No previous reports to date have characterized the national profiles of soft-tissue sarcomas (STSs). In the present study, we reviewed current practice for STSs in Japan using data from a nationwide ...organ-specific cancer registry for bone and soft-tissue tumors in Japan, the Bone and Soft Tissue Tumor (BSTT) Registry.
In the registry, we identified 8228 patients with STSs during the period 2006–2012, and extracted data on patient demographics, treatment, and outcome at the last follow-up for each patient. Disease-specific survival was analyzed using the Cox proportional hazards model.
STSs showed a slight male predilection. The age distribution had a single peak in the seventh decade, the proportion of elderly patients aged >60 years being approximately 53%. For most of the histologic subtypes, the most frequent tumor location was the lower extremity, whereas it was the trunk in patients with malignant peripheral nerve sheath tumor, dedifferentiated liposarcoma, and primitive neuroectodermal tumor. Based on data for 2432 patients with STSs, we found significant associations between disease-specific survival and age, sex, histologic subtype, tumor size, tumor depth, tumor location, additional surgery, limb salvage status, and surgical margin; elderly patients showed the poorest disease-specific survival.
Using the BSTT Registry, this study has clarified the epidemiology, treatment, and prognosis of patients with STSs in Japan. Our experiences with the BSTT Registry will be of help to other countries where aging of the population is occurring. Continuous accumulation of clinical data in the BSTT Registry should provide more informative data on STSs, thus improving both the level of medical care offered by clinicians and the outcomes for patients through sharing of such data and promotion of clinical research.
No previous reports to date have characterized the national profiles of bone sarcoma overall. In the present study, we aimed to describe the nationwide statistics of bone sarcoma in Japan by ...analyzing data from the Bone and Soft Tissue Tumor (BSTT) Registry in Japan, which is a nationwide organ-specific cancer registry for bone and soft tissue tumor.
We identified 2773 patients with bone sarcomas using the BSTT Registry during 2006-2012. We extracted the data regarding patient demographics, treatment, and prognosis at the last follow-up for each patient.
There was a slight male preponderance. The age distribution had 2 peaks overall: one in the second decade and the other in the sixth to seventh decade with the proportion of the elderly patients over 60 years approximately 30%. The most frequent tumor locations were the lower extremity (N = 1342; 48.4%) and the trunk (N = 1038; 37.4%). We also showed the significant association between disease-specific survival and patient's age, histologic grade and subtype, tumor size and location, and limb salvage status based on 1401 patients with bone sarcoma, and demonstrated the worst disease-specific survival in the elderly patients.
The present study is the first study to have analyzed data from the BSTT Registry and has provided an overview of the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of patients with bone sarcoma in Japan based on cases assumed to have received relatively uniform treatment strategies. It is essential to document our data regarding the outcomes of elderly patients so that other countries showing similar population aging trends can learn from our experiences.
The survival impact of geographic access to specialized care remains unknown in patients with soft-tissue sarcomas (STS). This study aimed to clarify the association between the patient travel ...distance and survival outcome and investigate the factors lying behind it. A total of 34 528 patients with STS registered in the National Cancer Data Base, diagnosed from 2004-2016, were investigated. Tumor stage correlated with travel distance: patients with metastatic disease stayed closer to home. However, the type of facility showed greatest variation: 37.0%, 51.0%, 73.5%, and 75.9% of patients with less than or equal to10 miles, 10.1-50 miles, 50.1-100 miles, and >100 miles, respectively (P100 miles: HR = 0.877; P = 0.001) and management at academic/research (versus non-academic/research) centers (HR = 0.857; P100 miles) to an academic/research center, with a 26.9% survival benefit (HR = 0.731; P<0.001), compared with those traveling short distance (less than or equal to10 miles; 95.4% living in metropolitan area) to a non-academic/research center. There was no significant correlation between travel distance and survival in patients who had care at academic/research centers, whereas a survival benefit of management at academic/research centers was observed in every group of travel distance, regardless of tumor stage. This national study demonstrated that increased travel distance was associated with superior survival, attributable to a higher proportion of patients receiving sarcoma care at distant academic/research centers. These data support centralized care for STS. Overcoming referral and travel barriers may enable more patients to be treated at specialized centers and may further improve survival rates for patients with STS, even when it imposes an increased travel burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the reduction in oil reserves and steady increases in the price of oil, alternative carbon sources like methanol are promising, but an efficient conversion process to fuels and other chemicals ...is still desired. In this study, we demonstrated for the first time the production of lactic acid from methanol using a lactate dehydrogenase copy number amplifying strategy in
Pichia pastoris
. We engineered methylotrophic yeast (
Pichia pastoris
) producing
d
-lactic acid by
d
-lactate dehydrogenase gene (
d
-LDH
) integration into the non-transcribed spacer of the ribosomal DNA (rDNA) locus and post-transformational amplification. The resultant engineered strains GS115/S8/Z3 and GS115/S16/Z3 produced 3.48 and 3.26 g/L of
d
-lactic acid from methanol, respectively, in a 96-h test tube fermentation. To our knowledge, this is the first report about
d
-lactic acid production from methanol by an engineered
P. pastoris
strain. The technique of gene integration into the rDNA locus and post-transformational gene amplification could be useful for metabolic engineering in
P. pastoris
, and the chemical production from methanol by engineered
P. pastoris
represents a promising industrial technology.
