A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma.

Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.

BIRC5 Gene Polymorphisms Are Associated with a Higher Stage of Local and Regional Disease in Oral and Oropharyngeal Squamous Cell Carcinomas.

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the most common types of cancers in the head and neck region (HNSCC). Despite very aggressive treatment modalities, the five-year survival rate has not changed for decades and is still around 60%. The search for potential specific biomarkers of aggressiveness or outcome indicators could be of great benefit in improving the treatment of these patients. One of the potential biomarkers is survivin, the protein product of the BIRC5 gene. In this study, we investigated the occurrence of BIRC5 gene polymorphisms in 48 patients with OSCC and OPSCC compared with healthy controls. A total of 18 polymorphisms were found, 11 of which occurred in HNSCC with a minor allele frequency (MAF) of more than 5%. Five polymorphisms (rs3764383, rs9904341, rs2071214, rs2239680, rs2661694) were significantly associated with tumor size, tumor stage, and advanced regional disease, but had no impact on survival.

TREATMENT OF SUBGLOTTIC STENOSIS: A SINGLE INSTITUTION EXPERIENCE.

The aim of this article is to present experiences of the Department of Otorhinolaryngology and Head and Neck Surgery, Zagreb University Hospital Center with the treatment of patients with subglottic stenosis. Subglottic stenosis is a rare congenital or acquired disorder of airway patency that is part of a wider complex of disorders known as laryngotracheal stenosis with the ultimate effect in the form of respiratory insufficiency that can be life-threatening. As an acquired condition, it is most often the result of iatrogenic damage to the larynx and trachea during invasive airway management, whether it is intubation or tracheotomy. In the case of intubation as the etiologic factor, cases of prolonged intubation were most common. Retrospective analysis of patient medical histories over a ten-year period was performed and 29 patients met the inclusion criteria. All patients were monitored for at least two years after completion of treatment. Out of a total of 29 treated patients, 20 were permanently decannulated, of which 4 have paresis of one or both vocal cords. In conclusion, there is no clear treatment protocol for patients with subglottic stenosis. The optimal modality of treatment is combined endoscopic and open surgical treatment.

AWAKE FIBEROPTIC TRACHEAL INTUBATION AND AT-RISK EXTUBATION IN A PATIENT WITH ANTICIPATED DIFFICULT AIRWAY DUE TO POST-TRAUMATIC ANKYLOSIS OF TEMPOROMANDIBULAR JOINTS.

In this case report we present successful airway management in a patient with predicted difficult airway using the Difficult Airway Society guidelines. Our patient presented with recurrence of severely reduced mouth opening due to post-traumatic bilateral temporomandibular ankylosis, and was scheduled for surgical resection of the mandibular articular processes. Awake fiberoptic intubation was planned. After light sedation and thorough topicalization of the nasal cavity the flexible optic bronchoscope was successfully navigated into the trachea with 'spray-as-you-go' technique and the endotracheal tube was railroaded over it. After a two-point check of the endotracheal tube placement the patient was put under anesthesia. The surgery was uneventful. Finally, a plan with surgeons for safe extubation was made and the patient was extubated uneventfully on the next day using the airway exchange catheter in the intensive care unit.

Impact of Age and Sex on Electrical Impedance Values in Healthy Oral Mucosa.

BACKGROUND: Electrical impedance (EI) is a property of all living tissues and represents the resistance to the electric current flow through a living tissue. EI depends on the structure and chemical composition of the tissue. The aim of this study was to determine the influence of age, sex, and electrode pressure on the EI values of healthy oral mucosa. The study involved 101 participants with healthy oral mucosa who were divided into three age groups. EI was measured in seven anatomical regions. RESULTS: Significant differences between different age groups were found. Younger participants (20-40 years) had significantly higher EI values than the older participants (60+). Significantly higher EI values were found in women at all localisations at all measured frequencies, except on the hard palate. EI values measured with higher sub-pressure were significantly lower than values measured with lower sub-pressure at all frequencies and localisations, except the tongue dorsum, tongue border, and sublingual mucosa. CONCLUSIONS: This study found that EI values in healthy oral mucosa depend on age and sex and may also depend on the pressure of the measuring device. These factors should be kept in mind when EI is used as a diagnostic method for different oral lesions.

