Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery.

Low expression of CD40L in tumor-free lymph node of oral cavity cancer related with poor prognosis.

BACKGROUND: Recently, the genetic alterations associated with tumor progression and impaired host immunity against transformed cells draw increased attention. Here, we characterized the differential gene expression patterns and protein expression in tumor-free lymph node from recurrent and non-recurrent tumors to identify independent prognostic markers for oral squamous cell carcinoma (OSCC). METHODS: A cDNA microarray analysis was performed to identify the differentially expressed genes in regional tumor-free lymph nodes from OSCC patients with and without recurrence. Then, the protein expression of the selected genes was analyzed by immunohistochemistry in 60 OSCC patients to determine their association with survival. RESULTS: Widespread down-regulation of genes involved in antigen processing and recognition in lymph nodes was a distinctive feature. In univariate Kaplan-Meier analysis, lower expression of CD40L and CD80 in tumor-free lymph nodes was significantly correlated with poorer survival. In multivariate Cox regression analysis, CD40L was identified as an independent prognostic marker of disease-free survival. CONCLUSION: Our data indicate that impaired host immunity (decreased CD40L expression) along with the TNM staging might be an important factor determining the prognosis of OSCC.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

PURPOSE: Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry. METHODS: The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs. RESULTS: Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC. CONCLUSION: This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/ß-Catenin and ERK Pathways.

In this study, we investigated the effect and mechanism of Undariopsis peterseniana, an edible brown alga, on hair growth. The treatment of vibrissa follicles with U. peterseniana extract ex vivo for 21 days significantly increased the hair-fiber lengths. The U. peterseniana extract also significantly accelerated anagen initiation in vivo. Moreover, we found that U. peterseniana extract was able to open the KATP channel, which may contribute to increased hair growth. The U. peterseniana extract decreased 5α-reductase activity and markedly increased the proliferation of dermal papilla cells, a central regulator of the hair cycle. The U. peterseniana extract increased the levels of cell cycle proteins, such as Cyclin D1, phospho(ser780)-pRB, Cyclin E, phospho-CDK2, and CDK2. The U. peterseniana extract also increased the phosphorylation of ERK and the levels of Wnt/ß-catenin signaling proteins such as glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin. These results suggested that the U. peterseniana extract had the potential to influence hair growth by dermal papilla cells proliferation through the activation of the Wnt/ß-catenin and ERK pathways. We isolated a principal of the U. peterseniana extract, which was subsequently identified as apo-9'-fucoxanthinone, a trichogenic compound. The results suggested that U. peterseniana extract may have a pivotal role in the treatment of alopecia.

Comparison of Learning Curves for Retroauricular and Transaxillary Endoscopic Hemithyroidectomy.

OBJECTIVE: This study aimed to evaluate and compare learning curves for the retroauricular (RA) and transaxillary (TA) approaches in endoscopic hemithyroidectomy. METHODS: The medical records of 290 patients who underwent hemithyroidectomy by either the RA or TA approach from November 2007 through December 2015 were retrospectively reviewed (113 patients with RA and 177 with TA). The two groups were compared with regard to patient characteristics, perioperative clinical results, and complications. Learning curves for the two approaches were compared based on the number of cases required to reach a consistent operation time and drainage amount. RESULTS: Age at diagnosis, tumor size and location, and thyroid size were not significantly different between the two approach groups. Multiplicity and extrathyroid extension were more prevalent in the RA approach (p = 0.048 and 0.020, respectively). Operation time and hospital day were significantly shorter in the RA approach (p < 0.001 and p = 0.030), while postoperative bleeding was less common in the TA approach (p = 0.021). Operation time and drainage amount stabilized after 50 cases for RA and 90 cases for TA. Additionally, operation time, amount of drainage, hospital stay, and complication rates significantly decreased after stabilization of the learning curve. When comparing the two approaches before stabilization, postoperative bleeding was more frequent in the RA approach (p = 0.044), while no difference was observed after stabilization. CONCLUSIONS: The RA approach seems to be beneficial for reducing operation time and hospital stay, and for stabilization of the learning curve. Postoperative bleeding should be considered during the period of early experience for the RA approach.

A prospective 1-year comparative study of transaxillary total thyroidectomy regarding functional outcomes: Is it really promising?

