Non-genetic factors and breast cancer: an umbrella review of meta-analyses.

BACKGROUND: Previous research has found associations between various non-genetic factors and breast cancer (BrCa) risk. This study summarises and appraises the credibility of the available evidence on the association between non-genetic factors and BrCa risk. METHODS: We conducted an umbrella review of meta-analyses. Medline, Scopus, and the Cochrane databases were systematically searched for meta-analyses examining non-genetic factors and BrCa incidence or mortality. The strength of the evidence was graded in four categories (i.e., weak, suggestive, highly suggestive, convincing). RESULTS: A total of 781 meta-analyses from 280 publications were evaluated and graded. We included exposures related to anthropometric measurements, biomarkers, breast characteristics and diseases, diet and supplements, environment, exogenous hormones, lifestyle and social factors, medical history, medication, reproductive history, and pregnancy. The largest number of examined associations was found for the category of diet and supplements and for exposures such as aspirin use and active smoking. The statistically significant (P-value < 0.05) meta-analyses were 382 (49%), of which 204 (53.4%) reported factors associated with increased BrCa risk. Most of the statistically significant evidence (n = 224, 58.6%) was graded as weak. Convincing harmful associations with heightened BrCa risk were found for increased body mass index (BMI), BMI and weight gain in postmenopausal women, oral contraceptive use in premenopausal women, increased androstenedione, estradiol, estrone, and testosterone concentrations, high Breast Imaging Reporting and Data System (BIRADS) classification, and increased breast density. Convincing protective factors associated with lower BrCa risk included high fiber intake and high sex hormone binding globulin (SHBG) levels while highly suggestive protective factors included high 25 hydroxy vitamin D [25(OH)D] levels, adherence to healthy lifestyle, and moderate-vigorous physical activity. CONCLUSIONS: Our findings suggest some highly modifiable factors that protect from BrCa. Interestingly, while diet was the most studied exposure category, the related associations failed to reach higher levels of evidence, indicating the methodological limitations in the field. To improve the validity of these associations, future research should utilise more robust study designs and better exposure assessment techniques. Overall, our study provides knowledge that supports the development of evidence-based BrCa prevention recommendations and guidance, both at an individual level and for public health initiatives. TRIAL REGISTRATION: PROSPERO CRD42022370675.

Beyond the physical risk: Psychosocial impact and coping in healthcare professionals during the COVID-19 pandemic.

AIMS AND OBJECTIVES: This study aimed to examine the psychosocial impact and identify risk factors for poor psychosocial outcomes in healthcare professionals during the Coronavirus disease 2019 (COVID-19) pandemic in Cyprus. BACKGROUND: Healthcare professionals are in the forefront of the COVID-19 pandemic facing an unprecedented global health crisis, which can have consequences on their psychosocial health. There is a need to identify risk factors for poor psychosocial outcomes to inform the design of tailored psychological interventions. DESIGN: Cross-sectional online study. METHODS: A total of 1071 healthcare professionals completed self-report questionnaires. Measures included sociodemographic information, COVID-19-related characteristics, quality of life (Brief World Health Organization Quality of Life; WHOQOL-Bref), anxiety (Generalized Anxiety Disorder-7; GAD-7), depression (Patient Health Questionnaire-8; PHQ-8), occupational burnout (Copenhagen Burnout Inventory; CBI), and coping (Brief Coping Orientation to Problems Experienced; Brief COPE). This article follows the STROBE reporting guidelines. RESULTS: The prevalence of moderate to severe anxiety and clinically significant depression was 27.6% and 26.8%, respectively. Significant risk factors for poor psychological outcomes included being female, being a nurse or doctor (vs non-medical professional), working in frontline units (inpatient, intensive care), perceptions of inadequate workplace preparation to deal with the pandemic, and using avoidance coping. Depression and occupational burnout were significant risk factors for poor quality of life. CONCLUSION: The findings suggest several individual, psychosocial, and organisational risk factors for the adverse psychological outcomes observed in healthcare professionals during the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: This study highlights the urgent need for screening for anxiety and depression and psychological interventions to combat an imminent mental health crisis in healthcare professionals during the COVID-19 pandemic. Pandemic response protocols and public health initiatives aiming to improve and prevent mental health problems in healthcare professionals during the current and future health crises, need to account for the various factors at play.

State of knowledge of human papillomavirus (HPV), HPV vaccine and testing: a cross-sectional study among female university students in Cyprus.

