Perioperative surveillance of myocardial injury after non-cardiac surgery in patients with hip fracture: A retrospective cohort study.

Myocardial injury after non-cardiac surgery is due to ischaemia either during non-cardiac surgery or within 30 days after it. Our surveillance protocol includes hip fracture template and high-sensitivity troponin stratification, as recommended in European countries. Our retrospective study cohort included surgical patients for hip fracture at our hospital in Japan. The primary outcome was the rate of myocardial injury after non-cardiac surgery in comparison to patients managed with (213) and without (176) hip fracture template. The hip fracture template was used more in patients with myocardial injury after non-cardiac surgery than those without myocardial injury after non-cardiac surgery. When hip fracture template was used, patients had a higher likelihood of myocardial injury after non-cardiac surgery after adjusting for age, time to operation, diabetes mellitus, and chronic kidney disease (odds ratio 41.3; 95% confidence interval: 12.1, 259.6). Patients with myocardial injury after non-cardiac surgery had higher in-hospital mortality than those without myocardial injury after non-cardiac surgery, even in adjusted analysis. There was a high detection rate of myocardial injury after non-cardiac surgery when patients with hip fractures were managed with hip fracture template. Myocardial injury after non-cardiac surgery was associated with in-hospital mortality.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan.

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.

Impact of Flagging/Risk Stratification System on Complications in Hospitalist Hip Fracture Co-management: Retrospective Cohort Study.

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications. Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis. Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31-0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03-10.84). Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT.

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan.

PURPOSE: A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. RESULTS: Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P < .001) and <5 versus ≥10 cm (P < .001); Child-Pugh score A/B versus C (P < .001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P < .008) and <1 versus >2 cm (P < .001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. CONCLUSIONS: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events.

Proton beam therapy for extrahepatic biliary tract cancer: Analysis with prospective multi-institutional patients' registration database, Proton-Net.

Background and purpose: To examine the role of proton beam therapy (PBT) in the treatment of extrahepatic biliary tract cancer (EBC). Methods and materials: We analyzed the data accumulated in the Proton-Net database, which prospectively registered all individual patient data treated with PBT in all Japanese proton institutions from May 2016 to June 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS), and toxicity. Results: Ninety-three patients with unresectable and/or recurrent EBC were treated with PBT using a median prescribed dose of 67.5 Gy (RBE) (range, 50-72.6 Gy) in 25 (22-30 fractions). With a median follow-up of 16.3 months, the median survival time was 20.1 months and the 2-year OS was 37.8%. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Poor liver function (Child-Pugh B, C), a narrower distance between the tumor and digestive tract (2 cm >), and a larger tumor diameter (2 cm <) were identified as poor prognostic factors for OS. PBT-related grade 3 ≤ acute and late adverse events occurred in 5.4% and 4.3% of patients, respectively, including one gastrointestinal late toxicity (duodenal ulcer). Conclusions: This is the largest prospectively accumulated series of PBT for EBC, and PBT showed favorable outcomes with acceptable toxicity profiles.

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

Revision surgery in a middle-aged patient with pertrochanteric fracture nonunion due to wedge effect caused by cephalomedullary nail: A case report.

Trochanteric femur fractures have traditionally been treated surgically with compression hip screws or cephalomedullary nails. With the increasing use of cephalomedullary nails, potential complications from this technique have surfaced. One of them is the potential for varus malreduction of trochanteric femur fractures, known as the "wedge effect", which is the distraction of fracture fragments generated during reamer and nail passage resulting in varus malalignment at the neck-shaft angle. Although trochanteric nonunion in the non-elderly is exceedingly rare, we experienced one such case after nailing due to the wedge effect that was subsequently successfully treated with a compression hip screw without bone grafting. Therefore, in the case of stable pertrochanteric fractures (AO/OTA 31A1) in younger patients, compression hip screw surgery may be the better choice of initial surgery to avoid later nonunion.

Proton beam therapy followed by pembrolizumab for giant ocular surface conjunctival malignant melanoma: A case report.

