Laryngopharyngeal Reflux Scoring in a Pediatric Population.

In recent years, the prevalence of laryngopharyngeal reflux has risen, especially among pediatric patients. The diagnosis of laryngopharyngeal reflux relies on patient history and clinical assessment using the Reflux Finding Score and Reflux Symptom Index as crucial diagnostic tools. Some studies have proposed a link between pepsin and laryngopharyngeal reflux, potentially triggering palatine tonsil hypertrophy. Our study aimed to investigate the correlation between laryngeal and pharyngeal manifestations of laryngopharyngeal reflux through two questionnaires and the presence of pepsin in saliva and palatine tonsils in a pediatric population. Pepsin in saliva was detected using a Western blot method, while immunohistochemistry assessed its presence in palatine tonsils. Although no statistically significant differences in Reflux Finding Score and Reflux Symptom Index were found between the immunohistochemistry-positive (IHC-positive) and immunohistochemistry-negative (IHC-negative) groups, median reflux symptom index and Reflux Finding Score values consistently trended higher in the IHC-positive group. This suggests a potential connection between elevated index values and pepsin presence in tonsillar tissue. Further investigations are essential to fully comprehend the clinical implications of these findings.

Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. The levobupivacaine PCA group had the best-preserved HGS after 1 year (P = 0.022). The most significant predictor of the 5-year outcome was HGS (P = 0.03). Survival at 10 years was 85%, 92%, and 77% in the diclofenac, levobupivacaine bolus, and levobupivacaine PCA groups (ns. P = 0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival (P = 0.03). A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study-trial number NCT05829707.

SERUM LEPTIN LEVEL IN BREAST CANCER.

Leptin is a polypeptide which is mostly produced in white fat tissue and is an important proinflammatory, proangiogenic, proinvasive and mitotic factor. There is ever more evidence suggesting the key role of leptin in the occurrence of breast cancer. The aim of the study was to investigate serum leptin levels in patients with benign breast tumors, as well as in various breast cancer phenotypes, taking into account leptin levels connected to menopausal status and body mass index (BMI). The study included 97 patients having their breast tumor surgically removed. Serum leptin level was determined by ELISA method in all study patients. Study results showed that significantly more women, regardless of having malignant or benign tumors, were postmenopausal and had a significantly higher level of leptin compared to the premenopausal group. The highest level of leptin was recorded in the group of postmenopausal obese women compared to other postmenopausal women but also compared to premenopausal women. According to BMI alone, obese women had a significantly higher level of leptin regardless of the type of tumor. The most significant differences in leptin levels observed through BMI were found in the Luminal B1 group. In conclusion, serum leptin level was shown to be a good diagnostic parameter suggesting a higher possibility of breast cancer development.

Unrecognized Bowen's disease in previously treated condylomata acuminata: indication of a common etiology?

Bowen's disease (BD) is an intraepidermal squamous cell carcinoma (SCC) with the capacity to become invasive SCC giving rise to distant metastasis. In rare cases it can be associated with human papillomavirus (HPV) infection, specifically with HPV types 16, 18, 31, 32, and 34. Here we report a case of an immunocompetent white male, age 37, with an erythematous, irregularly-shaped patch in his suprapubic region, appearing 1 year after treatment for condylomata acuminata with cryotherapy and podophyllin in the same area. At the time of clinically active disease, a urethral smear was positive for high-risk HPV types. The lesion was considered a scar by several physicians because it emerged in an area of previous postinflammatory hyperpigmentation. The aim of this report is to raise awareness of the emerging causative association between anogenital HPV infection and the development of BD, which was the possible etiological agent in the case of the patient presented here. Hereby we also advocate primary preventive measures in terms of safe sexual habits and HPV vaccination.

IMPACT OF NEUROTROPIC VIRUSES ON SURVIVAL OF PATIENTS WITH SURGICALLY TREATED GLIOBLASTOMA.

Introduction: Glioblastoma represents the most aggressive tumor of the brain with an estimated survival rate of twelve to fifteen months after the primary diagnosis. The role of neurotropic viruses in pathogenesis of the tumor has remained unclear to date. During the last two decades, many studies were conducted with the aim of confirming viral influence in the development of glioblastoma. Methods: We conducted a retrospective study in a time period of five years using formalin-fixed paraffin-embedded tissues of glioblastoma. Immunohistochemistry was performed for three viruses: CMV, EBV and HSV-1, using an automated staining system. Results: Mean age of patients in our group was 66.7±8.5 years. A slight male dominance was noted. Negative immunohistochemistry results were obtained for CMV and EBV, which were excluded from further investigation. Based on IRS score, we confirmed six HSV-1 samples which were rated as IRS score 2. Five more samples of HSV-1 were rated as IRS score 1 and were excluded from the study. Conclusion: According to our retrospective study and its results, we found no impact of neurotropic viruses in the survival rate of glioblastoma. Further studies should be conducted including a wider range of viral detection methods.

