Correlation between plasma ccfDNA, mtDNA changes, CTCs, and epithelial-mesenchymal transition in breast cancer patients undergoing NACT.

Background/aim: Breast cancer is the most prevalent cancer in women, emphasizing need for noninvasive blood biomarkers to aid in treatment selection. Previous studies have demonstrated elevated levels of plasma circulating cell-free DNA (ccfDNA) in breast cancer patients. Both ccfDNA and mitochondrial DNA (mtDNA) are fragments released into the bloodstream. In this study, we investigated effectiveness of ccfDNA and mtDNA as indicators of treatment response and explored their potential as monitoring biomarkers. Additionally, we compared these markers with circulating tumor cell (CTC) data and assessed their relationship with epithelial-mesenchymal transition (EMT). Materials and methods: Thirty-six female breast cancer patients and 21 healthy females were included in the study. Quantitative polymerase chain reaction (qPCR) was performed on plasma samples to measure levels of ND1, ND4, ALU115, ALU247, and GAPDH, and DNA integrity was determined by calculating ratios of ALU247/ALU115 and ND4/ND1. Results: After treatment, patients had a significant decrease in ccfDNA levels and a significant increase in mtDNA copy number (mtDNAcn). However, there was no significant change in ccfDNA and mtDNA integrity. When comparing all groups, patients exhibited higher levels of ALU115 and ALU247 compared to controls. Moreover, patients demonstrated significantly lower ccfDNA integrity than controls. Conclusion: This study represents the first comprehensive investigation of plasma ccfDNA levels, mtDNAcn, and integrities collectively. Furthermore, it is the first study to explore the relationship between these markers and CTCs, cancer stem cell markers, treatment response, and metastatic status. Our findings suggest that plasma ccfDNA and mtDNA may serve as potential biomarkers for assessing chemotherapy response and can be employed alone or in combination with other biomarkers to monitor treatment efficacy in breast cancer patients.

Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Relationship between graft failure following anterior cruciate ligament reconstruction and hamstring autograft diameter.

With the increase in the number of individuals participating in sports, anterior cruciate ligament (ACL) injuries are also increasing gradually and the number of patients requiring surgical treatment is increasing in parallel. The primary aim of this study was to investigate the relationship between the need for revision surgery and graft diameter following primary ACL reconstruction (ACLR) using hamstring autografts. The secondary aim of the study was to clarify relationships between anthropometric characteristics and graft diameter. Patients who underwent ACLR with hamstring autografts were included in this retrospective study. The age, body mass index, height, and weight of all patients were recorded preoperatively and the diameters of the grafts were recorded during surgery. The relationship between revision rate and graft diameter and the relationships between anthropometric measurements and graft diameter were investigated for these patients at least one year after surgery. This study included 58 people with graft diameters of ≤7 mm and 261 people with graft diameters of >7 mm. A statistically significant difference was found between the graft diameters of the group that needed revision surgery and the group that did not (p<0.001). A positive relationship was also found between the patient's height and graft diameter (r=0.168). In this study, it was found that the risk of ACL revision surgery increased by 5.5 times among patients with graft diameters of ≤7 mm. The positive relationship between the patient's height and graft diameter can make a significant difference in terms of the need for revision surgery.

Immediate and Late Repair of Microhybrid Resin Composites: Effect of Silane Coupling Agent, Universal Adhesives and Photo Polymerization.

This study investigated the effect of silane coupling agent and universal adhesive application on repair bond strength of resin-based composite after bur grinding. Microhybrid resin composite (Charisma Smart) blocks (N=80; 8x8x4 mm3) were prepared, aged (37°C; 1 month), roughened, etched and randomly divided into two groups. Silane was applied to half of the groups (Porcelain Primer, Bisco), before one of the following universal primers/adhesives was applied: a) Scotchbond Universal (3M), b) All-Bond Universal (Bisco), c) G-Premio Bond (GC), and d) Clearfil SE Bond (Kuraray). In each adhesive group half of the group was photo-polymerized. The blocks were repaired with the same size resin composite and segmented into beams. Half of the beams were subjected to micro-tensile bond test (1 mm/min), while the other half was aged (37°C; 6 months) prior to testing. Failure modes were analyzed using Scanning Electron Microscopy (SEM). Data were analyzed using repeated measures of ANOVA, Tukey's post-hoc, and paired t-tests (alpha=0.05). The silane application did not affect the repair bond strength regardless of photo-polymerization of the adhesive resin. The repair bond strength decreased significantly after 6 months when adhesive resin was not photopolymerized (p⟨0.05). Photo-polymerizing universal adhesives might ensure higher repair bond strength and its maintenance after aging.

