Methionine restriction of glioma does not induce MGMT and greatly improves temozolomide efficacy in an orthotopic nude-mouse model: A potential curable approach to a clinically-incurable disease.

Glioma is a highly recalcitrant disease with a 5-year survival of 6.8 %. Temozolomide (TMZ), first-line therapy for glioma, is more effective in O6-methylguanine-DNA methyltransferase (MGMT)-negative gliomas than in MGMT-positive gliomas as MGMT confers resistance to TMZ. Methionine restriction is effective for many cancers in mouse models including glioma. The concern is that methionine restriction could induce MGMT by decreasing DNA methylation and confer resistance to TMZ. In the present study, we investigated the efficacy of combining methionine restriction with TMZ for the treatment of MGMT-negative glioma, and whether methionine restriction induced MGMT. Human MGMT-negative U87 glioma cells were used to determine the efficacy of TMZ combined with methionine restriction. Recombinant methioninase (rMETase) inhibited U87 glioma growth without induction of MGMT in vitro. The combination of rMETase and TMZ inhibited U87 cell proliferation more than either agent alone in vitro. In the orthotopic nude-mouse model, the combination of TMZ and a methionine-deficient diet was much more effective than TMZ alone: two mice out of five were cured of glioma by the combination. No mice died during the treatment period. Methionine restriction enhanced the efficacy of TMZ in MGMT-negative glioma without inducing MGMT, demonstrating potential clinical promise for improved outcome of a currently incurable disease.

Denosumab administration for bone metastases from solid tumors: a retrospective cross-sectional study.

BACKGROUND: Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab administration in patients with bone metastases from solid tumors. METHODS: Data of patients treated with denosumab were collected from electronic medical charts (n = 496). Eligible participants in this study were adult patients (age ≥ 18 years) with metastatic bone lesions from solid tumors treated with denosumab. SREs, surgical interventions, the spinal instability neoplastic score (SINS) for spinal region, and Mirels' score for the appendicular region were evaluated. To assess whether denosumab could prevent SREs and associated surgery, the SINS and Mirels' score were compared between patients with and without SREs. RESULTS: A total of 247 patients (median age, 65.5 years old; median follow-up period, 13 months) treated with denosumab for metastatic bone lesions from solid tumors were enrolled in this study. SREs occurred in 19 patients (7.7%). SREs occurred in 2 patients (0.8%) who took denosumab administration before SREs. Surgical interventions were undertaken in 14 patients (5.7%) (spinal and intradural lesions in five patients and appendicular lesions in nine patients). The mean SINS of patients without SREs compared to those with SREs were 7.5 points and 10.2 points, respectively. The mean Mirels' scores of non-SREs patients and those with SREs were 8.07 points and 10.7 points, respectively. Patients with SREs had significantly higher Mirels' score than non-SREs patients (p < 0.01). Patients with SREs had higher SINS than non-SREs patients (p = 0.09). CONCLUSIONS: SREs occurred in patients with higher SINS or Mirels' scores. Two patients suffered from SREs though they took denosumab administration before SREs. Appropriate management of denosumab for patients with bone metastasis is significant. Surgical interventions may be needed for patients who with higher SINS or Mirel's scores.

Superiority of [11C]methionine over [18F]deoxyglucose for PET Imaging of Multiple Cancer Types Due to the Methionine Addiction of Cancer.

Positron emission tomography (PET) is widely used to detect cancers. The usual isotope for PET imaging of cancer is [18F]deoxyglucose. The premise of using [18F]deoxyglucose is that cancers are addicted to glucose (The Warburg effect). However, cancers are more severely addicted to methionine (The Hoffman effect). [11C]methionine PET (MET-PET) has been effectively used for the detection of glioblastoma and other cancers in the brain, and in comparison, MET-PET has been shown to be more sensitive and accurate than [18F]deoxyglucose PET (FDG-PET). However, MET-PET has been limited to cancers in the brain. The present report describes the first applications of MET-PET to cancers of multiple organs, including rectal, bladder, lung, and kidney. The results in each case show that MET-PET is superior to FDG-PET due to the methionine addiction of cancer and suggest that the broad application of MET-PET should be undertaken for cancer detection.

Efficacy of intravenous dexamethasone on postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid: a systematic review and meta-analysis.

