Diabetes mellitus causes secondary osteoporosis and muscle atrophy. The ability of alfacalcidol (ALF) and exercise (Exe) to inhibit osteoporosis and muscle atrophy in type 2 diabetes mellitus (T2DM) ...model rats was examined. Twenty-week-old Otsuka Long-Evans Tokushima Fatty rats were randomized to ALF (orally 0.1 μg/kg/day), Exe (treadmill exercise at 10 m/min, 60 min/day, 5 days/week), Comb (ALF and Exe), and Cont (T2DM control treated with vehicle and no exercise) groups (n = 8-10 per group). Sedentary Long-Evans Tokushima Otsuka rats were used as a non-hyperphagic control. After treatment for 2 or 6 weeks, blood glucose (BG) levels, cross-sectional area (CSA) of tibialis anterior muscle fibers, femoral bone mineral density (BMD), and relative quantities of muscle anabolic markers (Pax7, MyoD, and myogenin) and catabolic markers (Atrogin-1, MuRF1, and REDD1) of the soleus muscle assessed by real-time polymerase chain reaction assays were measured. Exe and Comb treatments for 6 weeks decreased BG levels compared with those of the Cont group. ALF, Exe, and Comb treatments for 2 and 6 weeks recovered the CSA compared with that of the Cont group. ALF and Comb treatments for 6 weeks increased femoral BMDs compared with those of the Cont group. After 2 weeks of treatment, Comb treatment increased MyoD expression and decreased MuRF1 expression. ALF or Exe monotherapy significantly decreased Atrogin-1 or MuRF1 expression after 2 weeks of treatment, respectively. After 6 weeks of treatment, ALF and Comb treatments decreased Atrogin-1 and REDD1. These results demonstrate that a combination of ALF and Exe improved CSA from the early phase of treatment by stimulating skeletal muscle differentiation and suppressing muscle catabolic genes. Improvements in BG, BMD, and CSA were observed as long-term effects of the combination therapy. Continued suppression of muscle catabolic genes was observed as a background to these effects.
Myxofibrosarcoma (MFS) is a rare and aggressive mesenchymal malignancy characterized by complex karyotypes with heterogeneous clinical features. The standard treatment for primary MFS is curative ...resection; however, the utility of systemic chemotherapy and radiotherapy has not been established. Although patient-derived cancer cell lines are a key bioresource for developing novel therapies, the number of MFS cell lines available from public cell banks is limited by the rarity of the disease, and large-scale drug screening has not yet been performed. To address this issue, we aimed to establish and characterize a novel MFS cell line. We successfully established a cell line, NCC-MFS6-C1, which harbors genetic abnormalities common in MFS and exhibits aggressive phenotypes such as continuous growth, spheroid formation, and invasion in tissue culture conditions. We performed drug screening using NCC-MFS6-C1 along with five MFS cell lines established in our laboratory and clarified the response spectrum of 214 existing anticancer agents. We found that two anticancer agents, gemcitabine and romidepsin, showed considerable antiproliferative effects, and these observations were concordant with the findings of our previous report, in which these agents attenuated the proliferation of five previously reported MFS cell lines. We conclude that NCC-MFS6-C1 is a useful resource for studying MFS.
Purpose: With de novo cancer, esophagectomy after lung transplantation (LTx) can be challenging because of intrathoracic adhesions, delayed wound healing, and postoperative pulmonary complications, ...which might be lethal.Case Presentation: A 52-year-old woman with esophageal cancer had undergone bilateral LTx for end-stage diffuse panbronchiolitis at 50 years of age. Thoracoscopic esophagectomy was performed. Bilateral bronchial arteries and subcarinal and bilateral bronchial lymph nodes were preserved to maintain blood supply to the transplanted bronchi. No ischemic changes were observed in either bronchi. The patient’s postoperative course was uneventful. Although she underwent chemoradiation therapy for recurrence at the left cervical paraesophageal lymph node, she remains alive with good disease control and well-maintained respiratory function.Conclusion: Minimally invasive surgery with careful attention to blood supply to the transplanted bronchi was useful for treating esophageal cancer after LTx.
Background
The impact of sarcopenia on digestive cancer is widely known. Muscle mass, defined as the psoas muscle index (PMI), is an important parameter of sarcopenia. However, the relationship ...between esophageal cancer and PMI has not been fully investigated, especially in patients receiving neoadjuvant therapy.
Methods
To elucidate the influence of the PMI on patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy, the progression of sarcopenia defined by the PMI, the relationship between pretherapeutic/preoperative sarcopenia and patient characteristics, and patient survival were retrospectively investigated in 82 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy.
Results
The PMI decreased by more than 20 mm
2
/m
2
between the pretherapeutic and preoperative periods in 75.6% of the patients. Pretherapeutic sarcopenia (low PMI) correlated with the pathological therapeutic response, postoperative recurrence, and pretherapeutic body mass index. Neoadjuvant chemoradiotherapy was associated with the progression of sarcopenia. The pretherapeutic sarcopenia group (low PMI) had worse disease-free survival (DFS) than the non-sarcopenia group. Furthermore, pretherapeutic sarcopenia (low PMI) was an independent prognostic risk factor of DFS according to univariate and multivariate analyses.
