Does Prosthesis-Based Breast Reconstruction Affect the Clinical Outcome of Postmastectomy Radiotherapy?

BACKGROUND: In the last 5 decades, there has been significant advancement of breast reconstruction and postmastectomy radiotherapy for breast cancer care. There has been concern that breast reconstruction may adversely affect the efficacy of postmastectomy radiotherapy. This, however, has not been proven by clear clinical evidence. METHODS: By comparing the locoregional recurrence rates and overall survival after postmastectomy radiotherapy between those with and without prosthesis-based breast reconstruction, a retrospective cohort study of the breast cancer patients was done. Multivariable Cox proportional hazards analysis was used to control the confounding factors. RESULTS: From January 1, 1998 to December 31, 2011, 1015 patients receiving postmastectomy radiotherapy were identified. Among them, 111 patients had prosthesis-based breast reconstruction, and the other 904 did not have breast reconstruction. Thirty-four of 904 (3.8%) patients in the nonreconstructed group and 4 of 111 (3.6%) patients in the reconstructed group developed locoregional recurrence. Multivariable survival analysis found no significant difference both in locoregional recurrence-free survival (hazard ratio, 0.852; P = 0.771) and in overall survival (hazard ratio = 1.317; P = 0.246) between the nonreconstructed group and reconstructed group. CONCLUSIONS: Although postmastectomy radiotherapy has been shown to affect the surgical and cosmetic outcomes of breast reconstruction, prosthesis-based breast reconstruction does not seem to have significant adverse impacts on the locoregional recurrence-free survival and overall survival of postmastectomy radiotherapy.

Investigation of Prognostic Features in Primary Cutaneous and Soft Tissue Angiosarcoma After Surgical Resection: A Retrospective Study.

Primary cutaneous and soft tissue angiosarcoma is a rare but highly aggressive malignancy. To date, surgical resection is the mainstay of treatment, but poor prognosis is expected. To investigate whether there are factors associated with poor prognosis after surgical resection and to develop a treatment guideline for current therapy, we retrospectively collected data on 28 patients who underwent surgery as initial treatment and reviewed patient demographics, tumor characteristics, disease courses, and prognoses from September 1996 to May 2013. Of these 28 patients, 17 (60.7%) were men and the mean age at first diagnosis was 66.57 ± 18.57 years. Anatomically, 17 (60.7%) tumors were in the scalp and 11 (39.3%) were in other sites of the body. Of the 28 patients, 23 (82.1%) had achieved negative surgical margins, 24 (85.7%) received adjuvant radiation therapy, and 17 (60.7%) received adjuvant chemotherapy. Twenty-one patients (75%) died during a mean follow-up time of 35.86 ± 28.91 months, and all deaths were caused by angiosarcoma. The 5-year overall survival rate was 17.86%. Sixteen (57.1%) patients had locoregional tumor recurrence, and 20 (71.4%) had distant metastases, with a median of 9.17 (range, 1.9-98.07) months to recurrence or metastasis. Possible predictors of poor prognosis (P < 0.05) in terms of disease-free survival after surgical resection were male sex, cardiovascular disease, smoking, and scalp angiosarcomas, those in terms of overall survival were older than 70 years, male sex, cardiovascular disease, smoking, scalp angiosarcomas, distant metastases, and not receiving adjuvant chemotherapy. In conclusion, although multimodal treatments are used, the overall prognosis after surgical resection is still poor, especially for patients with the above predictive factors. An early diagnosis and complete resection of the primary tumor with or without adjuvant radiotherapy and chemotherapy are suggested for a potential better outcome. For those who have a diffuse lesion pattern with the involvement of vital structures, recurrence, or metastasis, palliative resection could be an alternative treatment choice.

A clinical clerkship collaborative program in Taiwan: Acquiring core clinical competencies through patient care responsibility.