PURPOSE: Intravenous dexamethasone is recommended in elective caesarean delivery to decrease postoperative pain. However, the efficacy of spinal anaesthesia with an intrathecal long-acting opioid such as morphine or diamorphine for caesarean delivery has not been systematically investigated. METHODS: We searched all randomized controlled trials (RCTs) of pregnant women undergoing caesarean delivery under spinal anaesthesia with an intrathecal morphine or diamorphine via MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov on May 18, 2022. Primary outcomes were time to first rescue analgesia, consumption of oral morphine equivalents, and incidence of drug-related adverse reactions. We evaluated the risk of bias for each outcome using the Risk of Bias 2. We conducted a meta-analysis using a random effects model. We evaluated the certainty of evidence with the GRADE approach. RESULTS: Five RCTs (455 patients) were included. The results of intravenous dexamethasone were as follows: time to first rescue analgesia (mean difference [MD] 0.99 h, 95% confidence interval [CI] - 0.86 to 2.84; very low certainty) and consumption of oral morphine equivalents (MD - 6.55 mg, 95% CI - 17.13 to 4.02; moderate certainty). No incidence of drug-related adverse reactions was reported (very low certainty). CONCLUSION: The evidence was very uncertain about the efficacy of intravenous dexamethasone on time to first rescue analgesia and the incidence of drug-related adverse reactions. Intravenous dexamethasone probably reduces the consumption of oral morphine equivalents. Anaesthesiologists might want to consider intravenous dexamethasone for postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid.

Veno-accompanying artery fasciocutaneous flaps following wide excision of soft tissue tumors in the lower legs.

BACKGROUND: Soft tissue defects following wide excision of malignant soft tissue tumors (STTs) are sometimes too large for primary closure, especially in the lower legs where available soft tissue is limited. This study aimed to determine the clinical outcomes of reconstruction of a defect after wide excision of an STT with a veno-accompanying artery fasciocutaneous (VAF) flap in the lower leg. METHODS: This study comprised 9 patients with malignant STTs who had undergone reconstructive surgeries using VAF flaps after wide excisions, between October 2010 and September 2017. We retrospectively reviewed and collected data involving age, sex, follow-up period, histological diagnosis, surgical procedures, size and location of defects, size and location of the flaps, venous source of the flaps, direction of the pedicles, closing of donor sites, perioperative chemotherapies, postoperative complications, and the presence of postoperative local recurrence and metastasis. RESULTS: The median follow-up period was 91.5 (range, 15.5-189.0) months. Four patients had defects located around the knee, 3 patients had defects located on the calf, and 2 patients had defects located around the ankle. The mean flap size was 95.6 × 119.4 (range, 50 × 100-130 × 140) mm. Six patients had venous sources from the small saphenous vein and 3 patients had venous sources from the great saphenous vein. The pedicles were proximally based in 4 patients and distally based in 5 patients. All flaps remained viable without any complications. CONCLUSIONS: Our findings showed that the VAF flap was easily elevated and reliable. Furthermore, it was effective in reconstructing soft tissue defects following wide excisions of STTs in the lower leg.

Haprin-deficient spermatozoa are incapable of in vitro fertilization.

Haprin (TRIM36) is a ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It is expressed in the testes in both mice and humans and is thought to be involved in spermiogenesis, the acrosome reaction, and fertilization. However, the functional role of Haprin is poorly understood. The aim of this study was to investigate the physiological role of Haprin in fertility. Homozygous haprin-deficient mice were generated and these mice, and their spermatozoa, were analyzed to detect morphological and fertility-related abnormalities. In these models, normal spermatogenesis was observed but sperm quality was reduced with haprin-deficient mice having poorer sperm morphology and motility than wild-type mice. Interestingly, haprin-deficient mice showed normal in vivo fertility but could not fertilize oocytes under standard in vitro fertilization conditions. In conclusion, this study demonstrated that Haprin deficiency causes morphological abnormalities in spermatozoa, indicating that Haprin is involved in spermiogenesis.

Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient with spastic paraplegia derived from a single-nucleotide deletion in PLP1.

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder caused by abnormalities in the gene PLP1. Most females harboring heterozygous PLP1 abnormalities are basically asymptomatic. However, as a result of abnormal patterns of X-chromosome inactivation, it is possible for some female carriers to be symptomatic. Whole-exome sequencing of a female patient with unknown spastic paraplegia was performed to obtain a molecular diagnosis. As a result, a de novo heterozygous single-nucleotide deletion in PLP1 [NM_000533.5(PLP1_v001):c.783del; p.Thr262Leufs*20] was identified. RNA sequencing was performed in a patient-derived lymphoblastoid cell line, confirming mono-allelic expression of the mutated allele and abnormal inactivation of the wild-type allele. The patient-derived lymphoblastoid cell line was then treated with VX680 or 5azadC, which resulted in restored expression of the wild-type allele. These two agents thus have the potential to reverse inappropriately-skewed inactivation of the X-chromosome.

Renal medullary carcinoma in a young mixed-race man in Japan.

Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.

Effect of Lepidium meyenii on in vitro fertilization via improvement in acrosome reaction and motility of mouse and human sperm.