The present study describes proton beam therapy as a clinical option to achieve local control of giant conjunctival melanoma in an aged person, instead of orbital exenteration. An 80-year-old woman with one-year history of left-eye injection and hemorrhage experienced rapid growth of the ocular surface black mass. At the initial visit, a black, elastic hard, hemorrhage-prone, thickened mass in the size of 30x40 mm with a presumed wide stalk covered the total area of the lid fissure on the left side. Biopsy of the mass demonstrated anomalous melanin-containing cells in fibrin and hemorrhage, which were positive for cocktail-mix antibodies against tyrosinase, melanoma antigen recognized by T cells-1 and human melanoma black-45, indicative of malignant melanoma. One month after the initial visit, the patient underwent proton beam therapy at the total dose of 70.4 Gy (relative biological effectiveness) in 32 fractions (~10 min each) in one and a half months. One month after the end of proton beam therapy, 3.5 months from the initial visit, the patient was found by computed tomographic scan to have multiple metastatic lesions in bilateral lung fields. With the evidence of absent BRAF mutation, the patient underwent intravenous administration of pembrolizumab 77.2 mg every three weeks five times in total. Then, three months after proton beam therapy, ocular surface melanoma almost subsided and the clear cornea allowed visualization of the intraocular lens inside the eye. In three weeks, spontaneous corneal perforation was plugged with iris incarceration. The patient died suddenly of unknown cause 7.5 months from the initial visit. The local control of giant conjunctival melanoma was achieved by proton beam therapy, leading to patient's satisfaction and better quality of life. Proton beam therapy, followed by immune checkpoint inhibitors, would become the future standard of care for unresectable giant conjunctival melanoma.

Spinal Subarachnoid Hematoma After Cerebrospinal Fluid Drainage in Thoracoabdominal Aortic Aneurysm Repair: Case Report and Literature Review.

BACKGROUND: Cerebrospinal fluid (CSF) drainage reduces the risk of paraplegia in thoracoabdominal aortic aneurysm (TAAA) repair. Intracranial hemorrhage after TAAA repair has been reported as a rare complication of CSF drainage; however, spinal subarachnoid hematoma has never been reported. Here, we present a case of lumbosacral subarachnoid hematoma after CSF drainage in TAAA repair. CASE DESCRIPTION: The patient was a 76-year-old man who was hospitalized for TAAA repair. Just before the operation, a CSF drainage catheter was inserted into the L4/5 vertebral interspace. Continuous CSF drainage was performed during the operation. The CSF drain was clamped just after the operation, and the drainage catheters were removed at 24 hours after the operation. On postoperative day 1, the patient experienced pain and paralysis in both lower limbs that worsened over time. Magnetic resonance imaging of the brain and spinal cord was indicative of a spinal subarachnoid hematoma. Removal of hematoma with thoracolumbar and lumbosacral laminectomy was performed, and immediately after the surgery, the pain and paralysis in both lower limbs improved. Six months after the removal of the hematoma, the paralysis in both lower limbs completely resolved and the patient achieved the preinjury activity level. CONCLUSIONS: We present a rare case of lumbosacral subarachnoid hematoma after CSF drainage in TAAA repair. We should consider spinal subarachnoid hematoma when paralysis in the lower limbs occurs after CSF drainage.

Dose distribution of intensity-modulated proton therapy with and without a multi-leaf collimator for the treatment of maxillary sinus cancer: a comparative effectiveness study.

BACKGROUND: Severe complications, such as eye damage and dysfunciton of salivary glands, have been reported after radiotherapy among patients with head and neck cancer. Complications such as visual impairment have also been reported after proton therapy with pencil beam scanning (PBS). In the case of PBS, collimation can sharpen the penumbra towards surrounding normal tissue in the low energy region of the proton beam. In the current study, we examined how much the dose to the normal tissue was reduced by when intensity-modulated proton therapy (IMPT) was performed using a multi-leaf collimator (MLC) for patients with maxillary sinus cancer. METHODS: Computed tomography findings of 26 consecutive patients who received photon therapy at Okayama University Hospital were used in this study. We compared D2% of the region of interest (ROI; ROI-D2%) and the mean dose of ROI (ROI-mean) with and without the use of an MLC. The organs at risk (OARs) were the posterior retina, lacrimal gland, eyeball, and parotid gland. IMPT was performed for all patients. The spot size was approximately 5-6 mm at the isocenter. The collimator margin was calculated by enlarging the maximum outline of the target from the beam's eye view and setting the margin to 6 mm. All plans were optimized with the same parameters. RESULTS: The mean of ROI-D2% for the ipsilateral optic nerve was significantly reduced by 0.48 Gy, and the mean of ROI-mean for the ipsilateral optic nerve was significantly reduced by 1.04 Gy. The mean of ROI-mean to the optic chiasm was significantly reduced by 0.70 Gy. The dose to most OARs and the planning at risk volumes were also reduced. CONCLUSIONS: Compared with the plan involving IMPT without an MLC, in the dose plan involving IMPT using an MLC for maxillary sinus cancer, the dose to the optic nerve and optic chiasm were significantly reduced, as measured by the ROI-D2% and the ROI-mean. These findings demonstrate that the use of an MLC during IMPT for maxillary sinus cancer may be useful for preserving vision and preventing complications.

