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Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel.From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors.Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)].In patients with pre-treatment CA19-9500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.

Background Peritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis. Methods We retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010–2014; group B, 2015–2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS). Results Among 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum. Conclusions The prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX.

Background The prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. Methods We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. Results A total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). Conclusions In our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.

Objectives A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. Methods We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. Results A total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). Conclusions This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

Platinum nanoparticles (Pt NPs) have been selectively anchored by photodeposition on titanium oxide (TiO 2 ) matrix which is formed by hydrolysis of titanium isopropoxide on cup–stacked carbon nanotubes (CSCNT) in isopropanol, producing the composite Pt catalyst useful for oxygen reduction reaction (ORR) in acidic media, i.e. , Pt NPs/TiO 2 /CSCNT. Using scanning transmission electron microscopy (STEM) with a high–angle annular–dark–field (HAADF) detector it has been clarified that Pt NPs are sunk into the TiO 2 moieties and have the unique polyhedral shape surrounded mainly by the Pt (1 1 1) and Pt (1 0 0) facets. X–ray photoelectron spectroscopy (XPS) allowed us to confirm changes in electronic properties of both Pt NPs and TiO 2 support, induced by the so-called strong metal–support interactions (SMSI) and the significantly increased ORR activity was attained in 0.1 M HClO 4 , compared with the Pt NPs deposited on CB (Vulcan carbon) and CSCNT. The surface structure of the Pt NPs was characterized by transmission electron microscopy (TEM), indicating the improved durability of the Pt NPs deposited on the TiO 2 /CSCNT, i.e., the only slight increase in the particle size after the durability test (typically 2000 times’ potential cycling at 10 mV s −1 in the potential ranges of 0.05 to 1.1 V and 1.0 to 1.5 V vs. RHE in 0.1 M HClO 4 ). The results obtained demonstrate that the anchoring of Pt NPs on the TiO 2 support material deposited on CSCNT is an effective way to enhance the ORR activity of Pt NPs by the SMSI as well as to prohibit Pt NPs from aggregating, i.e. , the degradation of the ORR activity of Pt NPs.

Aims The increased risk of fractures in patients with type 2 diabetes can partly be explained by poor bone quality and extra-skeletal factors. A retrospective study was conducted to compare the outcome of alendronate (ALN) treatment for 3 years in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Methods One-hundred and fifty-one postmenopausal osteoporotic Japanese women (mean age at baseline: 67.8 years) who had been treated with ALN for more than 3 years in our outpatient clinic were analysed. The lumbar spine bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and the serum levels of alkaline phosphatase (ALP) were monitored during the 3-year treatment period. The incidence of osteoporotic fractures was also assessed. Results Sixteen women had type 2 diabetes and were receiving pharmacological treatment, and 135 were non-diabetic. The urinary NTX and serum ALP levels significantly decreased and the lumbar spine BMD significantly increased, compared with the baseline values, without causing any severe adverse events including osteonecrosis of the jaw, femoral diaphysis atypical fractures, and atrial fibrillation, in a manner that was similar among women with type 2 diabetes and non-diabetics. However, the incidence of non-vertebral fractures was significantly higher among women with type 2 diabetes than among the non-diabetics. Conclusions ALN treatment appeared to have the similar effect on surrogate markers in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Because of lacking in statistical power for fracture incidence due to the small sample size, further studies are warranted to confirm the results of the fracture incidence.

The present study examined changes of cancellous and cortical bone in rats with combined methionine–choline deficiency (MCD). In addition, the effects of vitamin K2 on cortical and cancellous bone mass and hepatic lipids were investigated in rats with MCD. Six-week-old male Sprague–Dawley rats were randomized into three groups of ten, including an age-matched control (standard diet) group, an MCD diet group, and an MCD diet + vitamin K2 (menatetrenone at 30 mg/kg/d orally, 5 times a week) group. After the one-month experimental period, histomorphometric analysis was performed on cortical and cancellous bone from the tibial diaphysis and proximal metaphysis, respectively, while histological examination of the liver was performed after staining with hematoxylin and eosin and Oil Red O. MCD rats displayed weight loss, diffuse and centrilobular fatty changes of the liver, and a decrease of the cancellous bone volume per tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular, periosteal, and endocortical bone formation along with increased trabecular and endocortical bone resorption. Administration of vitamin K2 to rats with MCD attenuated weight loss, accelerated the decrease of cancellous BV/TV due to an increase of bone remodeling, and ameliorated the decrease of percent Ct Ar by increasing periosteal and endocortical bone formation. Vitamin K2 administration also prevented MCD-induced diffuse fatty change of the liver. These findings suggest a beneficial effect of vitamin K2 on cortical bone mass and hepatic lipid metabolism in rats with MCD. The loss of cancellous bone mass could possibly have been due to re-distribution of minerals to cortical bone.