MANAGEMENT OF CHYLE LEAK FOLLOWING HEAD AND NECK SURGERY: REVIEW OF CURRENT TREATMENT STRATEGIES AND ALGORITHMIC APPROACH TO THE TREATMENT.

Postoperative chyle leak is a rare but serious complication of head and neck surgery. Chyle leak can lead to a systemic metabolic imbalance, a prolonged wound healing and longer hospital stay. Early identification and treatment are crucial for good surgical outcome. The diagnosis can be made intraoperatively or in the early postoperative period. Various treatment options described in the literature can be divided into conservative and surgical modalities. Currently, there is no evidence that any approach is superior to the other due to relatively small number of studies describing chyle leak management. There are no official guidelines for the treatment of postoperative chyle leak. The aim of this article is to present the therapeutic possibilities and to offer an algorithm for chyle leak management.

THE IMPACT OF COVID-19 ON HEAD AND NECK CANCER TREATMENT DELAY.

The aim of this study was to demonstrate the impact of COVID-19 pandemic on the number and characteristics of head and neck cancer patients in two consecutive periods, pre-pandemic and pandemic. For this purpose, we performed a retrospective analysis of patients with primary carcinomas of head and neck mucosal sites, salivary gland tumors, as well as neck metastases. Two pre-COVID-19 years (2018-2019) and two pandemic years (2020-2021) were compared. Demographic data, overall number of patients, TNM classification of the two most affected sites (oral cavity and larynx), time from symptom onset to first outpatient admission to our department, and time from first admission to treatment initiation were noted. Study results revealed a higher number of patients during the pandemic period and difference in the distribution of tumor sites (χ2=33.68, df=9, p<0.001). Oral cavity cancer prevailed over laryngeal cancer during the pandemic period. A statistically significant difference was observed in delay of initial presentation to head and neck surgeon for oral cavity cancer during the pandemic period (p=0.019). Furthermore, significant delay was found for both sites concerning time from initial presentation to the beginning of treatment (larynx: p=0.001 and oral cavity: p=0.006). Despite these facts, there were no differences in TNM stages comparing two observed periods. Study results indicated that there was a statistically significant delay of surgical treatment for both cancer sites observed (oral cavity and larynx) during the COVID-19 pandemic. A survival study is necessary in the future to definitely reveal the true consequences of COVID-19 pandemic on treatment outcomes.

GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3ß.

Several signaling pathways are aberrantly activated in head and neck squamous cell carcinoma (HNSCC), including the Hedgehog-Gli (HH-GLI), WNT, EGFR, and NOTCH pathways. The HH-GLI pathway has mostly been investigated in the context of canonical signal transduction and the inhibition of the membrane components of the pathway. In this work we investigated the role of downstream inhibitors GANT61 and lithium chloride (LiCl) on cell viability, wound closure, and colony forming ability of HNSCC cell lines. Five HNSCC cell lines were treated with HH-GLI pathway inhibitors affecting different levels of signal transduction. GANT61 and LiCl reduce the proliferation and colony formation capabilities of HNSCC cell lines, and LiCl has an additional effect on wound closure. The major effector of the HH-GLI signaling pathway in HNSCC is the GLI3 protein, which is expressed in its full-length form and is functionally regulated by GSK3ß. LiCl treatment increases the inhibitory Ser9 phosphorylation of the GSK3ß protein, leading to increased processing of GLI3 from full-length to repressor form, thus inhibiting HH-GLI pathway activity. Therefore, downstream inhibition of HH-GLI signaling may be a promising therapeutic strategy for HNSCC.

Predictors of Mental Health Outcomes in Road Traffic Accident Survivors.

