days following RT. We monitored clinical mucositis and performed gene-expression analysis on tissue samples. We obtained control tissue from nine healthy individuals. After RT, expression was upregulated in apoptosis inducer and inhibitor genes, EDA2R and MDM2, and in POLH, a DNA-repair polymerase. Expression was downregulated in six members of the histone cluster family, e.g., HIST1H3B. Gene expression related to proliferation and differentiation was altered, including MKI67 (downregulated), which encodes the Ki-67-proliferation marker, and KRT16 (upregulated), which encodes keratin16. These alterations were not associated with the clinical mucositis grade. However, the expression of LY6G6C, which encodes a surface immunoregulatory protein, was upregulated before treatment in three cases of clinical none/mild mucositis, but not in four cases of ulcerative mucositis. CONCLUSION: RT caused molecular changes related to apoptosis, DNA-damage, DNA-repair, and proliferation without a correlation to the severity of clinical mucositis. LY6G6C may be a potential protective biomarker for ulcerative mucositis. Based on these results, our study model of consecutive human biopsies will be useful in designing a prospective clinical validation trial to characterize molecular mucositis and identify predictive biomarkers.

A systematic review of molecular responses to cancer therapy in normal human mucosa.

OBJECTIVE: Cancer therapy-induced inflammation of oral and gastrointestinal mucosae affects patients nonuniformly. Preventive strategies are limited; no biomarker exists for pretreatment identification of patients likely to be severely affected. Animal models are preferred for studying molecular responses in mucosae during chemotherapy, but translation into clinical practice is difficult. We performed a systematic review to retrieve articles that described molecular changes in human mucosae during cancer therapy. STUDY DESIGN: We searched MEDLINE and Ovid Embase searches for studies reported in the English language literature from January 1990 to November 2016 and studies referenced in selected articles, which analyzed mucosae from patients at risk of developing mucositis during cancer therapy. Two authors extracted data according to predefined data fields, including study quality indicators. RESULTS: We identified 17 human studies on chemotherapy (n = 9) and radiotherapy (n = 8), but no studies on targeted therapy. Studies were heterogeneous with regard to patient cohorts, analysis methods, cancer treatments, biopsy timings, and correlations to clinical mucositis. Consequently, a meta-analysis was not feasible. CONCLUSIONS: Few human studies described the molecular responses of the normal mucosa to cancer therapy. Studies were heterogeneous and had sparse correlations to clinical mucositis. We proposed a model for acquiring data on treatment- and disease-specific phenotypes and transcriptomes for predictive or preventive initiatives.

Molecular Characteristics of High-Dose Melphalan Associated Oral Mucositis in Patients with Multiple Myeloma: A Gene Expression Study on Human Mucosa.

BACKGROUND: Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. METHODS AND FINDINGS: Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5-6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups. CONCLUSIONS: Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity.

Spontaneous fractures of the mandible concept & treatment strategy.

BACKGROUND: Spontaneous fractures of the mandible dispose a surgical challenge in comparisons to fractures caused by trauma due to several complicating factors. Additionally: controversies exist concerning the terminology of the field. MATERIAL AND METHODS: We conducted a retrospective study of all patients with mandibular fractures, with exclusion of fractures of the coronoid process and the alveolar process, treated at the Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, Denmark between February 2003 and February 2013. Data collected from the medical records included sex, age, cause of fracture, site of fracture, and treatment. RESULTS: We identified 517 patients with 684 mandible fractures. Twenty-five of these were spontaneous fractures and 659 fractures were of traumatic origin. Condylar fractures rarely occur spontaneously, but constitute the majority of the traumatic fractures. Excluding these fractures from the analysis, we found a non-surgical approach in 14 of 24 (58%) of the spontaneous fractures and 110 of 376 (29%) of the traumatic fractures. This was statistically significant. CONCLUSIONS: We found a statistical significant difference in favor of non-surgical approach in spontaneous fractures and we discussed the treatment challenges of these fractures. We addressed the terminological controversies regarding pathological fractures, and suggested the term spontaneous fractures denoting a fracture occurring during normal jaw function being either pathological or non-pathological.