Assessment and management of B3 breast lesions with atypia: a focused review.

Breast lesions with atypia are a spectra of diseases that confer increased risk of breast cancer because of an increased probability of finding concomitant cancer after excision, or evolution toward in situ or invasive cancer over the long term. The widespread use of radiologic tools and core needle breast biopsies, in recent years, has led to an increase in the diagnosis of these atypical breast lesions. Concurrent with this has been an improvement in the classification and pathogenesis of these lesions. Current evidence suggests that the recognition and treatment of patients with atypical histology after biopsy and surgical excision requires a multidisciplinary approach to decrease the overdiagnosis and overtreatment risks. This focused review investigates the controversy and current management of atypical ductal hyperplasia, lobular neoplasia, flat epithelial atypia, and intraductal papilloma with atypia along with the risk-reducing strategies.

How do the surface coating and one-year water aging affect the properties of fluoride-releasing restorative materials?

OBJECTIVE: To evaluate the effects of surface coating and 1-year water aging on flexural strength, compressive strength (CS) and surface roughness of fluoride-releasing restorative materials. MATERIALS AND METHODS: The specimens were prepared from seven materials: GCP Glass Fill (GCP), Amalgomer CR (AHL), Zirconomer (Shofu), Fuji IX GP Capsule (GC), Beautifil II (Shofu), Estelite Σ Quick (Tokuyama), and reliaFIL LC (AHL). The specimens were randomly divided into two groups for each test: surface coated with G-Coat Plus (GC) and uncoated. Each group was subdivided into two groups stored in distilled water at 37°C for 24 h and 1 year before testing (n = 10). The flexural and CS were evaluated according to ISO standards on a universal testing machine. The surface roughness was assessed with AFM. After flexural strength test, a cross-section of the coated specimens was evaluated with SEM. Data were analyzed with one-way analysis of variance, Duncan and independent t-tests (P = 0.05). RESULTS: After 24 h, a significant increase was observed on the flexural and CS of Amalgomer CR, Zirconomer, and Fuji IX GP by coating (P < 0.05). After 1 year, the coating increased the flexural strength of Amalgomer CR and Zirconomer, and CS of GCP Glass Fill (P < 0.05). The coating decreased the surface roughness of GCP Glass Fill, Amalgomer CR, and Zirconomer after 1 year (P < 0.05). The water aging decreased the mechanical properties of glass ionomer-based materials and increased their surface roughness (P < 0.05). CONCLUSION: The mechanical properties and surface roughness of glass ionomer-based materials were affected by coating and water aging.

Orthognathic surgery with two-segment le fort i and sagittal split ramus osteotomies of open bite deformity in an amelogenesis imperfecta patient via virtual planning: A case report.

Amelogenesis imperfecta (AI) is an enamel defect and is often associated with the anterior open bite (AOB) and transverse maxillary deficiency. It is known that in such cases when AI and AOB appeared together, posterior maxillary impaction with or without bilateral mandibular ramus osteotomies is a frequently preferred treatment option. Virtual planning is more reliable rather than the conventional model surgery planning, especially for complicated cases. Usage area of virtual 3D anatomical models reconstructed from Cone Beam Computed Tomography (CBCT) data is expanding day by day for both diagnosis and surgical planning. The aim of this study is to present a patient with AI and AOB and transverse maxillary deficiency and management of this case with virtually planned two-segment Le fort I and sagittal split ramus osteotomies followed by prosthetic rehabilitation.

Selection of essential medicines for the prevention and treatment of cardiovascular diseases in low and middle income countries.