BACKGROUND: The purpose of this study was to evaluate postoperative voice outcomes and functional parameters in total thyroidectomy via a transaxillary (TA) approach. METHODS: Seventy-six patients who underwent total thyroidectomy via a TA approach (TA group) were included. A total of 204 patients who underwent conventional open total thyroidectomy (conventional group) in the same time period were analyzed as a control group. All patients underwent prospective functional evaluations before surgery and at 1 week and 1, 3, 6, and 12 months postoperatively using a comprehensive battery of functional assessments. RESULTS: There was no conversion to conventional open thyroidectomy in the TA group. Operation time and the amount of drainage were significantly higher in the TA group than in the conventional group (p < 0.001 and p = 0.033, respectively), while vocal cord paralysis, hypoparathyroidism, and hematoma were not different among two groups (p = 0.215, 0.290, and 0.385, respectively). Regarding GRBAS, the TA group showed a more aggravated tendency postoperatively, although statistical significance was attained only at postoperative 6 months (p = 0.043). The voice handicap index abruptly increased postoperatively in the TA group, showing significant differences with the conventional group at postoperative 1 week and 1 month (p < 0.001 and p = 0.001, respectively). Fundamental frequency and maximal vocal pitch did not significantly change postoperatively in either group. The conventional group showed a more rapid decline in pain than the TA group, and paresthesias on the neck and chest were more aggravated in the TA group during the early postoperative period. The dysphagia handicap index was higher in the TA group, while cosmesis was better in the TA group at all postoperative periods. CONCLUSIONS: Although cosmetic outcome was better with the TA approach, the longer operation time, aggravated subjective voice outcomes, paresthesia, and swallowing function need to be considered in selecting the operative approach.

A prospective 1-year comparative study of endoscopic thyroidectomy via a retroauricular approach versus conventional open thyroidectomy at a single institution.

OBJECTIVE: The objective of this study was to evaluate the feasibility and safety of performing an endoscopic thyroidectomy (ETE) via a retroauricular approach. METHODS: Forty-seven patients who underwent ETE via a retroauricular approach were included, and a total of 47 patients who underwent conventional open thyroid lobectomy in the same period were analyzed as a control group. All patients underwent prospective functional evaluations before the operation and 1 week, and 1, 3, 6, and 12 months postoperatively using a comprehensive battery of functional assessments. RESULTS: The mean total operative time was 152 ± 48 min, with a mean endoscopic procedure time of 58 ± 18 min. One patient developed temporary vocal fold paralysis. Although most of the parameters for the functional outcome were worse in the ETE group, these differences were transient. Subjective worsening on the voice handicap index and dysphagia handicap index normalized by 3 months postoperatively. The average pain score on a visual analog scale at 1 week after surgery was 2.84, representing a tolerable range of discomfort. The mean paresthesia/hyperesthesia score was worse in the ETE group than the open surgery group by postoperative month 6; however, these differences eventually disappeared. Thirty-six of the 47 patients in the ETE group were satisfied or extremely satisfied with the retroauricular incision by 6 months after surgery. CONCLUSIONS: ETE via a retroauricular approach is a safe, feasible, and cosmetically desirable treatment option, with outcomes comparable to conventional open thyroidectomy in the longer term.

Protective role of NecroX-5 against neomycin-induced hair cell damage in zebrafish.

NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial reactive oxygen species and reactive nitrogen species scavenger that inhibits cell death against various kinds of oxidative stresses. The objective of the present study was to evaluate the effects of NecroX-5 on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization, zebrafish larvae were exposed to 125 µM neomycin and one of the following NecroX-5 concentrations for 1 h: 10, 25, 50, and 75 µM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy (n = 10). The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage. Ultrastructural changes were evaluated using scanning electron microscopy. NecroX-5 decreased neomycin-induced hair cell loss in the neuromasts (NecroX-5 50 µM: 13.4 ± 2.0 cells, 125 µM neomycin only: 8.1 ± 1.2 cells; n = 10, P < 0.05) and decreased the TUNEL reaction. The ultrastructural analysis showed that the structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 µM neomycin and 50 µM NecroX-5. NecroX-5 decreased apoptosis and mitochondrial damage. In conclusion, NecroX-5 attenuated neomycin-induced hair cell loss in zebrafish.

Protective role of edaravone against neomycin-induced ototoxicity in zebrafish.

