Fibrin Glue Reduces the Duration of Lymphatic Drainage after Lumpectomy and Level II or III Axillary Lymph Node Dissection for Breast Cancer: A Prospective Randomized Trial

This randomized prospective study investigated the effect of fibrin glue use on drainage duration and overall drain output after lumpectomy and axillary dissection in breast cancer patients. A total of 100 patients undergoing breast lumpectomy and axillary dissection were randomized to a fibrin glue group (N=50; glue sprayed onto the axillary dissection site) or a control group (N=50). Outcome measures were drainage duration, overall drain output, and incidence of seroma. Overall, the fibrin glue and control groups were similar in terms of drainage duration, overall drain output, and incidence of seroma. However, subgroup analysis showed that fibrin glue use resulted in a shorter drainage duration (3.5 vs. 4.7 days; p=0.0006) and overall drain output (196 vs. 278 mL; p=0.0255) in patients undergoing level II or III axillary dissection. Fibrin glue use reduced drainage duration and overall drain output in breast cancer patients undergoing a lumpectomy and level II or III axillary dissection

Prognostic Value of p53 and bcl-2 Expression in Patients Treated with Breast Conservative Therapy

Prognostic value of p53 and bcl-2 expression on treatment outcome in breast cancer patients has been extensively evaluated, but the results were inconclusive. We evaluated the prognostic significance of these molecular markers in patients treated with breast conserving surgery and radiotherapy. One hundred patients whose immunostaining of p53 and bcl-2 expression was available among 125 patients who underwent radiotherapy after breast conserving surgery and axillary lymph node dissection were enrolled into this study. Eighty-seven patients also received adjuvant chemotherapy and/or hormonal therapy. Conventional clinicopathologic variables and treatment-related factors were also considered. The 5-yr loco-regional relapse-free and distant metastasis-free survival rates were 91.7% and 90.9%, respectively. On univariate analysis, age, T stage and the absence of bcl-2 & estrogen receptor (ER) expression were associated with loco-regional relapse-free survival. When incorporating these variables into Cox proportional hazard model, only bcl-2(-)/ER(-) phenotype was an adverse prognostic factor (P=0.018). As for the distant metastasis-free survival, age, T stage, and p53 expression were significant on univariate analysis. However, p53 expression was the only prognosticator on multivariate analysis (P=0.009). A bcl-2(-)/ER(-) phenotype and p53 expression are useful molecular markers predicting loco-regional relapse-free and distant metastasis-free survival, respectively, in patients treated with breast conserving surgery and radiotherapy

The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency

In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4+/+ BMDCs was not observed in TLR4-/- BMDCs. Furthermore, FAP induced DC-mediated CD8+ T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis

IntroductionTo evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM).MethodsWe retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas.ResultsA total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800).ConclusionSupradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC.Trial registrationClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1)

Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells

Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism

Limitations of Conventional Contrast-enhanced MRI in Selecting Sentinel Node Biopsy Candidates among DCIS Patients

