Background The current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC). Methods A total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems. Results Positive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) ( P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models. Conclusions A positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.
Abstract Background: The immune senescence marked by inflation of memory T cell is established in end-stage renal disease (ESRD) patients with peritoneal dialysis(PD). These patients suffer high incidence of infectious disease, which has been relevant to immune dysfunction. However the association of immune senescence with infection in PD patients is not clear. This prospective study is aim to investigate relationship between proportion of T cell subsets and infection event in patients on PD. Methods: We enrolled patients on PD> 6 months from January 1,2016 to December 30,2016 and followed until April 30,2020. Baseline T cell subsets from blood were collected at the time of recruitment. The primary end point was infection event including peritonitis, exit site infection, pneumonia, urinary tract infection and other infection. Results: There were 94 patients (46 male) with a mean age of 56.1±14.9 years old enrolled during follow-up period, and 26 patients suffered infection events. Higher proportion of effector memory(EM) CD8+ T cell was found in patients with infection than those without infection. There was no difference of distribution of EM CD8+ T cell between PD-related and non-dialysis infection. Increased level of EM CD8+ T cell was risk factor for first infection event in PD patients. Conclusion: High level of EM CD8+ T cell could be a significant predictor of infection event in patients on PD.
Scarf osteotomy is a well-established procedure for hallux valgus, yet recurrence rates range from 3.6% to 10%. Pes planus, which often coexisting with hallux valgus, is a risk factor for recurrence. This study aimed to evaluate the effectiveness of simultaneous correction of hallux valgus and flexible pes planus. A total of 85 feet with hallux valgus associated with adult flexible pes planus were retrospectively reviewed. All patients were treated with scarf osteotomy (SO). Subtalar arthroereisis using a HyProCure implant (SOH) was performed to correct hindfoot valgus based on shared decision-making. We collected and compared pre- and at least 2 year postoperative clinical outcomes (American Orthopaedic Foot & Ankle Society (AOFAS) forefoot, hindfoot score, Visual Analog Scale (VAS) pain intensity) and radiographic outcomes (hallux valgus angle (HVA), intermetatarsal angle (IMA), Meary's angle, talonavicular coverage angle (TNCA), and calcaneal pitch (CP) angle in both groups. Of the cases reviewed, 51 feet were allocated to SO group, and 34 feet were in SOH group. Recurrence frequency was 5 feet (9.8%) in the SO group, while no recurrences were reported in the SOH group. There was no significant difference in AOFAS forefoot and VAS scores between the groups, However, the SOH group demonstrated significant improvement in AOFAS hindfoot scores and CP angle, as well as a greater reduction in Meary's angle and TNCA, compared to the SO group. Changes in HVA and IMA did not differ significantly between the groups. Three feet in the SOH group experienced sinus tarsi pain, which resolved after removal of the HyProCure implant. Subtalar arthroereisis with a HyProCure implant is an effective treatment option for adult flexible pes planus associated with scarf osteotomy for hallux valgus, leading to a steady improvement in the patients forefoot deformity and increased patient satisfaction at least 2 years postoperatively.
Background Glucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH. Purposes To investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH. Methods From September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels. Results In the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH. Conclusions GONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.
Objective: Chemoresistance in ovarian cancer results in treatment failure, yet underlying mechanisms that regulate chemoresistance remain largely unclear. There is emerging evidence relating ovarian cancer drug resistance with bioactive sphingolipids and regulation of sphingolipid metabolism. This work investigated the expression and function of ceramide kinase (CerK), a lipid kinase that regulate central bioactive sphingolipids, in ovarian cancer, as well as the therapeutic potential of targeting CERK. Design: The level of ceramide, C1P and Cerk in ovarian cancer and normal counterpart were measured. Functions of Cerk in ovarian cancer was examined. Materials, Setting, Methods: Immunohistochemistry, ELISA and mass spectrometry methods were used to measure the level of ceramids, C1P and CerK in primary tissues. Proliferation and apoptosis assays were performed in ovarian cancer cells after CERK depletion, CERK overexpression and NVP-231 treatment in the absence or presence of cisplatin. Results: Compared to normal ovarian cells, CerK and its-mediated bioactive sphingolipids ceramide and ceramide 1-phosphate (C1P) were decreased in ovarian cancer tissues. Interestingly, cisplatin-resistant ovarian cancer cells displayed increased CerK, decreased ceramide and increased C1P, and furthermore that CerK level was closely associated with ceramide and C1P levels in ovarian cancer cells. Functional analysis demonstrated that CerK overexpression was sufficient to promote growth and confer chemo-resistance in ovarian cancer cells. CerK inhibition via both genetic and pharmacological approaches suppressed growth and induced apoptosis in cisplatin-resistant cells, and furthermore that significantly augmented cisplatin’s efficacy. Limitations: The functional analysis of C1P was performed in in vitro ovarian cancer cells. In vivo studies were needed to further confirm the effects of CERK inhibition. Conclusions: Our work is the first to show the critical role of CerK as the underlying mechanism of ovarian cancer chemoresistance, through regulating ceramide and C1P.
Objectives To study primary MRI of lumbar bone marrow before and after chemotherapy and correlation belween MRI and pathology for adult acute leukemia.Methods Eleven newly patients of adult acute leukemia were performed on MR check of bone marrow before treatment,two and four weeks' after therapy.T 1-weighted spin echo and short time inversion recovery were Selected as imaging sequence.The relative signal intensity before treatment was compared with clinical bone marrow biopsy.Relative signal intensity before and after treatment was analyzed with t-test.Relative signal intensity before and after treatment and clinical bone marrow biopsy were analyzed in six patients dynamically.Results 1.The relative signal intensity before treatment was positively correlated with clinical biopsy.2.The relative signal intensity before and after treatment had significantly difference.3.During the course of treatment the relative signal intensity was gradually declined.4.The relative signal intensity was declined in six patients when content of no-differentiated cell was decreased.Conclusion MRI of bone marrow is useful in observing therapeutic effect of adult acute leukiemia.
Abstract Introduction: The peak incidence of ER+ breast cancer occurs in women around the age of 70. Compared to younger cohorts, we and others have shown that older patients with ER+ breast cancer have an enrichment of luminal disease and experience fewer recurrences, suggesting overtreatment. Differences in the biological phenotypes of tumors in older women remain poorly understood and treatment remains challenging as older patients are underrepresented in clinical trials. In this study, we hypothesized that aging alters both local and systemic hormones and inflammatory cytokines, creating a permissive environment for tumor formation and growth. To address this hypothesis, we employed a systems biology approach across multiple model systems and tissue samples. Methods: Our study included specimens from two cohorts of patients: (1) n = 90 women without breast cancer obtained from the Komen Tissue Bank, from whom we obtained matched plasma and non-cancerous breast tissue (n = 30 across age groups comprising of young donors (35-45yo), middle-aged donors (55-69yo), and older donors (≥ 70yo); and (2) n = 115 women with ER+ breast cancer (n = 25 young patients, n = 57 middle-aged patients, and n = 33 older patients) obtained from our institutional biobank, including matched plasma, tumor tissue, and tumor-adjacent tissue. From each of these sets of specimens, we measured estrogen disposition using mass spectrometry, a 22-plex panel of inflammatory markers, and transcriptomic changes using RNA-seq. Using scRNA-seq and multiplexed IHC, we further characterized the immune changes that occur with age. Lastly, we used an aged, carcinogen-induced ER+ tumor model in F344 rats (obtained from the NIA) to model tumor development and growth. Results: In the plasma, estradiol (E2) drastically decreased in post-menopausal women, leaving estrone (E1) as the predominant circulating estrogen in older women. However, the breast tumor microenvironment (TME) showed comparable levels of E1 and E2 across age groups. Multi-class concordance analysis of breast cancer tissue from RNA revealed significant increases in gene expression of the HSD17B7 enzyme and decreases in HSD17B2 enzyme across age, likely elevating local E1-to-E2 conversion and yielding high local E2 levels despite low circulating levels specifically in older women. In older patients with ER+ breast cancer, there was a significant increase in a chemokine network characterized by CCL2 and CXCL9 within the TME. scRNA-seq revealed enrichment of inflammatory M2-like macrophages in the aged TME. Immune dysfunction and decreased immunosurveillance in older patients manifested with widespread decreases in the presence of cytotoxic lymphocytes and decreased pathway enrichment of key immune pathways, such as JAK/STAT and IFNy signaling. mIHC analysis revealed decreases in CD4 and CD8 T cells and increases in M2-like macrophages in older patients in both tumor and stromal regions. Lastly, in the carcinogen-induced F344 rat model, aged rats (~ 24mo, human equivalent 60-70yo) had a shorter tumor-free interval than the younger rats (~ 4-6mo, human equivalent 20-30yo), likely due to increases in tumor-promoting inflammation and decreased immune surveillance. Ongoing mechanistic work is focused on macrophage-patient derived organoid co-cultures evaluating the functional relevance of E2, CCL2, and CXCL9 in shaping the aged TME. Conclusions: Our study of systemic and local breast hormones and cytokines in both healthy individuals and breast cancer patients showed that older women with ER+ breast cancer harbor different systemic and local environments compared to younger women. The aged TME is characterized by high E2, cytotoxic lymphocyte depletion, and immune dysfunction, creating a permissive environment for tumor formation. Future translational work should be aimed at chemo-preventative strategies to reduce the age-related chronic inflammation and immune dysfunction. Citation Format: Neil Carleton, Jian Zou, Sanghoon Lee, Dixcy Jaba Sheeba John Mary, Ruxuan Li, Jennifer Atkinson, Ziyu Huang, Hatice Osmanbeyoglu, Peter Lucas, Emilia Diego, Michael Lotze, George Tseng, Jagmohan Hooda, Ioannis Zervantonakis, Priscilla McAuliffe, Steffi Oesterreich, ADRIAN LEE. Age-related remodeling of the systemic and breast microenvironment promotes a tumor-permissive locale for ER+ breast cancer in older women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-09.
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