Aminoglycosides such as neomycin are one of the most commonly prescribed types of antibiotics worldwide. However, these drugs appear to generate free radicals within the inner ear, which can result in permanent hearing loss. We evaluated the effects of edaravone, a neuroprotective agent, on neomycin-induced ototoxicity in transgenic zebrafish. The 5-day post fertilization (dpf) zebrafish larvae were exposed to 125 µM neomycin and various concentrations of edaravone for 1 h. Hair cell survival was calculated as average numbers of the hair cells in the control group, which was not exposed to neomycin. Ultrastructural changes were evaluated using a scanning electron microscope (SEM) and transmission electron microscope (TEM). Edaravone protected against neomycin-induced hair cell loss in the neuromasts (1000 µM: 11.6 ± 1.1 cells, neomycin only: 5.5 ± 0.5 cells; n = 10, P<0.05) and decreased the TUNEL reaction for detecting apoptosis. In ultrastructural analysis, structures of mitochondria and hair cells within neuromasts were preserved in zebrafish exposed to 125 µM neomycin and 1000 µM edaravone for 1 h. Edaravone protected against neomycin-induced hair cell loss by preventing apoptosis.

Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin.

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

Biological advantages of porous hydroxyapatite scaffold made by solid freeform fabrication for bone tissue regeneration.

Presently, commercially available porous bone substitutes are manufactured by the sacrificial template method, direct foaming method, and polymer replication method (PRM). However, current manufacturing methods provide only the simplest form of the bone scaffold and cannot easily control pore size. Recent developments in medical imaging technology, computer-aided design, and solid freeform fabrication (SFF), have made it possible to accurately produce porous synthetic bone scaffolds to fit the defected bone shape. Porous scaffolds were fabricated by SFF and PRM for a comparison of physical and mechanical properties of scaffold. The suggested three-dimensional model has interconnected cubic pores of 500 µm and its calculated porosity is 25%. Whereas hydroxyapatite scaffolds fabricated by SFF had connective macropores, those by PRM formed a closed pore external surface with internally interconnected pores. SFF was supposed to be a proper method for fabricating an interconnected macroporous network. Biocompatibility was confirmed by testing the cytotoxicity, hemolysis, irritation, sensitization, and implantation. In summary, the aim was to verify the safety and efficacy of the scaffolds by biomechanical and biological tests with the hope that this research could promote the feasibility of using the scaffolds as a bone substitute.

Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish.

Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20 µm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100 µm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100 µm concentration of apocynin and a 20 µm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250 µm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

Acid-sensitive stable polymeric micelle-based oxidative stress nanoamplifier as immunostimulating anticancer nanomedicine.

Oxidative stress amplifying compounds could elicit selective killing of cancer cells with minimal toxicity to normal cells and also induce immunogenic cell death (ICD). However, compared to conventional anticancer drugs, oxidative stress amplifying compounds have inferior therapeutic efficacy. It can be postulated that the anticancer therapeutic efficacy and immunostimulating activity of oxidative stress amplifying hybrid prodrug (OSamp) could be fully maximized by employing ultrastable polymeric micelles as drug carriers. In this work, we developed tumour-targeted oxidative stress nanoamplifiers, composed of OSamp, amphiphilic poly(ethylene glycol) methyl ether-block-poly(cyclohexyloxy ethyl glycidyl ether)s (mPEG-PCHGE) and a lipopeptide containing Arg-Gly-Asp (RGD). Tumour targeted OSamp-loaded mPEG-PCHGE (T-POS) micelles exhibited excellent colloidal stability and significant cytotoxicity to cancer cells with the expression of DAMPs (damage-associated molecular patterns). In the syngeneic mouse tumour model, T-POS micelles induced significant apoptotic cell death to inhibit tumour growth without noticeable body weight changes. T-POS micelles also induced ICD and activated adaptive immune responses by increasing the populations of cytotoxic CD4+ and CD8+ T cells. Therefore, these results suggest that T-POS micelles hold great translational potential as immunostimulating anticancer nanomedicine.

Tumor-targeted redox-regulating and antiangiogenic phototherapeutics nanoassemblies for self-boosting phototherapy.

