Band 41, Heft 3

Background Ovarian carcinoma is a poor prognosis cancer mainly due to its late diagnosis. Its incidence is relatively low but mortality is high. The symptomatology is only slightly specific, which complicates diagnostic management. It would therefore be interesting to be able to establish a diagnosis as early as possible in order to improve the prognosis of patients suffering from ovarian cancer. Materials and methods Currently, the combination of an ultrasound examination with a cancer antigen (CA)-125 assay is the most effective diagnostic technique, but not already admitted as a screening method. Therefore, we realized an exhaustive analysis of the most important studies in the last 15 years, in order to find new approaches in ovarian cancer screening. Results The age for initiating screening and its frequency are issues that are not fully resolved. The false positives and morbidity that result from screening are currently notable limitations. Conclusions The latest data do not support effective screening in the general population.

Objectives To review non-surgical prevention strategies in women with hereditary breast and ovarian cancer syndromes. Content Women with a g BRCA1 or 2 mutations face a high cumulative breast and ovarian cancer risk. While bilateral mastectomy (PBM) and bilateral salpingo-oophrectomy (PBSO) profoundly reduce the respective cancer risks, they are also associated with considerable side effects. There is therefore an urgent need for alternative and non-surgical risk reduction options. Tamoxifen and aromatase inhibitors have both been evaluated in secondary prevention, but their benefit in primary prevention is currently unknown in BRCA mutation carriers. In addition, their use is compromised by their side effect profile which makes them less appealing for a use in chemoprevention. Summary and outlook Denosumab is a well-tolerated osteoprotective drug, which has been demonstrated to have a potential preventive effect particularly in BRCA1 -deficient models in vitro . The prospectively randomized double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germ line mutation carriers.

In the treatment of advanced-stage epithelial ovarian cancer (EOC)-associated surgery and chemotherapy with intravenous platinum/taxane-based therapy most patients had early or late recurrence. Prevention of progression and recurrence is a major objective for the management of EOC. Recently, many clinical studies have evaluated the strategy with hyperthermic intraoperative intraperitoneal (IP) drug delivery. This is an update of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in EOC and a view for future strategies. Until recently studies on HIPEC in patients with EOC were mostly retrospective and heterogeneous. Thanks to recent clinical trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is an interesting approach in the management of EOC without increasing morbidity.

Background Clinical practices and testing strategies in patients with ovarian cancer differ worldwide. We therefor wanted to give an overview over the current data to advise best clinical practice. Materials and methods A systematic review of the literature was performed with the aim to define which ovarian cancer patients to refer for genetic counseling and how to perform genetic testing. We also discuss the timing of genetic testing and clinical relevance of the BRCA mutation status. Results The germline mutation rate in patients with ovarian cancer is high, independent of family history, age at diagnosis and histology. BRCA mutation carriers with ovarian cancer have improved survival rates. In recurrent ovarian cancer treatment by poly ADP ribose polymerase (PARP) inhibitors improves the disease-free survival in patients with BRCA mutations or homologous recombination deficiency with hazard ratios up to 0.23. But also patients with BRCA wild type show a benefit. The recently published SOLO-1 trial demonstrated a significant benefit for patients with germline BRCA mutations in the first line setting. By tumor testing about 7% additional BRCA mutations can be found but the somatic testing and interpretation of the results remains a challenge. Despite the clinical impact, analysis of our own data and also international publications show insufficient referral rates for genetic counseling. Conclusions Genetic testing in ovarian cancer has a prognostic and predictive value. Referral rates must be improved.

Despite optimal treatment, three-quarters of the patients with advanced ovarian cancer, experiment relapse and its treatment has become a public health issue. Initially debated, surgery is gaining legitimacy in the treatment of late relapse patients, compared to chemotherapy alone. Secondary complete cytoreduction should be proposed only to a highly selected population. The type of surgery depends on the recurrence localization and the relapse extension in the pelvis and to other organs. Innovating techniques of surgery have become widespread including heated intra peritoneal chemotherapy (HIPEC), laparoscopy and robotic surgery. These specialized treatments should only be carried out in reference centers by oncological surgeons.