BACKGROUND: The incidence and mortality of cardiovascular diseases (CVDs) in low and middle income countries (LMICs) have been increasing, while access to CVDs medicines is suboptimal. We assessed selection of essential medicines for the prevention and treatment of CVDs on national essential medicines lists (NEMLs) of LMICs and potential determinants for selection. METHODS: Only operational NEMLs were considered eligible for this study. A selection of medicines listed under "cardiovascular medicines" or "blood products and plasma substitutes" in the NEMLs were included if they were present on international guidelines for the prevention and treatment of CVDs (hyperlipidemia, hypertension, platelet inhibition, ischemic stroke, stable ischemic heart disease, acute coronary syndromes, heart failure, atrial fibrillation, peripheral arterial disease and acute limb ischemia). The number and diversity of essential medicines selected for CVDs were studied. Moreover, determinants of selection of essential medicines for CVDs at a national level were explored. Data analysis was done using univariate linear regression and non-parametric tests. RESULTS: All medicine groups listed by the international guidelines were selected by the majority of the 34 countries studied with the exception of adenosine diphosphate receptor inhibitors which appeared on less than half of the NEMLs studied (41% of countries). The total number of essential medicines for the prevention and treatment of cardiovascular diseases (median 24 (range 16-50)) differed significantly across income levels (median range: 19.5-25, p = 0.014) and across regions (median range: 20-32, p = 0.049). When recommendations of the international guidelines were considered, over 75% of the NEMLs contained essential medicines for the majority of CVDs. CONCLUSION: The main medicine classes for the management of CVDs were represented on NEMLs. Consequently, for the majority of CVDs, evidence-based guideline-recommended treatment is possible as far as selection of essential medicines is concerned. Selection will therefore not be the limiting step in access to medicines for cardiovascular diseases.

The impact of vitamin E supplementation on semen parameters and pregnancy rates after varicocelectomy: a randomised controlled study.

In this study, we aimed to investigate the impact of vitamin E supplementation on semen parameters and pregnancy after varicocelectomy. Forty-five infertile male patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 22 receiving vitamin E for 12 months, and 23 as the control group without receiving any supplementation. The pre-operative parameters of semen analyses and pregnancy rates of both groups were compared with those of post-operative parameters. There were no statistically significant differences between the groups in terms of sperm count and motile sperm percentage, in pre-operative, post-operative 3rd month, post-operative 6th month and post-operative 12th month periods. Repeated-measures anova was performed, and sperm count, percentage of change in sperm count, motile sperm count and percentage of change in motile sperm count of the groups were compared. The administration of vitamin E increased all of these parameters; however, they were not found to be statistically significant. In conclusion, vitamin E supplementation might improve the sperm parameters after varicocelectomy; however, further studies including larger number of samples are needed to make a proper decision on vitamin E supplementation after varicocelectomy.

Radiofrequency ablation of benign symptomatic thyroid nodules: prospective safety and efficacy study.

BACKGROUND: Radiofrequency ablation (RFA) is a relatively novel procedure in the management of benign nodular goiter. This study was conducted to evaluate the safety and efficacy of ultrasound (US)-guided percutaneous RFA for benign symptomatic thyroid nodules as an alternative to surgery. METHODS: The study involved patients for whom a fine needle aspiration biopsy had proved a diagnosis of benign nodular goiter and had nodule-related symptoms such as dysphagia, cosmetic problems, sensation of foreign body in the neck, hyperthyroidism due to autonomous nodules or fear of malignancy. Percutaneous RFA was performed as an outpatient procedure under local anesthesia. The primary outcome was an evaluation of the changes in symptom scores (0-10) for pain, dysphagia and foreign body sensation at the 1st, 3rd, and 6th months after the RFA procedure. Secondary outcomes were assessing volume changes in nodules, complication rates, and changes in thyroid function status. RESULTS: A total of 33 patients (24% female, 76% male) and a total of 65 nodules were included into the study. More than one nodule was treated in 63.6% of the patients. We found a statistically significant improvement from baseline to values at the 1st, 3rd, and 6th months, respectively, as follows: pain scores (2.9 ± 2.7, 2.3 ± 2.01, 1.8 ± 1.7, and 1.5 ± 1.2, p 0.005), dysphagia scores (3.9 ± 2.7, 2.6 ± 1.9; 1.7 ± 1.6, and 1.1 ± 0.3, p 0.032), and foreign body sensation scores 3.6 ± 3, 2.5 ± 2.2; 1.6 ± 1.5, and 1.1 ± 0.4, p 0.002).The mean pre-treatment nodule volume was 7.3 ± 8.3 mL. There was a statistically significant size reduction in the nodules at the 1st, 3rd, and 6th months after RFA (3.5 ± 3.8, 2.7 ± 3.4, and 1.2 ± 1.7 mL, p 0.002). The volume reduction was found to be 74% at 6th months following the RFA (p 0.005). 8 patients had autonomously functioning nodules in the pre-treatment period, 50% (n: 4) became euthyroid at the 6th month after RFA. There were no complaints other than pain (12%). CONCLUSION: RFA can be an alternative treatment modality in the management of benign symptomatic thyroid nodules. The results showed that it is a safe and effective procedure.

