Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

The impact of intraoperative cavity shaving on re-excision rates in breast-conserving surgery.

BACKGROUND AND OBJECTIVES: This trial aimed to investigate the effects of circumferential shaving on reducing the reoperation rates during breast-conserving surgery (BCS). METHODS: In the study, before 2014, 404 (39.9%) breast cancers (BCs) out of a total of 1012 BCs underwent BCS without intraoperative cavity shaving (ICS) and constituted the no-ICS group. After this date, ICS was added to 608 (60.1%) BCSs (ICS group) and intraoperative margin analysis was not requested from pathologists during these second BCS procedures. RESULTS: The patient and BC characteristics in the no-ICS and ICS groups were similar. Carcinoma detection at the margin and reoperation rates were 13.9% in the no-ICS group and 7.6% in the ICS group (p = 0.001). No significant difference was detected between patients who underwent BCS with intraoperative frozen section analysis (FSA) and patients who underwent BCS with additional ICS (5.6% vs. 7.6%, p = 0.383). CONCLUSIONS: ICS decreased the rates of positive margins and reoperations among patients with BCS to an acceptable level compared with intraoperative FSA. It may be concluded that ICS is feasible to achieve BC margin control.

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q.

BACKGROUND/OBJECTIVE: Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey. METHODS: SF-12 (V2) forms were completed during visits of patients who were living 36 months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3 years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65 years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. RESULTS: There were 81 patients in this analysis; 68% of patients (n = 55) had LRT, and 32% (n = 26) received ST. General health was good or very good in 62% (n = 34) in the LRT group and 66% (n = 17) in the ST-only group (p = 0.63). Mean PCS-12 score was 40.8 + 1.6, and mean MCS-12 score was 43.4 + 2.0 (p = 0.34 and p = 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3 + 12.8 and MCS-12 = 46.8 + 13.0) and stage I-III BC patients (PCS-12 = 51.1 ± 0.5, MCS-12 = 45.7 ± 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3 years vs. at diagnosis of BC in de novo stage IV BC patients (p > 0.05), these variables were significantly better in stage I-III BC patients (p < 0.001). CONCLUSION: The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3 years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.

The relative importance of factors influencing the surgeons' choice between mastectomy and breast-conserving surgery for women with breast cancer.

The authors' aim is to provide breast surgeons' perspectives on the relative importance of the criteria for choosing an appropriate surgery method between mastectomy (total removal of a breast) and breast-conserving surgery (removal of a breast cancer tumor and some of the normal tissue that surrounds it) for women with breast cancer by using the multicriteria decision-making method (MCDM). The Analytic Hierarchy Process (AHP), the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), and Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) methods are utilized. A decision hierarchy is set with a goal, criteria, and alternatives. We developed our model based on three main criteria, tumor-related, patient-related, and post-operative process-related factors and nineteen sub-criteria, as well as two alternatives, mastectomy and breast-conserving surgery (BCS). An online questionnaire was sent to the breast surgeons; we showed that the most important criteria are post-operative process-related factors, especially the demand for esthetic appearance based on 39 breast surgeons. Conversely, the least significant criteria are tumor-related factors. Furthermore, breast-conserving surgery is selected as the most appropriate surgery method for breast cancer patients using the AHP, TOPSIS, and VIKOR.

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.

Improved False-Negative Rates with Intraoperative Identification of Clipped Nodes in Patients Undergoing Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy.

BACKGROUND: Identification and resection of a clipped node was shown to decrease the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for patients presenting with initially node-positive breast cancer. METHODS: Between March 2014 and March 2016, a prospective trial analyzed 98 patients with axilla-positive locally advanced breast cancer (T1-4, N1-3) to assess the feasibility and efficacy of placing clips into most suspicious biopsy-proven node. The study considered blue, radioisotope active, and suspiciously palpable nodes as sentinel lymph nodes (SLNs). RESULTS: The SLN identification rate was 87.8%. The median age of the patients with an SLNB (n = 86) was 44 years (range 28-66 years). Of these patients, 77 (88.4%) had cT1-3 disease, and 10 (11.6%) had cT4 disease. The majority of the patients (n = 66, 76.7%) had cN1, whereas 21 patients (23.3%) had cN2 and cN3. A combined method was used for 37 patients (43%), whereas blue dye alone was used for the remaining patients (57%). The clipped node was the SLN in 70 patients (81.4%). For the patients with cN1 before NAC, the FNR was found to be 4.2% (1/24) when the clipped node was identified as an SLN. However, the FNR was estimated to be as high as 16.7% (1/6) for the patients with cN1 before NAC when the clipped node was found to be a non-SLN. CONCLUSIONS: The study results also suggest that axillary dissection could be omitted for patients presenting initially with N1 disease and with a negative clipped node as the SLN after NAC due to the low FNR.

Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.

BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year-OS (P=.001) and 10 year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

Sentinel lymph node biopsy and aberrant lymphatic drainage in recurrent breast cancer: Findings likely to change treatment decisions.

