Force-sensing treadmill gait analysis system can detect gait abnormalities in haemophilia patients without arthropathy.

BACKGROUND: Joint damage in patients with haemophilia (PwH) is commonly assessed by imaging, but few reports have described how structural changes in joints, for example, haemophilic arthropathy (HA)-affect gait ability. OBJECTIVES: We evaluated gait function among PwH with HA, PwH without HA, and people without haemophilia (non-PwH) using a Zebris FDM-T treadmill (FDM-T), an easy-to-use gait assessment instrument with a force sensor matrix. METHODS: The following gait parameters were collected: centre of pressure trajectory intersection (COPi) anterior/posterior variability, COPi lateral variability, COPi anterior/posterior symmetry, COPi lateral symmetry, single-limb support line (SLSL) length, and SLSL variability. Participants walked at their typical gait speed. The physical function of the PwH was assessed by the Hemophilia Joint Health Score (HJHS). Parameters were compared among the three groups. RESULTS: Twelve PwH with HA, 28 PwH without HA, and 12 non-PwH were enrolled. Gait speed significantly differed between groups (non-PwH, 3.1 ± 0.7; PwH without HA, 2.0 ± 0.7; PwH with HA; 1.5 ± 0.4). The COPi anterior/posterior variability, COPi lateral variability, SLSL length, and SLSL variability were greater in the PwH groups than in the non-PwH group. The COPi lateral symmetry differed between PwH with HA and the other groups. The HJHS was not correlated with gait parameters among PwH with HA. CONCLUSIONS: Gait parameters and speed were abnormal in both PwH with HA and PwH without HA. The FDM-T can be used to identify early stages of physical dysfunction that cannot be detected by conventional functional assessments such as the HJHS.

Reoperation after surgery for bone metastasis of renal cell carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. METHODS: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. RESULTS: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. CONCLUSION: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.

Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review.

PURPOSE: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs. METHODS: This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies. RESULTS: Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively. CONCLUSION: Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures.

Comparison of pre-operative and post-operative radiotherapy in patients with localized myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma is more radiosensitive than other soft tissue sarcomas, and radiotherapy has been reported to reduce tumour size. This study was performed to compare the rates of local recurrence, survival and wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. METHODS: From the Japanese Nationwide Bone and Soft Tissue Tumor Registry database, 200 patients with localized myxoid liposarcoma who received pre- (range, 30-56 Gy) or post-operative (range, 45-70 Gy) radiotherapy and surgery were included in this retrospective study. Propensity score matching was used to adjust for background differences between patients who received pre- and post-operative radiotherapy. RESULTS: Local recurrence occurred in five (5.0%) and nine (9.0%) patients in the pre- and post-operative radiotherapy groups, respectively (both n = 100). The median follow-up time from diagnosis was 40.5 months (IQR, 26.3-74). Univariate analysis showed a similar risk of local recurrence between the pre- and post-operative radiotherapy groups (5-year local recurrence-free survival 94.9% [95% CI 87.0-98.1] vs. 89.0% [95% CI 79.6-94.3]; P = 0.167). Disease-specific survival was similar between the pre- and post-operative radiotherapy groups (5-year disease-specific survival 88.1% [95% CI 75.5-94.6] vs. 88.4% [95% CI 77.3-94.5]; P = 0.900). The incidence of wound complications was similar between the pre- and post-operative radiotherapy groups (7.0% vs. 12.0%; P = 0.228). CONCLUSIONS: There was no difference in local recurrence, survival or incidence of wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. Therefore, pre-operative radiotherapy for myxoid liposarcoma provides clinical results equivalent to post-operative radiotherapy.

Influences of comorbidities on perioperative rehabilitation in patients with gastrointestinal cancers: a retrospective study.

BACKGROUND: Older patients are more likely to have comorbidities than younger patients, and multiple comorbidities are associated with mortality in patients with cancer. Therefore, we hypothesized that a functional comorbidity index could predict the therapeutic effects of rehabilitation. OBJECTIVES: In this study, we investigate whether the comorbidities influenced the execution and therapeutic effects of rehabilitation. METHODS: A consecutive cohort of 48 patients with gastrointestinal cancer who underwent surgery between January 1 and November 30, 2020, was analyzed. Charlson Comorbidity Index (CCI) scores were calculated based on data derived from medical records. The primary outcomes were ambulation status, duration (days) from the start of postoperative rehabilitation, and length of hospital stay. We investigated the relationship between CCI scores and primary outcomes. RESULTS: The CCI did not correlate with the duration of rehabilitation or the length of hospital stay. Subsequently, patients with functional recovery problems were evaluated, and we identified the conditions that were not included in the list using CCI scores. Most conditions are associated with surgical complications. Furthermore, using the Clavien-Dindo classification (CDC), we assessed the clinical features of the severity of complications. We found that the length of stay and the duration to start rehabilitation were significantly longer in the patients with higher severity of surgical complications (CDC≧III) than in those with lower severity (CDC≦II). CONCLUSIONS: Treatment-related conditions may significantly impact the perioperative period more than the original comorbidities. In addition to original comorbidities, events related to surgical complications should be assessed to determine the therapeutic effects of rehabilitation in patients with gastrointestinal cancer.

Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells.

High mobility group box-1 (HMGB1) is known to be a chemotactic factor for mesenchymal stem/stromal cells (MSCs), but the effect of post-translational modification on its function is not clear. In this study, we hypothesized that differences in the oxidation state of HMGB1 would lead to differences in the function of MSCs in cancer. In human colorectal cancer, MSCs infiltrating into the stroma were correlated with liver metastasis and serum HMGB1. In animal models, oxidized HMGB1 mobilized three-fold fewer MSCs to subcutaneous tumors compared with reduced HMGB1. Reduced HMGB1 inhibited the proliferation of mouse bone marrow MSCs (BM-MSCs) and induced differentiation into osteoblasts and vascular pericytes, whereas oxidized HMGB1 promoted proliferation and increased stemness, and no differentiation was observed. When BM-MSCs pretreated with oxidized HMGB1 were co-cultured with syngeneic cancer cells, cell proliferation and stemness of cancer cells were increased, and tumorigenesis and drug resistance were promoted. In contrast, co-culture with reduced HMGB1-pretreated BM-MSCs did not enhance stemness. In an animal orthotopic transplantation colorectal cancer model, oxidized HMGB1, but not reduced HMGB1, promoted liver metastasis with intratumoral MSC chemotaxis. Therefore, oxidized HMGB1 reprograms MSCs and promotes cancer malignancy. The oxidized HMGB1-MSC axis may be an important target for cancer therapy.

Marginal resection for patients with atypical lipomatous tumours of the extremities and trunk wall: a systematic review and meta-analysis.

BACKGROUND: This systematic review assessed and compared the efficacy of marginal resection to wide resection in patients with atypical lipomatous tumours (ALT) by evaluating the local recurrence rates, overall survival and adverse event rates. METHODS: We evaluated studies published between 1 January 1990 and 31 January 2019. The risks of bias in the selected studies were analyzed using the Cochrane Collaboration Risk of Bias Tool. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Three case-control studies and three case series studies were identified. A meta-analysis was performed of six studies to evaluate the local recurrence rate after resection. Comparison of marginal and wide resections showed that the local recurrence rate was not significantly higher in the marginal resection group (14.2 and 1.4%, odds ratio: 2.88, 95% confidence interval 0.99-8.33, P = 0.05). We observed no difference in overall survival. In one study, the rates of adverse events were 14.7% in the marginal resection group and 45.4% in the wide treatment group (odds ratio, 0.32; 95% confidence interval 0.11-80.91, P < 0.05). CONCLUSIONS: In our analyses, five of six studies reported no recurrence for wide resection, compared to three to seven recurrences in the marginal resection group. One study reported only one case of recurrence for wide resection. Because ALT has a relatively good prognosis, the use of marginal resection is acceptable to preserve musculoskeletal function.

Effect of adjuvant chemotherapy on periosteal osteosarcoma: a systematic review.

BACKGROUND AND OBJECTIVE: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis. METHODS: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total. RESULTS: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187). CONCLUSIONS: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies.

Electroencephalographic-Based Functional Connectivity Networks of Visual Hallucinations and Visuospatial Dysfunctions in Parkinson's Disease.

Visual dysfunction is an important nonmotor symptom of Parkinson's disease (PD). Visual hallucinations (VHs) and visuospatial dysfunctions (VSDs) are common visual dysfunctions in PD; however, the underlying mechanisms remain unclear. Our study aimed to evaluate neuronal synchronization between patients with PD with and without VH or VSD using electroencephalographic (EEG) coherence analysis. Twenty-four patients with sporadic PD were evaluated for the presence of VH and VSD, and were divided into VH-negative and VH-positive groups, and these groups were further subdivided by VSD status. Coherence analysis was performed on EEG data. Whole-brain and regional coherences were calculated and compared between the groups. There was a significant difference in frontal-frontal coherence between the VH+ VSD- and VH+ VSD+ groups (p = 0.026). Our findings suggest that reduced EEG coherence in frontal regions might be involved in VSD in patients with PD. Reduced neuronal synchronization between the frontal lobes may contribute to the disruption of visual processing in PD.

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Novel knit fabric rehabilitation equipment for finger impairment.

[Purpose] Intensive training can at least partially improve finger movement dysfunction observed after stroke or any neurodegenerative disease. Wearable equipment can significantly improve patients' quality of life. However, long-term use of conventional training gloves containing metal can injure joints. In this study, we investigated the safety and efficacy of a novel, metal-free, wearable strength-building device. [Participants and Methods] We enrolled 20 healthy participants in whom we measured grip and pinch strength before and while the equipment was worn. Additionally, we investigated the adverse effects and discomfort experienced while participants wore the equipment. [Results] The grip strength was reduced by approximately 20% while participants wore the equipment. We did not observe any serious adverse events. [Conclusion] The knitting equipment described in this study resists movements associated with gripping the hand and acts on all fingers, and may be useful for rehabilitation to improve finger function during routine activities.

Improvement in lower extremity hemiplegia in a post-operative brain tumor patient by applying an integrated volitional control electrical stimulator.

[Purpose] This study aimed to evaluate the improvement in lower extremity hemiplegia following brain tumor operation with an integrated volitional control electrical stimulator (IVES). [Participant and Methods] A 40 year-old male with anaplasic oligodendroglioma in the right frontal lobe underwent IVES in the rectus femoris and tibialis anterior muscles using the power-assist and sensor-trigger modes. Lower extremity motor function was assessed before and after the therapy sessions. An assessment was conducted using various techniques, including static posturography and surface electromyography. [Results] Static posturography showed an improvement in the center of pressure and sway area after IVES gait training. Based on a time-series statistical parametric mapping analysis, the activation pattern of each muscle after the treatment was different. Muscle synergy analysis revealed decreased total variance accounted for by a single synergy in the affected and normal sides after the treatment. [Conclusion] Patients with chronic hemiplegic lower extremity impairment responded well to IVES gait training. Electromyography-triggered functional electrical stimulation may enhance sensory-motor integration. Proprioceptive feedback plays a crucial role in improving motor control.

Clinical questions on rehabilitation in cancer patients with skeletal metastasis: a content analysis of the multidisciplinary tumor board records.

PURPOSE: Cancer rehabilitation addresses the functional needs of patients who have various impairments. Disease control is a critical oncological consideration, while physical intervention increased weights of importance in several situations. To identify the clinical status that necessitates active physical intervention in cancer patients with skeletal metastasis, we performed a content analysis in the multidisciplinary tumor board (MDTB) records. METHODS: From January 2017 to September 2019, the MDTB discussed 168 consecutive patients with skeletal metastasis. We reviewed the MDTB records and asked responsible physicians to frame clinical questions. Based on these data, we identified the predictor valuables with the association to rehabilitation-related clinical questions using univariate and multivariate analyses. Moreover, we investigated a predictor of the change in Barthel index (BI) scores using univariate analyses. RESULTS: Rehabilitation-related questions arose more frequently in older patients (p = 0.011), in patients with slow-growth vs. rapid-growth tumor (p = 0.002), and in patients with skeletal-related events (p = 0.001) at MDTB. The tumor growth speed was associated with the change in BI scores, as slower-growth tumors had the benefit of BI gains (p = 0.017). CONCLUSIONS: Regarding rehabilitation in patients with skeletal metastasis, we should pay attention to three parameters: occurrence of skeletal events, patient age, and growth speed of tumors. Rehabilitation-related questions may reflect patients' functional needs that occur more frequently in patients with pathological fractures or neurological symptoms, older patients, and patients with slow-growth tumors.

Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

BACKGROUND: This study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors. METHODS: We retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up. RESULTS: An event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p = 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23-30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19-29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p = 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p = 0.976). CONCLUSION: Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

Role of Glycated High Mobility Group Box-1 in Gastric Cancer.

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. Nε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.

What's new in the management of metastatic bone disease.

Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease.

Detectability of prostate cancer in different parts of the gland with 3-Tesla multiparametric magnetic resonance imaging: correlation with whole-mount histopathology.

BACKGROUND: We investigated whether the detectability of prostate cancer with 3-Tesla (3T) multiparametric magnetic resonance imaging (mpMRI) differs by tumor location. METHODS: We identified 136 patients with prostate cancer who underwent 3-T mpMRI before prostatectomy at a single academic center. Two uroradiologists scored all MRIs with Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2). A genitourinary pathologist mapped tumor foci from serial whole-mount radical prostatectomy sections. We assessed concordance of images with cancer sites. Tumor foci with Gleason score ≥  3 + 4 or volume ≥ 0.5 mL were considered significant. RESULTS: A total of 122 foci in 106 cases were identified with mpMRI. Twenty-four were PI-RADS 3, 52 were 4, and 46 were 5. A total of 274 tumor foci were identified with whole-mount pathology. The sensitivity stratified by location to detect significant cancer with a PI-RADS cutoff value of 3 was 56.0% overall, 50.0% in the peripheral zone (PZ), 71.2% in the transitional zone (TZ), 62.4% anterior, 49.5% posterior, 42.0% apical, 63.6% in the midgland, and 43.8% in the gland base. In multivariate analysis, tumor location was not a significant predictor of identification by mpMRI. Tumor volume, Gleason score, and index tumor status were significantly associated with identification by mpMRI. CONCLUSIONS: mpMRI detected the majority of high-grade and large cancers, but had low sensitivity in the PZ, posterior, and apex and base of the gland. The high prevalence of low-volume, low-Gleason score index tumors, as well as satellite tumors in those areas, accounted for the difference.

Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.

BACKGROUND: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established. QUESTIONS/PURPOSES: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage? METHODS: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis. RESULTS: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group. CONCLUSIONS: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

Impairment-driven cancer rehabilitation in patients with neoplastic spinal cord compression using minimally invasive spine stabilization.

BACKGROUND: Neoplastic spinal cord compression is a cause of severe disability in cancer patients. To prevent irreversible paraplegia, a structured strategy is required to address the various impairments present in cancer patients. In this study, we aimed to identify the status where rehabilitation with minimally invasive spine stabilization (MISt) effectively improves ADL. METHODS: We retrospectively reviewed 27 consecutive patients with neoplastic spinal compression who were treated with MISt. We classified the impairments of patients through our multidisciplinary tumor board based on spine-specific factors, skeletal instability, and tumor growth. The neurological deficits, progress of pathological fracture, incidence of vertebral collapse, and postoperative implant failure were examined. Changes of the Barthel index (BI) scores before and after surgery were investigated throughout the clinical courses. RESULTS: The average duration to ambulation was 7.19 ± 11 days, and we observed no collapse or progression of paralysis except in four cases of complete motor paraplegia before the surgery. Neurological deficiency was improved to or maintained at Frankel's grade E in 16 patients, remained unchanged in 6 patients (in grades B, C, D), and worsened in 5 patients. BI score comparisons before and after surgery in all patients showed statistically significant increments (p < 0.05). On further analysis, we noted good functional prognosis in patients capable of ambulation within 7 days (p < 0.05) and in patients who could survive longer than 3 months after the surgery (p < 0.05). CONCLUSIONS: In various cancer patients with neoplastic spinal cord compression, skeletal instability as the primary impairment is a good indication for MISt, as the patients showed early ambulation with improved BI scores.

Anti-Stem Cell Property of Pterostilbene in Gastrointestinal Cancer Cells.

Pterostilbene (PTE) is a natural sterbenoid contained in blueberries that has an antioxidant effect. In contrast, PTE also generates oxidative stress in cancer cells and provides an antitumor effect. Here, we examined the potential mechanism of this contrasting effect of PTE using three gastrointestinal cancer cell lines, namely CT26, HT29, and MKN74. PTE showed a dose-dependent inhibition of cell proliferation, sphere-forming ability, and stem cell marker expression in all three cell lines. Furthermore, the cells treated with PTE showed an increase in mitochondrial membrane potential and an increase in mitochondrial oxidative stress and lipid peroxide. Upon concurrent treatment with vitamin E, N-acetyl-L-cysteine, and PTE, the PTE-induced mitochondrial oxidative stress and growth inhibition were suppressed. These findings indicate that PTE induces oxidative stress in cancer cells, suppresses stemness, and inhibits proliferation. These antitumor effects of PTE are considered to be useful in cancer treatment.