This study aimed to evaluate human papillomavirus (HPV)-related knowledge of women aged 18-25 years and estimate the reported uptake of HPV vaccine and testing. A cross-sectional study was conducted among female students of the University of Cyprus between March and April 2017. The participants self-completed a questionnaire, which consisted of 37 items on demographics, general HPV-related knowledge, and HPV vaccination and testing. In total, 283 young females (mean age: 19.7 ± 1.5 years) took part in the study. Of these, about half (53.7%) reported that they were aware of HPV; one-third (30.7%) reported having been vaccinated; 38.8% had been informed of the recent introduction of the HPV vaccine in the National Immunization Schedule in Cyprus, while 14.3% reported a previous Pap-test and 3.4% a previous HPV DNA test. The mean Overall Knowledge Index (max: 25 correct answers) was 6.1 (±3.8) and was positively associated with the reported uptake of the HPV vaccine (adjusted Odds ratio: 1.14, 95% Confidence Interval (CI): 1.04-1.24). Knowledge about HPV has to be improved as it is associated with increased reported rates of HPV vaccination.

Short Term Success of Treatments to Salvage Thrombosed or Failing Synthetic Arteriovenous Grafts in End Stage Renal Disease: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: There is currently uncertainty regarding the ideal treatment to salvage thrombosed or failing synthetic arteriovenous grafts (AVGs) in patients with end stage renal disease. Therefore, a systematic review up to December 2018 and network meta-analysis of randomised control trials (RCTs) that compared three month failure risk of available treatments was carried out. METHODS: Medline, Scopus, Embase, and the Cochrane Library were the data sources. Pairwise meta-analyses were based on random effects models. Network meta-analysis was conducted within a frequentist framework with a multivariable random effects approach to model treatment effects across studies. The metric of choice was the odds ratio (OR) along with the associated 95% confidence interval (CI). RESULTS: Sixteen two arm RCTs were included involving 2011 patients who were randomised to six different treatments (plain balloon angioplasty, open surgical repair, stents, stent grafts, drug eluting balloons (DEBs), and cutting balloons). The network of RCTs had a star like geometry with plain balloon angioplasty being the common comparator. There were no significant differences between treatments with regards to risk of failure at three months with the exception of stent graft use that significantly reduced the risk of failure compared with plain balloon angioplasty (OR 0.53, 95% CI 0.34-0.84). Based on surface under the cumulative ranking curve (SUCRA) values, the best interventions to salvage thrombosed or failing AVGs were DEB and stent grafts. CONCLUSIONS: Stent graft seems to perform better than plain balloon angioplasty in terms of saving thrombosed or failing AVGs. However, this network meta-analysis was limited by the lack of closed loops and thus unable to assess consistency between direct and indirect evidence. The efficacy of DEBs as a promising treatment deserves further investigation and new RCTs are required.

Immunohistochemical expression patterns of S100, synaptophysin, chromogranin A and neuron specific enolase in predicting malignant behaviour in paragangliomas.

PURPOSE: The purpose of this study was to evaluate the role of immunohistochemical markers in the prediction of malignancy in paragangliomas. METHODS: Our institute's patient records between 1990-2012 were retrieved in order to identify patients who were treated for paragangliomas. Size and location of the tumour, existence of concurrent metastatic disease, patient demographics and survival were recorded. Haematoxylin-eosin stained slides were reviewed and all tumours were stained specifically for neuron specific enolase (NSE), chromogranin, synaptophysin and S100 protein positivity. Positivity and expression patterns of the above markers were evaluated and compared between malignant and benign tumours. Malignant behaviour was defined when patient had concurrent or subsequent lymph node involvement, local recurrence and/or metastases. RESULTS: A total of 22 patients with a diagnosis of paraganglioma were treated in our institutes. Female to male ratio was 1.75: 1. The mean age was 43.5 and 51.6 years for women and men, respectively. In 5 patients the tumors had malignant clinical behavior. Their mean size was 3.65 cm for benign and 4.56 cm for malignant neoplasms. NSE expression was diffuse in 47.1% and 0% for benign and malignant tumors, respectively (p=0.10). S100 expression in the periphery of the tumour was typical in 88.2% and 0% for benign and malignant tumors, respectively (p<0.001). CONCLUSION: Immunohistochemical profile from the combination of NSE, synaptophysin chromogranin and S100 staining patterns can serve as a cheap and valuable tool for correctly distinguishing between malignant and benign paragangliomas with high diagnostic accuracy.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

Carney complex: a case report of bilateral breast myxoid fibroadenomas.