BACKGROUND AND OBJECTIVES: It is not clear whether sentinel lymph node biopsy (SLNB) can be applied to patients with a second breast cancer or recurrence occurring at previously treated breast. The purpose of this study was to assess the feasibility of SLNB procedure in patients with recurrent breast cancer. METHODS: Patients with non-metastatic recurrent N0 breast cancer at ipsilateral breast were included. Patients were grouped according to their initial breast, axilla, and overall surgery. Presence of drainage and its pattern as well as SLNB success rate and overall axillary involvement rates were assessed. Findings were compared. RESULTS: Out of 75 patients, mean age was 52.5 years and disease-free interval was 82 (9-312) months. Lymphatic drainage was successful in 42 (56%) patients. Drainage positivity was more frequent in patients who were previously treated with SLNB (82.6%) than in patients who underwent axillary lymph node dissection (ALND) (44.2%; P = 0,002). Aberrant lymphatic drainage was detected in 64.3% of drainage positive patients. Success rate of reoperative SLNB was 92.9%. Adjuvant treatment plan was altered in 12 (16%) patients. In 15 patients, negative SLNB prevented axillary dissection. CONCLUSIONS: Reoperative SLNB seems to be technically feasible in N0 recurrent breast cancer patients. It may further avoid unnecessary ALND and lead changes in adjuvant treatment plans. J. Surg. Oncol. 2016;114:796-802. © 2016 2016 Wiley Periodicals, Inc.

Effect of intraperitoneal cetuximab administration on colonic anastomosis and early postoperative adhesion formation in a rat model.

OBJECTIVE: We aimed to evaluate the effect of intraperitoneal cetuximab administration on the healing of anastomosis and development of early adhesion formation in a rat model. MATERIALS AND METHODS: Twenty-four female rats were used. A colon segment was resected and end-to-end anastomosis was performed. The rats were randomized into three groups after the performance of colonic anastomosis and received 10 mL of intraperitoneal solution including study drugs after closure of abdominal cavity: normal saline was administered to the normal saline group (n=8), cetuximab (400 mg/m(2)) was administered to the postoperative 1 group (n=8) 1 day after surgery, and cetuximab (400 mg/m(2)) was administered to the peroperative group (n=8) during surgery. RESULTS: The mean adhesion grade was 2.63±0.92, and 0.50±0.76 and 0.63±0.74 for control and test groups, respectively. Cetuximab reduced adhesion formation in test groups (p<0.05). When all groups were compared, it was found that vascular endothelial growth factor levels decreased significantly only in the abdomen (p<0.05). Hydroxyproline levels and anastomosis bursting pressure were examined, and a statistical difference was found between groups (hydroxyproline p<0.05, bursting pressure p<0.05). However, when postoperative 1 day group was compared with the control group, it was found that there was no difference between groups according to these parameters (p>0.05), but when peroperative group was compared with the control group a significant decrease was observed in both parameters. Histopathological healing score was also evaluated. No statistical difference between groups was found. CONCLUSION: Twenty-four hours later from the operation, intraperitoneal cetuximab therapy may be a safe and feasible treatment for metastatic colorectal patients.

Is there any effect of first-day usage of a totally implantable venous access device on complications?

BACKGROUND: Our aim was to evaluate whether it is safe to use a totally implantable venous access device (TIVAD) on the day of implantation. METHODS: We investigated data from 1315 cancer patients divided into two groups according to the time interval between TIVAD placement and the first use of the TIVAD to adminster chemotherapy: patients whose devices were used during the first 24 h after placement were enrolled into group 1 and patients whose devices were first used more than 24 h after device placement were enrolled into group 2. RESULTS: Early complications were all related to device insertion and occurred before chemotherapy administration. Infection and venous thrombosis were the most frequent complications during the first 6 months after TIVAD insertion in both groups. However, the frequency of late complications was statistically the same for the two groups. CONCLUSIONS: The early use of TIVADs appears safe. Usage of the catheter for chemotherapy administration during the first 24 h after insertion has no effect on the rate of complications.

Intraoperative ultrasound reduces the need for re-excision in breast-conserving surgery.

BACKGROUND: The purpose of this study was to evaluate ultrasound-guided surgery for palpable breast cancer by comparing the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumor-free margins, and cosmetic outcomes. METHODS: This was a prospective, observational cohort study conducted from January 2009 to July 2011. Breast cancer patients, diagnosed via biopsy, were operated in guidance with either ultrasound or palpation. Patient demographics, tumor features, intraoperative findings, pathologic and cosmetic results, intraoperative-measured ultrasound margins, and pathology margins were compared. RESULTS: Ultrasound (US)-guided lumpectomy was performed on 84 women and palpation-guided lumpectomy on 80 women. Patient demographics and tumor characteristics showed no differences. The rate of re-excision was 17 % for the palpation-guided surgery group, and 6 % for the US-guided group (p = 0.03). There was good correlation between the closest margins recorded by US and pathology margins (r = 0.76, p = 0.01). Volume of resection was significantly larger in the palpation-guided group despite the similar size of tumors (p = 0.048). Cosmetic outcome of surgery was equivalent between groups. CONCLUSIONS: Intraoperative ultrasound guidance for excision of palpable breast cancers is feasible and gives results in terms of pathologic margins that are comparable with those achieved by standard palpation-guided excisions.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Guidelines for extended lymphadenectomy in gastric cancer: a prospective comparative study.

AIMS: To assess the efficacy of extended lymph node dissection in gastric cancer and to identify factors affecting lymph node detection. METHODS: A prospective study of 126 gastric cancer patients was conducted. Patients eligible for curative resection received total gastrectomy and extended lymphadenectomy (D2) and paraaortic lymph node sampling as the standard of care (study group). Supramesocolic total lymphadenectomy of the upper gastrointestinal tract was performed on 23 autopsy cases as a control group. RESULTS: Fifty-five gastric carcinoma patients were included in the study group. Median age was 58 years (range 31-80 years); 14 patients were female (25%), and 41 were male (75%). The median number of lymph nodes harvested from the specimen was 47 (24-95), and the median number of metastatic lymph nodes was 15 (1-71). In contrast, in the autopsy comparative group, the median number of harvested lymph nodes was 72 (50-91). The median number of stational lymph nodes excised (lymph nodes excised from stations 4, 5, 10, 11, 12, and 16) was significantly higher in the control group than in the study group (P<0.05). Lymph node detection was adversely affected by body mass index (BMI) (P<0.03). In the study group, stations 5, 12, 11, and 10 had the highest lymph node absence (LNA) (noncompliance) ratio with percentages of 53, 36, 33, and 22%, respectively. In the autopsy group, LNA (noncompliance) was not detected. CONCLUSIONS: Lymph nodes should be dissected by surgeons with sufficient technical and anatomical experience, and then examined and counted by experienced pathologists to reduce the occurrence of LNA. The results of this anatomical study can serve as a guideline to assess the success of lymph node dissection during gastric cancer surgery. Similar studies should be conducted in every country to establish national guidelines.

Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation.

AIM: The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. MATERIALS AND METHODS: A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. RESULTS: The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. CONCLUSION: IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.

Investigation of mRNA Expression Levels of Tip60 and Related DNA Repair Genes in Molecular Subtypes of Breast Cancer.

INTRODUCTION: Studies in breast cancer (BC) have been shown that many tumor cells carry mutations that disrupt the DNA damage response mechanism. In eukaryotic cells, the overexpression or deprivation of DSBs repair genes is linked closely to a higher risk of cancer. PATIENTS AND METHODS: In this study, mRNA expression levels of some genes, such as Tip60, ATM, p53, CHK2, BRCA1, H2AX, which are associated with DNA damage repair, were measured using RT-PCR method in tumor and matched-normal tissues of 58 patients with BC. RESULTS: According to the study results, 55% in Tip60, 59% in ATM, 57% in BRCA1, 48% in H2AX, 66% in CHK2, and 43% in p53 decreased in tumor tissue of patients compared to the matched normal tissue. When evaluated according to molecular subtypes, expression of all genes in the pathway was found significantly higher in normal tissues than in tumor tissues especially in Luminal B and Luminal B+HER2 groups. One of the most important results of the study is that CHK2 mRNA expressions in normal tissues were higher than tumor tissue in 90% of patients in Luminal B and Luminal B-HER2 + groups. This is the first study showing DNA repair genes' expressions in molecular subtypes of breast cancer. In general, the decrease in the expression of DNA damage repair genes in tumor tissue indicates that these genes may have a role in the development of BC. Our study results also suggest that CHK2 may be a candidate marker in the molecular classification of breast cancer.

Pushing the Limits of Breast-Conserving Surgery with Extreme Oncoplasty.

Introduction: We aimed to report the long-term surgical outcomes of extreme oncoplasty techniques in selected patients with unifocal (UF)/cT3 or multifocal-multicentric tumors (MFMC). Material and Methods: Patients who were initially recommended to have mastectomy underwent extreme oncoplastic breast-conserving surgery (eOBCS) including therapeutic reduction mammoplasty, racquet, and round-block mammoplasty, Grisotti flap, or combined technique were included. Preoperative tumor parameters, clinical outcomes, rate of local recurrence, survival, and patients' satisfaction were assessed. Results: Eighty-six patients with a median age of 51 years were followed for a median follow-up of 75 (8-154) months; 31 (36%) had cT3 and 55 (64%) had MFMC tumors. The majority of patients (83.6%) had invasive cancer. The median UF tumor size was 58 mm (range 51-100) on imaging and 51 mm (range 50-60) on final pathology. The median tumor span for MFMC was 65 mm (range 53-95) on imaging, whereas the median of the largest tumor size was 30 mm (range 22-60) on final pathology. Seventy-one patients (82.5%) were ER-positive, 17 (19.7%) were HER2 positive, and 8 (9.3%) were triple-negative breast cancer. Four patients (4.7%) required further intervention for having positive margins (3 re-excisions, 1 completion mastectomy). Three local recurrences (3.4%) and 10 (11.6%) distant metastasis occurred. The cosmetic outcome was excellent in 37 (43%) patients. No major complications were observed. Conclusions: eOBCS can be a good option for patients who initially require mastectomy. Appropriate patient selection, a multidisciplinary approach, and patient consent are essential steps of the procedure.

Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.