Cancer cells are equipped with abundant antioxidants such as glutathione (GSH) that eliminate reactive oxygen species (ROS) to deteriorate the therapeutic efficacy of photodynamic therapy (PDT). Another challenge in PDT is circumventing PDT-induced hypoxic condition that provokes upregulation of pro-angiogenic factor such as vascular endothelial growth factor (VEGF). It is therefore reasonable to expect that therapeutic outcomes of PDT could be maximized by concurrent delivery of photosensitizers with GSH depleting agents and VEGF suppressors. To achieve cooperative therapeutic actions of PDT with in situ GSH depletion and VEGF suppression, we developed tumor targeted redox-regulating and antiangiogenic phototherapeutic nanoassemblies (tRAPs) composed of self-assembling disulfide-bridged borylbenzyl carbonate (ssBR), photosensitizer (IR780) and tumor targeting gelatin. As a framework of tRAPs, ssBR was rationally designed to form nanoconstructs that serve as photosensitizer carriers with intrinsic GSH depleting- and VEGF suppressing ability. tRAPs effectively depleted intracellular GSH to render cancer cells more vulnerable to ROS and also provoked immunogenic cell death (ICD) of cancer cells upon near infrared (NIR) laser irradiation. In mouse xenograft models, tRAPs preferentially accumulated in tumors and dramatically eradicated tumors with laser irradiation. The design rationale of tRAPs provides a simple and versatile strategy to develop self-boosting phototherapeutic agents with great potential in targeted cancer therapy.

A new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy.

Background: Unintended parathyroidectomy occasionally happens despite meticulous capsular dissection and the histopathological location of removed parathyroid glands were traditionally classified as extracapsular, subcapsular, and intrathyroidal location. This study aimed to investigate the new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy that was difficult to be found with naked eye despite capsular dissection. Methods: This study investigated unintended parathyroidectomy that occurred in 743 patients who received thyroid surgery by reviewing pathology reports and slides. The histopathological location of unintentionally removed parathyroid glands was classified as intracapsule and extracapsule, and the intracapsular glands were further classified as completely buried in the thyroid parenchyme, partially buried, and subcapsular locations. Results: The incidence of unintended parathyroidectomy was 12.8%. Among the 103 unintentionally removed parathyroid glands, 74 (71.8%) were found intracapsular and 29 were extracapsular. Among the intracapsular glands, 57 (55.4%) parathyroid glands were found in difficult locations such as completely buried (40.8%) and partially buried (14.6%). Conclusions: The partially buried parathyroid gland can act as a risk factor for unintended parathyroidectomy comparable to intrathyroidal parathyroid gland despite the surgeon's best effort with meticulous capsular dissection. However, continued advances in visualizing technique such as autofluorescence imaging may lower the chance of incidentally removed partially buried parathyroid glands in the future.

H2O2-activatable hybrid prodrug nanoassemblies as a pure nanodrug for hepatic ischemia/reperfusion injury.

Self-assembling prodrugs are able to form stable nanoparticles without additional excipients and therefore have gained increasing interest in the field of drug delivery. As a natural derivative of vitamin A, all-trans retinoic acid (atRA) exerts antioxidant, anti-inflammatory, and immunostimulatory effects. However, the clinical translation of atRA has been hampered by its insufficient therapeutic efficacy. In this work, to fully maximize the therapeutic potential of atRA, we developed delicately designed self-assembling RABA (atRA-based hybrid prodrug) as a hybrid prodrug of atRA and hydroxybenzyl alcohol (HBA). RABA could form nanoassemblies and decompose to release atRA and HBA simultaneously in response to hydrogen peroxide (H2O2). In a mouse model of hepatic ischemia/reperfusion (IR) injury, RABA nanoassemblies accumulated in liver preferentially and exerted highly potent antioxidant, anti-inflammatory, and antiapoptotic effects, leading to effective protection of liver from IR injury. RABA nanoassemblies exhibited significantly higher therapeutic efficacy than the combination of equivalent atRA and HBA. Given its H2O2-responsiveness, self-assembling and self-immolating behaviors, and cooperative therapeutic actions, RABA nanoassemblies have great potential as a pure nanodrug for hepatic IR injury. This study also provides a new valuable addition in the development of prodrug self-assemblies that will emerge as next generation of drugs.

Generation of induced pluripotent stem cell line (KRIBBi004-A) from adult bone marrow CD34+ cells from a patient carrying 46,XX,t(1;5)(p31.1;35.1) karyotype.

Induced pluripotent stem cell (iPS) technology may be advantageous for the study of genetic aberrations in terms of recapitulating the full manifestation of pathological features in vitro, identifying underlying pathways, and developing personalized therapeutics rather than procuring somatic cells from patients. Here, we derived an iPSC line from a patient with reciprocal chromosome translocation, t(1;5)(p31.1;35.1), as a novel alternative model to identify clinical phenotypes induced by genetic instability. The resulting iPSC line generated from somatic cells with an existing instability showed representative characteristics of PSCs, and might serve as an unparalleled cellular resource for the development of a custom remedy.

Motility induction in breast carcinoma by mammary epithelial laminin 332 (laminin 5).

