Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels. METHODS: A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system. RESULTS: Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response. CONCLUSION: Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.

Management of endocrine surgical disorders during COVID-19 pandemic: expert opinion for non-surgical options.

PURPOSE: The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic. METHODS: We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire. RESULTS: Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± ß-blocker combination for Graves' disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma. CONCLUSION: This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

Comparison of 5 Thyroid Ultrasound Stratification Systems for Differentiation of Benign and Malignant Nodules and to Avoid Biopsy Using Histology as Reference Standard.

OBJECTIVE: We aimed to compare the thyroid ultrasound risk stratification systems (RSSs) of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), European TI-RADS, Korean TI-RADS, and American Thyroid Association (ATA), American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi guidelines to differentiate benign from malignant thyroid nodules and to avoid unnecessary fine needle aspiration (FNA). METHODS: The records of 1143 nodules ≥1 cm that underwent FNA biopsy and thyroidectomy between 2012 and 2020 at our institution were reviewed. Ultrasound categories and FNA recommendation indications of 5 international RSSs were compared with histopathological findings as benign or malignant. The ultrasound categories and recommended FNA indications, the proportion of the avoidable FNA procedures, and false negative rates (FNRs) by different systems were compared with each other. RESULTS: Of the 1143 nodules, 45% had thyroid malignancy. FNA recommendation and ultrasound risk classification of ATA guidelines had the highest area under curves of 0.619, and 0.715, respectively. ACR TI-RADS, American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines, European TI-RADS, ATA guidelines, and Korean TI-RADS would have avoided FNA for 34.7%, 31%, 25.7%, 20%, and 6% of nodules with an FNR of 24%, 28.5%, 22%, 7.2%, and 1.9%, respectively. CONCLUSION: Our findings showed that all RSSs classified the nodules appropriately for malignancy. ATA guidelines had the highest area under curves and a low FNR, whereas ACR TI-RADS would have spared more patients from FNA with a high FNR.

Does a Close Surgical Margin for Ductal Carcinoma In Situ Associated with Invasive Breast Carcinoma Affect Breast Cancer Recurrence?

Purpose: Our aim was to determine if a close surgical margin (<2 mm, but no ink on tumor) for ductal carcinoma in situ (DCIS) associated with invasive breast cancer (IBC) leads to an increased rate of ipsilateral breast tumor recurrence (IBTR).Patients and Methods: Six hundred and twenty-eight patients with T1-2 IBC who underwent breast conserving therapy (BCT) and had no ink on tumor between 2009 and 2017 in our institution were included in the study. Age, tumor size, axillary lymph node status, resection margin status of DCIS as closer than 2 mm or ≥2 mm, DCIS as present or absent, extensive intraductal component as yes or no were investigated. All patients were followed-up for IBTR.Results: The median age was 50 years (range, 29-82), and median tumor size was 25 mm (range, 5-50). Median follow-up time was 56 months (range, 12-114). Of the 628 IBC patients, 440 (70%) were found to be associated with DCIS. Of the 440 patients with DCIS, 119 (27%) had a close margin (<2 mm) and 321 (73%) had a margin ≥2 mm for DCIS. Among 440 IBC patients associated with DCIS, there were three local recurrences. One developed in a patient who had a close surgical margin for DCIS, and in the other two patients, surgical margins were ≥2 mm.Conclusions: No ink on tumor is an adequate margin for IBC associated with DCIS in patients who undergo BCT and it is not associated with increased IBTR.

Surgical Trends in Breast Cancer in Turkey: An Increase in Breast-Conserving Surgery.

PURPOSE: Breast cancer is the most frequent cancer in women, and there is a great variability in surgical practice for treating that cancer in different countries. The aims of this study were to analyze the effect of guidelines from the Turkish Federation of Breast Diseases Societies on academic institutions that have breast centers and to evaluate surgical practice in Turkey in 2018. PATIENTS AND METHODS: Between January and March 2019, a survey was sent to breast surgeons who were working in breast centers in academic institutions. The sampling frame included 24 academic institutions with breast centers in 18 cities in Turkey to evaluate interdisciplinary differences among breast centers and seven regions in Turkey regarding patients' choices, surgical approaches, and academic institutions. RESULTS: All surgeons responded to the survey, and all 4,381 patients were included. Most of the surgeons (73.9%) were working in a breast center. Multidisciplinary tumor boards were performed in 87% of the breast centers. The average time between clinical evaluation and initiation of treatment was 29 days; the longest time was in Southeast Anatolia (66 days). Only 6% of patients had ductal carcinoma in situ. Sentinel lymph node biopsy was available in every region across the country and was performed in 64.5% of the patients. In 2018, the overall breast-conserving surgery rate was 57.3% in Turkey, and it varied from 72.2% in the Black Sea region to 33.5% in Central Anatolia (P < .001). Oncoplastic breast surgery options were available at all breast centers. However, 25% of the breast centers from the Black Sea region and half the breast centers from Eastern Anatolia and the Mediterranean region did not perform this type of surgery. CONCLUSION: Increasing rates of nonpalpable breast cancer and decreasing rates of locoregional recurrences favored breast-conserving surgery, especially in developed countries. Guidelines from the Turkish Federation of Breast Diseases Societies resulted in more comprehensive breast centers and improved breast health in Turkey.

The Adventure of Axillary Treatment in Early Stage Breast Cancer.

Axillary lymph node dissection (ALND) which was an essential part of breast cancer treatment and the gold standard in evaluation of the status of axillary lymph node had notorious with increased arm morbidity and reduction of quality of life. Sentinel lymph node biopsy (SLNB) accurately stages the axilla in early breast cancer and ALND is omitted in SLNB negative patients. In patients with positive SLNB the omission of ALND with or without replacement of axillary radiotherapy has also been recommended by guidelines. The neoadjuvant chemotherapy (NAC) which has been increasingly used for large breast cancers to downstage the tumours for allowing breast conserving surgery and decreasing mastectomy rate has also been used in axillary node positive patients to reduce the need for ALND. The issues surrounding the treatment of axilla in patients treated with NAC; application and false negative rate of SLNB, number of identified sentinel lymph nodes, and axillary radiotherapy instead of ALND are currently the discussed and practiced hot topics. The quests for decreasing arm morbidity without compromising outcome in breast cancer treatment which have begun with the invention of SLNB continue for axilla conserving surgery. This article reviews the adventure of axillary treatment in breast cancer patients treated with or without NAC.

Management of the Axilla in T1-2 Breast Cancer Patients with Macrometastatic Sentinel Node Involvement Who Underwent Breast-Conserving Therapy.

PURPOSE: The aims of our study were to determine the incidence of axillary recurrence and arm morbidity in T1-2 invasive breast cancer patients with macrometastases on the sentinel lymph node (SLN) who underwent breast-conserving therapy (BCT), with or without axillary lymph node dissection (ALND). METHODS: One hundred and nine T1-2 invasive breast cancer patients with macrometastases on the SLN who underwent BCT in our institution were included in the study. Patients with 1-2 positive SLN and without extra nodal extension (ENE) on the SLN did not undergo ALND (SLN-only group) and patients with ENE or patients who had >2 metastatic nodes underwent level I, II ALND (ALND group). The SLN-only group received radiotherapy to three axillary levels, the supraclavicular fossa, and ± mammaria interna. ALND group received radiotherapy to axillary level III, the supraclavicular fossa, and ± mammaria interna. The incidence of axillary recurrence and arm morbidity were investigated. RESULTS: Of the 109 patients, 18 patients with >2 metastatic SLNs and 10 with ENE on the SLN underwent ALND and 81 patients underwent SLN only. Median follow-up time was 37 months (3-77). There was no axillary recurrence in SLN-only group. However, in the ALND group 1 patient had developed axillary metastasis. There were 2 objective lymphoedema and 3 arm-shoulder restriction cases in the SLN-only group, and 2 and 3 in the ALND group, respectively. CONCLUSIONS: Axillary dissection could safely be omitted in patients with 1-2 macrometastatic SLN and without ENE who undergo BCT and axillary radiotherapy.

Echoes from the 40th Annual San Antonio Breast Cancer Symposium, 2017.

The Annual San Antonio Symposium was held on 5-9, December, 2017 in San Antonio, Texas, USA (1). As expected, many new studies were presented for the first time at the sessions. The unofficial opening lecture in my point of view was given on locoregional recurrence by Monica Morrow from MSKCC, New York. As always, Morrow's lecture on "Challenges in the surgical management of locoregional recurrence" attracted great interest. The other prominent conferences were given on "Individualizing Management of the Axillary Nodes" by Tari A. King from Dana-Farber Cancer Institute and on "Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis" by Shah C from Cleveland Clinic.

Risk factors associated with malignancy and with triage to surgery in thyroid nodules classified as Bethesda category IV (FN/SFN).

BACKGROUND: Thyroid nodules diagnosed as Bethesda category IV [follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)] are recommended for surgery. However, only 10%-40% of these nodules turn out to be malignant on histopathological examination. Therefore, selection for surgery of nodules diagnosed as Bethesda category IV is important. We aimed to define predictive factors for malignancy and factors associated with triage to surgery. METHODS: The records of all patients with nodules who underwent fine needle aspiration biopsy (FNAB) and classified by Bethesda reporting system as FN/SFN between January 2011 and July 2017 at our institution were reviewed. Univariate and multivariate analysis were performed to select independent factors associated with thyroid cancer, and with triage to surgery. Using independent risk factors for malignancy predictive index categories were created. RESULTS: Among 6910 nodules that underwent FNAB, 180 (2.6%) were diagnosed as FN/SFN. Of the 180 patients, 139 (77%) underwent surgery with the associated malignancy rate of 37% (51/139) (upper boundary). Risk of malignancy among all FN/SFN nodules was 28% (lower boundary). Solid structure, size ≥ 4 cm, microcalcification, hypoechogenicity, and increased vascularization were found to be significant and independent risk factors associated for malignancy. None of the clinical and ultrasound factors were associated with triage to surgery. CONCLUSIONS: Our findings showed that using predictive factors for malignancy in the Bethesda IV category as risk indices, 17% of patients who had nodules without any risk factors could be spared surgery. Predictive indices could be considered for the malignancy risk and for selection of patients for surgery.

The Main Topics at the Oncoplastic Breast Surgery Course and Expert Panel.

The Oncoplastic and Reconstructive Breast Surgery course was held in Izmir by the Izmir Breast Diseases Federation in collaboration with the Breast Diseases Federation of Turkey. The techniques of oncoplasty, the application details and experience in this subject were shared. In this text, the main topics and outcomes are briefly summarised. These evaluations can be considered highly valuable on both local and regional scales.

Factors predicting non-sentinel lymph node metastasis in T1-2 invasive breast cancer with 1-2 axillary sentinel lymph node metastases: Presentation of Ondokuz Mayis scoring system.

PURPOSE: To evaluate the predicting factors for non-sentinel lymph node (SLN) metastases in T1-2 invasive breast cancer with 1-2 metastatic SLN that fully matched the ACOSOG Z0011 criteria. Also, to develop a scoring system to predict the risk of non-SLN metastasis and to discriminate the low-risk patients for omission of the axillary lymph node dissection (ALND) in this population. METHODS: Two hundred and seven T1-2 invasive breast cancer patients with 1-2 metastatic SLN who underwent ALND at our Institution were included in the study. Independent factors predicting the non-SLN metastasis were found using logistic regression analysis, and a scoring system to predict the non-SLN metastasis was created. RESULTS: Seventy (34%) out of 207 patients had non- SLN metastasis. Multivariate logistic regression analysis demonstrated that tumor size, presence of lymphovascular invasion (LVI), number of negative SLNs, and size of SLN metastasis were independent factors predicting non-SLN metastasis. There were 68 (33%) and 108 (52%) patients with a the score of ? 4 (predicted probability of ?10%) with a false negative rate (FNR) of 4.4%, and ?5 (predicted probability of ?15%) with a FNR of 7.4%, respectively. The area under the curve (AUC) value for the Ondokuz Mayis scoring system was 0.88 (95% CI 0.83-0.93). CONCLUSIONS: The present Ondokuz Mayis model with an AUC of 0.88 showed excellent discrimination capacity to distinguish patients at low risk for positive non-SLN from high risk patients and could help spare ALND in an important portion of patients.

Malignancy rate associated with Bethesda category III (AUS/FLUS) with and without repeat fine needle aspiration biopsy.

BACKGROUND: Selection of nodules for surgery diagnosed as Bethesda category III [atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category] is important. It was aimed to define the malignancy rates associated with and without repeat fine needle aspiration biopsy (FNAB) and to define the contribution of repeat FNAB to triage to surgery or observation in nodules with AUS/FLUS FNAB. METHODS: The records of all patients with nodules who underwent FNAB and classified by Bethesda reporting system as AUS/FLUS at their institution were reviewed. Malignancy rates for patients with AUS/FLUS FNAB with and without repeat FNAB were calculated. RESULTS: Of the 582 patients who were classified as AUS/FLUS on initial FNAB, 179 underwent surgery with an associated malignancy rate of 22.9% (upper boundary). Risk of malignancy among all patients with AUS/FLUS nodules was 7% (lower boundary). The upper and lower boundaries of the malignancy rates with and without repeat FNAB were 38.6% and 15.6% for resected patients, and 13% and 4.6% for all patients, respectively. Reclassification rate with repeat FNAB was 56%. CONCLUSION: The findings showed that repeat FNAB for initial AUS/FLUS category was associated with a significantly increased malignancy rate compared with those without repeat FNAB. Repeat FNAB could help selection of patients with AUS/FLUS to triage to surgery. Therefore, repeat FNAB for nodules with AUS/FLUS on initial FNAB was suggested.

Erratum: Factors predicting non-sentinel lymph node metastasis in T1-2 invasive breast cancer with 1-2 axillary sentinel lymph node metastases:Presentation of Ondokuz Mayis scoring system.

In this article published in Volume 21, issue 5, the Results section of the Pubmed abstract appeared as: "There were 68 (33%) and 108 (52%) patients with a the score of ? 4 (predicted probability of ?10%) with a false negative rate (FNR% of 4.4%, and ?5 (predicted probability of ?15%) with a FNR of 7.4%, respectively. The area under the curve (AUC) value for the Ondokuz Mayis scoring system was 0.88 (95% CI 0.83-0.93%)." The correct Results section of the abstract is: "There were 68 (33%) and 108 (52%) patients with a the score of ≤4 (predicted probability of ≤10%) with a false negative rate (FNR) of 4.4%, and ≤5 (predicted probability of ≤15%) with a FNR of 7.4%, respectively. The area under the curve (AUC) value for the Ondokuz Mayis scoring system was 0.88 (95% CI 0.83-0.93)." This error appeared only in the PubMed database and not in the print form of the Journal.

Percutaneous Endoscopic Gastrostomy: Technical Problems, Complications, and Management.

Percutaneous endoscopic gastrostomy (PEG) is an important technique for the provision of nutrition. The present study presents data from our analysis of the PEG procedure. Patients administered with PEG at the endoscopy unit of the 19 Mayis University General Surgery Department between 2007 and 2013 were analyzed retrospectively, and technical problems, indications, and complications related to the PEG procedure in 221 patients were evaluated. Of the patients, 60 % were male and the median age was 61 years (18-92 years). The most frequent indication was admittance to the intensive care unit, accounting for 46 % of the total, followed by neurological disease, with 41 %. The success rate of the procedure was 98 %, and the overall rate of complications was 22 %. No mortalities were reported as resulting from the procedure. The most common complication was the development of granulomas around the tube (8 %). PEG is a safe method of long-term feeding but is associated with a high rate of morbidity that can be treated easily using conservative treatment methods.

Prognostic factors affecting disease-free survival in patients at age 35 or younger with invasive breast cancer.

