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Chylous fistulas (CF) are rare surgical complications and there is no standard treatment. This study presents the treatment modalities performed on patients who developed CF over a 10-year period. During the observation period, CF developed in 29 patients, 16 of whom were women. The mean age was 55.76± 13.48. Lymphatic duct injury was mostly seen in the abdomen (58.6%) and the most common reason was nephrectomy (20.7%). Extended lymphatic dissection due to malignancy was performed in 82.7% of all cases. Chylous leakage started postoperatively on 3.78±3.94 days (range: 1-19 days). Fasting, total parenteral nutrition (TPN), and somatostatin treatment were applied to all patients, and 75.8% of the fistulas were resolved completely with medical treatment. Surgical ligation of the lymphatic canal was performed in 7 patients. One was not successful and underwent percutaneous embolization of the thoracic lymphatic leakage cavity. All fistulas were resolved in 18.18±10.4 days. The resolution time and hospital stay were significantly higher in thoracic fistulas (p=0.017; p=0.003, respectively). In addition, malignant cases had longer resolution time (32.40±28.72 vs 16.27±11.25, p=0.036) and hospital stay (35.0±29.74 vs 16.25±14.05p= 0.002 respectively) than non-malignant. There was no chylothorax, chylous ascites, or recurrence at 20.55±22.88 months follow-up. Treatment of CF with fasting, TPN, and somatostatin somatostatin analogs are effective. Other interventions such as surgical ligation with or without fibrin glue and interventional radiology treatments may be considered when conservative treatments fail. [ABSTRACT FROM AUTHOR]

Background: This study aims to identify factors predicting recurrence and unfavorable prognosis in cN+ patients who have undergone sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC)., Methods: The retrospective multi-centre "MF18-02" and the prospective multi-centre cohort registry trial "MF18-03" (NCT04250129) included patients with cT1-4N1-3M0 with SLNB+/- axillary lymph node dissection (ALND) post-NAC., Results: A total of 2407 cN+ patients, who later achieved cN0 status after NAC and subsequently underwent SLNB, were studied. The majority had cT1-2 (79.1%) and N1 (80.7%). After a median follow-up time of 41 months, the rates of locoregional recurrence and axillary recurrence (AR) were 1.83% and 0.37%, respectively. No significant difference in locoregional recurrence or AR rates was observed between the SLNB/targeted axillary dissection-only (n = 1470) and ALND (n = 937) groups. Factors significantly linked with AR included age younger than 45 years, nonpathological complete response (non-pCR) in the breast, and nonluminal pathology. Locoregional recurrences were associated with nonluminal or HER2(+) pathology, non-pCR in the breast, and ALND. Poor prognostic factors for disease-free survival (DFS) included having cT3-T4, no breast pCR (non-pCR), ypN(+), and nonluminal pathology. No significant difference was found in DFS or disease-specific survival (DSS) rates among ypN0, ypN-isolated tumour cells, ypNmic, and ypN1. However, significant decreases in DFS and DSS rates were observed when comparing ypN2 or ypN3 disease with ypN0., Conclusions: The present large registry data indicate that younger patients (<45), those with nonluminal pathology, and those who only partially respond in the breast are more susceptible to axillary and locoregional recurrences., Competing Interests: Disclosures: The authors declare that they have no conflict of interest., (© 2024. Society of Surgical Oncology.)