BACKGROUND/PURPOSE: Traditionally, clinical clerkship training in Taiwan does not provide medical students with sufficient patient care responsibilities and often results in inadequate clinical skills. METHODS: We implemented a pilot clerkship program at a comprehensive cancer center that emphasizes core clinical competency through direct patient care and dedicated faculty and mentors. Students were an integral part of the patient care team held accountable for providing coordinated and holistic care. Students' self-assessment of clinical competencies, faculty evaluation, and objective structured clinical examination were compared against their peers trained by traditional clerkship at a main teaching hospital. RESULTS: Fifty medical students completed the clerkship program in the first 3 years. At the end of the clerkship, participants rated themselves significantly higher than their peers in almost all patient care and clinical skill domains. The most significant areas included physical examination, clinical reasoning, developing management plan, holistic approach, handling ethical issues, and time management skills. The students rated their clerkship teachers significantly higher in time spent with students, skills and enthusiasm in teaching, as well as giving students appropriate patient care responsibilities. There was no significant difference in the end-of-clerkship objective structured clinical examination performance, but participants of the program achieved better grades in their subsequent internship. CONCLUSION: This pilot collaborative program presented a successful model for clinical education in the teaching of core clinical competencies through direct patient care responsibilities at the clerkship stage. It is hoped that the project will become a catalyst for medical education reform in Taiwan and regions with similar traditions.

The association among multiple-site chronic pain, sedentary behavior, and major depressive disorders: a mendelian randomization study.

OBJECTIVE: Observational studies have reported that major depressive disorder (MDD) is associated with sedentary behavior (SB) and multiple chronic pain (MCP), but their associations remain unclear. Mendelian randomization analysis was used to assess the association. METHODS: Single nucleotide polymorphisms (SNPs) associated with MCP, SB [time spent watching television (Tel), using a computer (Com), or driving (Dri)], and MDD were collected from genome-wide association studies and screened as instrumental variants with a threshold of 1 × 10-5. Mendelian randomization was performed to examine their associations. Sensitivity analyses were conducted to evaluate robustness. RESULTS: MCP was associated with a higher risk of MDD [odds ratio (OR) inverse variance weighting (IVW) = 1.88; 95% confidence interval (CI), 1.64-2.15; P = 4.26 × 10-8), and causally related to SB (Tel: ORIVW = 1.23; 95% CI, 1.19-1.26; P = 6.02 × 10-38) (Dri: ORIVW = 1.05; 95% CI, 1.03-1.08; P = 3.92 × 10-5). Causality of SB on MCP was detected for Tel (ORIVW = 1.46; 95% CI, 1.39-1.53; P = 1.40 × 10-54) and Com (ORIVW = 0.88; 95% CI, 0.83-0.93; P = 2.50 × 10-6). No association was observed for SB on MDD. There is currently insufficient evidence to support that leisure activities are a mediating factor in MCP-induced MDD. CONCLUSION: There are complex relationships among MCP, SB, and MDD. More research and learning about potential relationships and mechanisms among these phenotypes should be supplied.

Differential impacts of initial treatment status on long-term survival in patients with sarcomas treated in a referral center according to histologic type and anatomic site.

OBJECTIVE: The aim of this work was to estimate the magnitude of the differential impacts of initial treatment status relative to the impact of classic clinicopathologic factors on the long-term overall survival (OS) of sarcoma patients in a referral cancer center. METHODS: From the institutional database, we identified 2185 patients who presented to the institutional multidisciplinary team (MDT) prior to (N = 717, 32.8%) or after (N = 1468, 67.2%) initial treatment, with a first diagnosis of sarcoma from January 1999 to December 2018. Descriptive, univariate and multivariate analyses were applied to identify the factors related to OS. By performing propensity score matching of each completely MDT-treated patient to a referral patient with similar characteristics, the differential impacts of the identified risk and prognostic factors on OS in the 2 groups were estimated by the Kaplan‒Meier survival curves, log-rank test and Cox proportional hazard regression; the results were compared using calibrated nomograph models and forest plots. RESULTS: Adjusted for the clinicopathologic factors of patient age, sex, primary site, tumor grade, tumor size, resection margin and histology, hazard ratio-based modeling analysis indicated that the initial treatment status was an independent but intermediate prognostic factor associated with long-term OS. The major impacts of the initial and comprehensive MDT-based management on significant improvement of the 20-year OS of sarcomas were reflected in the subgroup of patients with stromal, undifferentiated pleomorphic, fibromatous, fibroepithelial, or synovial neoplasms and tumors in the breast, gastrointestinal tract, or soft tissues of limb and trunk. CONCLUSIONS: This retrospective study supports early referral of patients with soft tissue masses of unknown identity to a specialized MDT before biopsy and initial resection to reduce the risk of death but highlights an unmet need for a greater understanding of some of the most difficult sarcoma subtypes and subsites and their management.