Epidural analgesia for acute ischemic pain after intra-arterial zolpidem injection in opioid-addicted patient-A case report.

A patient taking opioid maintenance therapy unintentionally injected dissolved zolpidem pills into the femoral artery and suffered acute limb ischemia. High amounts of opioids with supplemental therapies were inefficient for intractable ischemic pain, suggesting the presence of opioid-induced hyperalgesia (OIH). Epidural analgesia efficiently relieved pain and symptoms of OIH.

Adenoma Characteristics and the Influence of Alcohol and Cigarette Consumption on the Development of Advanced Colorectal Adenomas.

Background: Colorectal cancer (CRC), one of the leading public health problems worldwide, is a disease that can be prevented when it is detected in time. The objectives of this cross-sectional study were to investigate the characteristics of colorectal adenomas and whether alcohol consumption and cigarette smoking correlated with the development of advanced adenomas in participants in The National Programme for Early Detection of Colorectal Cancer (NP) in Osijek-Baranja County (OBC), Croatia. Methods: The screening methods were the guaiac Faecal Occult Blood Test (gFOBT), colonoscopy, histological analysis, and risk factor questionnaire. Results: The results showed the presence of adenomas in 136 men (57.4%) and 101 women (42.6%), p < 0.001. There was one adenoma in 147 (62%) most commonly located in sigmorect, in 86 (59%) participants, and 44 (18.6%) participants had multiple adenomas, most commonly found in multi loc, p < 0.001. According to size, 118 (49.8%) of all adenomas were between 0.1 and 0.9 cm, while adenomas of 3 cm 19 (8%) were the fewest, p < 0.001. There were 142 (59.9%) advanced adenomas. Conclusions: Adenoma development in the OBC population was correlated with predictors: adenoma size, high-grade dysplasia, smoking and alcohol consumption of 20 g per day. Non-smoking was found to be a health protective behaviour.

Impact of Meteorological Factors on Suicide Attempts and Completed Suicides in Croatia, Osijek-Baranja County.

BACKGROUND: Significant changes in the values of temperature, pressure, humidity and cloud cover can participate in the human behaviour including the mood disorders (especially depression and bipolar disorders) which can trigger suicidal ideas or their realization. The aim of this study is to estimate the connection between the aforesaid weather changes and a committed suicide along with the suicide attempts. SUBJECTS AND METHODS: We conducted a retrospective study in Osijek-Baranja County in the period from 2000 to 2011. Meteorological, demographic and epidemiological analysis was performed on 569 suicides and 478 suicide attempts (total of 1047 events). We analyzed the values of the above-mentioned meteorological parameters at the exact time when the event had happened, as well as three days before the event and one day after the event, comparing it with the monthly mean values. RESULTS: The results showed that the changes of temperature and pressure were significantly related with the suicides i.e. suicide attempts in general, while by separating genders, a connection with all examined meteorological factors was found by woman whereas men expressed significance only in the matter of temperature changes. CONCLUSIONS: Despite the fact that suicidality is caused by numerous factors, this study confirms that a sudden change of weather in the days preceding the suicide can be a trigger to suicidal behaviour. The study also suggests that in the matter of suicidal behaviour, female population is more susceptible to sudden weather changes.

Intestinal Morphology in Broiler Chickens Supplemented with Propolis and Bee Pollen.

The aim of this study was to determine the influence of dietary supplementation with propolis and bee pollen on the intestinal morphology and absorptive surface areas of chickens. Two hundred day-old Ross 308 chickens (100 male and 100 female) were equally allocated into five groups. Throughout the whole study, the control group of chickens was fed with a basal diet, while the experimental groups of chickens were fed with the same diet supplemented with propolis and bee pollen: P1 = 0.25 g of propolis/kg + 20 g of bee pollen/kg; P2 = 0.5 g of propolis/kg; P3 = 1.0 g of propolis/kg; P4 = 20 g of bee pollen/kg. The duodenal villi of chickens from all experimental groups were significantly higher and wider (p < 0.001), while their duodenal villi crypts were significantly deeper (p < 0.001) in comparison with these parameters in chickens from the control group. The villus height to crypt depth ratio, as well as the absorptive surface areas of broiler chickens, were significantly increased (p < 0.001) in experimental groups of chickens in comparison with the control group. These findings suggest that dietary supplementation with propolis and bee pollen has a beneficial effect on broilers chickens' intestinal morphophysiology.