PURPOSE: The direct effects of Lepidium meyenii (Maca) on sperm remain unclear. Herein, we examined the direct effect of Maca on in vitro fertilization. METHODS: We examined the fertilization rate in a mouse model and the rate of acrosome reaction in sperm from transgenic mice expressing enhanced green fluorescent protein (EGFP) in a Maca extract-containing human tubal fluid (HTF) medium. Using human sperm, we assessed acrosome status via fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA) staining and performed detailed analysis using a sperm motility analysis system (SMAS). RESULTS: In the mouse model, the fertilization rate in the Maca extract-containing HTF was significantly higher than that in the control medium. The acrosome reaction rate in sperm from transgenic mice expressing EGFP was also significantly higher in the Maca extract-containing HTF than that in the control medium. Similarly, a high acrosome reaction rate, identified via FITC-PNA staining of human sperm samples, was found in the Maca extract-containing HTF compared with that in the control medium. Human sperm motility in the Maca extract-containing HTF was also increased compared with that in the control medium as measured using an SMAS. CONCLUSIONS: Maca improved in vitro fertilization rates by inducing an acrosome reaction and increasing sperm motility.

Rare coexistence of multiple osteochondromas and solitary osteoid osteoma: A case report.

Multiple osteochondromas (MOs) are inherited in an autosomal-dominant manner, with a penetrance of ~96 and 100% in female and male patients, respectively. Osteochondromas primarily involve the metaphyses and diaphyses of long bones, including the ribs. Osteoid osteomas account for ~3 and 11% of all bone tumors and benign bone tumors, respectively. Furthermore,1 the male-to-female ratio is 2-3:1, and they generally occur in the long bones of the lower extremities, with the femoral neck being the most frequent site. The present study describes the case of a 16-year-old male patient with a bony mass around the left knee joint and pain in the left calf. Radiography revealed MOs in the upper and lower extremities, while computed tomography showed a nidus in the cortex of the tibial shaft. The patient's family history included the presence of MOs, and the patient was diagnosed with MOs and a solitary osteoid osteoma. Surgical excision of the osteochondroma and curettage of the osteoid osteoma in the proximal tibia and tibial shaft, respectively, were performed simultaneously. Postoperative pathological examination revealed osteochondroma and osteoid osteoma. Furthermore, the pain resolved, and no recurrence was observed 7 months post-operation. To the best of our knowledge, no reports exist on coexisting MOs and osteoid osteoma; therefore, the present study describes the first case of such a condition. Marginal excision for osteochondroma and curettage for osteoid osteoma effectively improved the symptoms.

Loss of Malignancy of Super-Methotrexate-resistant Osteosarcoma Cells Is Associated With an Increase of Methylated Histone Marks H3K9me3 and H3K27me3.

BACKGROUND/AIM: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTXSR) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells. MATERIALS AND METHODS: Previously selected 143B-MTXSR cells which are 5,500 times more MTX resistant than parental cells, were used for this study. The status of methylated histone H3K9me3 and H3K27me3 marks was examined with western immunoblotting and compared between 143B-MTXSR and parental 143B-P cells. RESULTS: Histone H3K9me3 and H3K27me3 marks were over-expressed in 143B-MTXSR compared to 143B-P (p<0.05, p<0.01, respectively). CONCLUSION: Over-expression of histone H3K9me3 and H3K27me3 marks may be related to super-MTX resistance and to the loss of malignancy of super MTX-resistant osteosarcoma cells due to the fundamental relationship of methylation and cancer.

Reduced Malignancy of Super Methotrexate-resistant Osteosarcoma Cells With Dihydrofolate Reductase Amplification Despite Paradoxical Gain of Oncogenic PI3K/AKT/mTOR and c-MYC expression.

BACKGROUND/AIM: Methotrexate (MTX) resistance in osteosarcoma leads to a very poor prognosis. In the present study, in order to further understand the basis and ramifications of MTX resistance in osteosarcoma, we selected an osteosarcoma cell line that has a 5,500-fold-increased MTX IC50 Materials and Methods: The super MTX-resistant 143B osteosarcoma cells (143B-MTXSR) were selected from MTX-sensitive parental human 143B osteosarcoma cells (143B-P) by continuous culture with step-wise increased amounts of MTX. To compare the malignancy of 143B-MTXSR and 143B-P, colony-formation capacity was compared with clonogenic assays on plastic and in soft agar. In addition, tumor growth was compared with orthotopic xenograft mouse models of osteosarcoma. Expression of dihydrofolate reductase (DHFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and myelocytomatosis oncogene (MYC) was examined with western immunoblotting and compared in 143B-MTXSR and 143B-P cells. RESULTS: 143B-MTXSR had a 5,500-fold increase in the MTX IC50 compared to the parental 143B-P cells. Expression of DHFR was increased 10-fold in 143B-MTXSR compared to 143B-P (p<0.01). 143B-MTXSR cells had reduced colony-formation capacity on plastic (p=0.032) and in soft agar (p<0.01) compared to 143B-P and reduced tumor growth in orthotopic xenograft mouse models (p<0.001). These results demonstrate that 143B-MTXSR had reduced malignancy. 143B-MTXSR also showed an increased expression of PI3K (p<0.01), phosphorylated (activated) AKT (p=0.031), phosphorylated mTOR (p=0.043), and c-MYC (p=0.024) compared to 143B-P. CONCLUSION: The present study demonstrates that the increased expression of DHFR, PI3K/AKT/mTOR and c-MYC appears to be linked to super MTX resistance and, paradoxically, to reduced malignancy. The present results suggest that DHFR may be a powerful tumor suppressor when highly amplified.