Functional alterations of the suicidal brain: a coordinate-based meta-analysis of functional imaging studies.

Altered brain activities in suicidal subjects have been reported in a number of neuroimaging studies. However, the activity aberrances were inconsistent in previous investigations. Thus, we aimed to address activity abnormalities in suicidal individuals. Databases were searched to perform a meta-analysis of whole-brain functional MRI studies of suicidal individuals through January 14, 2020. Meta-analyses were conducted using Seed-based d Mapping software. Based on a meta-analysis of 17 studies comprising 381 suicidal individuals and 642 controls, we mainly found that increased activity in the bilateral superior temporal gyrus, left middle temporal gyrus, and bilateral middle occipital gyrus, along with decreased activity in the right putamen and left insula, were detected in suicidal individuals compared with nonsuicidal subjects. To reduce methodological heterogeneity between the included studies, subanalyses of behavioral domains were conducted, and the right superior temporal gyrus was found to increase in all subanalyses of domains. In subanalyses of suicidal attempters and ideators, suicide attempters displayed hyperactivation in the bilateral superior temporal gyrus and left middle temporal gyrus and blunted responses in the left insula relative to controls. Suicidal ideators demonstrated elevated activation in the right middle occipital gyrus and reduced activity in the right putamen relative to controls. The bilateral superior temporal gyrus was the most robust finding, replicable in all data sets in the jackknife sensitive analysis. Moreover, increased activity in the right superior temporal gyrus, left middle temporal gyrus, and right middle occipital gyrus was found to be involved with higher suicide ideation scores. This study revealed several brain regions associated with suicidality. These findings may contribute to our understanding of the pathophysiology of suicide and have important implications for suicide prevention and interventions.

Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework.

BACKGROUND: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. METHODS: Between 2013-2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). RESULTS: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient-Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. CONCLUSIONS: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.

The prognosis of patients with primary osteosarcoma who have undergone unplanned therapy.

OBJECTIVE: For diagnosing osteosarcoma correctly, a combination of clinical, radiological and histological examinations is required. Erroneous treatment may cause local contamination and systemic seeding in patients. The purpose of this study was to compare outcomes of planned and unplanned treatment for osteosarcoma. METHODS: A retrospective review of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (n = 134) and those who were misdiagnosed and received unplanned surgery (n = 16) between July 1995 and February 2005. RESULTS: Patients who received unplanned treatment were older (mean age: 29.7 vs. 19.7 years; P = 0.003) and had a smaller mean tumor volume (119 vs. 280 ml; P = 0.015). The 5-year survival rate was not statistically different between the groups. Patients who had unplanned treatment had a higher local recurrence rate (43.8 vs. 17.9%; P = 0.024) and a shorter mean time for recurrence (11.9 vs. 20.8 months; P = 0.036). Furthermore, in patients who underwent unplanned treatment, lung metastases occurred earlier (6.1 vs. 16.2 months P = 0.021) and the final limb salvage rate was less (68.7 vs. 87.3%; P < 0.001). CONCLUSIONS: Unplanned treatment for high-grade osteosarcoma can result in failure of local control and earlier systemic metastases.

A novel human stem cell coculture system that maintains the survival and function of culture islet-like cell clusters.