Importance: Increasing evidence supports the oncologic safety of de-escalating axillary surgery for patients with breast cancer after neoadjuvant chemotherapy (NAC)., Objective: To evaluate the oncologic outcomes of de-escalating axillary surgery among patients with clinically node (cN)-positive breast cancer and patients whose disease became cN negative after NAC (ycN negative)., Design, Setting, and Participants: In the NEOSENTITURK MF-1803 prospective cohort registry trial, patients from 37 centers with cT1-4N1-3M0 disease treated with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) alone or with ypN-negative or ypN-positive disease after NAC were recruited between February 15, 2019, and January 1, 2023, and evaluated., Exposure: Treatment with SLNB or TAD after NAC., Main Outcomes and Measures: The primary aim of the study was axillary, locoregional, or distant recurrence rates; disease-free survival; and disease-specific survival. Number of axillary lymph nodes removed was also evaluated., Results: A total of 976 patients (median age, 46 years [range, 21-80 years]) with cT1-4N1-3M0 disease underwent SLNB (n = 620) or TAD alone (n = 356). Most of the cohort had a mapping procedure with blue dye alone (645 [66.1%]) with (n = 177) or without (n = 468) TAD. Overall, no difference was found between patients treated with TAD and patients treated with SLNB in the median number of total lymph nodes removed (TAD, 4 [3-6] vs SLNB, 4 [3-6]; P = .09). Among patients with ypN-positive disease, those who underwent TAD were more likely to have a lower median lymph node ratio (TAD, 0.28 [IQR, 0.20-0.40] vs SLNB, 0.33 [IQR, 0.20-0.50]; P = .03). At a median follow-up of 39 months (IQR, 29-48 months), no significant difference was found in the rates of ipsilateral axillary recurrence (0.3% [1 of 356] vs 0.3% [2 of 620]; P ≥ .99) or locoregional recurrence (0.6% [2 of 356] vs 1.1% [7 of 620]; P = .50) between the TAD and SLNB groups, with an overall locoregional recurrence rate of 0.9% (9 of 976). The initial clinical tumor stage, pathologic complete response, and use of blue dye alone as a mapping procedure were not associated with the outcome. Even though patients with TAD demonstrated an increased disease-free survival rate compared with the SLNB group, this difference did not reach statistical significance (94.9% vs 92.6%; P = .07). Factors associated with decreased 5-year disease-specific survival were cN2-3 axillary stage (cN1, 98.7% vs cN2-3, 96.8%; P = .03) and nonluminal type tumor pathologic characteristics (luminal, 98.9% vs nonluminal, 96.9%; P = .007)., Conclusions and Relevance: The short-term results suggest very low rates of axillary and locoregional recurrence in a select group of patients with cN-negative disease after NAC treated with TAD alone or SLNB alone followed by regional nodal irradiation regardless of the SLNB technique or nodal pathology. Whether TAD might provide a clear survival advantage compared with SLNB remains to be proven in studies with longer follow-up.

Background: The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC., Methods: A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation., Results: Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n = 353) or TAD alone (n = 148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n = 2) and 0.8% (n = 4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LN of one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence., Conclusions: The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Papillary microcarcinomas (PMCs) are papillary carcinomas ≤1 cm in size, with an increasing incidence. Although generally indolent, some cases exhibit aggressive behavior. Recently, active surveillance has been recommended to avoid surgical treatment. Identifying molecular changes that predict aggressiveness in PMCs has gained importance, but studies are limited. We aimed to demonstrate TERT expression and BRAF V600E positivity immunohistochemically in PMCs and correlate them with histomorphological features, subtypes, and clinicopathological findings. We included 95 PMC cases diagnosed between 2010 and 2019 at the Department of Pathology, Faculty of Medicine, XXX University. We investigated TERT expression using RT-PCR. We evaluated BRAF V600E mutation immunohistochemically. We evaluated the relationship between genetic, histomorphological, and clinicopathological findings. In patients with multifocality and those with a tumor size ≥0.5 cm, the frequency of lymph node metastasis was significantly higher. A positive correlation was shown between BRAF V600E positivity and lymph node metastasis, lymphovascular invasion, advanced disease stage, and classical subtype by univariate analyses. We detected TERT expression in 18 of 95 patients (7.8 %). No relationship could be detected