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Purpose: The pathogenesis of cystic fluid storage in solitary bone cysts remains unclear. We aimed to compare the results of the biochemical analysis of cystic fluid with clinical findings. We identified a significant marker of postoperative recurrence. Methods: Twenty-seven male and eight female patients were studied; the median age at diagnosis was 11 (5–23) years. The mean follow-up period was 60 months (range: 14–146 months). Clinical information including sex, age, affected site, radiological findings of phase (active or latent), surgical procedure, outcome, and biochemical analysis of serum and cystic fluid was obtained. Results: The 5-year healing rate was 64.0%. Biochemical analysis revealed that total protein and albumin values in the cystic fluid were significantly lower, compared to those in the serum. Levels of bone turnover markers, such as alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b were remarkably elevated in the cystic fluid than in the serum. R values were 0.127, 0.076, and 0.095 for alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b, respectively. Areas under the receiver operating characteristic curves, calculated to assess the association of alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b levels in the cystic fluid with postoperative recurrence, were 0.57, 0.51, and 0.70, respectively. Conclusions: No clear correlation of bone turnover marker levels between the serum and cystic fluid was observed. The high tartrate-resistant acid phosphatase 5b level in the cystic fluid was associated with postoperative recurrence. The bone resorption caused by osteoclasts is considered to affect postoperative recurrence. Level of evidence: Level IV.

Abstract In the engineering field, it is necessary to construct a numerical model that can reproduce multiphase flows containing three or more phases with high accuracy. In our previous study, by extending the conservative Allen–Cahn (CAC) model, which is computationally considerably more efficient than the conventional Cahn–Hilliard (CH) model, to the multiphase flow problem with three or more phases, we developed the conservative Allen–Cahn type multi-phase-field (CAC–MPF) model. In this study, we newly construct the improved CAC–MPF model by modifying the Lagrange multiplier term of the previous CAC–MPF model to a conservative form. The accuracy of the improved CAC–MPF model is evaluated through a comparison of five models: three CAC–MPF models and two CH–MPF models. The results indicate that the improved CAC–MPF model can accurately and efficiently perform simulations of multiphase flows with three or more phases while maintaining the same level of volume conservation as the CH model. We expect that the improved CAC–MPF model will be applied to various engineering problems with multiphase flows with high accuracy. Graphic abstract

Background/Aim: We determined the impact of sarcopenia on the treatment outcomes of malignant bone and soft tissue tumors in elderly patients. Patients and Methods: We retrospectively reviewed 76 patients (age ≥65 years) who were treated for malignant bone and soft tissue tumors. Sarcopenia was assessed by measuring the cross-sectional area of the psoas muscles at the L3 vertebra from preoperative computed tomography images and categorized using the total psoas area/m2 (TPA/m2) ≤5.0 cm2/m2. The patients’ clinical data were then evaluated. Results: The operation time, length of hospital stay, and median overall survival were not different between the sarcopenia (n=41) and no-sarcopenia (n=35) groups. The local recurrence rate (p=0.01) and incidence of postoperative complications (p=0.02) significantly differed between both groups. The TPA/m2 of both groups significantly decreased at the final follow-up. Conclusion: Sarcopenia negatively influenced wound healing and local recurrence, and was significantly exacerbated postoperatively in all elderly patients.

Photo-induced crawling motion of a crystal of 3,3'-dimethylazobenzene (DMAB) on gold surfaces having different surface properties and various patterns was studied. DMAB crystals crawl continuously when exposed to UV and visible lights simultaneously from different directions. On a gold surface functionalized by a thiol having a hydroxyl group at the terminal (16-hydroxy-1-hexadecanethiol (HOC16SH)), the crystals crawled with a relatively high velocity (ca. 4 μm min-1), and they changed the crystal shape while keeping a distinct crystal face. On a gold surface functionalized by a thiol having an alkyl chain terminal (1-hexadecanethiol (C16SH)), the crawling was observed with a slower velocity (ca. 1.5 μm min-1). However, the shape of the crystals became a droplet-like shape soon after the irradiation started, and the shape persisted during the motion. Light intensity dependence of the crawling velocity of the droplet-like crystal on this surface showed that UV light has stronger dependence for the motion than the visible light. On a substrate with a stripe pattern of alternating C16SH-modified gold and hexadecyltrimethylsilane (HDTMS)-modified glass, crystals crawled only on the surface of the C16SH-modified gold, which may be due to the wettability hysteresis at the surface. On a substrate with a stripe pattern of HOC16SH-modified gold and HDTMS-modified glass, crystals were attracted to the gold side. On a gold substrate with a periodic pattern of different height (ca. 50 nm) but having a uniform treatment with C16SH, crystals crawled up and down the steps without significant disturbance at the boundary of the step. Therefore, wettability of the surface has a greater impact on controlling the motion of the crystal than the surface structure. The present results not only unveil the crawling behavior on various surfaces but also offer a guide to controlling the motion toward applications for novel carriage vehicles to transport molecules/objects on a surface.

Solitary bone cysts in the calcaneus (calcaneal bone cysts) are often asymptomatic. Pathological fractures are rare, and few reports are available concerning its risk assessment. Therefore, the indication for operative interventions remains debatable, and further discussion on the treatment of symptomatic cysts and pathological fractures in calcaneal bone cysts is necessary. Clinical data of 21 patients with calcaneal bone cysts (16 men and five women) was retrospectively reviewed. The average age was 13.3 (range, 7–23) years. Clinical data, such as concerning symptoms, radiological findings, pathological findings and outcomes, were investigated, and the pathogenesis of symptomatic cysts was studied. Thirteen cysts were symptomatic, and eight were incidentally discovered. Computed tomography revealed no fracture in 12 cases, microfracture in eight and complete fracture in one. The areas under the curves of the receiver operating characteristic curves calculated to establish an association between cyst size and symptoms and cyst size and pathological fractures (microfracture and complete fracture) were 0.78 and 0.71, respectively. Symptomatic cysts and pathological fractures were associated with the cyst ratio (cyst size/calcaneus ≥ 0.20). On magnetic resonance imaging (MRI), fluid levels were observed in 11 of 21 (52%) patients. At the time of surgery, blood from the haemorrhage was aspirated from 15 of 21 (71%) cysts. Orthopaedic surgeons should be aware that the cyst ratio is associated with clinical symptoms and pathological fractures. MRI and gross findings revealed haemorrhage in the cystic fluid. In calcaneal bone cysts, repeated microfractures and spontaneous healing might occur.

Background Soft tissue tumors are often accompanied with elevated skin temperature; however, studies concerning the relationship between soft-tissue tumors and skin temperature elevation are scarce. We aimed to evaluate the clinical significance of skin temperature elevation in soft-tissue tumors and identify factors related to skin temperature elevation. Patients and methods This study comprised 118 patients at our hospital with soft-tissue tumors, excluding lipomatous tumors, whose pathological diagnosis was surgically confirmed between February 2017 and March 2021. Sixty-one and 57 patients had been diagnosed with benign lesions and malignant tumors, respectively (men, 64; women, 54; median age, 61 [range, 20–92] years). The relationship between skin temperature, monitored using a thermography camera, and the presence of soft-tissue malignancy was investigated. We reviewed clinical data to identify factors related to elevated skin temperature. Results Temperature differences ≥ 0.2 °C compared to the unaffected side were significantly associated with the presence of malignant tumors (p

Although the inhibition of acid ceramidase (AC) is known to induce antitumor effects in various cancers, there are few reports in pancreatic cancer, and the underlying mechanisms remain unclear. Moreover, there is currently no safe administration method of AC inhibitor. Here the effects of gene therapy using siRNA and shRNA for AC inhibition with its mechanisms for pancreatic cancer were investigated. The inhibition of AC by siRNA and shRNA using an adeno‐associated virus 8 (AAV8) vector had antiproliferative effects by inducing apoptosis in pancreatic cancer cells and xenograft mouse model. Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. These results elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy., Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. The current study elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy.

It has been demonstrated that peripheral inflammation induces cognitive dysfunction. Several histone deacetylase (HDAC) inhibitors ameliorate cognitive dysfunction in animal models of not only peripheral inflammation but also Alzheimer's disease. However, it is not clear which HDAC expressed in the central nervous system or peripheral tissues is involved in the therapeutic effect of HDAC inhibition on cognitive dysfunction. Hence, the present study investigated the effect of peripheral HDAC inhibition on peripheral inflammation-induced cognitive dysfunction. Suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor that is mainly distributed in peripheral tissues after intraperitoneal administration, was found to prevent peripheral inflammation-induced cognitive dysfunction. Moreover, pretreatment with SAHA dramatically increased mRNA expression of interleukin-10, an anti-inflammatory cytokine, in peripheral and central tissues and attenuated peripheral inflammation-induced microglial activation in the CA3 region of the hippocampus. Minocycline, a macrophage/microglia inhibitor, also ameliorated cognitive dysfunction. Furthermore, as a result of treatment with liposomal clodronate, depletion of peripheral macrophages partially ameliorated the peripheral inflammation-evoked cognitive dysfunction. Taken together, these findings demonstrate that inhibition of peripheral HDAC plays a critical role in preventing cognitive dysfunction induced by peripheral inflammation via the regulation of anti-inflammatory cytokine production and the inhibition of microglial functions in the hippocampus. Thus, these findings could provide support for inhibition of peripheral HDAC as a novel therapeutic strategy for inflammation-induced cognitive dysfunction.

Lysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy‐lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. In this study, we show evidence that suppression of acid alpha‐glucosidase (GAA), one of the lysosomal enzymes, improves chemosensitivity and exerts apoptotic effects on PC cells through the disturbance of expression of the transcription factor EB. The levels of lysosomal enzyme were elevated by gemcitabine in PC cells. In particular, the levels of GAA were responsive to gemcitabine in a dose–dependent and time–dependent manner. Small interfering RNA against the GAA gene (siGAA) suppressed cell proliferation and promoted apoptosis in gemcitabine‐treated PC cells. In untreated PC cells, we observed accumulation of depolarized mitochondria. Gene therapy using adenoviral vectors carrying shRNA against the GAA gene increased the number of apoptotic cells and decreased the tumor growth in xenograft model mice. These results indicate that GAA is one of the key targets to improve the efficacy of gemcitabine and develop novel therapies for PC., In this study, we demonstrated that enhancement of lysosomal activity with gemcitabine was involved in resistance to treatment in PC cells. Furthermore, suppression of GAA, a lysosomal enzyme, improves the sensitivity to gemcitabine and induces apoptosis in PC cells through modulation of TFEB translocation.

Aim This study aimed to identify the risk of pathological fractures after bone tumour biopsy. Materials and methods Fifty rabbit femurs were divided into groups according to defect size: Control (no defect), type 1 (10% width), type 2 (20% width), type 3 (30% width), and type 4 (40% width). Another 20 were also divided into control, type A (27% length), type B (40% length), and type C (53% length) groups. Performing femoral head compression testing allowed each parameter (maximum load, displacement, elastic modulus, and fracture energy) to be calculated individually. Results Compressive maximum load was significantly higher for type 1 than for the other types when testing rectangular defects of different widths, while there were no significant differences between the three types when testing by defect length. Conclusion It may be useful for orthopaedic oncologists to make a rectangular biopsy hole with a width measuring less than 10% of the circumference and to enlarge the hole longitudinally to avoid pathological fracture.

Background: The spread of coronavirus disease 2019 (COVID-19) has caused severe damage to routine medical care. This study aimed to investigate the impact of COVID-19 on bone and soft tissue tumor treatment at a single center. Methods: A retrospective comparative study was conducted between two groups of patients who received treatment at Osaka City University Hospital during the peak of the COVID-19 pandemic (February-December 2020, Group C) and during the same period the previous year (February to December 2019, Group NC). Clinical data, including patient's age, sex, tumor site, type of neoplasms, number of surgical cases for inpatients and outpatients, operation time, use of implant, length of hospital stay, inpatient hospitalization costs, number of inpatients receiving anticancer drugs, and postoperative complications in these two groups were retrospectively evaluated. Results: The number of cases of malignant bone and soft tissue tumors that were resected during hospitalization was predominantly higher in Group C than in Group NC ( P =0.01). There were no significant differences in operation time, use of implant, and postoperative complications between Groups C and NC; however, there were significant differences in the length of hospital stay and hospitalization cost ( P

Giant cell tumor of soft tissue (GCT-ST), histologically resembling the GCT of the bone, is a rare tumor. The tumor has been categorized to have low malignancy. Few reports of local recurrence or distant metastasis and the use of chemotherapeutic agents for metastatic GCT-ST exist. Herein, we report the efficacy of pazopanib in a 78-year-old Japanese woman with GCT in the intrinsic back musculature with both post-operative local recurrence and lung metastasis. The patient visited the hospital with a three-month history of a palpable mass in the intrinsic back musculature. Following magnetic resonance imaging, the tumor predominantly exhibited slight hyperintensity on T2-weighted images and intense heterogeneous enhancement on contrast-enhanced T1-weighted images. A percutaneous needle biopsy was performed, and the pathological diagnosis was GCT-ST. The patient underwent surgery, and three months later she presented with not only local recurrence but also multiple lung metastases. The patient was immediately treated with pazopanib 400 mg once daily. One month after initiating treatment, a partial response in the pulmonary lesions was observed, and stable disease (SD) effects lasted for 11 months without severe adverse effects. Therefore, pazopanib treatment for metastatic malignant giant cell tumor of soft tissue achieved reasonable success.

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors’ and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Only a few studies have examined the impact of carcinoembryonic antigen variation in patients before and after curative resection of colorectal liver metastasis . This study examined the correlation between carcinoembryonic antigen levels and patient prognosis.Patients who underwent curative resection for colorectal liver metastasis between 2000 and 2017 were enrolled. This study examined patients with high preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis and the correlation between prognosis and time-dependent changes in carcinoembryonic antigen levels. The similarity in the risk of recurrence in patients with normal preoperative carcinoembryonic antigen levels was evaluated.A total of 143 consecutive patients were included in the study cohort and classified into the normal preoperative (46 patients), normalized postoperative (57 patients), and elevated preoperative and postoperative (40 patients) carcinoembryonic antigen groups. All clinicopathologic characteristics were comparable between patients grouped according to carcinoembryonic antigen levels. The 5-year disease-free survival and overall survival rates for all patients were 30.4% and 56.0%, respectively. Multivariate analysis confirmed that elevated preoperative and postoperative carcinoembryonic antigen levels (hazard ratio = 1.73, 95% confidence interval: 1.04-2.87) were independently associated with poor disease-free survival; normalization of postoperative carcinoembryonic antigen (hazard ratio = 0.94, 95% confidence interval: 0.57-1.53) was statistically indistinguishable from normal preoperative carcinoembryonic antigen levels. The risk of recurrence was similar to that of patients with normal preoperative carcinoembryonic antigen levels CONCLUSION: Patients with elevated preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis were not at risk of poor disease-free survival. Elevated carcinoembryonic antigen levels after surgery are independent prognostic factors for disease-free survival.

Recent literature indicates that calcaneal bone cysts have different clinical features compared to long bone cysts. Yet, previous studies have mainly focused on pathogenesis of long bone cysts. In this study, the pathogenesis of calcaneal bone cysts was investigated from radiological and pathological findings. Patients comprised 18 males and 6 females diagnosed with calcaneal bone cysts at a median age ± standard deviation of 13.0 ± 3.6 years. Plain radiographs, computed tomography, magnetic resonance imaging, cystography, bone scintigraphy, and pathology were reviewed. All cysts occupied the central triangular area of the bone, with six extending posteriorly and two developing anteriorly. Fifteen of 20 cases (75%) showed the expanded foramen structures at the anterior margin of the posterior facet. According to cystography, four cysts showed absence of leakage to subtalar joint. Cystic fluid caused chronic haemorrhaging in 18 cases and pathologically detected cholesterol clefts were noted in 14 cases. The location of the expanded foramen structures was consistent with the nutrient foramens of the sinus tarsi artery in the unaffected population. Hence, initial cysts may originate from the collapse of the sinus tarsi artery. Subsequent haemorrhage may extend into the central triangle area, which is biomechanically free of stress. Because of poor bone remodelling, degenerative change of the haemorrhage is prolonged. The results of this study showed that circulation collapse of the sinus tarsi artery and mechanical factors are important in the formation of calcaneal bone cysts.

Background/aim Biopsy hole for bone tumour biopsy may cause pathological fractures. This study aimed to identify the optimal shape of bone tumour biopsy hole using the rabbit femoral head compression test to avoid pathological fracture. Materials and methods A compression test with no defect was performed to identify bone fracture location. Three shapes of biopsy holes (same size) were made artificially. Sixty rabbit femurs were randomly divided (n=15 each) into control (no defect), Shape 1 (round), Shape 2 (square), and Shape 3 (rectangular) groups. Results Twelve out of fifteen femurs were fractured on the femoral shaft; the femoral shaft was targeted for the compression test. Compressive maximum load and fracture energy were significantly higher for Shape 3 than for the other Shapes. Conclusion A rectangular biopsy hole helps minimise reduction in bone strength. The defect width may be related to fragility of the affected bone.