Single institutional experience of radiation therapy for angiosarcoma of the scalp without cervical lymph node metastases: Impact of concurrent chemoradiation with maintenance chemotherapy using taxanes on patient prognosis.

Cutaneous angiosarcoma is a rare aggressive malignant tumor. Concurrent chemoradiation (CCRT) with maintenance chemotherapy using taxanes is one of the primary treatments. The aim of the present study was to retrospectively analyze the efficacy of CCRT with maintenance chemotherapy using taxanes in localized angiosarcoma of the scalp without cervical lymph node metastases. A total of 19 patients treated with radiation therapy for localized angiosarcomas of the scalp without cervical lymph node metastases were enrolled. The overall survival (OS), progression-free survival (PFS), and local control (LC) rates were calculated using Kaplan-Meier analysis. Univariate analyses were performed for various potential prognostic factors for OS, PFS, and LC. The median radiation dose was 70 Gy (range, 60-70 Gy), and the fractional dose was 2 Gy. Radiation therapy alone, radiation therapy + interleukin-2, surgery + CCRT with maintenance chemotherapy, CCRT with maintenance chemotherapy, and CCRT without maintenance chemotherapy were administered to 2, 4, 2, 9 and 2 patients, respectively. The 1- and 3-year OS, PFS, and LC rates were 88 and 52%, 47 and 33%, and 74 and 56%, respectively. CCRT with maintenance chemotherapy and surgery were significant prognostic factors for PFS (P=0.036 and 0.025, respectively). Therefore, CCRT with maintenance chemotherapy using taxanes might be effective in treating localized angiosarcomas of the scalp without cervical lymph node metastases.

Triweekly administration of parathyroid hormone (1-34) accelerates bone healing in a rat refractory fracture model.

BACKGROUND: Some reports have shown that intermittent parathyroid hormone (PTH) (1-34) treatment for patients with delayed union or nonunion have led to successful healing. In this study, we investigated whether systemic intermittent administration of PTH (1-34) has a beneficial effect on bone healing in a rat refractory fracture model. METHODS: We created a refractory femoral fracture model in 32 rats with periosteal cauterization that leads to atrophic nonunion at 8 weeks after surgery. Half the rats received subcutaneous intermittent human PTH (1-34) injections at a dosage of 100 µg/kg, thrice a week for 8 weeks. The other half received the vehicle only. At 8 weeks after fracture, radiographic, histological and mechanical assessments were performed. RESULTS: Radiographic assessments showed that the union rate was significantly higher in the PTH group than in the control group (P < 0.05). The degree of fracture repair as scored using the Allen grading system in histological assessment was significantly greater in the PTH group than in the control group (P < 0.05). The ultimate stress and stiffness measurements were significantly greater in the PTH group than in the control group (p < 0.05). CONCLUSIONS: We demonstrated that triweekly administration of PTH (1-34) increased union rate and accelerated bone healing in a rat refractory fracture model, suggesting that systemic administration of PTH (1-34) could become a novel and useful therapy for accelerating fracture healing in patients at high risk of delayed union or nonunion.

Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study.

We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.1- 11.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and non- ADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

Comparison of field-in-field radiotherapy with conformal radiotherapy for unilateral cervical malignant lymphoma.

This study compared field-in-field (FIF) radiotherapy with conformal radiotherapy with physical wedges for the treatment of unilateral cervical malignant lymphoma. Two treatment plans, the FIF technique and conformal RT, were generated for each of 32 patients with unilateral cervical malignant lymphoma. To compare the 2 treatment plans, dose-volume histograms of the planning target volume (PTV), the thyroid, submandibular gland, carotid artery, mucosa, spinal cord, and surrounding normal tissue, and monitor unit (MU) were analyzed. The FIF technique showed significant reduction in the mean dose of thyroid, submandibular gland, carotid artery and mucosa, the maximum dose of the spinal cord and PTV, and the volume receiving＞107% of the prescribed dose of surrounding normal tissue (p＜0.001). In addition, there were gains in the homogeneity index of the PTV for FIF. Furthermore, the total MU was also lower for the FIF technique than for the wedge technique (p＜0.001). Compared with the wedge technique, the FIF technique improved the dose homogeneity of the PTV, reduced the dose to normal structures, and was associated with fewer MUs in the treatment of patients with cervical malignant lymphoma.