Conclusions
The PMI may decrease during neoadjuvant therapy, especially during neoadjuvant chemoradiotherapy. Pretherapeutic sarcopenic (low PMI) patients should be followed-up more carefully postoperatively because higher risks of recurrence and poorer rates of disease-free survival are associated with these patients.
Introduction
Postmenopausal osteoporosis and dyslipidemia are well-known skeletal and metabolic changes in middle-aged women. We investigated the effects of combined treatments with a selective ...estrogen receptor modulator (SERM) and exercise on bone and fat parameters in ovariectomized (OVX) rats.
Materials and Methods
Sixteen-week-old female Sprague–Dawley rats underwent bilateral ovariectomy, and rats were randomized to BZA (bazedoxifene at 0.3 mg/kg/day), Exe (treadmill exercise at 12–15 m/min, 60 min/day, 5 days/week), Comb (BZA and Exe), and Cont (control treated with vehicle and no exercise) groups 8 weeks after ovariectomy. After 4 or 8 weeks of treatment, bone mineral density (BMD) of the total femur and lumbar spine and whole-body percentage fat mass were determined by dual-energy X-ray absorptiometry, and mechanical testing of the femoral shaft, and bone and fat histomorphometric analyses of the proximal tibia were performed.
Results
Treadmill exercise had decreased bone marrow adipocytes from 4 weeks of treatment and whole-body percentage fat mass at 8 weeks. BZA increased BMD at the lumbar spine and decreased the whole-body percentage fat mass from 4 weeks and bone marrow adipocytes at 8 weeks. Combination therapy increased BMD for the lumbar spine and decreased bone marrow adipocytes and whole-body percentage fat mass from 4 weeks.
Conclusion
Combination therapy with BZA and exercise appears effective to improve bone and fat parameters in OVX rats.
Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is ...quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined.
Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study.
A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality.
The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.
●The mean time to dedifferentiation was 101 months in dedifferentiation type.●The 5-year local recurrence and metastasis-free survival were 71.6% and 75.7%.●The 5-year disease-specific survival rate was 84.7%.●Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis.●Grade, extension, and margin in the dedifferentiated area are critical to outcomes.
Esophageal carcinosarcoma is a rare tumor composed of neoplastic squamous epithelium and sarcomatous spindle cells. The origin of spindle cells remains unknown; however, the majority of sarcomatous ...components are currently considered to be derived from existing carcinomatous cells via epithelial-mesenchymal transition (EMT). We report a case of esophageal carcinosarcoma harboring basaloid squamous cell carcinoma successfully treated with preoperative chemotherapy. A 78-year-old man complaining dysphagia was diagnosed as esophageal carcinosarcoma. After two courses of preoperative chemotherapy with cisplatin and 5-fluorouracil, curative esophagectomy with lymph node dissection was performed thoracoscopically. Histopathological findings of the resected specimen revealed the mixture of basaloid squamous cell carcinoma and sarcomatous spindle cells. A transitional zone between both components was also detected. As fibrosis was identified around both two components, the findings indicated that both carcinomatous and sarcomatous neoplasms disappeared by preoperative chemotherapy. Final pathological diagnosis was esophageal carcinosarcoma with basaloid squamous cell carcinoma. No recurrent lesions have been detected for 25 months after the surgery. Sarcomatous spindle cells could be derived from the components of basaloid squamous cell carcinoma in our present case due to the presence of histological transition between two components. In addition, the marked immunoreactivity of vimentin (an EMT marker) detected in the tumor cells of basaloid squamous cell carcinoma could be consistent with the concept of monoclonal origin via EMT. The regimen targeting squamous cell carcinoma could also be effective in the treatment of sarcomatous components. Preoperative therapy might achieve the improvement of clinical outcome of patients with esophageal carcinosarcoma.
Objectives
Indications for peroral endoscopic myotomy (POEM) and endoscopic submucosal dissection (ESD) in patients with achalasia concomitant with esophageal carcinoma (EC) are unclear. This study ...aimed to clarify the role of POEM in cases of achalasia concomitant with EC and to elucidate the indications for ESD and efficient surveillance for EC.
Methods
We conducted a multicenter cohort study at 14 hospitals in Japan, including 3707 cases of achalasia‐related esophageal motility disorders (EMDs). Factors contributing to EC risk, the characteristics of EC, and clinical outcomes of POEM/ESD were analyzed.
Results
In patients undergoing POEM, screening and surveillance endoscopy throughout a 1‐year period resulted in diagnosis of 72.1% new EC cases. Of 62 patients with 123 ECs, 40.3% had multiple or metachronous lesions within 37.5 months. EC was predominantly observed in the middle thoracic esophagus (58.5%) and posteriorly (73.2%). POEM had comparable safety and efficacy in cases of concomitant EC even after ESD. Endoscopic en bloc resection was performed in 95.8% and 89.3% of ECs diagnosed before and after POEM, respectively (P = 0.351); however, ESD on the POEM‐line was impaired by fibrosis. Multivariate analysis revealed risk factors for EC, including regular alcohol consumption, a history of smoking, advanced age, and extended disease duration. Alcohol intake and smoking had a synergistic effect on EC development.
Conclusions
Screening and surveillance of POEM help in detecting EC. ESD is feasible in achalasia, although on the POEM‐line is challenging. Surveillance endoscopy for EC is recommended for cases with specific risks and a history of ECs.
Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly ...associated with a pathogenic mutation in the
H3-3A
gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited
H3-3A
gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.
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