Carney complex is a rare autosomal dominant familiar multiple neoplasia syndrome combined with cardiocutaneous manifestations. Our report describes a Carney complex case with bilateral myxoid fibroadenomas that led to a bilateral mastectomy. An 18-year-old female patient presented at our clinic with complaints of multiple palpable lumps in her breasts bilaterally. On physical examination the patient had also multiple pigmented lentiginous lesions on her face, body and her sclerae, blue nevi on her trunk and upper extremities and a round moon-shaped face. The diagnosis of Carney syndrome was decided upon imaging, biopsies and genetic analysis. The patient underwent a bilateral mastectomy as a prophylactic treatment plan with tissue expanders' placement. Breast myxomatosis due to Carney complex is a common characteristic in female patients. Prophylactic mastectomy must be considered as a therapeutic intervention in these cases since it provides a definite treatment, with minimal side effects and excellent outcomes.

Inferior vena cava obstruction and collateral circulation as unusual manifestations of hepatobiliary cystadenocarcinoma.

BACKGROUND: Hepatobiliary cystadenocarcinoma represents a rare epithelial malignant tumor derived from the intrahepatic bile duct. METHODS: A 71-year-old woman, who had undergone laparoscopic drainage of a cystic lesion of the right hepatic lobe, was misdiagnosed as having hepatic echinococcal disease, and received intracystic infusion of 95% ethanol four years ago. She was admitted to our hospital for further treatment. RESULTS: Physical examination revealed dilated superficial veins across the right abdominal wall. After mapping the direction of blood flow in these vessels, we assumed that this was a sign of inferior vena cava obstruction. Abdominal ultrasound, computed tomography, magnetic resonance imaging combined with magnetic resonance angiography showed a large cystic mass in the right upper quadrant and epigastrium, displacing the adjacent structures, adherent to the inferior vena cava, which was not patent, resulting in dilation of superficial epigastric veins. The patient underwent an exploratory laparotomy. Total excision of the huge mass measuring 16X15 cm was possible under selective vascular exclusion of the liver. Removal of the tumor resulted in immediate restoration of flow in the inferior vena cava. On the basis of the pathology and findings of immunohistochemical analysis, a hepatobiliary cystadenocarcinoma was diagnosed. CONCLUSIONS: In the present case, hepatobiliary cystadenocarcinoma was accompanied by dilated superficial venous collaterals due to inferior vena cava obstruction. Selective vascular exclusion of the liver allowed a safe oncological resection of the tumor.

Right Kocher's incision: a feasible and effective incision for right hemicolectomy: a retrospective study.

BACKGROUND: The choice of surgical incision is determined by access to the surgical field, particularly when an oncological resection is required. Special consideration is also given to other factors, such as postoperative pain and its sequelae, fewer complications in the early postoperative period and a lower occurrence of incisional hernias. The purpose of this study is to compare the right Kocher's and the midline incision, for patients undergoing right hemicolectomy, by focusing on short- and longterm results. METHODS: Between 1995 and 2009, hospital records for 213 patients that had undergone a right hemicolectomy for a right- sided adenocarcinoma were retrospectively studied. 113 patients had been operated via a Kocher's and 100 via a midline incision. Demographic details, operative data (explorative access to the peritoneal cavity, time of operation), recovery parameters (time with IV analgesic medication, time to first oral fluid intake, time to first solid meal, time to discharge), and oncological parameters (lymph node harvest, TNM stage and resection margins) were analyzed. Postoperative complications were also recorded. The two groups were retrospectively well matched with respect to demographic parameters and oncological status of the tumor. RESULTS: The median length of the midline incision was slightly longer (12 vs. 10 cm, p < 0.05). The duration of the surgery for the Kocher's incision group was significantly shorter (median time 70 vs 85 min, p < 0.001). In three patients we performed wedge resection of liver metastasis and in one patient we performed a typical right hepatectomy that lasted 190 min. No major operative complications were noted. There was no immediate or 30- day postoperative mortality. The Kocher's incision group had a significantly shorter hospital stay (median time 5 vs 8 days). All patients underwent wide tumor excision and clear resection margins were obtained in all cases. No significant difference was noted regarding analgesia requirements and early postoperative complications. Late postoperative complications included 2 incisional hernias and three patients presented with one episode of obstructive ileus, that resolved conservatively. CONCLUSIONS: The Kocher's incision approach for right- sided colon cancer is technically feasible, safe and overall very well tolerated. It can achieve the same standards of tumor resection and surgical field accessibility as the midline approach, while reducing postoperative recovery.

Trends of Online Search of COVID-19 Related Terms in Cyprus.