Aggressive progression of Takayasu's arteritis in infancy: a case report.

Takayasu's arteritis (TA) affects the aorta and its branches. Immunosuppressants are the usual course of therapy, while surgery has been used in acute cases. There is only scant information on TA in infancy, and the nonspecific symptoms in the initial stage of the disease make the diagnosis difficult and delayed, thus increasing the mortality rate. We describe a case of aggressive progression of TA in an infant. This child was the youngest to be affected with the disease as reported in the literature. A 3.5-month-old boy presented with cyanosis of both legs, tachycardia and antithrombin III deficiency. Computed tomography angiography (CTA) revealed thrombosis of distal aorta and both iliac arteries. Thrombectomy was performed at the level of both common femoral arteries. In addition, thigh amputation of the left leg had to be performed. TA was diagnosed postmortem with thrombosis of the distal aorta, its branches and upper mesenteric artery which was not occluded on previous CTA, glomerulonephritis and pulmonary parenchymal granulomatous infiltrations.

Prognostic role of Nectin-4 expression in luminal B (HER2 negative) breast cancer.

Nectins are Ca2+-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions and regulate several cellular activities including the entry of some viruses. Nectin-4 has recently been shown as a metastasis-associated protein in several cancers. In the following study, we have evaluated the expression of Nectin-4 inthe luminal B HER2 negative subtype breast cancer. The study group consisted of 147 patients presenting with primary unilateral breast carcinoma with no evidence of distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry and the results were correlated with the clinical data using Kaplan-Meier curves, univariate and multivariate stepwise proportional-hazard analysis (Cox model). Nectin-4 overexpression was significantly correlated with the tumour size (p<0.05; Fisher's Exact Test), also Nectin-4 expression was negatively associated with overall survival, disease free survival and distant relapse free survival with the same significance (p<0,001; Kaplan-Meier, Cox model). We did not find statistically significant correlation between Nectin-4 and age, ER, PR, age, lymph node metastasis, tumour differentiation, histologicalsubtype and Ki-67proliferation index. We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer.

Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology.

BACKGROUND: Unexpected differences in Ki-67 values among HER2 & ER/PgR defined subgroups were found. This study aims to detect possible subdivisions beyond the conventional breast cancer types. METHODS: One thousand one hundred eighty consecutive patients with invasive ductal breast carcinoma were included and distributed in 16 subgroups (four HER2 phenotypes (0+, 1+, 2+ and 3+) times four ER/PgR phenotypes). Complex distributions of Ki-67 values were tested by expectation maximization (EM) clustering. RESULTS: Pooled Ki67 values of all patients showed the presence of three EM clusters (defined as LMA-low mitotic activity, IMA-intermediate mitotic activity and HMA-high mitotic activity) with expected mean Ki-67 values of 1.17%, 40.45% and 77.79%, respectively. Only ER-PgR- tumors significantly dispersed in three clusters (29.75% tumors in LMA, 46.95% in IMA and 23.30% in the HMA cluster), while almost no detected HMA tumors were of ER + PgR+ or ER + PgR- phenotypes. Among 799 ER + PgR+ patients distribution in clusters was HER2 dependent (p = 0.000243), due to increased number of IMA HER2 3+ tumors on the expense of LMA HER2 3+ tumors (52 IMA out of 162 HER2 3+ patients versus113 IMA out of 637 HER2 < 3+ patients). This was not found among ER + PgR- patients (p = 0.186968). Among ER-PgR- patients, HER2 overexpression also increased number of IMA tumor, but by reducing the number of HMA tumors (p < 0.000001). Here, difference between HER2 absent (0+) and HER2 3+ patients was evident (10 HMA out of 125 HER2 3+ patients versus 42 HMA out of 103 HER2 0+ patients). CONCLUSIONS: Results suggest that distributions of breast cancers in three clusters of mitotic activity depend on different mechanisms for ER + PgR+ and ER negative tumors. Although HER2 overexpression increases number of IMA tumors in both settings, in the former it is done by reducing number of LMA tumors, while in the latter it reduces the number of HMA tumors. Mitotic activity of ER + PgR- tumors seems unrelated to the HER2 status, possibly as an indicator that ER dysfunctionality in cancers that lack PgR expression. Among ER negative tumors, the absence of HER2 (0+) might be as important as the HER2 overexpression.

Histopathological Changes in Tracheal Mucosa Following Total Laryngectomy.

The aim of this study was to determine the long term histopathologic changes in tracheal mucosa after a total laryngectomy , and to find out the relationship between the progression of histopathologic changes in tracheal mucosa and the duration of breathing through the tracheostomy. Tracheal mucosal biopsies were taken from a total of 35 patients, of both sexes, who underwent a total laryngectomy for laryngeal carcinoma at least one year prior. Histologic specimens of tracheal mucosa were stained with hematoxylin and eosin and examined under light microscopy. Almost all of the patients demonstrated histopathologic changes or abnormalities. Based on the results, histological findings were grouped into seven categories: normal respiratory epithelium, mild, moderate and advanced basal cell hyperplasia, squamous metaplasia, and slight and moderate and dysplasia. The time elapsed since surgery was calculated for each histopathological change separately. In laryngeal carcinoma patients, after a total laryngectomy histopathologic changes occur in tracheal mucosa. The mildest histopathological changes are found in the patients who had a longer period between the operation and the examination.

Expression of proinflammatory cytokine interleukin-6 in tissue samples of human prostate obtained by needle biopsy.

Interleukin-6 (IL-6) has been associated with the development of prostate cancer. The aim of the study was to clarify whether IL-6 expression in prostate tissue could be a useful marker in differentiation of prostate diseases in small foci by pathologist visual scoring. Archival paraffin-embedded specimens of benign prostate hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (PIN), prostatitis and prostate adenocarcinoma were studied by immunohistochemistry with a mouse monoclonal antibody IL-6 using the streptavidin-biotin method. Significantly, lower IL-6 immunoreactivity was observed in normal epithelial cells (p=0.000) and basal cells (p=0.000) in the samples of prostate adenocarcinoma in comparison to the samples with BPH, PIN and prostatitis. There was no significant difference in IL-6 expression in malignant and premalignant cells (p=0.814) as well as in stromal cells among the four diagnoses (p=0.22). IL-6 was expressed in normal epithelial cells, premalignant epithelial cells and malignant epithelial cells as well as in stromal cells. However, in our research IL-6 was of limited utility as a single marker for differential diagnosis of the prostate diseases in small foci needle biopsy by pathologist visual scoring. The standardization of immunohistochemical (IHC) staining protocol for IL-6 is required to determine IL-6 expression in order to avoid possible misinterpretation of the IHC results.

Pathohistological changes of tracheal epithelium in laryngectomized patients.

Total laryngectomy results in a permanent disconnection of the upper and lower airways. Thus, the upper airways are bypassed and can no longer condition, humidify, and filter the inhaled air, leading to damage of the tracheobronchial epithelium. There is little scientific information available about the effects of tracheostoma breathing and the degree of mucosal damage in laryngectomized patients. The aims of this study were to determine the histopathologic findings and investigate the potential impact of using a heat and moisture exchanger (HME) on the tracheal epithelium in long-term tracheostomy patients. Tracheal mucosal biopsies were taken from a total of 70 patients. Specimens were stained with hematoxylin and eosin and examined by a light microscope. Normal pseudostratified ciliated columnar epithelium was found in only 9 (12.9%) cases; while, 17 (24.3%) cases had some degree of basal cell hyperplasia. Squamous metaplasia was the most common finding (50%). Pre-invasive lesions (mild and moderate squamous dysplasia) were found in only one patient who used an HME, and in eight (11.4%) non-users. Although the HME cannot completely restore the physiological functions of the upper respiratory track, it delivers a better quality of air to the lower airways and has a positive effect on tracheal mucosa.

A model of immunohistochemical differences between invasive breast cancers and DCIS lesions tested on a consecutive case series of 1248 patients.

BACKGROUND: A previous theoretic model (Tumour Biol 2013;34:1-7.) that breast tumor types differ in the relative rate of tissue invasion was elaborated and developed on a consecutive case series. METHOD: Histologic data of 68 ductal breast cancer in situ (DCIS) and 1180 invasive ductal cancer (IDC) patients were collected and analyzed. RESULTS: ER+PgR- phenotype was more common in Luminal B2 than among the pooled Luminal A&B1 (p = 0.0002), and more frequent in Luminal B1 than in Luminal A (p = 0.0167). The same phenotype was associated with the age older than 54 years in Luminal B1 and in B2 patients. HER2 type cancers were more frequent in older patients (p = 0.0038).Tumor progression from DCIS to IDC was found 39% faster than the average in Luminal B1 tumors, supporting the clinical importance of this tumor type. A rare combination of low Ki-67 in HER2 type cancers (only 14% of HER2 type cancers) showed very slow transition to IDC (occurring at only 53.55% of average progression rate), while triple-negative cancers progressed faster than the average, despite Ki-67 value (104.63% for low and 114.27% for high Ki-67 tumors).In three tumor types with positive steroid receptors the ER+PgR- phenotype showed slower IDC transition than the ER+PgR+ phenotype of the same tumor type (difference in progression rate was 38% for Luminal A, 46% for Luminal B1 and 67% for Luminal B2 with Ki67 > 14%).Triple-negative tumors in younger patients exceeded the expected average progression rate by 24%, while in HER2 type tumors, the rate of tissue invasion was in younger patients 20% lower than the expected value. CONCLUSIONS: The relative rate of tissue invasion differed substantialy among our patients. Differences depended on tumor types, steroid expression phenotypes and age. The dysfunctional ERs in the ER+PgR- phenotype showed slower rates of tissue invasion, suggesting that ligand binding to functional breast tumor ERs, beside promoting the PgR expression, possibly also promotes tumor transition to the invasive phase.In triple-negative tumors, an age dependent premenopausal mechanism possibly acted as an accelerator of tissue invasion, while faster tissue invasion by HER2-overexpressed tumors in older patients possibly depended on an unidentified mechanism that takes more time to be acquired, so it was less present in premenopausal patients.

Potential value and disadvantages of fine needle aspiration cytology in diagnosis of ameloblastoma.

Ameloblastoma is a benign, slow growing but locally aggressive tumor that is clinically manifested as swelling in a jaws. Prone to relapse (30%) even 30 years after inadequate primary operation. The most important cytological features of this tumor are small bazaloid cells in clusters, and single spindle and stellate shaped cells. We report on a case of 79-year-old patient, who was hospitalized due to tumor formation in the buccal region. FNA was performed and liquid material that contained only fagocites was collected. The conclusion was--cyst, while biopsy finding--adenoma baseo-cellulare, pointed to the salivary gland tumor. Patient refused the proposed surgical treatment. Four years later, the patient was urgently hospitalized due heavy bleeding from the tumor in the same region. It affected the crest portion of the upper jaw and a section of hard palate, and was bleeding on palpation. In second FNA we found phagocytes and a few small clusters of basaloid cells with palisade arrangement at the edges. Because of uniform and benign cytomorphological features it was concluded that it was a cystic tumor. On biopsy pattern the diagnose of ameloblastoma was determinated. The patient underwent surgery, however due to postoperative complications he died. Preoperative diagnosis is usually set on the basis of clinical and often nonspecific radiological findings. As it is very important to get the correct diagnose before planning an adequate surgical procedure, we would like to point out the potential value and disadvantages of FNA cytology in the diagnosis of ameloblastoma.

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.

Impaired kidney function in rats six months after unilateral nephrectomy - an old story, a new perspective.

AIM: Despite of routinely practised living kidney transplantation, data on consequences and impact of unilateral nephrectomy on the quality of life and health of donors are scarce. The aim of the present study was to examine long-term changes and function of the remnant kidney after unilateral nephrectomy in an animal model. METHODS: Thirty six female Sprague - Dawley rats at 4 months of age were randomized into the three groups: unilaterally nephrectomized, sham operated and naïve rats. The nephrectomy was done at inclusion in the experiment and their blood was taken at inclusion and six months thereafter. RESULTS: There was a significant increase in serum creatinine concentrations six months after unilateral nephrectomy (39.7 ± 0.8 µmol/l) in comparison with the sham operated (30.1 ± 1.1 µmol/l) and the naïve rats (26.3 ± 3 µmol/l) (p ≤ 0.001). Serum sodium levels remained unchanged (p=0.116). Blood haemoglobin concentration did not differ between the three groups (p=0.115). CONCLUSIONS: Although it has been very well established that kidney possesses huge capacity to compensate severe loss of renal mass, our results implicate that renal function undergoes significant deterioration with time after unilateral nephrectomy. Fortunately, in everyday clinical practice we do not see severe renal dysfunction in patients with a single kidney. However, prolongation of the human life span in the future could face us with renal impairment in living kidney donors. Future examination of specific biomarkers in our rat model (e.g. growth factors) could support our findings.

Morphometric characteristics of thyroid cartilage in people of Eastern Croatia.

The aim of this research was to describe thyroid cartilage morphometry in the population of Eastern Slavonia in detail. The research was carried out on 68 samples of adult thyroid cartilages. There was statistically significant difference between all analysed parameters in male and female samples, except for the distance between the superior horns tips. All parameters had greater values in men, except for the thyroid angle, which was greater in women. There was significant correlation between most of the measured parameters. The strongest correlation was noticed in the distance between the horns at all measured levels and between the pairs of parameters measured for the left and right side respectively. The difference of our results in comparison to the results obtained by other researchers is probably caused by the fact that the measurements were taken on the samples obtained from different populations.