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.

Should we consider topical silver nitrate irrigation as a definitive nonsurgical treatment for perianal fistula?

BACKGROUND: Surgery is currently the sole treatment modality for anal fistulas. However, surgery is associated with complications such as permanent incontinence, which reduces quality of life. OBJECTIVE: To determine the rate of complete clinical healing of anal fistulas after irrigation of the fistula tract with silver nitrate solution as a nonsurgical treatment. DESIGN: Prospective single arm study. SETTING: Tertiary university hospital PATIENTS: : Adult patients with symptomatic perianal fistula presenting between June 2012 and January 2013. INTERVENTION: Irrigation of the fistula tract with 1% silver nitrate solution. Irrigation was repeated every 2 weeks when necessary. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of complete clinical healing. RESULTS: Fifty-six consecutive patients with anal fistula were analyzed. Of those, 29 (52%) had complete clinical healing without recurrence for a median of 10 months. The median number of irrigations needed for complete clinical healing was 4 (1-10). The level of satisfaction was excellent in patients with complete clinical healing. The frequency of complaints was the only independent factor that had an impact on healing; patients with intermittent discharge had a significantly higher rate of complete clinical healing (67%) than those with continuous discharge (40%). There were no notable complications. LIMITATIONS: Short follow-up, small sample size, and no comparisons. CONCLUSION: This study demonstrates that the application of silver nitrate solution often produces a favorable outcome in the treatment of anal fistula. This method may be considered as a first-line treatment for the disease because it is simple, performed on an outpatient basis, minimally invasive, and lacks the complications encountered with current conventional surgical modalities.

The role of bilirubin and its protective function against coronary heart disease.

BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality both in industrialized and developing countries. Atherosclerosis is a chronic inflammatory disease of the arterial wall, which also involves deposition and peroxidation of lipids. Bilirubin, an important endogenous antioxidant, may limit lipid peroxidation and retard the progression of atherosclerosis. Previous studies have reported an inverse relationship between serum bilirubin levels and the risk of coronary artery disease (CAD). Taking into account that atherosclerosis is a complex process that is initiated and accelerated by diverse risk factors, we aimed to test the antiatherosclerotic effects of bilirubin in a population with multiple risk factors for CAD. METHODS: The study included 221 patients who underwent coronary angiography owing to symptoms suggestive of ischemia and/or positive noninvasive stress test results. Of the patients, 76 had normal coronary angiograms and served as the control group. The remaining 145 patients with documented CAD and two or more cardiovascular risk factors constituted the study group. The study group (n=145) was further classified according to the Gensini score as follows: group 1 if Gensini score was 1-19 (minimal CAD, n=82), and group 2 if Gensini score was 20 or higher (significant CAD, n=63). Biochemical assessments including total and direct serum bilirubin levels were carried out using standard methods in automated systems. RESULTS: All of the cardiovascular risk factors were found significantly more frequently in the study group (groups 1 and 2) than in the control group. Total and direct serum bilirubin levels did not differ significantly between the control group, group 1, and group 2. There was a moderate and significant positive correlation between direct bilirubin levels and the Gensini score (r = 0.158, p = 0.019). There was no significant correlation between total bilirubin levels and the Gensini score. CONCLUSION: In conclusion, our findings suggest that in the presence of multiple risk factors, similar concentrations of serum bilirubin may not confer the same level of protection against CAD as in an individual with a more favorable risk profile. The relationship between direct bilirubin levels and the Gensini score is unlikely to be causative, given the established antiatherosclerotic effects of bilirubin.

Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: a randomized controlled trial.