Knowledge of trends in web searches provides useful information for various purposes, including responses to public health emergencies. This work aims to analyze the popularity of internet search queries for Coronavirus Disease 2019 (COVID-19) and COVID-19 symptoms in Cyprus. Query data for the term Coronavirus were retrieved from Google Trends website between 19 January and 30 June 2020. The study focused on Cyprus and the four most populated cities: Nicosia, Limassol, Larnaca, and Paphos. COVID-19 symptoms including fever, cough, sore throat, shortness of breath, and myalgia were considered in the analysis. Daily and weekly search volumes were described, and their correlation with the evolution of the COVID-19 pandemic and important announcements or events were examined. Three periods of interest peaks were identified in Cyprus. The highest interest in COVID-19-related terms was found in the city of Paphos. The most popular symptoms were fever and cough, and the symptom with the highest increase in popularity was myalgia. At the beginning of the pandemic, the search volume of COVID-19 grew substantially when governments, major organizations, and high-profile figures, globally and locally, made important announcements regarding COVID-19. Health authorities in Cyprus and elsewhere could benefit from constantly monitoring the online interest of the population in order to get timely information that could be used in public health planning and response.

Recurrent pulmonary embolism due to giant hepatic hamangioma treated with hepatectomy under vascular exclusion.

Giant hepatic hemangiomas are benign tumors that measure more than 4 cm and are usually asymptomatic. Pulmonary embolism (PE) is an extremely rare manifestation of giant hepatic hemangiomas. We report a case of a 44-year-old woman who suffered of recurrent pulmonary emboli that, after thorough work up, were attributed to thrombi formation inside a giant hepatic hemangioma. A right hepatectomy under vascular exclusion was performed and the hemangioma, measuring 17 cm, was resected. Two years later the patient remains asymptomatic. The report highlights the value of investigating giant liver hemangiomas in case of PE. In such cases, the hemangioma should be resected preferably under occlusion of the venous outflow of the liver to avoid PE intraoperatively.

Combination of right nephrectomy and total pancreaticoduodenectomy for Von Hippel-Lindau disease.

CONTEXT: Von Hippel-Lindau disease is an inherited syndrome of multiorgan neoplasia caused by a germline mutation in the von Hippel-Lindau gene and can include central nervous system tumors, renal cell carcinomas and benign pancreatic cystic tumors. CASE REPORT: We report the case of a 56-year-old patient who had a past history of cerebellar hemangioblastoma and presented with abdominal pain. Imaging revealed renal tumors and multiple pancreatic tumors which caused duodenal and pancreatic duct compression. The patient was treated with a combination of radical right nephrectomy, total pancreaticoduodenectomy and splenectomy. Pathology identified a multifocal unilateral clear cell renal carcinoma which interestingly coexisted with multiple large pancreatic serous microcystic adenomas with infiltration of the fibrous capsule. CONCLUSION: In past cases of von Hippel-Lindau disease, pancreatic adenomas with malignant transformation have not been reported. In our case, the infiltration of the fibrous capsule by parenchymal cells may indicate malignant transformation.

A novel laparoscopic pulse oximeter device. An easy, efficient and cost- effective way of detecting arterial structures.

The introduction of laparoscopy has revolutionized surgery. However, these new techniques have brought new problems into the surgical field. Due to the loss of depth and tactile sensation, time- consuming efforts must be made in order to identify normal anatomy and detect any aberrations. Even well experienced surgeons could face difficulties during demanding procedures, such as operations on inflammatory conditions. Therefore, there is still a strong need for developing additional tools to help mapping the anatomy. We designed a laparoscopic pulse oximeter device, which offers an easy, efficient and cost- effective way of using pulse oximetry in combination with a standard laparoscopic clamp in order to identify arterial structures.

The introduction of a simple maneuver to reduce the risk of postoperative bleeding after major hepatectomies.

BACKGROUND/PURPOSE: In major hepatectomies, postoperative increases in central venous pressure (CVP) may cause suture failure and massive bleeding. The aim of our study is to test the application of an intraoperative maneuver to reduce the risk of postoperative bleeding. METHODS: Our study included 172 consecutive patients who had major liver resection with selective hepatic vascular exclusion and sharp transection of the liver parenchyma. An intraoperative maneuver (5 s occlusion of the hepatic vein) was applied in an alternating way, and the patients were assigned to two groups: Cohort A (n = 86), that was granted the maneuver, and Cohort B (n = 86), that was used as a control group. RESULTS: In Cohort A, application of the maneuver was successful in demonstrating bleeders under low CVP levels. Cohort A had lower rate of massive bleeding requiring emergency reoperation (2.3 vs 5.8%, P = 0.049), less postoperative blood transfusions (13 vs 24%, P = 0.042), lower morbidity (20 vs 35%, P < 0.045) and shorter hospital stay compared to Cohort B. CONCLUSIONS: Hepatectomies conducted under low CVP are prone to postoperative hemorrhage which can be prevented if the final bleeding control is performed under high pressure in the hepatic veins. Application of our testing maneuver effectively unmasked previously undetectable bleeding veins.