Host interactions with tumor cells contribute to tumor progression by several means. This study was done to determine whether mammary epithelium could interact with breast carcinoma by producing substances capable of inducing motility in the cancer cells. Conditioned medium of immortalized 184A1 mammary epithelium collected in serum-free conditions induced dose-dependent motility in the MCF-7 breast carcinoma cell line by both a semiquantitative scattering assay and a Boyden chamber assay. Purification of the motility factor revealed that it was laminin 332 (formerly laminin 5) by mass spectroscopy. A Western blot of the 184A1 conditioned medium using a polyclonal antibody confirmed the presence of laminin 332 in the conditioned medium. Blockage of the motility with antibodies to the laminin 332 and its receptor components, alpha(3) and beta(1) integrins, provided further evidence that tumor cell motility was caused by the laminin 332 in the conditioned medium. Invasion of MCF-7, BT-20, and MDA-MB-435 S was induced by purified laminin 332 and 184A1 conditioned medium and blocked by an anti-alpha(3) integrin antibody. Staining of carcinoma in situ from breast cancer specimens revealed that laminin 332 in the myoepithelium adjacent to the preinvasive cells provided a source of laminin 332 that could potentially encourage the earliest steps of stromal invasion. In metaplastic breast carcinomas, the presence of laminin 332-producing cells coexpressing alpha(3) integrin and the greater metastatic potential of tumors with higher laminin 332 levels suggest that laminin 332 expression is associated with aggressive features in these human breast cancers.

Residual breast cancer diagnosed by MRI in patients receiving neoadjuvant chemotherapy with and without bevacizumab.

PURPOSE: To investigate the impact of antiangiogenic therapy with bevacizumab on pathological response and the diagnostic performance of magnetic resonance imaging (MRI) in breast cancer patients. METHODS: Thirty-six patients (aged 31-69 years) with breast cancer were included. Sixteen patients received neoadjuvant chemotherapy (NAC) containing bevacizumab, and 20 patients received the same NAC protocol without bevacizumab. Serial MRI studies were performed to evaluate response. All patients received surgery after completing NAC. The extent of residual disease was examined by histopathology, and classified into three types (pCR-pathologic complete response, confined nodules, and scattered cells). Fisher's exact test and general logistic regression models were applied to analyze differences between two groups. RESULTS: pCR rates and residual disease (nodular and scattered cell) patterns were comparable between the two groups. The diagnostic accuracy rate of MRI (true positive and true negative) was 13/17 (76%) for patients with bevacizumab, and 14/20 (70%) for patients without bevacizumab. The size measured on MRI was accurate for mass lesions that shrank down to nodules, showing <0.7 cm discrepancy from pathological size. For residual disease presenting as scattered cells within a large fibrotic region, MRI could not predict them correctly, resulting in a high false-negative rate and a large size discrepancy. CONCLUSION: The pathological response and the diagnostic performance of MRI are comparable between patients receiving NAC with and without bevacizumab. In both groups MRI has a limitation in detecting residual disease broken down to small foci and scattered cells/clusters. When MRI is used to evaluate the extent of residual disease for surgical treatment, the limitations, particularly for nonmass lesions, should be considered.

Comparison of functional outcomes after total thyroidectomy and completion thyroidectomy: Hypoparathyroidism and postoperative complications.

OBJECTIVE: This study aimed to investigate differences in functional outcomes of postoperative complications and hypoparathyroidism between patients who underwent completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT) as an initial treatment. MATERIALS AND METHODS: We retrospectively analyzed the differences of functional outcomes after completion thyroidectomy and total thyroidectomy without lymph node dissection. We reviewed the medical records of 396 patients who underwent CT or TT for thyroid disease at Korea University Guro Hospital from March 2002 to August 2016. RESULTS: Of the 396 patients, 32 underwent CT and 364 underwent TT. There were 72 male patients and 324 female patients. Transient hypoparathyroidism was observed in 4 (9.4%) of the CT patients and 97 (26.6%) of the TT patients, with a statistically significant difference (p=0.031). Permanent hypoparathyroidism was observed in 1 patient (3.1%) in the CT group and in 13 patients (3.6%) in the TT group, which was not significantly different. There were no significant differences in the postoperative complication of temporary recurrent laryngeal nerve injury, wound infection, and hematoma between two patients group. CONCLUSION: The incidence of transient hypoparathyroidism in CT patients was significantly lower than in TT patients. These safety and functional superiority of CT should be considered when determining the scope and extent of operation in patients requiring surgery for thyroid disease.