OBJECTIVE: To assess the impact of prophylactic antibiotics on the prevention of surgical site infection (SSI) and the cost-effectiveness of this prophylaxis for breast cancer surgery in overweight or obese women. BACKGROUND DATA: SSI is higher than expected after breast surgery. Obesity was found to be one of the risk factors. METHODS: The trial was designed as a phase IV randomized, controlled, parallel-group efficacy trial. It was conducted at a tertiary university hospital. Overweight or obese women with clinically early-stage breast cancer who had been assigned to undergo surgery were eligible. Patients were randomly allocated to either a prophylaxis or a control group by using a computer-generated list. The prophylaxis group received 1 g ampicillin-sulbactam intravenously at anesthesia. The control group received no intervention. Patients and observers were blinded to the assignments. The primary outcome was the comparison of SSI incidences of the 2 groups. Patients were monitored for 30 days. RESULTS: A total of 369 patients were included in final analysis, out of which 187 were allocated for prophylaxis and 182 were randomly assigned to the control group. Analysis was done according to the intention-to-treat principle. Prophylaxis significantly reduced the SSI rate (4.8%) in the prophylaxis group when compared with that in the control group [13.7%; relative risk (RR) 0.35; 95% CI: 0.17-0.73]. No adverse reaction was observed. The mean SSI-related cost (20.26 USD) was found to be significantly higher in the control group when compared with that (8.48 USD) in the prophylaxis group. CONCLUSION: Antibiotic prophylaxis significantly decreased SSI incidence after elective surgery and was shown to be cost-effective in obese breast cancer patients. ClinicalTrials.gov Identifier: NCT00356148.

Transumbilical multiple-port laparoscopic cholecystectomy using standard laparoscopic instruments.

INTRODUCTION: As a complement to standard laparoscopy, single incision laparoscopic cholecystectomy (SILS) is gaining popularity. We report our technique and our initial experience with transumbilical multi-port laparoscopic cholecystectomy (TUMP-LC) without an access device, with standard laparoscopic instruments, and report the clinical outcomes. MATERIAL AND METHODS: Twenty-five (23 F: 2 M) consecutive patients with symptomatic cholelithiasis were included. The surgical outcomes such as length of stay, complications and perioperative morbidity were analyzed. For evaluation of surgical stress preoperative and postoperative C-reactive protein (CRP) values at 6 h and 24 h were measured. Postoperative pain was evaluated using a standard 10-point visual analogue scale (VAS). RESULTS: The mean duration of the surgery was 44.56 minutes (range, 18-110). Additional trocars were needed in two (8%) cases. Mean pain scores post-operatively at 4 h, 12 h and 24 h were 4 ± 1.19, 3.64 ± 1.03 and 2.24 ± 0.96, respectively (p < 0.0001). Plasma CRP values increased at 6 h and started to decrease at 24 h (p < 0.0001). None of the cases were converted to open surgery and no major complications occurred. DISCUSSION: TUMP-LC using standard laparoscopic instrumentation without an access device is an effective alternative to standard four-incision laparoscopic cholecystectomy. Our technique maintains the principles of the conventional procedure and the instrumentation, but also improves the access.

Association of biochemical and clinical parameters with parathyroid adenoma weight. Turkish-Bulgarian endocrine and breast surgery study group, hyperparathyroidism registry study.

BACKGROUND: Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in different geographical regions reveals differences in the laboratory results and pathological findings, but studies on this subject are not sufficient. The article focuses on biochemical and pathological effects of geographical differences in parathyroid adenoma. In addition, the present study seeks to elaborate on treatment methods and effectiveness of screening in geographical area of Bulgaria and Turkey. METHOD: In this prospective study, 159 patients were included from 16 centres. Demographic characteristics, symptoms, biochemical markers and pathologic characteristics were analysed and compared between 8 different regions. RESULTS: Patients from Turkish Black Sea had the highest median serum calcium (Ca) level, whereas patients from Eastern Turkey had the lowest median serum phosphorus (P) level. On the other hand, there was no significant difference between Ca, parathormone (PTH) and P levels according to regions. Patients from Eastern Turkey had the highest adenoma weight, while patients from Bulgaria had the lowest adenoma weight. The weight of adenoma showed statistically significant differences between regions (p < 0.001). There was a correlation between adenoma weight and serum PTH level (p = 0.05) and Ca level (p = 0.035). CONCLUSION: This study has provided a deeper insight into the effect of the regional differences upon clinicopathological changing and biochemical values of pHTP patients with adenoma. Awareness of regional differences will assist in biochemical screening and treatment of this patient group.

Results of early surgical treatment of intra-articular complex fractures of the humerus in adults.