Purpose: A better predictive model for occult invasive disease in ductal carcinoma in situ (DCIS) patients is essential to guide the tailored use of sentinel node biopsies. We hypothesized that recent improvement of contrast-enhanced breast magnetic resonance imaging (MRI) could provide more accurate information on the presence of occult invasion in DCIS patients. Methods: From a prospectively maintained database, we identified 143 DCIS patients diagnosed with needle biopsies in whom MRI images were available. Results: Sixty-five patients (45.5%) were upstaged to invasive carcinoma after curative surgery. Ultrasonographic lesion size, mass-appearance on mammography, type of needle used, and the presence of suspicious microinvasive foci were associated with increased likelihood of upstaging. Among the features of MRI, only mass-appearance was significantly associated with the presence of invasive disease (p=0.002). However, up to 50% of masses in MRI cases had mass-appearance on mammography as well. Other morphologic and pharmacokinetic features of MRI, such as shape, margin, and patterns of enhancement and washout, did not have a significant association. Conclusion: Among various morphologic and pharmacokinetic parameters of contrast-enhanced MRI, only mass-appearance was associated with occult invasive disease. Our results show the limitations of current contrast-enhanced MRI in predicting invasive disease in patients with preoperative diagnoses of DCIS.Moon HG, 2009, ANN ONCOL, V20, P636, DOI 10.1093/annonc/mdn683Kuerer HM, 2009, J CLIN ONCOL, V27, P279, DOI 10.1200/JCO.2008.18.3103HU M, 2009, P NATL ACAD SCI USA, V106, P3372Gadre SA, 2008, HISTOPATHOLOGY, V53, P545, DOI 10.1111/j.1365-2559.2008.03152.xOkumura Y, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-287Sakorafas GH, 2008, CANCER TREAT REV, V34, P483, DOI 10.1016/j.ctrv.2008.03.001Morrow M, 2008, ANN SURG ONCOL, V15, P2641, DOI 10.1245/s10434-008-0083-zPorembka MR, 2008, ANN SURG ONCOL, V15, P2709, DOI 10.1245/s10434-008-9947-5Lee JW, 2008, J SURG ONCOL, V98, P15, DOI 10.1002/jso.21077Hu M, 2008, CANCER CELL, V13, P394, DOI 10.1016/j.ccr.2008.03.007Ansari B, 2008, BRIT J SURG, V95, P547, DOI 10.1002/bjs.6162Orel S, 2008, J CLIN ONCOL, V26, P703, DOI 10.1200/JCO.2007.14.3594Facius M, 2007, CLIN IMAG, V31, P394, DOI 10.1016/j.clinimag.2007.04.030Kuhl CK, 2007, LANCET, V370, P485Jung EJ, 2007, INT J CANCER, V120, P2331, DOI 10.1002/ijc.22434Nielsen BS, 2007, INT J CANCER, V120, P2086, DOI 10.1002/ijc.22340van der Velden APS, 2006, AM J SURG, V192, P172, DOI 10.1016/j.amjsurg.2006.02.026Goyal A, 2006, BREAST CANCER RES TR, V98, P311, DOI 10.1007/s10549-006-9167-2Mansel RE, 2006, J NATL CANCER I, V98, P599, DOI 10.1093/jnci/djj158Lyman GH, 2005, J CLIN ONCOL, V23, P7703, DOI 10.1200/JCO.2005.08.001Wilkie C, 2005, AM J SURG, V190, P563, DOI 10.1016/j.amjsurg.2005.06.011Groves AM, 2005, MAGN RESON IMAGING, V23, P733, DOI 10.1016/j.mri.2005.06.003Hylton N, 2005, J CLIN ONCOL, V23, P1678, DOI 10.1200/JCO.2005.12.002Leonard GD, 2004, J NATL CANCER I, V96, P906, DOI 10.1093/jnci/djh164Hata T, 2004, J AM COLL SURGEONS, V198, P190, DOI 10.1016/j.jamcollsurg.2003.10.008Hwang EW, 2003, ANN SURG ONCOL, V10, P381, DOI 10.1245/ASO.2003.03.085*AM COLL RAD, 2003, ACR BI RADS BREAST IMorrow M, 2002, CA-CANCER J CLIN, V52, P277Jackman RJ, 2001, RADIOLOGY, V218, P497Brown LF, 1999, CLIN CANCER RES, V5, P1041

Homing-Associated Cell Adhesion Molecules and Cell Cycle Status on the Nucleated Cells in the Bone Marrow, Mobilized Peripheral Blood and Cord Blood

Homing-associated cell adhesion molecules (H-CAM) on the CD34+ cells play an important role for the engraftment process following hematopoietic stem cell transplantation (HSCT). However, it seems that not only CD34+ cells but also other nucleated cells (NCs) with H-CAM could be implicated in the engraftment process and the proliferation of hematopoietic stem cells. We investigated the differences of H-CAM and cell cycle status on the NCs in cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PB). The proportions of CXCR4+ cells within the NC populations were greater in CB than in PB or BM (p=0.0493), although the proportions of CXCR4+, CD44+, and CD49d+ cells within the CB CD34+ cell populations were same within BM or PB. A lower proportion of CD34+CD49d+ cells within the CD34+ cell populations was more noted in CB than in PB or BM (p=0.0085). There were no differences in cell cycle status between CB and BM or PB. Our results suggest that the migrating potential of CB would be enhanced with increased CXCR4 expression on the NCs, but the adhesion potential of CB CD34+ cells would be less than that of PB and BM. These findings may help explain why the lower cell dose is required and engraftment is delayed in cord blood stem cell transplantation

Erratum to: Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made

Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence. Methods The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period. Results The summary PARs for modifiable reproductive factors were 16.7 % (95 % CI 15.8–17.6) for breast cancer (2404 cases) and 81.9 % (95 % CI 55.0–100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0 %), total period of breastfeeding (3.1 %), oral contraceptive use (5.3 %), and hormone replacement therapy use (0.3 %) for breast cancer and included breastfeeding experience (2.9 %), pregnancy (1.2 %), tubal ligation (24.5 %), and oral contraceptive use (53.3 %) for ovarian cancer. Conclusions Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7 % and 81.9 %, respectively