The purpose of the present study was to investigate the short-term effects of muscle strengthening exercises on the muscle strength in patients with osteoarthritis (OA) of the knee, and to determine whether the beneficial effects of the exercises on the muscles strength, if any, would be maintained over the long-term. Twenty-six patients (mean: 62.8 years) with mild-to-moderate OA of the knee were instructed to perform the exercises, which consisted of once-weekly facility-based strengthening exercises of the knee extensor and flexor muscles with a Medx knee machine at the intensity of 50% of the maximum peak torque (MPT) measured at the baseline (20 timesx3 sets per week), together with daily home-based isometric strengthening exercises (setting and straight leg raising) of the extensor and flexor muscles of the knee (30 times per day). The beneficial effects of the exercises on the MPT values of both the extensor and flexor muscles of the knee that began to be observed from 3 to 6 months after the start of the exercise regimen, regardless of the gender, age, body mass index, or baseline MPT values of the muscles, were maintained for up to 1-3 years, but tended to be no longer observed at 5 years. The present study showed the short-term efficacy of combined facility- and home-based muscle strengthening exercises for the muscle strength in patients with mild-to-moderate OA of the knee, as well as the loss of the beneficial effect of the exercise regimen on the muscle strength over the long-term.

A phase-space distribution of a weak electron-beam injected into a cold plasma is experimentally investigated in electron time scales. It is shown that electron-beam holes in phase-space evolve dynamically from appearance to collapse, as synchronized with a wave packet dominated by a beam mode. The dependence of the hole velocity radii on the packet crest amplitudes indicates that the holes are induced by self-trapping of the beam. It is found that the beam is well trapped while the packet grows linearly, but easy to be detrapped after that.

The purpose of the present open-labeled, randomized, prospective study was to compare the effects of cyclical etidronate combined with alfacalcidol with those of cyclical etidronate alone on lumbar bone mineral density (BMD), bone resorption, and back pain in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60-86 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group. One group was treated with cyclical etidronate (oral etidronate 200 mg daily for 2 weeks every 3 months) and the other was given cyclical etidronate combined with alfacalcidol (cyclical etidronate plus alfacalcidol 1 Ig daily continuously). The BMD of the lumbar spine (L1-L4) measured by dual-energy X-ray absorptiometry, urinary crosslinked N-terminal telopeptides of type I collagen (NTX) measured by an enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Both treatments significantly reduced the urinary NTX level and back pain. Cyclical etidronate combined with alfacalcidol significantly increased the lumbar BMD with a more significant reduction in the urinary NTX level than cyclical etidronate alone, but cyclical etidronate alone did not significantly increase the lumbar BMD. Alleviation of back pain was similar in the two groups. These results suggest that cyclical etidronate combined with alfacalcidol appears to be more useful than cyclical etidronate alone for increasing the lumbar BMD by more markedly suppressing bone resorption in postmenopausal women with osteoporosis.

The purpose of this study was to investigate the association of stress fractures with age, sex, sport level, sporting activity, and skeletal site in athletes seen at our sports medicine clinic between September 1991 and May 2001. During these 10 years, 10 726 patients (6415 males, 3861 females) visited our clinic because of sport-related injuries, and 196 patients [125 males (1.9%), 71 females (1.8%)] sustained stress fractures. The average age of the patients with stress fractures was 20.1 years (range 10-46 years); 84 patients (42.6%) were 15-19 years of age, and 68 (34.7%) were 20-24 years of age. Altogether, 74 patients (37.8%) were active at the high recreational level and 122 (62.2%) at the competitive level. The sites of the stress fractures varied from sport to sport. The ulnar olecranon was the most common stress fracture site among baseball athletes and the rib among the rowing athletes. Classical ballet, aerobics, tennis, and volleyball athletes predominantly sustained stress fractures of the tibial shaft. Basketball athletes predominantly sustained stress fractures of the tibial shaft and medial malleolus and the metatarsal bone, whereas track and field and soccer athletes predominantly sustained stress fractures of the tibial shaft and pubic bone. Our results show that stress fractures are seen even in high-level adolescent athletes, with similar proportions for males and females, and that particular sports are associated with specific sites for stress fractures.