Mental health outcomes of road traffic accidents (RTAs) are always investigated in assessments of those involved. The aim of this study was to investigate the psychological consequences and associated factors in all RTA survivors, irrelevant of their injury status. A cohort of 155 people was assessed one month after experiencing a RTA using self-reported measures for posttraumatic stress disorder (PTSD), depression, and anxiety. Associations between mental health outcomes and sociodemographic factors, pre-RTA health status, injury-related factors, and RTA details were analyzed. RTA survivors reported substantial rates of PTSD (32.3%) and depression (17.4%) symptoms, and low rates of anxiety (5.8%). Symptoms of depression were associated with below-average self-perceived economic status, irreligiousness, medication use, psychiatric medication use, and injury-related factors. PTSD symptoms were associated with female gender, below-average self-perceived economic status, previous psychiatric illness, medication use, psychiatric medication use, not being at fault in the relevant RTA, claiming compensation, and injury-related factors. Anxiety symptoms were associated with previous chronic or psychiatric illness, previous permanent pain, psychiatric medication use, and self-perceived threat to life, but not with sustaining injury. Along with the evaluation and treatment of RTA injuries, health care providers should evaluate the pre-RTA health status of all RTA victims. Psychological support to those at risk may prevent psychological disorders after RTAs.

Prophylactic Central Neck Dissection in Well-differentiated Thyroid Cancer.

Well-differentiated cancers, both papillary and follicular, account for 90% of all diagnosed thyroid cancers. They have an indolent disease course with a 20-year disease-specific survival over 90%. According to current guidelines, the therapy of choice for well-differentiated thyroid carcinoma is total thyroidectomy or lobectomy. The indication for prophylactic central neck dissection is still a controversial issue and the subject of unfinished and ongoing debate. There is no indication for prophylactic central neck dissection in follicular thyroid carcinomas, which primarily metastasize hematogenously. In small solitary papillary thyroid carcinomas (T1 and T2), prophylactic central neck dissection is not indicated as it does not bring benefits in terms of improved patient survival and at the same time significantly increases the risk of temporary and permanent postoperative complications. Prophylactic central neck dissection is indicated in advanced papillary thyroid cancers (T3 and T4) and all other high-risk well-differentiated thyroid cancer, as well as in the presence of metastatic lymph nodes in the lateral neck.

Assessment of Oro-Maxillofacial Trauma According to Gender, Age, Cause and Type of the Injury.

OBJECTIVES: The occurrence and causes of maxillofacial trauma varies in different regions of the world. The aim of this study was to identify the occurrence, types and causes of maxillofacial injuries according to the age and gender differences in patients treated at the Department of Maxillofacial Surgery, University Hospital Center Osijek, between January 2011 and December 2013. MATERIALS AND METHODS: A total of 64 patients, 41 males (64.1%) and 23 females (35.9%), aged from 18 to 86 years (mean age 42) participated in the study. Data collected and analyzed included gender, age, cause of injury and the type of maxillofacial injuries. RESULTS: The most common cause of injuries in both gender groups was falling down (39% males; 65% females). The second leading cause of injuries in males was interpersonal violence (29%) and in females traffic accident (26%) (p<0.05). The most common type of injury in both gender groups was bone injury (50%; in males zygomatic bones 55%, in females mandible 40%) (p>0.05). The most common causes of injuries in the youngest patients was violence (43%), and in others fall (50-70%; p<0.05). The most common reported type of injury in all age groups was bone injury (more than 50%; p>0.05). The majority of the falls and violence caused bone tissue injuries, and soft tissue and dentalveolar injuries were detected in traffic and sports accidents (p>0.05). CONCLUSION: Falling down was the most common cause of oro-maxillofacial injuries in both men and women and in all three age groups. The leading type of injury was bone injury. The data obtained from this study provide important information for future prevention from injuries.

Determining the quality of life after removing of impacted lower wisdom tooth using the principal component analysis method.

The main objective of this study was to determine to what extent a detailed oral instruction about treatment after surgical removal of a lower wisdom tooth affects postoperative quality of life (QoL). The research on QoL after removal of a lower wisdom tooth was conducted with 108 patients. Depending on the type of information given to each respondent individually, the examinees were divided into two groups: a test group which was given detailed written and oral instructions, and a control group which received only written instructions about treatment after the surgery. In this research the QoL was examined using modified Oral Health Impact Profile-14 (OHIP-14) criterion four, seven and thirty days after the operation depending on the type of information previously provided to the respondents. In order to reduce the dimensionality of the obtained data sets, as well as in order to explain the relationship between the examined variables that are interrelated the principal component analysis (PCA) was applied. Both groups expressed satisfaction with the postoperative period for the individual variables investigated in modified OHIP-14 questionnaire, with the intensity and the order of the major components of satisfaction determined by the PCA differing between the two groups of the patients. On the fourth postoperative day, the test group expressed the highest level of satisfaction with sleep, physical appearance and the ability to eat. In the later postoperative period the test group (on the seventh and thirtieth day) had the highest level of satisfaction with the absence of discomfort during removal of sutures, satisfaction with performed treatment, and the ability to eat. Detailed preoperative oral instructions to patients can significantly improve the quality of life after operative removal of a lower wisdom tooth.

The influence of surgical experience, type of instructions given to patients and patient sex on postoperative pain intensity following lower wisdom tooth surgery.

The aim of this study was to determine the extent to which the intensity of postoperative pain in the first seven days after lower wisdom tooth extraction is affected by operator experience, patient level of information and patient sex. Postoperative pain intensity after lower wisdom tooth extraction was assessed in 108 patients. Depending on the type of information given to each patient individually, the patients were divided into two groups: test group in which patients were provided with detailed standard written and verbal instructions and control group where patients only received detailed standard written instructions about treatment after surgery. Each of these two groups was divided into three subgroups depending on operator experience. Results of this study showed that the type of information irrespective of being given verbally or not had no effects on postoperative pain intensity, whereas operator experience and patient sex influenced postoperative pain intensity.

The effectiveness of the therapeutic ultrasound on the psycho-physiological functioning in patients who presented with neck pain.

The aim of this study was to investigate the effectiveness of the therapeutic ultrasound on the psycho-physiological functioning in patients who presented with neck pain. There is a limited number of scientific studies which provide information on clinical effectiveness of the therapeutic ultrasound and its effect on the psycho-physiological functions. The present study investigated 100 patients (average age 55), 69 females and 31 males, who presented with neck pain. Treatment protocol consisted of 15 treatments spread over three weeks (five treatments per week). Patients were separated into the two groups (test and control). Both groups of patients undertook programed isometric exercises specific for the cervical spine as well as transcutaneous electrical stimulation. The test group received continuous therapeutic ultrasound on the neck five times a day with the intensity of 0.5 w/cm2, while in the control group ultrasound machine was switched off during the therapy. It has been found that programed isometric exercises specific for the cervical spine in combination with transcutaneous electrical nerve stimulation (TENS) had the same therapeutic effect on the psycho-physiological functioning as the combination of these two therapies with the therapeutic ultrasound.

Hh-Gli signaling pathway activity in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The aim of this study was to examine the role of Hh-Gli signaling in oral and oropharyngeal squamous cell carcinoma (SCC). The role of this signaling pathway in SCC formation has not yet been elucidated. METHODS: Sixty-four tissue and blood samples were collected from 60 patients with SCC, all tobacco and alcohol users. An additional six buccal mucosa tissue samples were collected from nonsmokers and nondrinkers as control tissue. RESULTS: Hedgehog-Gli pathway components were associated with clinical and pathologic features. Broders' grade and N stage were associated with higher Ptch1 and lower Gli1 expression. Tumor stage was negatively associated with Smo expression, and tumor size was positively associated with p16 expression. Ptch1 and Shh were frequently detected in the surrounding stroma. Ptch1 was found to be correlated with p16 expression, as well as with survivin expression. CONCLUSIONS: The signaling pathway is activated in SCC and inducible in vitro by Shh protein.