Graphical abstract
There have been fewer improvements in the clinical outcomes of adolescent and young adult (AYA) patients with cancer than for children and older adults, possibly because fewer studies focus on ...patients in this age group. The aims of this study were (1) to determine survival rates of bone sarcoma among AYAs in Japan (for comparison with other age groups), and (2) to establish whether belonging to the AYA age group at diagnosis was correlated with poor cancer survival in Japan.
A total of 3457 patients diagnosed with bone sarcoma (1930 male and 1527 female) were identified from 63,931 records in the Bone and Soft Tissue Tumor (BSTT) registry, a nationwide Japanese database, from 2006 to 2013. The histologic subtypes of bone sarcoma were osteosarcoma, chondrosarcoma, and Ewing sarcoma. The primary endpoints for prognosis were the occurrence of tumor-related death. We compared the epidemiological features of AYAs with other age groups. The cancer survival rates were calculated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze the prognostic factors for cancer survival.
The majority of AYA had osteosarcoma 631 (56.2%), while 198 (17.6%) had chondrosarcoma. The frequency of bone sarcoma occurrence was highest among AYA patients, who accounted for a marked proportion of patients with each type of sarcoma. With the exception of sarcoma type, AYA patients did not significantly differ from patients in other age groups for any of the investigated clinicopathological parameters. Cancer survival of AYA patients was significantly higher than in the elderly. Univariate and multivariate analyses revealed that AYA status was not a predictor of poor cancer survival. However, older age (≥65 years) was a predictor of poor cancer survival in patients with overall bone sarcoma, osteosarcoma, chondrosarcoma.
This epidemiological study is the first to investigate AYA patients with bone sarcoma using the nationwide BSTT Registry. We found that cancer survival of AYA patients was significantly higher than that of the elderly. AYA status was not a predictor of poor cancer survival in Japan.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The SF-36 is widely used to evaluate the health-related quality of life of patients with musculoskeletal tumors. The minimum clinically important difference (MCID) is useful for interpreting changes ...in functional scores because it defines the smallest change each patient may perceive. Since the MCID is influenced by the population characteristics, MCIDs of the SF-36 should be defined to reflect the specific conditions of orthopaedic oncology patients.
(1) What is the MCID of SF-36 physical component summary (PCS) and mental component summary (MCS) scores in patients with orthopaedic oncologic conditions when calculated with distribution-based methods? (2) What is the MCID of SF-36 PCS and MCS scores in patients with orthopaedic oncologic conditions when calculated by anchor-based methods?
Of all 960 patients who underwent surgery from 1999 to 2005, 32% (310) of patients who underwent musculoskeletal oncologic surgery and completed two surveys during postoperative follow-up were reviewed. We evaluated a dataset that ended in 2005, completing follow-up of data accrued as part of the cooperative effort between the American Academy of Orthopaedic Surgeons and the Council of Musculoskeletal Specialty Societies to create patient reported quality of life instruments for lower extremity conditions. This effort, started in 1994 was validated and widely accepted by its publication in 2004. We believe the findings from this period are still relevant today because (1) this critical information has never been available for clinicians and researchers to distinguish real differences in outcome among orthopaedic oncology patients, (2) the SF-36 continues to be the best validated and widely used instrument to assess health-related quality of life, and unfortunately (3) there has been no significant change in outcome for oncology patients over the intervening years. SF-36 PCS and MCS are aggregates of the eight scale scores specific to physical and mental dimension (scores range from 0 to 100, with higher scores representing better health). Their responsiveness has been shown postoperatively for several surgical procedures (such as, colorectal surgery). Two different methods were used to calculate the MCID: the distribution-based method, which was based on half the SD of the change in score and standard error of the measurement at baseline, and anchor-based, in which a receiver operating characteristic (ROC) curve analysis was performed. The anchor-based method uses a plain-language question to ask patients how their individual conditions changed when compared with the previous survey. Answer choices were "much better," "somewhat better," "about the same," "somewhat worse," or "much worse." The ROC curve-derived MCIDs were defined as the change in scores from baseline, with sensitivity and specificity to detect differences in patients who stated their outcome was, about the same and those who stated their status was somewhat better or somewhat worse. This approach is based on each patient's perception. It considers that the definition of MCID is the minimal difference each patient can perceive as meaningful.
Using the distribution-based method, we found that the MCIDs of the PCS and MCS were 5 and 5 by half the SD, and 6 and 5 by standard error of the measurement. In the anchor-based method, the MCIDs of the PCS and MCS for improvement/deterioration were 4 (area under the curve, 0.82)/-2 (area under the curve, 0.79) and 4 (area under the curve, 0.72)/ (area under the curve, 0.68), respectively.
Since both anchor-based and distribution-based MCID estimates of the SF-36 in patients with musculoskeletal tumors were so similar, we have confidence in the estimates we made, which were about 5 points for both the PCS and the MCS subscales of the SF-36. This suggests that interventions improving SF-36 by less than that amount are unlikely to be perceived by patients as clinically important. Therefore, those interventions may not justify exposing patients to risk, cost, or inconvenience. When applying new interventions to orthopaedic oncology patients going forward, it will be important to consider these MCIDs for evaluation purposes.
Level III, diagnostic study.
Giant cell tumor of bone typically involves the epiphysis of the long bones of skeletally mature patients. It is genetically characterized by highly recurrent and specific mutations of the H3F3A ...gene, which encodes histone H3.3. The most common mutation H3F3A G34W can readily be detected by a recently developed mutation-specific antibody. Giant cell tumor of bone rarely transforms to a sarcoma (malignant giant cell tumor of bone), which has not been genetically characterized in detail. We studied seven clinicopathologically defined malignant giant cell tumors, as well as two H3F3A-mutant bone sarcomas without giant cell tumor histology using a combination of clinicopathological, immunohistochemical, and molecular methods (Sanger sequencing + pyrosequencing or next generation sequencing). The cases included five men and four women, with a median age at initial diagnosis of 27 years. The two H3F3A G34W-positive sarcomas without giant cell tumor histology involved the subarticular epiphyseal sites, suggesting relatedness with giant cell tumor of bone. In two of the seven clinicopathologically defined malignant giant cell tumor cases, the sarcoma tissue showed the H3F3A G34W mutation. However, in the remaining five cases, in contrast to their associated H3F3A G34W-mutant giant cell tumor, the sarcoma lacked the H3F3A G34W mutation, either entirely or sub-clonally in the samples tested. This discordant mutation status was confirmed in all instances by immunohistochemistry and sequencing. A FISH analysis suggested that the absence of the H3F3A G34W mutation may be related to deletion of the H3F3A gene. Therefore, we have demonstrated that H3F3A G34W mutation, a critical driver in giant cell tumor, is absent in a subset of malignant giant cell tumor of bone. This novel recurrent phenomenon has potential biological and diagnostic implications, and further study is required to better characterize this progression pathway and understand its mechanism.
J-KAREN-P is a high-power laser facility aiming at the highest beam quality and irradiance for performing state-of-the art experiments at the frontier of modern science. Here we approached the ...physical limits of the beam quality: diffraction limit of the focal spot and bandwidth limit of the pulse shape, removing the chromatic aberration, angular chirp, wavefront and spectral phase distortions. We performed accurate measurements of the spot and peak fluence after an f/1.3 off-axis parabolic mirror under the full amplification at the power of 0.3 PW attenuated with ten high-quality wedges, resulting in the irradiance of ~10
W/cm
and the Strehl ratio of ~0.5.
Abstract
Objective
The relationship between the adolescent and young adult age groups and poor overall survival in soft tissue sarcoma and the risk factors for poor outcomes in adolescent and young ...adult patients with soft tissue sarcoma were analyzed.
Methods
The medical records of 7759 Japanese patients diagnosed with soft tissue sarcoma from 2006–13 were accessed from the Bone and Soft Tissue Tumor registry. The epidemiological features of adolescent and young adult patients were compared with those of other age groups. The cancer survival rates were calculated using the Kaplan-Meier method. The prognostic factors for cancer survival were analyzed with the Cox proportional hazards models. The primary endpoint for prognosis was tumor-related death.
Results
There were 210 children, 1467 adolescent and young adults, 2771 adults and 3311 elderly among the 7759 patients identified with soft tissue sarcoma. Compared with other age groups, the proportions of myxoid/round cell liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, primitive neuroectodermal tumor and rhabdomyosarcoma in adolescent and young adult patients were the highest, but none was significantly more prevalent in adolescent and young adult patients. On multivariate analysis, age was not a prognostic factor for poor cancer survival among adolescent and young adult patients with soft tissue sarcoma. The cancer survival rates of adolescent and young adult patients with malignant peripheral nerve sheath tumor were poorer than those of the other age groups; however, adolescent and young adult age was not a prognostic factor on multivariate analysis in malignant peripheral nerve sheath tumor patients.
Conclusions
Our study is the first to investigate soft tissue sarcoma in adolescent and young adult patients using the nationwide Bone and Soft Tissue Tumor registry. Adolescent and young adult age is not a prognostic factor for poor cancer survival among those with soft tissue sarcoma in Japan.
Adolescent and young adult age is not a prognostic factor for poor cancer survival among those with soft tissue sarcoma in Japan.
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