The best prognosis for advanced ovarian cancer is provided by no residual disease after primary cytoreductive surgery. It is thus important to be able to predict resectability that will result in complete cytoreduction, while avoiding unnecessary surgery that may leave residual disease. No single procedure appears to be sufficiently accurate and reliable to predict resectability. The process should include a preoperative workup based on clinical examination, biomarkers, especially tumor markers, and imaging, for which computed tomography, as well as sonography, magnetic resonance imaging and positron-emission tomography, can be used. This workup should provide sufficient information to determine whether complete cytoreduction is possible or if not, to propose neoadjuvant chemotherapy which is preferable in this case. For the remaining patients, laparoscopy is broadly recommended as an ultimate triage step. However, its modalities are still debated, and several scores have been proposed for standardization and improving accuracy. The risk of false negatives requires a final assessment of resectability as the first stage of cytoreductive surgery by laparotomy. Composite models, consisting of several criteria of workup and, sometimes, laparoscopy have been proposed to improve the accuracy of the predictive process. Regardless of the modality, the process appears to be accurate and reliable for predicting residual disease but less so for predicting complete cytoreduction and thus avoiding unnecessary surgery and an inappropriate treatment strategy. Overall, the proposed procedures are heterogeneous, sometimes unvalidated, or do not consider advances in surgery. Future techniques and/or models are still needed to improve the prediction of complete resectability.

Ovarian cancer is the second most common malignant neoplasm of the genital tract. Staging procedures for ovarian cancer include longitudinal laparotomy, hysterectomy, bilateral salpingo-oophorectomy and infragastric omentectomy as well as systematic pelvic and para-aortic lymphadenectomy. In general, the goal of this primary procedure is to achieve the maximum cytoreduction of all abdominal diseases; a residual disease <1 cm defines optimal cytoreduction, however, a maximal effort should be made to remove all gross disease as this offers superior survival outcomes. The role of lymphadenectomy in ovarian cancer has been the focus of gynecological oncologists during recent years. The core issue of the controversy is whether the removal of lymph nodes should be performed only to stage the disease or if the removal itself improves survival. To further comprehend the issue, one must take into account that several studies have shown that systematic lymphadenectomy is associated with a risk of vascular injury, lymph cyst formation, pulmonary embolism and increased post-operative mortality even when performed by surgeons with extensive experience. We present an extensive review of the available literature on the matter, hoping to provide some insight into the true need for such a procedure.

Ovarian cancer has a high mortality rate. The most common serous type spreads rapidly throughout the peritoneal cavity when 5-year survival is 10%. If diagnosed in earlier stages where the cancer is still confined to the ovary, this survival rate is about 90%. This is the reason to be interested in screening at earlier stages in the average-risk general population. Thus, annual transvaginal ultrasound (TVS) alone or as a multimodal screening test following serum carbohydrate antigen 125 (CA125) has been investigated. Ultrasound lacks sensitivity and specificity; new contrast-enhanced approaches might improve these. When the serum marker is combined with ultrasound and interpreted by a rise in the level rather than by a fixed cut-off, improved sensitivity and specificity and a late but not significant reduction in mortality are observed. Further investigations could highlight the interest of a shorter than annual screening, of a long-term follow-up and new contrast-enhanced ultrasound techniques.

Inherited mutations in BRCA1 and BRCA2 genes increase the risk of development of cancer in organs especially in breast and ovary. Prevention and screening in BRCA mutation carriers are of high importance. Prophylactic surgeries are possible but are still insufficiently performed because they require surgical procedures in healthy patients. Guidelines for the management of BRCA mutations carriers must absolutely be part of the standard practice of all those involved in the management of these patients to increase the impact of the implementation of these preventive measures. There is no screening recommended for ovarian cancer. A risk-reducing bilateral salpingo-oophorectomy should be performed from age 35 to 40 years for BRCA1 mutation carriers and 40 to 45 years for BRCA2 mutation carriers. A screening for breast cancer should be performed annually from 30 years old by breast MRI and mammography. A risk-reducing bilateral mastectomy is recommended with nipple sparing mastectomy and immediate breast reconstruction from 30 years and before 40 years. A multidisciplinary care must be implemented for these patients with an important psychological support.