AIM: Our aim is to determine the disease-free survival (DFS) rate, and to investigate the prognostic factors among patients with invasive breast cancer at age 35 or younger. PATIENTS AND METHOD: The medical records of the 67 patients who underwent surgery for invasive breast cancer were retrospectively reviewed. Potential prognostic factors that affect the DFS were investigated. DFS curves were obtained using the Kaplan-Meier method. The comparisons were made by the long-rank test. The prognostic factors affecting the DFS were determined by stepwise Cox proportional hazard regression test. The P value < 0.05 was accepted as significant. RESULTS: The median age was 32 (range, 23-35). The median follow-up interval was 55 months (range, 10-108). The 5-year DFS rate was 69.3%. In univariate analysis the number of pathologic axillary lymph nodes (p=0.035), triplenegative status (p=0.014) and tumor size (p= 0.004) were found to be the prognostic factors affecting the DFS. The 5-year DFS rate was 81% in non-triple negative patients, whereas this was 35% in triple-negative patients. In the multivariate analysis, triple-negative status was the only independent prognostic factor which affected the DFS adversely (HR: 1.48, CI: 0.66-082, p=0.027). CONCLUSION: Triple-negative status was found to be the only independent and adverse prognostic factor which affects the DFS in patients with invasive breast cancer at age 35 or younger. KEY WORDS: Breast cancer, Disease-free survival, Triple negative breast cancer, Young age.

A breast cancer nomogram for prediction of non-sentinel node metastasis - validation of fourteen existing models.

BACKGROUND: To avoid performing axillary lymph node dissection (ALND) for non-sentinel lymph node (SLN)-negative patients with-SLN positive axilla, nomograms for predicting the status have been developed in many centers. We created a new nomogram predicting non-SLN metastasis in SLN-positive patients with invasive breast cancer and evaluated 14 existing breast cancer models in our patient group. MATERIALS AND METHODS: Two hundred and thirty seven invasive breast cancer patients with SLN metastases who underwent ALND were included in the study. Based on independent predictive factors for non-SLN metastasis identified by logistic regression analysis, we developed a new nomogram. Receiver operating characteristics (ROC) curves for the models were created and the areas under the curves (AUC) were computed. RESULTS: In a multivariate analysis, tumor size, presence of lymphovascular invasion, extranodal extension of SLN, large size of metastatic SLN, the number of negative SLNs, and multifocality were found to be independent predictive factors for non-SLN metastasis. The AUC was found to be 0.87, and calibration was good for the present Ondokuz Mayis nomogram. Among the 14 validated models, the MSKCC, Stanford, Turkish, MD Anderson, MOU (Masaryk), Ljubljana, and DEU models yielded excellent AUC values of > 0.80. CONCLUSIONS: We present a new model to predict the likelihood of non-SLN metastasis. Each clinic should determine and use the most suitable nomogram or should create their own nomograms for the prediction of non- SLN metastasis.

Non-operative treatment approach for blunt splenic injury: is grade the unique criterion?

BACKGROUND: We aimed to investigate the results of a non-operative approach to blunt spleen injury to re-evaluate the importance of injury grade. METHODS: Thirty-one blunt splenic trauma cases subjected to non-operative treatment were evaluated retrospectively. The patients were classified into two groups as isolated spleen trauma (ST) group and multi-trauma (MT) group. The hospitalization and blood replacement needs, success of non-operative follow-up, and post-traumatic complications were compared between the two groups. The patients were evaluated via follow-up abdominal ultrasonography (US) and computerized tomography (CT). The results were evaluated with regard to post-splenic trauma complications. RESULTS: According to the organ injury scale of the American Association for the Surgery of Trauma, 25.8% were grade-1, 32.2% grade-2, 29% grade-3, and 12.9% grade-4 injuries. It was observed that the transfusion amount was directly proportional to the injury grade. All patients with grade-4 injury and 14 patients with MT were treated successfully with the non-operative method. Splenic pseudoaneurysm developed in one patient in the MT group. One patient was diagnosed with late splenic rupture. CONCLUSION: Hemodynamic stability is the most important criterion for the indication of non-operative treatment. However, in well-selected cases, patients with grade 4 splenic traumas and those with extra-splenic injuries could also be treated successfully with the non-operative method.