LOH of PTCH1 region in BCC and ovarian carcinoma: microsatellite vs. HRM analysis.

Loss of heterozygosity (LOH) of tumor suppressor genes is a frequent event in tumorigenesis. LOH is most often analyzed by microsatellite typing, but here we offer a fast and efficient method for simultaneous SNP genotyping and mutation scanning, which can also be used for LOH detection. High resolution melting (HRM) provides simple variant detection, and can be adopted for a wide range of applications. When a melting profile for a specific SNP is determined, the screening can be done without the need for sequencing, and only the melting profiles differing from the established melting profiles should be sequenced. LOH of PTCH1 gene is often found in a series of different tumors, for example basal cell carcinoma (BCC) and ovarian carcinoma (OC). In this study LOH was detected in 50 % of BCC and 27.27 % of OC, and the detection rates of microsatellite typing and HRM were comparable. Both methods depended only on the heterozygosity of the loci analyzed, but HRM offers an additional advantage of detection of all sequence variants in the gene of interest.

Does body mass index and position of impacted lower third molar affect the postoperative pain intensity?

The main objective of this study was to determine to which extent body mass index and position of impacted lower third molar was affecting the pain intensity in the first seven postoperative days. The study was conducted following the extraction of the lower third molar in 108 patients. Depending on the type of information given to each particular patient, the patients were divided in two groups: the test group where patients were given detailed standard written and verbal instructions and the control group which received only standard written instructions about treatment after surgery. Using canonical discriminant analysis we investigated the influence of body mass index and the position of impacted lower third molar on postoperative pain intensity in two groups of patients. Results of this study showed that the body mass index or the tooth position did not have influence on intensity of postoperative pain. The body mass index and the position of impacted lower third molar do not affect the postoperative pain intensity.

Posttraumatic subperiosteal orbital hematoma.

BACKGROUND: Subperiosteal orbital hematoma (SOH) is a rare finding after midface trauma, causing compartment syndrome within the orbit. It should be consideration in the differential diagnosis of any case of proptosis and vertical globe displacement. PATIENTS: We present two patients with SOH treated by surgical evacuation and drainage. RESULTS: In both the hematomas resolved completely and uneventfully. CONCLUSION: Being a safe and simple method, surgical decompression combined with drainage enables complete evacuation of the blood clot and prevents possible sequelae. This method should be considered even in cases without significant visual impairment.

The importance of thorough preoperative diagnostics of maxillary ameloblastoma: report of three cases.

Ameloblastoma, especially maxillary, is a rare benign neoplasm of odontogenic origin. Diagnosis of significant number of lesions is usually established postoperatively, because ameloblastoma, especially the unicystic form, mimics wide range of more frequent jaw lesions. From January 1993 to December 2005, three cases of the maxillary ameloblastoma were surgically treated at our Department. The authors present clinical, radiological and pathohistological features of the ameloblastomas in this rare localization with special attention to need of accurate preoperative diagnostics.

The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas.

The Hedgehog/Patched signaling pathway plays a prominent role during mammalian development but it is also involved in oncogenic transformation. We investigated the methylation status of the Patched promotor in a set of basocellular carcinomas of the skin and ovarian tumors as an alternative to mutational causes of the pathway deregulation. Our aim was to define a possible role of genetic and/or epigenetic mechanisms of Hedgehog/Patched signal transduction in the development of these tumors. Bisulfite-converted DNA from tumors and from matched healthy tissue was amplified by a specific PCR and the CpG-rich regions of the Patched promoter were sequenced. Two promoter regions showed statistically significant hypermethylation compared to healthy controls in ovarian tumors; more significantly in the region in the vicinity of Gli1-binding sites and less significantly in the region containing the ATG codon. But, in basocellular carcinomas of the skin we observed no difference in methylation, suggesting different mechanisms of neoplasia in these tumors.