Background The impact of hormones on the development of breast cancer is despite extensive studies, incompletely understood. Combined estrogen-progestogen treatment augments the risk for breast cancer beyond that of estrogen alone, according to numerous studies. The role of breast cell proliferation as a promoter in the development and growth of breast cancer is well recognized. Materials and methods Seventy-nine patients from three randomised trials were subject to a re-analysis of breast cell proliferation: (1) 22 women received continuous combined treatment with oral estradiol (E2) 2 mg/norethisterone acetate (NETA) 1 mg once daily for 3 months. (2) Thirty-seven women received 2 months of sequential treatment with oral conjugated equine estrogens (CEE) 0.625 mg daily combined with medroxyprogesterone acetate (MPA) 5 mg for 14/28 days of each cycle. (3) Twenty women received oral estradiol-valerate (E2V) 2 mg daily combined with levonorgestrel (LNG) intrauterine system (IUS), 20 μg/24 h for 2 months. Fine needle aspiration (FNA) (studies 1 and 3) and core needle biopsy (CNB) (study 2) were used for the assessment of breast cell proliferation. Results There were no baseline proliferation differences, but at the end of treatment there was a highly significant between-group difference for E2V/LNG IUS versus the other two groups (p = 0.0025). E2/NETA and CEE treatments gave a 4–7-old increase in proliferation during treatment (p = 0.04) and (p = 0.007), respectively, which was absent in the E2V/LNG group, showing a significant correlation with insulin-like growth factor binding protein-3 (IGFBP-3) serum levels. Conclusion E2V in combination with very low serum concentrations of LNG in the IUS gives no increase in proliferation in the normal breast.

Background Irisin, a newly discovered hormone, is secreted into the circulation from skeletal muscles in response to physical exercise. The biochemical parameters related to irisin secretion have not been sufficiently investigated yet. The aim of this study was to examine the effectiveness of exercise on the level of irisin and its correlation with biochemical and oxidative stress parameters. Materials and methods In this pre- and post-test observational study, 39 healthy male volunteers from a military training setting were followed up on between September and November 2015. The individuals who were included in this study were between 22 and 27 years old with an average age of 24. Those with inflammatory disorders or chronic diseases such as diabetes mellitus were excluded from the study. The parameters were measured at the baseline, at 4 weeks, and at 8 weeks of intervention. Results The study found that the systolic and diastolic blood pressures substantially decreased after 8 weeks of intervention. The cholesterol-to-HDL ratio and glucose levels were significantly higher at the baseline compared to 8 weeks. Total protein and albumin were significantly higher following 4 weeks (0.25 and 0.21 g/dL) and 8 weeks (0.32 and 0.16 g/dL), respectively. Meanwhile, total globulin and irisin increased following 8 weeks of the intervention by only 0.16 g/dL and 0.41 μg/mL, respectively. The high sensitivity C-reactive protein (hs-CRP) decreased following 8 weeks (−0.81 μg/mL). The protein carbonyl (PC) decreased following 4 weeks by only 0.34 nmol/L. Conclusions This study demonstrated that military training enhanced irisin hormone secretion following 8 weeks of military exercise.

Objectives Chronic periodontitis is one of the most common diseases in the world. Periodontitis occurs more frequently in postmenopausal women due to hormonal changes and in patients with osteoporosis. Thus, the aim of our study was to compare levels of alveolar bone loss of mandible and maxilla and bone tissue remodeling markers in women of reproductive and postmenopausal periods. Methods Fifty-nine women aged 25–68 years were enrolled in a cross-sectional study and divided into two groups. Group I consisted of 42 women of reproductive age and Group II included 17 women in their postmenopausal period. The level of alveolar bone loss of mandible and maxilla was assessed using dental panoramic radiography, and the level of bone remodeling markers (Beta C-terminal telopeptide of type I collagen [ β -CTx] and osteocalcin) was obtained in both groups. Results Women in the postmenopausal period have higher level of alveolar bone loss in mandible and maxilla than women of reproductive age. The level of ß -CTx and osteocalcin was significantly higher in Group II, compared to Group I (p=0.002 and p=0.005, respectively). Conclusions In postmenopausal women, on the background of significantly higher bone remodeling, an increase of alveolar bone loss of mandible and maxilla was observed.