A rare coexistence of adrenal cavernous hemangioma with extramedullar hemopoietic tissue: a case report and brief review of the literature.

BACKGROUND: Cavernous hemangiomas of the adrenal gland are rare, benign, non-functioning neoplastic tumors. To our knowledge, 55 cases have been reported in the literature to date. CASE PRESENTATION: We report the first case of a large, non-functioning adrenal cavernous hemangioma that was incidentally found during the preoperative staging workup of a 75 year old woman with left breast adenocarcinoma. Imaging with US, CT scan and MRI showed a heterogeneous 8 cm mass with non-specific radiological features that was located on the left adrenal gland. The mass was surgically excised and pathology revealed an adrenal hemangioma with areas of extramedullar hemopoiesis. CONCLUSION: Although adrenal hemangiomas are rare and their preoperative diagnosis is difficult, they should always be included in the differential diagnosis of adrenal neoplasms.

Data on knowledge and beliefs of students, physicians and other health professionals about ethical issues in Cyprus.

This article presents data collected in a field, questionnaire-based survey about ethical issues in the Republic of Cyprus. The participants were students of the University of Cyprus, and physicians and other health professionals of the Medical School, University of Cyprus and of the Archbishop Makarios III Hospital. The questionnaire included items on sociodemographic characteristics of the participants, and on their knowledge and beliefs about three different ethical issues. Beliefs on the same ethical issues but under specific, hypothetical scenarios were also reported by the participants. The ethical issues examined included euthanasia, assisted suicide, and gender selection through in vitro fertilization. Data from 259 questionnaires were collected in March and April of 2018.

Efficacy and safety of biologic agents and tofacitinib in moderate-to-severe ulcerative colitis: A systematic overview of meta-analyses.

Background: Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib. Objectives: We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC. Methods: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events. Results: The overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab. Conclusions: Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision-making.

Special problems encountering surgical management of large retroperitoneal schwannomas.

BACKGROUND: Retroperitoneal schwannomas are rare, usually benign tumors that originate in the neural sheath and account for only a small percentage of retroperitoneal tumors. The aim of this clinical study is to present our experience in managing retroperitoneal schwannomas with a review of the current literature and to point out the surgical technical difficulties we faced, due to the tumor's strange behavior that eroded the vertebra in two cases without causing malignant invasion. METHODS: We reviewed the medical files of 69 patients treated in our department for retroperitoneal tumors from January 1991 until December 2006. Five patients had retroperitoneal schwannomas according to pathology report. RESULTS: There were two male and three female patients, with a mean age of 56 years (range 44-67 years). All patients were asymptomatic and none suffered from von Recklinghausen disease. Imaging workup included ultrasonography, computed tomography and magnetic resonance imaging. One patient, after having a non-diagnostic computed tomography fine needle aspiration (CT-FNA), underwent exploratory laparotomy and incisional biopsy that established the diagnosis of schwannoma. After complete excision of the tumors, postoperative course was uneventful in all patients. Tumors' maximum diameter was 12.7 cm (range 7-20 cm). No recurrences were detected during the follow up period (6-75 months). CONCLUSION: Preoperative establishment of diagnosis is difficult in case of retroperitoneal schwannomas, however close relationship of retroperitoneal tumors with adjacent neural structures in imaging studies should raise a suspicion. Complete surgical resection is the treatment of choice. Histology and Immunohistochemistry confirms the diagnosis.

Epidemiology of breast cancer in Cyprus: Data on newly diagnosed cases and survival rates.

This article presents analyzed data on new diagnoses and mortality of breast cancer, between 2005 and 2013, in the Republic of Cyprus. New diagnoses are presented by demographic and clinical/histological variables that include cancer grade, behaviour, stage, and histological type at diagnosis (always as a primary site). Breast cancer-related deaths are presented by gender. Net survival rates based on cohort and period methods are presented by age group, cancer grade, behaviour, and stage at diagnosis, for all cases and for cases of Greek-Cypriot ethnicity. The unprocessed data of the Cyprus Cancer Registry were provided by the Health Monitoring Unit of the Ministry of Health of the Republic of Cyprus.