Islet-like cell clusters (ICCs) have been suggested to be a source of insulin-producing tissue for xenotransplantation in type 1 diabetes. We designed an approach to maintain the cultured rat pancreatic ICC survival and function, when cocultured with human umbilical cord mesenchymal stem cells (HUMSCs). HUMSCs in coculture have the ability to maintain ICC survival and function, for which number and insulin secretion of ICCs are increasing and lasting for 3 months, while ICCs gradually crash, which results in cell death after a period of 12 days of culture without HUMSCs. Cytokine protein array showed it has more than a twofold increase in levels of several cytokines (interleukin-6, tissue inhibitor of metalloproteinases-1, tissue inhibitor of metalloproteinases-2, monocyte chemoattractant protein-1, growth related oncogene, hepatocyte growth factor, insulin-like growth factor binding proteins 4, and interleukin-8) on coculture medium, implying an important role of these cytokines in this coculture system. These findings suggest that coculture with HUMSCs may have a significant potential to protect ICCs from damage during culture, and may be employed in a novel culture approach to maintain islet cell survival and function before transplantation.

Risk of infection is associated more with drain duration than daily drainage volume in prosthesis-based breast reconstruction: A cohort study.

In prosthesis-based breast reconstruction, drains are used to prevent seroma formation and to reduce the risk of infection. However, prolonged drainage increases the risk of ascending infection. Although the volume often accepted for drain removal is ≤30 mL per day, the optimal timing to remove the drain for best clinical outcome remains controversial.We did a retrospective cohort study of 569 patients of prosthesis-based breast reconstruction with infection rate as the outcome variable; drain duration and last daily drainage volume as the main independent variables. Data on age, smoking history, diabetes mellitus history, body mass index, breast weight, tissue expander size, drain size, number of retrieved lymph nodes, tumor size, number of metastatic lymph nodes, tumor stage, mastectomy type, reconstruction type, submuscular implantation, skin defect, operative time, duration of antibiotics use, chemotherapy, and radiotherapy were collected as covariates. Multivariable logistic regression analysis was used to control for confounding.The total infection rate was 5.1% (29/569). The daily drainage volume ≥30 mL/d at the time of drain removal was not found associated with increased infection rate (P = 0.32). Of the various cutoff values of last daily drainage volume, none was found to be a determinant for drain removal where the risk of infection was concerned. By contrast, drain duration over 21 days significantly increased infection rate (P = 0.001). The multivariable logistic regression analysis showed an increase of 76.2% in the infection rate with each additional week of drain retention (P = 0.001). Breast weight also had a significant influence on risk of infection. Chemotherapy and drain size showed borderline effect on risk of infection whereas the last daily drainage volume was not associated with risk of infectionIn summary, our study revealed that drain duration, rather than the last daily drainage volume, significantly affects the infection rate in prosthesis-based breast reconstruction. We recommend that the drain is better removed no longer than 3 weeks postoperatively and can be removed as early as postoperative day 7, even when the drainage is over 30 mL in a 24-hour period.

Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes.

Proinflammatory cytokine interleukin-1ß (IL-1ß) stimulates several mediators of cartilage degradation and plays an important role in the pathogenesis of osteoarthritis (OA). Honokiol, a low molecular weight natural product isolated from the Magnolia officinalis, has been shown to possess anti-inflammatory effect. Here, we used an in vitro model of cartilage inflammation to investigate the therapeutic potential of honokiol in OA. Human OA chondrocytes were cultured and pretreated with honokiol (2.5-10 µM) with or without IL-1ß (10 ng/ml). Nitric oxide (NO) production was quantified by Griess reagent. Prostaglandin (PG)E2 , metalloproteinase-13 (MMP-13), and interleukin-6 (IL-6) productions were quantified by enzyme-linked immunosorbent assay. The expressions of collagen II, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor κB (NF-κB)-related signaling molecules were determined by Western blotting. Our data showed that IL-1ß markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE2 , and IL-6, which could be significantly reversed by honokiol. Honokiol could also suppress the IL-1ß-triggered activation of IKK/IκBα/NF-κB signaling pathway. Moreover, honokiol significantly inhibited the IL-1ß-induced MMP-13 production and collagen II reduction. Taken together, the present study suggests that honokiol may have a chondroprotective effect and may be a potential therapeutic choice in the treatment of OA patients.

EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee.

Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti-inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)- and IL-1ß-induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX-2 and iNOS in human chondrocytes. LPS was also seen to up-regulate the expressions of toll-like receptor-4 (TLR4), its downstream signal TNF receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB signaling. These LPS-induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL-1ß as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX-2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti-inflammatory effects on human articular chondrocytes and OA rats.