Initial conservative therapy is applied to all cases of chylothorax (CTx) with expected excellent outcomes. The indication for aggressive surgical treatment of early CTx remains uncertain and requires rigorous scientific scrutiny. Lymphangiography and lymphoscintigraphy are useful to localize the leak and assess thoracic duct patency as well as to differentiate partial from complete thoracic duct transection. The aetiology of the CTx, flow rate and patient condition dictate the preferred management. Octreotide/somatostatin and etilefrine therapy is highly efficacious in the conservative management of CTx. For patients in whom conservative management fails, those who are good surgical candidates, and those in whom the site of the leak is well identified, surgical repair and/or ligation using minimally invasive techniques is highly successful with limited adverse outcomes. Similarly, if the site of the chylous effusion cannot be well visualized, a thoracic duct ligation via video-assisted thoracic surgery is the gold standard approach. A pleuroperitoneal or less often a pleurovenous shunt is a final option and may be curative in some patients.
Tissue biopsy is the gold standard for diagnosis and morphological and immunohistochemical analyses to characterize cancer. However, tissue biopsy usually requires an invasive procedure, and it can be challenging depending on the condition of the patient and the location of the tumor. Even liquid biopsy analysis of body fluids such as blood, saliva, gastric juice, sweat, tears and cerebrospinal fluid may require invasive procedures to obtain samples. Liquid biopsy can be applied to circulating tumor cells (CTCs) or nucleic acids (NAs) in blood. Recently, urine has gained popularity due to its less invasive sampling, ability to easily repeat samples, and ability to follow tumor evolution in real-time, making it a powerful tool for diagnosis and treatment monitoring in cancer patients. With the development and advancements in extraction methods of urinary substances, urinary NAs have been found to be closely related to carcinogenesis, metastasis, and therapeutic response, not only in urological cancers but also in non-urological cancers. This review mainly highlights the components of urine liquid biopsy and their utility and limitations in oncology, especially in non-urological cancers.
Breast cancer is a diverse disease that requires a fully integrated multidisciplinary approach. Breast surgery has undergone a revolutionary change leading us from the conventional radical mastectomy of the Halstedian era to the current motion of nipple sparing mastectomy (NSM). Despite the lack of randomized controlled trials, the technique of NSM continues to gain popularity as a prophylactic procedure in high risk patients. The current indications for NSM, if any, in the treatment of early invasive breast cancer remains uncertain and requires rigorous scientific scrutiny. This article aims to critically review the indications and limitations of NSM, discuss evidence based intra-operative protocols and to discuss ways in which radiation therapy may be incorporated in treatment planning following NSM. A comprehensive search of the scientific literature was carried out using PubMed to access all publications related to nipple sparing mastectomy. The search focused specifically on technique, current management, safety, and complications of these procedures. Keywords searched included "Nipple sparing mastectomy,""breast conserving surgery,""Nipple areola complex preservation" and "skin sparing mastectomy." NSM offers an opportunity to preserve native breast envelope without mutilation of nipple-areola complex (NAC), and avoids multiple surgical procedures required for reconstruction. NSM may be a reasonable alternative for prophylactic and select breast cancer patients without NAC involvement; however, oncological safety of NSM has not yet been fully demonstrated. Best available evidence suggests that patients should be selected based on study of breast duct anatomy by breast Magnetic Resonance Imaging, mammographic distance between tumor and nipple and obligatory intra-operative frozen section from retro-areolar tissue. Additional factors such as tumor size, axillary lymph node status, lymphovascular invasion and degree of intraductal component are also being used to either include or exclude NSM candidates based on institutional protocols. Heterogeneity of patients selected for NSM is great and the lack of standardization of preoperative investigations, intra-operative technique and pathologic sampling of retro-areola tissues mandates a multi-institutional prospective study to define and validate a role for NSM in invasive breast cancer and DCIS. Nipple necrosis or sloughing is an important problem after NSM which can be greatly reduced using alternative skin incisions. Even if the nipple survives, an insensate nipple and lack of sexual function is common and requires preoperative counseling and discussion. Finally the relation and timing of intra-operative versus adjuvant breast radiation and tailoring of dosage and delivery methods has not been fully explored. Although NSM reduces the psychological trauma associated with nipple loss, the oncologic safety as well as functional and aesthetic outcomes needs additional investigation.
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with higher mortality than the others. Pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is considered as a surrogate to predict survival. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is a negative regulator of T cell activation, and reduction in ITPKC function is known to promote Kawasaki disease. Given the role of tumor infiltrating lymphocytes in NAC and since TNBC has the most abundant immune cell infiltration in breast cancer, we hypothesized that the ITPKC expression level is associated with NAC response and prognosis in TNBC. The ITPKC gene was expressed in the mammary gland, but its expression was highest in breast cancer cells among other stromal cells in a bulk tumor. ITPKC expression was highest in TNBC, associated with its survival, and was its independent prognostic factor. Although high ITPKC was not associated with immune function nor with any immune cell fraction, low ITPKC significantly enriched cell proliferation-related gene sets in TNBC. TNBC with low ITPKC achieved a significantly higher pCR rate after NAC. To the best of our knowledge, this is the first report to demonstrate that ITPKC gene expression may be useful as a prognostic and predictive biomarker in TNBC.
Mild cold stress induced by housing mice with a 4T1 triple-negative breast cancer (TNBC) cell implantation model at 22 °C increases tumor growth rate with a pro-tumorigenic immune microenvironment (lower CD8 +T cells, higher myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs)). Since cold stress also activates thermogenesis, we hypothesized that enhanced thermogenesis is associated with more aggressive cancer biology and unfavorable tumor microenvironment (TME) in TNBC patients. A total of 6479 breast cancer patients from METABRIC, TCGA, GSE96058, GSE20194, and GSE25066 cohorts were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) thermogenesis score. High-thermogenesis TNBC was associated with a trend towards worse survival and with angiogenesis, adipogenesis, and fatty acid metabolism pathways. On the other hand, low-thermogenesis TNBC enriched most of the hallmark cell-proliferation-related gene sets (i.e., mitotic spindle, E2F targets, G2M checkpoint, MYC targets), as well as immune-related gene sets (i.e., IFN-α and IFN-γ response). Favorable cytotoxic T-cell-attracting chemokines CCL5, CXCL9, CXCL10, and CXCL11 were lower; while the MDSC- and Treg-attracting chemokine CXCL12 was higher. There were higher M2 but lower M1 macrophages and Tregs. In conclusion, high-thermogenesis TNBC is associated with pro-tumor immune microenvironment and may serve as biomarker for testing strategies to overcome this immunosuppression.