AIM: We present our results for intra-articular fractures of the elbow which we have treated with early restoration of joint combined with the earliest possible motion. MATERIALS AND METHODS: Our study group consists of 27 patients and all operations were done in Ankara Atatürk Research and Training Hospital 3rd Orthopaedic Clinic between February 2004 and December 2008. According to AO classification, all of the cases were of type C. Mean age of patients was 24.8 years (17-32), mean follow-up period was 30 (22-38) months. All patients underwent early open reducation, stable osteosynthesis and early rehabilitation. RESULTS: Clinical results were evaluated according to the Mayo Elbow Performance Scores which were excellent in 20 patients (74%), good in 4 (14.8%), fair in 2 (7.4%), and bad in 1 patient (3.7%). Postoperative complications including infection found in 2 patients (7.4%), minor joint deformity (varus, valgus) in 8 (29.6%), loss of power (about 1.5 kg) in 14 (51.8%), and medium level heterotypic ossification in 2 patients (7.4%). CONCLUSION: We believe that early (first 48 hours) surgical osteosynthesis with rigid fixation of intra-articular humerus fractures combined with postoperative early rehabilitation gives excellent results (Fig. 6, Tab. 3, Ref. 18).

Therapeutic Targeting of Cancer Stem Cells in Lung, Head and Neck, and Bladder Cancers.

Resistance to cancer therapy remains a significant obstacle in treating patients with various solid malignancies. Exposure to current chemotherapeutics and targeted agents invariably leads to therapy resistance, heralding the need for novel agents. Cancer stem cells (CSCs)-a subpopulation of tumor cells with capacities for self-renewal and multi-lineage differentiation-represent a pool of therapeutically resistant cells. CSCs often share physical and molecular characteristics with the stem cell population of the human body. It remains challenging to selectively target CSCs in therapeutically resistant tumors. The generation of CSCs and induction of therapeutic resistance can be attributed to several deregulated critical growth regulatory signaling pathways such as WNT/ß-catenin, Notch, Hippo, and Hedgehog. Beyond growth regulatory pathways, CSCs also change the tumor microenvironment and resist endogenous immune attack. Thus, CSCs can interfere with each stage of carcinogenesis from malignant transformation to the onset of metastasis to tumor recurrence. A thorough review of novel targeted agents to act against CSCs is fundamental for advancing cancer treatment in the setting of both intrinsic and acquired resistance.

Inhibition of the ʟ-glutamine transporter ASCT2 sensitizes plasma cell myeloma cells to proteasome inhibitors.

Proteasome inhibitors (PIs), used in the treatment of plasma cell myeloma (PCM), interfere with the degradation of misfolded proteins leading to activation of unfolded protein response (UPR) and cell death. However, despite initial strong antimyeloma effects, PCM cells eventually develop acquired resistance to PIs. The pleiotropic role of ʟ-glutamine (Gln) in cellular functions makes inhibition of Gln metabolism a potentially good candidate for combination therapy. Here, we show that PCM cells, both sensitive and resistant to PIs, express membrane Gln transporter (ASCT2), require extracellular Gln for survival, and are sensitive to ASCT2 inhibitors (ASCT2i). ASCT2i synergistically potentiate the cytotoxic activity of PIs by inducing apoptosis and modulating autophagy. Combination of ASCT2 inhibitor V9302 and proteasome inhibitor carfilzomib upregulates the intracellular levels of ROS and oxidative stress markers and triggers catastrophic UPR as shown by upregulated spliced Xbp1 mRNA, ATF3 and CHOP levels. Moreover, analysis of RNA sequencing revealed that the PI in combination with ASCT2i reduced the levels of Gln metabolism regulators such as MYC and NRAS. Analysis of PCM patients' data revealed that upregulated ASCT2 and other Gln metabolism regulators are associated with advanced disease stage and with PIs resistance. Altogether, we identified a potent therapeutic approach that may prevent acquired resistance to PIs and may contribute to the improvement of treatment of patients suffering from PCM.

Sleeve gastrectomy-induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: role of the estrogen receptors.

BACKGROUND: Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before. OBJECTIVE: The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. SETTING: Physiology Research Lab at the University. METHODS: Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 ß, ER-α agonist, ER-ß agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples. RESULTS: In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss. CONCLUSIONS: SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications.