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.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Comparison of Color Flow Doppler Sonography (CFDS) and immunohistologic detection of microvessels for the assessment of the malignancy of thyroid nodules.

The assessment of tumor vascularization by color flow Doppler sonography (CFDS) has been suggested for the distinction between benign and malignant thyroid nodules. Our objective was to investigate if the CFDS results reflect the percentage of histologically determined microvessels in adenomas (As), adenomatous nodules (ANs), and papillary carcinomas (PCs). Tissue sections from 10 adenomas, 8 ANs and 13 PC and surrounding tissue of 10 PCs and 2 benign nodules were immunostained for CD34. A computerized image analysis was used to determine the microvessel density in four hot spots and ten systematically selected fields. Preoperatively CFDS was performed and classified according to Frates et al. We found a consistent percentage increase of CD34 stained microvessels in PCs (83 and 96%) as compared to adenomas and ANs (38 and 49%) determined by the hot spot analysis and systematic field analysis. A ROC analysis on the basis of the histologically determined number of microvessels demonstrated 70% microvessels as an optimal cut point for the diagnosis of PC with the highest sensitivity of 92% and highest specificity of 89%. The analysis of the CFDS-classification IV for the distinction between PCs and adenomas and ANs showed a sensitivity of 62% with a specificity of 100%. The lower sensitivity of the CFDS classification as compared with the immunohistologic determination of the microvessel density indicates that the CFDS classification detects the pathognomonic intranodular microvessels only incompletely. The higher CFDS specificity is most likely due to the detection of other vascular aspects of malignancy in addition to intranodular microvessels.

Is anterior oblique view alone in surgical position sufficient for preoperative sentinel lymph node mapping in breast cancer? A quantitative comparative analysis with conventional views.

PURPOSE: Since the anterior projection alone has several limitations in the conventional preoperative sentinel lymph node (SLN) mapping, multiple projections including anterior oblique (AO) view are preferred. There are many AO acquisition techniques described in the literature but none of them creates an image which fully reflects the surgical perspective. We aimed to compare the AO view in the surgical position with the conventional projections according to quantitative parameters. PATIENTS AND METHODS: Sixty female breast cancer patients entered the study. Two hours after the radiotracer injection, preoperative SLN mapping at anterior, lateral and 35 degrees AO projections in surgical position was performed. For each projection, mapping success rate (MSR), the mean number of SLNs, lymphatic channel visualization rate, image contrast and distance measurements between each SLN and between the SLNs and the injection site were recorded. RESULTS: The best MSR and image contrast for the first and the consecutive axillary SLNs were found at the AO projection. The longest distance between the injection site and the SLNs and between the two SLNs were observed at the AO views. Although the AO view gave the best results for intramammary SLNs the difference was not statistically significant from the anterior view. CONCLUSION: The 35 degrees AO view in the surgical position was superior to the anterior and lateral projections. Therefore, the simple 4-min AO view in the surgical position may entirely reflect the surgeon's perspective and could be used safely alone in the preoperative lymphatic mapping for breast cancer patients.

A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer.

The prevalence of enterotoxigenic Bacteroides fragilis (ETBF) was investigated in stool specimens from 73 patients with colorectal cancer and from 59 control patients. Stool specimens were cultured on Bacteroides Bile Esculin agar and B. fragilis was identified by conventional methods. After DNA extraction, the enterotoxin gene (bft) was detected by PCR in 38% of the isolates from colorectal cancer patients, compared with 12% of the isolates from the control group (p 0.009). This is the first study demonstrating an increased prevalence of ETBF in colorectal cancer patients.

Is hemithyroidectomy a rational management for benign nodular goitre? A Multicentre Retrospective Single Group Study.

BACKGROUND: The incidence and potential risk factors for the recurrence of benign nodular goitre after unilateral thyroidectomy are not clearly defined. The aim of this study was to assess the rate of progression of nodular goitre in the contralateral thyroid lobe and of hypothyroidism requiring replacement therapy after unilateral thyroid lobectomy for benign nodular goitre. PATIENTS AND METHODS: Patients who underwent hemithyroidectomy for benign nodular goitre between 2000 and 2009 were included in the study. The primary outcome of this study was the reoperation rate for recurrent goitre, the rate of progression of nodular goitre and the rate of hypothyroidism requiring L-T4 replacement therapy. Clinical factors that have an effect on progression were further analysed. RESULTS: 259 patients were included for study. Progression of the nodular goitre in the remnant lobe was observed in 32% (n = 83) of the patients. However, over time, only 2% of these 83 patients underwent contralateral hemithyroidectomy due to this progression. Fifty-six (22%) patients required L-thyroxin replacement due to persistent hypothyroidism after hemithyroidectomy. The factors shown to affect progression of nodular goitre were advanced age, preoperative hyperthyroidism, preoperative diagnosis of toxic nodular goitre and the presence of surgical indication for a toxic goitre causing hyperthyroidism and a definitive pathological diagnosis of nodular hyperplasia. CONCLUSION: There was a progression of the nodular goitre in the remnant lobe in about one-third of the patients who underwent hemithyroidectomy. However, only 2% of these patients underwent complementary contralateral hemithyroidectomy due to clinical progression in 31 months of follow-up.

Scientific publications at a Turkish medical school.

The authors studied the scientific publishing trend for 1991 to 1998 at Turkey's Marmara University School of Medicine. Although publications increased both in real numbers and in ratios per faculty member, most were not original, peer-reviewed articles. Mere quantity of publications cannot accurately reflect a school's research reputation.

Hyperbaric oxygen improves healing in experimental rat colitis.

This study was designed to investigate therapeutic effects of hyperbaric oxygen on experimentally induced colitis in rats by assessing oxidative tissue damage, neutrophil accumulation and histological changes. Six groups of animals were used. No procedures were done in the sham group. In the vehicle group, 50% ethanol-induced colitis, and in four other groups, 2,4,6-trinitrobenzene sulphonic acid-induced colonic inflammation was achieved. In acute and chronic colitis non-treatment groups, no other procedure was done. In acute and chronic colitis hyperbaric oxygen treatment groups, rats underwent hyperbaric oxygen treatment for two or fourteen days. On the third and fifteenth days respectively tissue and blood samples were taken for microscopic and macroscopic damage assessment, myeloperoxidase activity and serum carbonyl content measurements. There was significant colonic tissue damage in non-treatment groups at 48 hours and 14 days. Hyperbaric oxygen treatment ameliorated the macroscopic damage significantly in chronic colitis. Amelioration of microscopic changes was not significant in each hyperbaric oxygen-treated group. Hyperbaric oxygen treatment significantly reduced tissue myeloperoxidase activity in acute colitis and decreased plasma carbonyl content in chronic colitis. In the present study, hyperbaric oxygen treatment significantly ameliorated trinitrobenzene sulphonic acid-induced chronic colitis in rats.

Validation of breast cancer nomograms for predicting the non-sentinel lymph node metastases after a positive sentinel lymph node biopsy in a multi-center study.

OBJECTIVE: In the study, our aim was to evaluate the predictability of four different nomograms on non-sentinel lymph node metastases (NSLNM) in breast cancer (BC) patients with positive sentinel lymph node (SLN) biopsy in a multi-center study. METHODS: We identified 607 patients who had a positive SLN biopsy and completion axillary lymph node dissection (CALND) at seven different BC treatment centers in Turkey. The BC nomograms developed by the Memorial Sloan Kettering Cancer Center (MSKCC), Tenon Hospital, Cambridge University, and Stanford University were used to calculate the probability of NSLNM. Area under (AUC) Receiver Operating Characteristics Curve (ROC) was calculated for each nomogram and values greater than 0.70 were accepted as demonstrating good discrimination. RESULTS: Two hundred and eighty-seven patients (287) of 607 patients (47.2%) had a positive axillary NSLNM. The AUC values were 0.705, 0.711, 0.730, and 0.582 for the MSKCC, Cambridge, Stanford, and Tenon models, respectively. On the multivariate analysis; overall metastasis size (OMS), lymphovascular invasion (LVI), and proportion of positive SLN to total SLN were found statistically significant. We created a formula to predict the NSLNM in our patient population and the AUC value of this formula was 0.8023. CONCLUSIONS: The MSKCC, Cambridge, and Stanford nomograms were good discriminators of NSLNM in SLN positive BC patients in this study. A newly created formula in this study needs to be validated in prospective studies in different patient populations. A nomogram to predict NSLNM in patients with positive SLN biopsy developed at one institution should be used with caution.

Increased percentage of microvessels but decreased density of large vessels in papillary carcinomas as compared to hot and cold thyroid nodules.

OBJECTIVE: For thyroid tumors increased as well as decreased vessel densities have been reported. Because of different morphometric methods and specificities of previously used antibodies for small and large vessels our objective was to investigate and compare the density of large vessels and microvessels by different morphometric methods and antibodies in hot nodules(HN), cold nodules (CN), papillary carcinoma (PC) and Graves' disease (GD) to try to clarify some of these discrepancies. DESIGN: Tissue sections from 29 HN, 22 CN, 19 PC and 8 GD thyroids were stained with the antibodies for CD34 and alpha-SMA. A computerized image analysis was used to calculate the mean area of endothelium (mEA) and the mean endothelium to tumor epithelial nucleus area ratio (mE/N) in four hot spots and ten systematically selected fields. MAIN OUTCOME: We found a consistent increase of the CD34 stained percentage of microvessels in PC as compared to HN and CN determined by the hot spot analysis and systematic field analysis. This increased microvessel density in PC is of a similar magnitude as in GD, which is characterised by a prominent increase of vascularisation during its active disease stage. Our SMA staining results reveal a kind of mirror image of the CD34 staining results with higher vessel counts in the normal surrounding tissues as compared to HN, CN and PC. CONCLUSIONS: The specific immunohistologic detection of microvessels with the CD34 antibody combined with their specific evaluation is able to clearly differentiate PCs from normal tissue, HN and CN.

Prospective multicentre trials in developing countries: willingness of surgeons to participate.

OBJECTIVE: To assess the feasibility of conducting a multicentre study among surgeons in Turkey. DESIGN: Prospective open multicentre study. SETTING: Teaching hospitals in Turkey. SUBJECTS: Surgeons working in 23 university and 15 state hospitals. INTERVENTIONS: Surgeons willing to participate were asked to look for the presence of Meckel's diverticulum in all patients undergoing laparotomy. MAIN OUTCOME MEASURES: To find out the number of surgeons willing to participate in the study and once they agreed to see how they fulfilled the requirements. RESULTS: 14 agreed to participate (12 from universities and 2 from state hospitals) and completed the study. A total of 2781 patient records were collected. University hospitals were more willing to participate than state hospitals (52% compared with 13%) but state hospitals contributed 20% of the patients. The number of patients contributed in the first and second halves of the study did not differ, reflecting no diminution of the enthusiasm. CONCLUSION: This study, with no financial support, showed that it is possible to conduct multicentre studies among surgeons in developing countries such as Turkey. Increased awareness of the importance of publication may have helped to obtain this result.

Immunologic influences of hyperthermia in a rat model of obstructive jaundice.

In this study, the effect of hyperthermia on immune response and bacterial translocation from the gut in jaundiced rats was assessed. In hyperthermic (HP; N = 8) and normothermic (NP; N = 8) preconditioning groups, rats were preconditioned by hyperthermia for 15 min at 42 degrees C or 38 degrees C, respectively. After 8 hr, the common bile duct (CBD) of each animal was ligated. In thermal (TT; N = 8) and normothermic treatment groups (NT; N = 8) the CBD of the animals was ligated, and after seven days rats were treated by hyperthermia for 15 min at 42 degrees C and 38 degrees C, respectively. The rats in the preconditioning groups (HP and NP) were killed at day 7 and rats in the treatment groups (TT and NT) were killed 8 hr after they were put in a water bath. Determination of the immunophenotypes of lymphocytes and serum levels of bilirubin was done in serum samples taken just after death. The quantity and identify of translocated bacteria were determined in tissue samples of mesenteric lymph nodes, spleen, and liver. NK cell expression as well as CD4+/CD8+ ratio were elevated in HP group when compared to NP group. CD8+ expression was found to be low in HP group when compared to NP group. CD4+, CD11b+, and B cell expressions were not found to be different between HP and NP groups. All immunologic parameters were similar when TT and NT groups were compared to each other. In the TT group, half of the rats revealed bacterial translocation, whereas in all other groups, we determined translocation in only 1/8 rats. The application of hyperthermia as preconditioning rather than applying it after the establishment of jaundice seemed to be beneficial. Hyperthermic preconditioning led an improvement in immune responses whereas the latter resulted an increase in bacterial translocation with no favorable influence on immune system. Bacterial translocation was unrelated with the immune status.

Endothelin release is augmented with captopril in rat ischemia-reperfusion injury of the liver.

The reactive oxygen metabolites (ROMs) and the vascular endothelial factors such as endothelins (ETs) and thromboxane A2 (TxA2) were found to be mediators of the reperfusion component of ischemia-reperfusion (I/R) injury. Captopril (CPT), a sulfydryl (-SH) group containing angiotensin-converting enzyme inhibitor, has been shown to reverse I/R injury by its ROM scavenging effect. In this experimental study, the effects of CPT and BM 13.177 (a TxA2 receptor antagonist) were assessed on liver I/R injury in rats. Four groups of Wistar albino rats were either sham-operated, control, CPT or BM 13.177-treated. The middle and left lateral hepatic arteries and portal veins were occluded in each group but the sham and the corresponding agents were given to the animals prior to I/R injury. After I/R injury, blood was drawn from the suprahepatic inferior vena cava for ET-1-like activity assay and liver tissue samples were obtained for the determination of prostaglandin E2 (PGE2), leukotriene C4 (LTC4) and histopathologic examination. PGE2 and ET-1 levels were increased significantly in the control group compared with the sham-operated group. In the CPT group, LTC4, PGE2 and ET-1 levels were significantly increased compared with the control group, while only ET-1 levels were not different from those of the control group in the BM 13.177-treated group. It is concluded that ET-1 release increases in response to I/R injury in rat liver and CPT further increases this release. It also appears that CPT has a stimulatory effect on arachidonic acid metabolism in addition to its free radical scavenging effect.

Role of endothelins in trinitrobenzene sulfonic acid-induced colitis in rats.

To determine the role of endothelins (ET) on experimental colitis, following intracolonic trinitrobenzene sulfonic acid administration, rats were given orally either bosentan (BS), a nonselective ET receptor antagonist (100 mg/kg in 5% arabic gum), or arabic gum by gavage for 2 or 14 days. Macroscopic damage scores obtained in the vehicle (1.4+/-0.4), acute (4.8+/-0.6) and chronic (3.8+/-0.3) colitis groups were significantly higher than in the control group (0). BS treatment reduced the scores in both acute (3+/- 0.5) and chronic (2.3+/-0.5) colitis groups. Myeloperoxidase (MPO) activities of colonic tissues were elevated in acute and chronic colitis groups (325.1+/-44.9 and 431.8+/-54.6 U/g wet weight) as compared with the control group (73.6+/-11 U/g wet weight). Plasma protein oxidation levels were found to be significantly increased in the chronic colitis group (1,158.1+/-63.4 nmol/ml) compared with the control, ethanol and acute colitis groups (274.3+/-23.1, 490+/-52.2 and 422.2+/-50.5 nmol/ml). BS treatment significantly reduced both the protein oxidation level (375.5+/-46.9 nmol/ml) and MPO activity (167.5+/-35.8 U/g wet weight). The results of the present study suggest the involvement of ETs in the pathogenesis of colonic injury in this animal model of colitis.

Bombesin ameliorates colonic damage in experimental colitis.

In the present study we investigated the possible therapeutic effects of bombesin on an experimentally induced colitis model in rats. Inflammation of the colon was induced by a single intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) at 8 cm from the anus. Immediately after the induction of colitis, some rats were given bombesin (10 microg/kg; subcutaneously) three times a day for 14 days, while another group received vehicle treatment. On day 14, the rats were decapitated and plasma carbonyl content and tissue myeloperoxidase level, as an index of granulocyte infiltration into intestinal tissue, were determined in order to obtain an objective evaluation of colonic injury. In the colitis group, increased macroscopic damage score, elevated MPO level and high plasma carbonyl content, together with the microscopic appearance revealed severe inflammatory changes resembling IBD. Bombesin treatment attenuated the TNBS-induced colonic damage and stimulated histopathologically apparent mucosal proliferation, suggesting that bombesin may play a role in protecting gut integrity.