High-dose-rate brachytherapy using molds for lip and oral cavity tumors.

BACKGROUND: High-dose-rate (HDR) brachytherapy using the mold technique is a less invasive treatment for early lip and oral cavity cancer. However, limited reports exist regarding the feasibility of this method. In this retrospective study, we evaluated the outcome of this therapy and investigated its feasibility for lip and oral cavity tumors. METHODS: Between May 2002 and December 2010, 17 patients (median age, 80.0 years) with histologically confirmed squamous cell carcinoma of the lip or oral cavity were treated by means of HDR brachytherapy using the mold technique after external beam radiotherapy (EBRT). Tumor sites included the buccal mucosa in eight cases, the gingiva in three cases, the lips in two cases, the floor of the mouth in two cases, and the hard palate in two cases. For all patients, EBRT (30 Gy/15 fractions), was performed before HDR brachytherapy. Two 6-Gy fractions were delivered twice daily for 2 days a week with an interval of 6 hours between the fractions. The total HDR brachytherapy dose was 24 Gy. Prior to EBRT, two patients with neck metastasis underwent neck dissection, and one patient with an exophytic tumor underwent tumor resection. RESULTS: The median follow-up period was 53.4 (range, 4.8-83.4) months. Of the 17 patients, 14 (82.4%) achieved a complete response, and three (17.6%) displayed a partial response. The overall 3- and 5-year survival rates were both 68.8%, the 3- and 5-year disease-specific survival rates were both 86.7%, and the 3- and 5-year local control rates were both 54.1%. Seven patients developed local recurrence at a median time of 3.4 (range, 1.7-29.1) months after treatment. Nodal and lung metastases occurred separately in two patients. By the end of the follow-up period, two patients had died of the primary disease and four patients had died of other causes. CONCLUSIONS: Although there is a need to improve the technical aspects of the treatment protocol, HDR brachytherapy using the mold technique might be a therapeutic option for superficial lip or oral cavity tumors, especially in older patients who have a poor performance status or are in poor physical condition.

Comparative analysis of rat mesenchymal stem cells derived from slow and fast skeletal muscle in vitro.

PURPOSE: Skeletal muscle comprises different kinds of muscle fibres that can be classified as slow and fast fibres. The purpose of this study was to compare the yield, proliferation, and multi-potentiality of rat mesenchymal stem cells (MSCs) from the tibialis anterior (TA; fast muscle) and soleus (SO; slow muscle) in vitro. METHODS: The TA and SO muscles were harvested, and isolated cells were plated. After two hours, the cells were washed extensively to remove any cell that did not adhere to the cell culture plate. The adherent cells, namely MSCs, were then cultured. Both types of MSCs were differentiated toward the osteogenic, chondrogenic and adipogenic lineages using lineage specific induction factors. RESULTS: The colony-forming unit fibroblast (CFU-F) assay revealed that the SO contained significantly higher quantities of MSCs than the TA. The self-renewal capacity of MSCs derived from the TA was significantly higher at later passages (passage 9-11). Both types of MSCs exhibited similar cell surface antigens to bone marrow (BM)-derived MSCs and were positive for CD29, CD44, and CD90 and negative for CD11b, CD34, and CD45. TA-derived MSCs were superior in terms of osteogenic differentiation capacity, but there was no significant difference in chondrogenic and adipogenic differentiation capacity. CONCLUSION: Our results demonstrated significant differences in the properties of muscle-derived MSCs from different muscle types (i.e. fast or slow muscles). The greater expandability and osteogenic differentiation ability of TA-derived MSCs suggests that fast muscle may be a better source for generating large numbers of MSCs for bone regeneration.

Analysis of factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy.

PURPOSE: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. METHODS AND MATERIALS: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for >or=2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidence of a specific cause. RESULTS: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age (>or=50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was >or=50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. CONCLUSIONS: Age (>or=50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.