Objectives There is an association between diabetes and liver disorders. Oxidative stress plays a crucial role in the pathology of hepatic abnormalities in diabetes. In this study, the effect of Tropisetron on the oxidative damage and histological alterations in the liver of type 1 diabetes mellitus (DM) were evaluated. Methods Thiry-five male Wistar rats were randomly divided into five experimental groups (n = 7): control (C), tropisetron (T), diabetes (D), diabetes + tropisetron (D + T) and diabetes + glibenclamide (D + G). A single injection of streptozotocin (STZ, 50 mg/kg; i.p) was used to induce diabetes. Tropisetron (3 mg/kg; i.p), as a 5-HT3 receptor antagonist and glibenclamide (1 mg/kg; i.p), as a positive control were given once daily for 2 weeks. Finally, animals were euthanized and liver samples were obtained for histopathological examination and biochemical measurements including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) levels. Results There is a significant increase in MDA (p < 0.001) level and a significant decrease (p < 0.001) in SOD and GPx contents in diabetic animals. Tropisetron attenuated MDA levels (p < 0.001) and enhanced SOD (p < 0.05) and GPx (p < 0.01) activities accompanied by histopathological improvement in the diabetes liver. Similar results were achieved in the rats treated with the standard drug, namely: glibenclamide. Conclusions Our findings indicate that tropisetron mitigates liver damage in the diabetes rats in part by attenuation of oxidative stress.

Background The objective was to compare the effectiveness and tolerability of mefenamic acid and celecoxib in women with primary dysmenorrhea (PD) and to compare the quality of life of study participants pre- and post-treatment. Materials and methods This was a randomized crossover clinical trial conducted among sexually inactive female adults aged 18–25 years with PD. Participants were asked to rate their pain score and answer a validated quality of life questionnaire (EQ-5D-3L) before and after consumption of each medication in two menstrual cycles. The effectiveness of celecoxib and mefenamic acid in treating PD was compared with regard to reduction in pain score and the need for medical leave and rescue therapy. Drug tolerability was determined by comparing the occurrence of side effects of both drugs. Quality of life scores pre- and post-intervention were measured and compared. Results Mefenamic acid had a comparable effect to celecoxib in relieving symptoms of PD. Both drugs were equally tolerable and showed similar impacts on quality of life. Conclusions This study demonstrated that mefenamic acid and celecoxib had similar effectiveness in improving pain score and quality of life in women with PD.

Objectives Despite the low incidence of pancreatic injury in the abdominal blunt trauma (BTA), its early diagnosis is very important; since pancreatic injury is associated with high rates of morbidity and mortality. However, due to the high association of pancreatic injury with injury of other abdominal organs, its diagnosis may be delayed and complicated. The use of imaging modalities is also subject to limitations for reasons such as cost, unavailability, and harmfulness. Consequently, the present study aimed to investigate the predictive role of amylase and lipase enzyme levels in the final diagnosis of pancreatic injury in patients with BTA. Methods In a prospective diagnostic study, 384 patients with BTA referring to Imam Khomeini hospital of Sari (north of Iran) were enrolled according to the inclusion and exclusion criteria. Initial patient data including age and sex were recorded. Blood samples were analyzed in the laboratory to measure complete blood count (CBC), amylase and lipase enzyme levels. Patients were followed up during hospitalization and focal ultrasound for abdominal trauma (FAST), CT-Scan and laparotomy results were recorded. Finally, the data was analyzed using SPSS version 22. Results The level of amylase enzyme was significantly higher in males (p = 0.04), but the level of lipase enzyme was not significantly different between two genders (p > 0.05). The most common symptoms and signs in patients were pain, tenderness, and hematoma, respectively. The frequency of pancreatic injury in all patients with blunt abdominal trauma was 7.5% based of FAST, 7% based on CT-Scan and 12.4% based on laparotomy. Comparison of laboratory findings based on FAST, CT-Scan and laparotomy results showed that the level of amylase and lipase enzymes in patients with internal organ and pancreatic damage were higher than in patients without internal organ injury (p < 0.05). But based on FAST results; patients with pancreatic injury and injury of other organs had no significant difference (p > 0.05). However, comparison of laboratory findings based on CT-Scan and laparotomy results showed a significant increase in the level of amylase and lipase enzymes in patients with pancreatic trauma compared to patients with injury of other organs (p < 0.001). Conclusions The results of this study showed that pancreatic injury in blunt trauma is associated with a significant increase in levels of amylase and lipase enzymes. In addition, an increase in levels of amylase and lipase enzymes is associated with internal organ damage. Serum amylase and lipase levels can be used as useful biomarkers to decide whether to perform CT-Scan or laparotomy.

We report herein the case of a patient with low blood levels of different hormones during a systemic capillary leak syndrome (Clarkson’s disease) attack.