The purpose of this retrospective study was to compare the effects of long-term treatment (5 years) with elcatonin and alfacalcidol on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Fifty-six osteoporotic women, more than 5 years after menopause and 58-79 years of age, were enrolled in the study and allocated to an elcatonin treatment group (20 units IM, weekly; n = 30) or an alfacalcidol treatment group (1 micro g/day, daily; n = 26). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at baseline and every year for 5 years. There were no significant differences in age, body mass index, years since menopause, BMD, or number of prevalent vertebral fractures at baseline between the two groups. One-way analysis of variance with repeated measurements showed no significant longitudinal changes in BMD in either group, suggesting that both treatments sustained the BMD over 5 years. Two-way analysis of variance with repeated measurements also showed no significant differences in longitudinal changes in BMD between the two groups, suggesting that the effects of the two treatments on BMD were similar. However, the number of incident vertebral fractures per patient was significantly lower in the alfacalcidol treatment group than in the elcatonin treatment group (0.80 +/- 1.19 and 2.08 +/- 2.73, respectively; P0.05). These findings indicate that both treatments appeared to sustain lumbar BMD similarly over a 5-year period in postmenopausal women with osteoporosis, but alfacalcidol treatment may be superior to elcatonin treatment regarding the incidence of vertebral fractures. Further study with prospective observations are needed to confirm the results of the present study.

The purpose of the present study was to determine whether etidronate treatment could prevent bone loss caused by orchidectomy (ORX) and unilateral sciatic neurectomy (NX) in adult male rats. Seventy-four male Wistar rats, aged 10 months, were randomly divided into eight groups: baseline controls (n = 10); age-matched sham-operated controls (AMC; n = 9); ORX (n = 9); NX (n = 10); ORX + NX (n = 9); ORX + etidronate treatment (ORX + E; n = 7); NX + E (n = 10); and ORX + NX + E (n = 10). Etidronate treatment (10 mg/kg per day subcutaneously) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, bone mineral density (BMD) of the proximal and middle tibia (PT and MT, respectively), distal and middle femur (DF and MF, respectively), and fourth lumbar vertebral body (LVB) was measured by dual-energy X-ray absorptiometry (Model DCS-600, Aloka, Tokyo, Japan). The mechanical properties of the MF and third LVB were measured by three-point bending and compression tests, respectively. Levels of urinary deoxypyridinoline (Dpd) and serum osteocalcin (Oc) were also measured by enzyme-linked immunosorbent assay. Four weeks of aging had no significant effects on BMD, bone mechanical properties, or bone markers. ORX significantly increased the levels of urinary Dpd and serum Oc, which resulted in significant decreases in BMD of the PT, MT, DF, MF, and fourth LVB, as well as the mechanical strength (maximum load) of the MF and third LVB. NX significantly increased levels of urinary Dpd and decreased levels of serum Oc, resulting in a significant decrease in BMD of the PT, DF, and fourth LVB. The ORX-induced decrease in BMD of the PT was more pronounced when combined with NX. Etidronate treatment for NX, ORX, and ORX + NX rats significantly decreased levels of urinary Dpd and serum Oc, resulting in complete prevention of loss of BMD and/or bone mechanical strength. The present study demonstrates the efficacy of etidronate treatment for prevention of bone loss caused by testosterone deficiency and immobilization in adult male rats.

The aims of the present study were to clarify whether postmenopausal women with osteoarthritis (OA) of the knee show higher bone mineral density (BMD) than healthy controls, and to investigate the relationship between BMD and the Kellgren and Lawrence radiological grade in postmenopausal women with OA of the knee. A total of 674 postmenopausal women, 46–90 years of age, were enrolled in the study: 305 patients with OA of the knee and 369 healthy controls. Forearm (distal radius) BMD, measured by dual-energy X-ray absorptionetry (DXA), using a DTX-200 (Osteometer), was significantly higher in the OA group than in the control group (P < 0.001), even when adjusted for age, height, body weight, body mass index, years since menopause, and grip strength (P < 0.01). Analysis of variance (ANOVA) with Fisher's protected least significant difference (PLSD) test showed that BMD in radiological grades 2, 3, and 4 was significantly higher than that in grade 1 (P < 0.05, P < 0.001, and P < 0.05, respectively), and BMD in grade 3 was significantly higher than that in grade 2 (P < 0.01), but BMD in grade 4 was significantly lower than that in grade 3 (P < 0.05). These findings suggest that forearm BMD appears to be significantly higher in postmenopausal women with OA of the knee than in healthy controls. Although BMD may be increased in low to moderate radiological grades of OA, severe grade OA may not always develop from moderate grade OA. Some cases of severe grade OA may be associated with low BMD.

The effect of the systemic administration of prostaglandin (PG) E(1) on physical activity and bone resorption was examined in patients with intermittent claudication (gait disturbance). Twenty male patients (age, 67.2 +/- 7.8 years; mean +/- SD) with neurogenic intermittent claudication caused by lumbar spinal canal stenosis were included in the study. Lipo-PG E(1) was administered intravenously, at a daily dose of 10 microg, on 3 days a week, for 6 months in all patients. Clinical symptoms, levels of urinary cross-linked N-telopeptides of type I collagen (NTx), and metacarpal cortical bone mineral density (BMD) were assessed before and just after the 6 months of treatment. Subjective symptoms, including leg pain and/or tingling and gait disturbance, and restrictions of the activities of daily living were significantly improved. However, no significant changes were observed in either urinary NTx levels or metacarpal cortical BMD. These findings suggest that the systemic administration of PG E(1) appears to improve subjective symptoms and activities of daily living in elderly male patients with neurogenic intermittent claudication, but does not affect either bone resorption or metacarpal cortical BMD. Short-term systemic administration of PG E(1) and increased physical activity in elderly male patients with gait disturbance caused by lumbar spinal canal stenosis may not affect bone resorption.

The aim of the present study was to investigate the relationships between physical activity and metacarpal cortical bone mineral density (BMD) and bone resorption in hemiplegic patients. Seventy-two male hemiplegic patients with cerebrovascular disease (mean age, 67.0 years; range 48–83 years) were recruited. Metacarpal cortical BMD in bilateral hands was measured by computed X-ray densitometry, and the levels of urinary cross-linked N-telopeptides of type I collagen (NTx), as a bone resorption marker, were measured by an enzyme-linked immunosorbent assay (ELISA). BMD (mean ± SD) in the paralyzed hand was significantly lower than that in the nonparalyzed hand (2.52 ± 0.46 and 2.64 ± 0.45 mmAl; P < 0.05). On multiple regression analysis, BMD was significantly positively correlated with Brunnstrom stage (assessment of degree of paralysis) in the hand (P < 0.05), whereas urinary NTx levels were significantly negatively correlated with Brunnstrom stage in the hand, arm, and leg, and with walking ability (P < 0.05, P < 0.05, P < 0.01, and P < 0.01, respectively). These findings suggest that, in male hemiplegic patients, although metacarpal cortical BMD may be affected by only local physical activity, urinary NTx appears to be responsive to local and general physical activity.

We examined radiographs of the elbows of the pitching arms of 79 professional baseball pitchers (mean age, 25.1 years; mean duration of professional career, 4.7 years) and noted the frequency and size of spurs, bone fragments, and intra-articular loose bodies according to site. The influence of duration of professional baseball career on these osteoarthritic changes was also investigated. The olecranon tip was the most frequent site of spurs (62/79; 78.5%), and fragmentation of the spur was detected in 17 joints. The frequency of spurs was also high at the medial margin of the olecranon, the tip of the coronoid process, the medial margin of the sigmoid notch, the medial margin of the trochlea and the olecranon fossa. In 38 subjects, spurs were observed at the distal portion of the radial notch of the ulna. However, few pitchers had osteoarthritic changes in the humeral capitellum or radial head. Intra-articular loose bodies were detected in 4 of 79 joints (5.1%), and bone fragments were present below the medial humeral epicondyle in 25 of 79 joints (31.6%). Osteoarthritic changes in the elbow joint appeared to be attributable mainly to traction stress and impingement associated with extension and valgus strain. Significant osteoarthritic changes were often found in professional pitchers whose careers exceeded 5 years.

The influence of secondary damage to joint structures (menisci and articular cartilage) on return to sports activities following anterior cruciate ligament (ACL) reconstruction was investigated. Two hundred and sixty athletes who had undergone ACL reconstruction with the Leeds-Keio artificial ligament and had achieved satisfactory joint stability and range of motion were involved in this study. The follow-up period was 7–50 months (mean, 23.4 months). There was a clear correlation between the severity of damage to the joint structures (the menisci and articular cartilage) and the level of return to sports. The most common reason for not being able to return to the original level of sports activity was “pain”. Thus, it was concluded that irreversible secondary damage to joint structures was an important factor hindering return to sports after ACL reconstruction. This study showed that the incidence of meniscal injury and cartilage damage increased with the passage of time after ACL injury, and that, once meniscal injury develops, the incidence of cartilage damage increases. Since sports activity is a factor that accelerates or promotes processes that give rise to this meniscal injury and cartilage damage, it was concluded that it is vital to perform ACL reconstruction before irreversible secondary damage to joint structures occurs in athletes with ACL injuries who hope to continue their sports activities.