Cardiac safety of ribociclib evaluated with 24-hour rhythm Holter electrocardiogram.

OBJECTIVE: We aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG. MATERIAL AND METHOD: Forty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation. RESULTS: The mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference. CONCLUSION: This is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.

An Alternative and Up-To-Date Recommendation for a Proper Site for Parathyroid Transplantation: The Omentum.

OBJECTIVES: Various sites have been used for parathyroid allotransplant, such as injection into the forearm, sternocleidomastoid, or deltoid muscles. However, transplant efficiency in these regions varies according to the results reported in the literature and also obtained from our previous studies. Using the omentum "as a natural incubator" for composite tissue-derived cell transplants to increase transplant success is possible. MATERIALS AND METHODS: To examine the efficiency of transplant sites for parathyroid allotransplant, we compared clinical cases from the literature and our experience with 23 cases. The omental transplant process is performed under general anesthesia by laparoscopic intervention. The abdominal cavity is visualized with an endocamera from a 5-mm trocar. With the help of a flexible catheter from another 5-mm trocar, microencapsulated or naked parathyroid cells are deposited on the omentum in approximately 30 mL of isotonic saline. The trocar sites are then sutured, and the surgery is terminated. Recipients were followed for 6 months with examination of biochemical parameters (parathormone, calcium, and phosphorus levels), medication use, and clinical scoring. RESULTS: In the 23 patients who received parathyroid allotransplants over the omentum, 7 recipients did not exhibit any changes according to the scoring system criteria. However, on average, serum calcium and phosphorus levels remained within the healthy reference range. In addition, use of oral medications among patients decreased, indicating successful transplant survival. These results were consistent with a significant decrease in hypocalcemia symptoms among patients. CONCLUSIONS: In the 23 patients, the success rate was 69.5% for the first 6-month period after transplant. Recent developments and large cohorts are needed to demonstrate the higher efficacy of parathyroid allotransplant over the omentum.

Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas.

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.

Xenotransplantation of Microencapsulated Parathyroid Cells as a Potential Treatment for Autoimmune-Related Hypoparathyroidism.

OBJECTIVES: Hypoparathyroidism occurs as a part of a complex autoimmune syndrome or iatrogenically after neck surgery. The disease presents many challenges, such as hypocalcemia, hyperphosphatemia, and low/undetectable parathormone levels. Allotrans - plantation of parathyroid tissue or cells has been reported as a promising option to overcome these effects. Transplantation of microencapsulated parathy - roid tissue or cells offers an immune escape, which particularly restores the parathyroid function for autoimmune-related hypoparathyroidism. So far, clinical and in vivo studies have demonstrated limited graft survival and instability for the available biocompatible materials. In addition, the transplant site, proper local isolation, and biocompatibility of materials are directly related to survival rate. MATERIALS AND METHODS: A microencapsulated parathy - roid xenotransplant model by using high guluronic acid-containing ultrapure alginate transplanted into rat omentum was tested in vivo for 1 year. RESULTS: After stability of empty microcapsules was ensured, parathyroid cells were microencapsulated and transplanted in rats, with results compared versus rats with naked (nonencapsulated) parathyroid cells (both groups followed for 64 weeks). Rats remained normocalcemic, and preinflammatory cytokine levels showed dramatic changes. Despite a delay posttransplant, parathormone levels increased significantly. All retrieved microencapsules elicited pericapsular fibrotic overgrowth; however, the fibrosis area was shown to be well tolerated. CONCLUSIONS: The possible role of accumulation/cell infiltration of immune response remains to be elucidated. In conjunction with this, the use of nonencapsulated parathyroid cells was also positively correlated with survival rates. A similar evaluation using ultrapure alginate materials and omental transplantation may enable the future determination for the long-term effects of correction of parathor - mone insufficiency in patients with severe hypocalcemic responses and other endocrine diseases.

Graft survival effect of HLA-A allele matching parathyroid allotransplantation.

Permanent hypoparathyroidism is an endocrine disease that is mostly associated with the disruption of the parathyroid glands during surgery. Allotransplantation is the most promising approach for treatment particularly for its cost-effective and exact curative potential. Herein our aim was to evaluate human leukocyte antigen (HLA)-A allele matching effect on clinical improvement and graft survival after parathyroid transplantation. We performed parathyroid transplantation between ABO/Rh compatible recipient and an unrelated donor who has chronic kidney disease. Preoperative immunological tests include panel reactive antibody, T-flow cytometry crossmatch, B-flow cytometry crossmatch, autoflow cytometry crossmatch, and complement-dependent cytotoxicity crossmatch tests were performed. After histopathological evaluation, half of the resected parathyroid gland cells were isolated and transplanted to the omentum surface by laparoscopy. The transplantation outcome was followed up throughout 382 days. The recipient discharged 2 days after transplantation without any complication. During follow-up, calcium and vitamin D supplementation reduced to a one-third dose; even the intact PTH levels remained low. However, clinical improvement was observed by serum calcium levels. The recipient still continues with low-dose supplementation after 382 days of post-transplantation. Parathyroid cell transplantation to the omental tissue is the most promising option even with only one allele matching for patients with using lifelong high-dose supplementation. Clinical improvements and long-term effect of HLA-A allele matching should be evaluated with more studies and in larger cohorts as well.

Analysis of the DOK1 gene in breast cancer.

Breast cancer, which is the most common type of cancer among women, is a heterogenous disease. It results from progressive accumulation of genetic and epigenetic alterations in different genes. The Dok1 protein has been identified as the major substrate of protein tyrosine kinases in hematopoietic cells. It is considered as a tumor suppressor due to the reports which describe its inhibitory effect on major oncogenic signaling pathways such as Mek/Erk/PI3k/Akt and Wnt/ß-catenin. In this study, we investigated the mutation frequency of the DOK1 gene in 118 breast tumors using Sanger sequencing and DOK1 mRNA expression level in 63 breast cancer samples using qRT-PCR methods. Although the mutation frequency was low DOK1 mRNA expression levels were significantly reduced (63.5%) in the tumors compared to adjacent non-cancerous tissue. We also correlated expression changes with clinicopathological characteristics. Low mRNA levels correlated with age (p = 0.01) and c-erbB-2 (p = 0.05). In most of the previous reports, down-regulation of DOK1 mRNA expression has been associated with promoter methylation. We identified four different coding sequence alterations in 5.1% (6/118) of the tumor samples. However, all of these alterations were located in the functional domains of the protein. Therefore, these mutations may affect the function and/or cellular localization of the protein and contribute to cancer progression by this way. In conclusion our data indicate that DOK1 acts as a tumor suppressor in breast cancer and association of Dok1 with the c-erbB-2 mediated mechanism of action in breast cancer needs to be investigated.

The role of miRNAs as a predictor of multicentricity in breast cancer.

Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at - 80 °C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.

Evaluation of local hemostatic effect of microporous polysaccharide hemospheres products in thyroid surgery: a prospective randomized controlled study.

OBJECTIVES: Bleeding is a rare and dangerous complication of thyroid surgery. One of the hemostatic agents used during surgery are microporous polysaccharide hemospheres (MPH) which are local hemostatic agents acquired from purified potato starch. The aim of this study was to evaluate the efficiency of two MPH, produced with different biotechniques, in decreasing hemorrhages and drainage following thyroidectomy. MATERIAL AND METHODS: A statistical power analysis predicted that totally 20 patients per each group was needed within 95% confidential interval. Patients were randomized into 3 groups as control, Haemocer TM and Arista TM to be 20 patients in each group. Following bilateral total thyroidectomy, no additional procedures were performed in the first group, 5 g Haemocer was administered to the second group, 5 g Arista was administered to the third group into the operational field, and the operation was ended by placing a double-sided hemovac drain. At post-operative day one, drainage amount, calcium (Ca), phosphate (P) and parathyroid hormone (PTH) levels were noted. RESULTS: No significant difference was noted between the groups for age, gender, removed tissue weight and malignant pathology rates. Also, no significant difference was noted between post-operative drainages and Ca, P, PTH levels of groups either. Hoarseness or hematoma were not observed in any patient. CONCLUSION: MPHs are not proven in effectiveness in decreasing post-operative hemorrhages, which might be a key to avoiding unnecessary expenses.

Intraoperative palpation of sentinel lymph nodes can accurately predict axilla in early breast cancer.

Recent randomized trials have shown that completion axillary lymph node dissection (ALND) is not required in all patients with a positive sentinel lymph node (SLN) who will receive radiation therapy. Although routine intraoperative pathologic assessment (IPA) becomes unnecessary and less indicated by breast surgeons in the United States and some European countries, it is still widely used all around the world. In this prospective study, the feasibility of intraoperative nodal palpation (INP) as opposed to IPA of the SLN has been analyzed. Between March 2014 and June 2015, 305 patients with clinical T1-2/N0 breast cancer from two different breast clinics (cohort A; [n = 225] and cohort B; [n = 80]) who underwent any breast surgery with sentinel lymph node biopsy (SLNB) were included in this study. Surgeons evaluated the SLNs by manual palpation before sending for IPA, and findings compared with the final pathology. The positive predictive values (PPV) of INP and IPA were 81.8% and 97.9%, respectively, whereas the negative predictive values (NPV) of INP and IPA were 83% and 92.4%. The accuracies of INP and IPA were 82.6% and 94.1%, respectively. If patients with SLNB including micrometastasis were also considered in the final pathologic assessment (FPA) (-) group that would not require a further axillary dissection, the revised NPV of INP and FPA were found to be 92.6% and 98.1%, respectively. The revised accuracy of INP also found to be increase to 86.9%. Our study, which is the only prospective one about palpation of dissected SLNs in the literature, suggests that INP can help to identify patients who do not need ALND, which encourages omitting IPA in cT1-2 N0 breast cancer.

Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation.

Breast cancer is the most common malignant tumor in women worldwide. Breast tumors mostly exhibit aberrant gene expression and DNA hypermethylation patterns that predispose the disease. Understanding the genetic and epigenetic factors that contribute to breast cancer development is important to identify novel diagnostic and prognostic markers. SCARA5: Scavenger receptor class A, member 5; is a member of the scavenger receptor family located on chromosome 8p21 which is a frequently deleted region in human cancers. SCARA5 has been identified as a candidate tumor suppressor gene in various kinds of cancer. However, its role in breast cancer remains unclear. Therefore, in the present study SCARA5 expression levels in breast tumors and matched noncancerous tissue samples from 77 patients were analyzed by qRT-PCR and the expression levels were correlated with the methylation level of SCARA5 gene promoter. We found that SCARA5 expression was significantly decreased in tumors (92.2%) compared to non-cancerous tissue samples and this down-regulation was associated with hypermethylation of the promoter (p < 0.001). A significant correlation was also detected between SCARA5 expression and the histological grade of the breast tumors (p = 0.017). Taken together, our results indicate that SCARA5 may play an important role in tumorigenesis of breast cancer via promoter methylation.

Review of Novel Sentinel Lymph Node Biopsy Techniques in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

Breast cancer patients who present with nodal metastasis receive neoadjuvant chemotherapy (NAC) with increasing frequency and can have complete pathologic response after treatment. In this clinical scenario, sentinel node mapping and biopsy are gaining acceptance instead of axillary dissection to avoid morbidity. Biopsy proven positive lymph nodes must be reliably excised and examined after NAC to further decrease the false negativity rate of sentinel lymph node (SLN) surgery. The standard method for axillary staging in breast cancer patients even after NAC is SLN biopsy (SLNB) with a radioisotope, blue dye, or both (dual technique). Currently, preoperative axillary staging with ultrasound and biopsy, along with placement of an image-detectable marker to be removed at the time of definitive surgery is recommended. In this study, we evaluated some methods of SLNB for patients treated with NAC like indocyanine green fluorescence, superparamagnetic iron oxide nanoparticles, indigocarmine blue dye, contrast-enhanced ultrasound using microbubbles, and tattooing. Some methods are also needed to ensure that the initially biopsy proven positive node is removed at the time of surgery to be carefully evaluated for residual disease after chemotherapy like clip placement to the suspected or involved nodes before NAC, and removing the clipped node with the guidance of 125I-labeled radioactive seed or guide wires.

The role of PET and MRI in evaluating the feasibility of skin-sparing mastectomy following neoadjuvant therapy.

Objective To investigate the role of positron emission tomography (PET) and magnetic resonance imaging (MRI) in evaluating the feasibility of skin-sparing mastectomy in patients with locally-advanced breast cancer (LABC) who will undergo neoadjuvant chemotherapy (NAC) by evaluating the sensitivity and specificity of PET and MRI compared with skin biopsy results before and after NAC treatment. Methods Patients with LABC who were treated with NAC between November 2013 and November 2015 were included in this study. Demographic, clinical, radiological and histopathological features of the patients were recorded. Results A total of 30 patients were included in the study with a mean age of 52.6 years (range, 35-70 years). Sensitivity and specificity for detecting skin involvement in LABC was 100%/10% (62%/85%) with MRI and 60%/80% (12%/92%) with PET before (after) NAC, respectively. When radiological skin involvement was assessed in relation to the final histopathological results, the preNAC PET results and histopathological skin involvement were not significantly different; and there was no difference between postNAC MRI and histopathological skin involvement. Conclusions As preNAC PET and postNAC MRI more accurately determined skin involvement, it might be possible to use these two radiological evaluation methods together to assess patient suitability for skin-sparing mastectomy in selected patients.

Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in the characterization of papillary breast lesions.

Papillary lesions have a broad spectrum of appearances on magnetic resonance imaging (MRI). The purpose of this study was to evaluate whether apparent diffusion coefficient (ADC) values of papillary lesions can be used to characterize lesion as benign or malignant. This retrospective study included 29 papillary lesions. Diagnostic values of dynamic contrast-enhanced MRI (DCE-MRI), DWI-ADC, and DCE-MRI plus DWI-ADC were separately calculated. The malignant papillary lesions (0.744×10-3  mm2 /s) exhibited significantly lower mean ADC values than the benign lesions (1.339×10-3  mm2 /s). Addition of DWI to standard DCE-MRI provided 100% sensitivity. We hypothesized that this combination may prevent unnecessary excisional biopsies.

The correlation between breast cancer and urinary iodine excretion levels.

Objective To compare urinary iodine excretion levels in patients with breast cancer and control subjects. Methods In this prospective pilot study, patients with breast cancer and normal controls were recruited. Age and menopausal status were recorded. Levels of serum thyroid-stimulating hormone, blood urea nitrogen and creatinine and urine iodine concentration (UIC) were measured. UIC levels were divided into three categories: low (<100 µg/l), normal (100-200 µg/l) or high (>200 µg/l). Results A total of 24 patients with breast cancer and 48 controls were included in the study. There were no statistically significant differences between the two groups with regard to thyroid-stimulating hormone, blood urea nitrogen or creatinine levels. When considered overall, there was no statistical difference in UIC between patients and controls. However, comparisons within each category (low, normal or high UIC) showed a significantly higher percentage of patients with breast cancer had a high UIC compared with controls. Conclusions A high UIC was seen in a significantly higher percentage of patients with breast cancer than controls. UIC may have a role as a marker for breast cancer screening. Further studies evaluating UIC and iodine utilization in patients with breast cancer are warranted.

p53 expression and relationship with MDM2 amplification in breast carcinomas.

Carcinoma of the breast, like other malignancies, is a genetic disease with multiple genetic events leading to the malignant phenotype. p53 mutations are the most common genetic events in human cancer. Inactivation of p53 can be a result of mutation in gene sequence. One of the main structures that regulate p53 stabilization is MDM2. It suppresses p53 transcriptional activation by recognizing transactivation domain of p53. The loss of MDM2 function on p53 regulation results in deprivation of p53 tumor suppressor ability. Single nucleotide polymorphisms (SNP309 T->G exchange) or MDM2 amplification has been proposed to play a role in this issue. In the present study, our aim is to analyze p53 and MDM2 status and investigate their interactions in human sporadic breast carcinoma. The study groups were separated according to their molecular classifications. In each group, histologic type of the tumor, conventional prognostic parameters, p53, and MDM2 interactions were compared statistically. Tumors are divided into 4 subtypes due to estrogen and progesterone receptor status, HER-2, and Ki-67 proliferation index results. According to this classification, 23 cases are in the luminal A, 32 cases are in the luminal B, 15 cases are in the HER-2 positive, and 22 cases are in the triple-negative group, with a total of 92 cases. p53 expression is low in luminal breast carcinomas than HER-2 and triple-negative subtypes. MDM2 amplification frequency was found to be 5.4% in total. MDM2 gene amplification does not have a significant role in breast carcinogenesis, but other possible mechanisms may play a role in its inactivation.

Efficacy of glycerol and flax seed oil as anti-adhesive barriers after thyroidectomy.

BACKGROUND: We evaluated the effects of local flax seed oil and glycerol application for reducing adhesion formation after thyroidectomy. MATERIAL AND METHODS: We randomly assigned 18 female Wistar albino rats (median weight: 275 g, median age: 4.5 mth) to 3 groups: 0.1 ml 0.9% NaCl, glycerol, and flax seed oil were sprayed in a perithyroidal area after thyroidectomy operation on all animals as anti-adhesive barriers. Rats were sacrificed on the postoperative 14th day and adhesions were evaluated macroscopically and microscopically. RESULTS: The median macroscopic adhesion score was 3.0±0.0 in the 0.9% NaCl group, 1.33±0.52 in the glycerol group, and 1.67±0.53 in the flax seed oil group. The median histopathological fibrosis scores were 2.33±0.82, 0.67±0.52, and 0.83±0.75, respectively. Both glycerol and flaxseed oil group macroscopic and microscopic scores were significantly lower than the 0.9% NaCl group (p<0.05). There was no significant difference among the groups (p>0.05). CONCLUSIONS: Glycerol and flax seed oil both decrease the incidence of post-thyroidectomy adhesion in rats, but glycerol is more effective.

Feasibility of breast conserving surgery in multifocal breast cancers.

BACKGROUND: Multifocal breast cancers (MFBCs) present a challenge to surgeons. Although its feasibility is still controversial, breast-conserving surgery (BCS) is not contraindicated for MFBCs. The investigators retrospectively evaluated the feasibility of BCS and reviewed histopathologic findings in patients with MFBC. METHODS: A total of 222 patients with MFBC who were treated with either BCS (119 patients) or mastectomy (103 patients) at a single institution between January 2002 and December 2011 were retrospectively evaluated. RESULTS: The median follow-up time was 55 months (range, 10 to 102 months). Lymphovascular invasion and lymph node involvement were significantly less frequent in the BCS group (48.8% vs 62.2% for lymphovascular invasion, P = .04; 52.1% vs 71.8% for lymph node involvement, P = .002). There were no differences in local recurrence rates between the 2 groups. The overall survival rates were 92% in the BCS group and 72% in the mastectomy group (P = .000). CONCLUSIONS: BCS is a feasible and safe procedure for the removal of multifocal tumors. Extended lymphovascular invasion is associated with mortality in patients who undergo mastectomy.

An unusual case caused by a common reason: Mondor's disease by oral contraceptives.

INTRODUCTION: Mondor's disease (MD) of the breast is a rare condition at breast clinics. We do not have enough data to establish its real prevalence. As a known data, most of the patients that were admitted to breast clinics are not breast cancer. Also MD is a rare entity and diagnosing this entity and informing the patient about it is very important. We present here this case to remind breast clinic practitioners that MD can be seen without trauma (neither surgical nor physical). Also clinical and radiological findings and the treatmentof the MD were discussed. PRESENTATION OF CASE: A 35 year old woman was admitted our clinic with cutaneous breast retraction. She had no risk for thrombosis else using oral contraceptives. Mondor's Disease was diagnosed and supported by radiological findings. Rheumatologic and hematologic causes were also explored. Patient healed in four weeks only with non-steroidal anti-inflammatory drug. DISCUSSION: Mondor's Disease is rarely related with breast cancer. This rare entity can be diagnosed with doubt and patient should be informed about it. Anti-coagulant treatment does not required if disease is idiopathic. CONCLUSION: Mondor's Disease should be reminded at a patient with retracted breast skin.

Jejunogastric intussusception: a rare complication of gastric surgery.

Jejunogastric intussusception is a rare complication of gastric surgery. It usually presents with severe epigastric pain, vomiting, and hematemesis. A history of gastric surgery can help in making an accurate and early diagnosis which calls forth an urgent surgical intervention. Only reduction or resection with revision of the previously performed anastomosis is the choice which is decided according to the operative findings. We present a case of JGI in a patient with a history of Billroth II operation diagnosed by computed tomography. At emergent laparotomy, an efferent loop type JGI was found. Due to necrosis, resection of the intussuscepted bowel with Roux-en-Y anastomosis was performed. Postoperative recovery was uneventful.

Remission of ulcerated necrobiosis lipoidica diabeticorum after bariatric surgery.

A 32-year-old woman with type 2 diabetes mellitus suffering from morbid obesity with BMI 45,14 kg/m(2) was operated on. Not only the type 2DM but also one of its complication known as necrobiosis lipoidica diabeticorum remitted postoperatively. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals but an epidemic that threatens global well-being. It causes or exacerbates many health problems, and in particular, it is associated with the type 2 diabetes. Necrobiosis lipoidica is a granulomatous skin disease of unknown etiology, associated mainly with diabetes mellitus. We presented in this paper a morbid obese case of necrobiosis lipoidica diabeticorum with dramatic good response to bariatric surgery.