Animation Deformity: Evaluating the Role of Morphotopologic Features in Suggesting Preventive Surgical Procedures.

BACKGROUND: Animation deformity is an undesirable complication after subpectoral implant reconstruction and is defined as skin distortion during activation of the pectoralis major muscle. However, detailed anatomical features of deformities have yet to be clarified. This study aimed to elucidate how (morphology) and where (topology) animation deformity occurs in reconstructed breasts, and to assess causes and prevention of animation deformity. METHODS: This study included 100 consecutive patients with breast cancer, who underwent unilateral subpectoral implant reconstruction. Animation deformity was evaluated, and the patients were grouped according to both morphologic and topologic features. Univariate and multivariate analyses were performed to identify independent factors associated with deformities. RESULTS: The patients were divided into three groups based on skin distortions with or without implant movement: group I, 60 patients with upper-medial dimpling; group II, 41 patients with upper-lateral folding; and group III, 52 patients with mid-lower lines. Overall, 86 patients (86 percent) showed one or more types of deformity. Among the patients with animation deformity, 24 (28 percent) had implant movement. The authors' study identified axillary dissection as an independent factor for the upper-lateral folding group (OR, 0.30), implant volume for the mid-lower lines group (OR, 1.01), and age for implant movement (OR, 1.06). CONCLUSIONS: Animation deformity was commonly observed in the cohort of patients who underwent subpectoral implant reconstruction and exhibited three morphotopologic patterns of deformity. The current study demonstrated that the morphotopologic grouping of animation deformity may assist in suggesting possible causes and preventive surgical procedures for these deformities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Cardiopulmonary Bypass Surgery in a Patient with Unexpected Heparin-Induced Thrombocytopenia.

We report a case of a 77-year-old woman with massive pulmonary embolism associated with heparin-induced thrombocytopenia. Before developing a pulmonary embolism, the patient underwent gastrectomy due to gastric cancer and received subcutaneous heparin calcium for deep venous thrombosis prophylaxis for 5 d. Then, thrombectomy with cardiopulmonary bypass using full heparinization was successfully performed. The patient was definitively diagnosed with this condition postoperatively, based on elevated serum antibody levels, in addition to pre- and postoperative thrombocytopenia and thrombosis. Intravenous heparin therapy was switched to argatroban. Although it is uncommon, clinicians should consider this condition in patients with a history of heparin exposure.

Off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in a patient with total laryngectomy and a permanent tracheostoma.

Median sternotomy is the standard approach for coronary artery bypass grafting. Herein, we performed off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in an unstable angina pectoris patient with total laryngectomy and a permanent tracheostoma. In this patient, median sternotomy had high risks of surgical-site infection and tracheal injury. To avoid these risks, we selected left anterior thoracotomy. Initially, it was difficult to expose the ascending aorta and postdescending branch. With extension of the skin incision to the median area and division of the 5th and 6th ribs and costal arch, we could expose the anastomotic sites, including the ascending aorta and postdescending branch, without median sternotomy conversion. We performed multiple coronary artery bypass graft procedures safely. This approach might be an additional surgical option in patients with total laryngectomy and a permanent tracheostoma.

Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature.

We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines.

Eventual relapse of tumor growth is commonly observed in head and neck cancer patients, following treatment with platinum-based chemotherapies. This occurrence is believed to be related to the failure to eradicate drug resistant, cancer stem cell (CSC) niches, thereby enriching their population in tumors after treatment. In this study, we show that in contrast to free cisplatin (CDDP), the polymer micelle-based nanomedicine incorporating cisplatin (CDDP/m), can eradicate both the undifferentiated cell and the differentiated cancer cell populations within a head and neck tumor model. Immunohistochemistry of treated tumors showed that opposing to CDDP treatment, CDDP/m could reduce tumor growth without concentrating the CSC-like population. We further showed that CDDP/m, but not CDDP, can localize into hypoxic regions, possibly CSC-rich areas, in the tumors, and can overcome their detoxification mechanism based-on high cellular expression of glutathione to successfully deliver Pt to nuclear DNA. Our data suggests CDDP/m to be a replacement for current platinum therapies, for its ability to eradicate both bulk and CSC-like populations, and in turn to prevent recurrence of tumor growth.

cRGD-installed polymeric micelles loading platinum anticancer drugs enable cooperative treatment against lymph node metastasis.

Lymph node metastasis (LNM) is correlated with decreased survival, indicating high tumor malignancy and being a potential source for subsequent fatal metastases. Targeted therapies inhibiting the formation of LNM, while eliminating established metastatic foci, could provide synergistic effects by reducing the incidence and growth of metastasis. Based on the inhibitory activity of cRGD peptide against the development of metastasis, and the LNM targeting ability of systemically injected drug-loaded polymeric micelles, herein, we studied the capability of cRGD-installed polymeric micelles incorporating the platinum anticancer drug (1,2-diaminocylohexane)platinum(II) (DACHPt) for cooperatively inhibiting the formation and progression of LNM. As cRGD-installed DACHPt-loaded micelles (cRGD-DACHPt/m) presented similar size, drug loading and surface charge to non-conjugated micelles (MeO-DACHPt/m), the differences in the biological performance of the micelles were endorsed to the effect of the ligand. In a syngeneic melanoma model, both MeO-DACHPt/m and cRGD-DACHPt/m showed comparable antitumor activity against the primary tumors and the established metastatic foci in lymph nodes. However, cRGD-DACHPt/m significantly enhanced the efficacy against LNM draining from primary tumors through the effective inhibition of the spreading of cancer cells. This improved inhibition was associated with the ability of cRGD-DACHPt/m to reduce the migration of melanoma cells, which was higher than that of MeO-DACHPt/m, free cRGD and their combination. These results support our strategy of using cRGD-installed micelles for attaining cooperative therapies against LNM exploiting the inhibitory function of the peptide and the cytotoxic effect of the micelles.

Systemic Targeting of Lymph Node Metastasis through the Blood Vascular System by Using Size-Controlled Nanocarriers.

Occult nodal metastases increase the risk of cancer recurrence, demoting prognosis and quality of life of patients. While targeted drug delivery by using systemically administered nanocarriers can potentially control metastatic disease, lymph node metastases have been mainly dealt by locally injecting nanocarriers, which may not always be applicable. Herein, we demonstrated that sub-50 nm polymeric micelles incorporating platinum anticancer drugs could target lymph node metastases in a syngeneic melanoma model after systemic injection, even after removing the primary tumors, limiting the growth of the metastases. By comparing these micelles with clinically used doxorubicin-loaded liposomes (Doxil) having 80 nm, as well as a 70 nm version of the micelles, we found that the targeting efficiency of the nanocarriers against lymph node metastases was associated with their size-regulated abilities to extravasate from the blood vasculature in metastases and to penetrate within the metastatic mass. These findings indicate the potential of sub-50 nm polymeric micelles for developing effective conservative treatments against lymph node metastasis capable of reducing relapse and improving survival.

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.