between TERT expression alone or combined with BRAF positivity and clinicopathological features. Although TERT mutations are associated with aggressiveness in thyroid cancers, this association was absent in PMCs. The presence of TERT expression was demonstrated in some cases. However, TERT expression could not be associated with clinicopathological findings, which is consistent with the literature suggesting that TERT plays a role in advanced stages of carcinogenesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of our study is to determine the value of Thyroid Imaging Reporting and Data Systems (TIRADS) scoring in predicting malignancy in thyroid nodules by examining its relationship with fine needle aspiration biopsy and postoperative histopathological results., Materials and Methods: In this study, patients who underwent surgery after ultrasonographic examination and fine needle aspiration biopsy for thyroid nodules at the General Surgery Clinic of Çukurova University Faculty of Medicine between January 2014 and November 2021 were retrospectively analyzed. The thyroid ultrasonography and fine needle aspiration biopsy of the included patients were performed by a clinician with 15 years of experience. The ultrasonographic features of the nodules were re-evaluated by the same clinician, and the American College of Radiology (ACR) TIRADS score was determined. Fine needle aspiration biopsy results were grouped according to Bethesda criteria. Postoperative histopathological examination results were divided into two groups: benign and malignant. The ACR TIRADS score was compared with fine needle aspiration biopsy and histopathological results. The performance of the ACR TIRADS score in predicting malignancy was determined., Results: 79.8% of the 397 patients were female, and the mean age was 50.9 ± 12.8 years. The mean diameter of the nodules was 27.4 ± 15.8 mm. There was a significant, positive, but weak correlation between ACR TIRADS and Bethesda (p < 0.001) (r = 0.33). When the ACR TIRADS score was compared with histopathological results, it was found that the rate of malignancy increased as the TIRADS score increased (p < 0.001). The rates of malignancy diagnosis were 0% for TR1, 13.2% for TR2, 21.7% for TR3, 50.3% for TR4, and 72.4% for TR5. The area under the receiver operating characteristic curve for TIRADS in predicting malignancy was 0.747 (95% CI: 0.699-0.796, p < 0.001). TIRADS can distinguish malignancy with 75% accuracy. The optimal cutoff point was determined as TR4 with 80.3% sensitivity and 60.8% specificity., Conclusion: The ACR TIRADS scoring system is an effective risk classification system for thyroid nodules, providing 75% accuracy in predicting malignancy, with 80.3% sensitivity and 60.8% specificity values., (© 2024 Wiley Periodicals LLC.)

Macroautophagy/autophagy is an evolutionarily conserved cellular stress response mechanism. Autophagy induction in the tumor microenvironment (stroma) has been shown to support tumor metabolism. However, cancer cell-derived secreted factors that initiate communication with surrounding cells and stimulate autophagy in the tumor microenvironment are not fully documented. We identified CTF1/CT-1 (cardiotrophin 1) as an activator of autophagy in fibroblasts and breast cancer-derived carcinoma-associated fibroblasts (CAFs). We showed that CTF1 stimulated phosphorylation and nuclear translocation of STAT3, initiating transcriptional activation of key autophagy proteins. Additionally, following CTF1 treatment, AMPK and ULK1 activation was observed. We provided evidence that autophagy was important for CTF1-dependent ACTA2/α-SMA accumulation, stress fiber formation and fibroblast activation. Moreover, promotion of breast cancer cell migration and invasion by activated fibroblasts depended on CTF1 and autophagy. Analysis of the expression levels of CTF1 in patient-derived breast cancer samples led us to establish a correlation between CTF1 expression and autophagy in the tumor stroma. In line with our in vitro data on cancer migration and invasion, higher levels of CTF1 expression in breast tumors was significantly associated with lymph node metastasis in patients. Therefore, CTF1 is an important mediator of tumor-stroma interactions, fibroblast activation and cancer metastasis, and autophagy plays a key role in all these cancer-related events. Abbreviations: ACTA2/α-SMA: actin, alpha 2, smooth muscle CAFs: cancer- or carcinoma-associated fibroblasts CNT Ab.: control antibody CNTF: ciliary neurotrophic factor CTF1: cardiotrophin 1 CTF1 Neut. Ab.: CTF1-specific neutralizing antibody GFP-LC3 MEF: GFP-fused to MAP1LC3 protein transgenic MEF LIF: leukemia inhibitory factor IL6: interleukin 6 MEFs: mouse embryonic fibroblasts MEF-WT: wild-type MEFs OSM: oncostatin M TGFB/TGFβ: transforming growth factor beta.