Non-invasive Fluorescence Imaging of Breast Cancer Metastasis to the Brain in an Orthotopic Nude-mouse Model With Very-narrow-band-width Laser Excitation of Red Fluorescent Protein Resulting in an Ultra-bright Signal Without Skin Autofluorescence.

BACKGROUND/AIM: Breast-cancer metastasis to the brain is an intractable disease. To discover improved therapy for this disease, we developed a precise non-invasively-imageable orthotopic nude-mouse model, using very-narrow-band-width laser fluorescence excitation. MATERIALS AND METHODS: Female nu/nu nude mice, aged 4-8 weeks, were inoculated through the midline of the skull with triple-negative human MDA-MB-231 breast cancer cells (5×105) expressing red fluorescent protein (RFP). The mice were imaged with the Analytik Jena UVP Biospectrum Advanced at 520 nm excitation with peak emission at 605 nm. RESULTS: Three weeks after injection of MDA-MB-231-RFP cells in the brain, non-invasive fluorescence images of the breast tumor growing on the brain were obtained. The images of the tumor were very bright, with well-defined margins with no detectable skin autofluorescence background. Images obtained at various angles showed that the extent of the tumor margins could be precisely measured. A skin flap over the skull confirmed that the tumor was growing on the surface of the brain which is a frequent occurrence in breast cancer. CONCLUSION: A precise orthotopic model of RFP-expressing breast-cancer metastasis to the brain was developed that could be non-invasively imaged with very-narrow-band-width laser excitation, resulting in an ultra-bright, ultra-low-background signal. The model will be useful in discovering improved therapeutics for this recalcitrant disease.

Differential Diagnosis of Lipomatous Tumors Using 18F-Fluorodeoxygulcose Positron Emission Tomography/Computed Tomography: A Retrospective Observational Study.

Background/Aim: Lipomatous tumors, including lipomas, atypical lipomatous tumors (ALTs), myxoid liposarcomas (MLs), and dedifferentiated liposarcomas (DLs), are often diagnosed using magnetic resonance imaging (MRI). Differential diagnosis of lipomas and ALTs by MRI is often challenging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been used for the diagnosis and evaluation of tumor staging and recurrence of soft tissue tumors. The maximum standardized uptake value (SUVmax) is positively associated with malignant grade in several cancers. This study aimed to evaluate SUVmax of 18F-FDG PET/CT in the differential diagnosis of lipomatous tumors. Patients and Methods: Patients who underwent 18F-FDG PET/CT for the diagnosis of lipomatous tumors between January 2013 and September 2021 were included in the study. Patients with lipomatous tumors, confirmed by pathological diagnosis or surgical specimens, were evaluated for lipomatous tumor SUVmax. Results: This study included 44 patients with lipomas (n=19), ALTs (n=12), MLs (n=9), and DLs (n=4). The mean SUVmax of lipomas, ALTs, MLs, and DLs was 0.99±1.41, 1.92±0.95, 5.21±4.94, and 9.29±1.43, respectively. Lipomas showed a significantly lower SUVmax than did ALTs, MLs, and DLs (p<0.05). ALTs demonstrated a significantly lower SUVmax than did MLs and DLs (p<0.05). No significant differences were observed between MLs and DLs. Conclusion: Lipomas or ALTs had a significantly lower SUVmax than lipomatous sarcomas. Lipomas had a significantly lower SUVmax than ALTs, aiding in their preoperative differentiation. 18F-FDG-PET/CT could serve as a potent tool for the differential diagnosis of lipomatous tumors.

Precise Non-invasive Imaging Mouse Model of Pancreatic Cancer: Very Narrow Band-width Laser Fluorescence Excitation of Green Fluorescent Protein Provides Ultra-bright Tumor Images With no Skin Autofluorescence.

Background/Aim: Pancreatic cancer is a recalcitrant disease with 5-year survival of only 12%. Improved mouse models of pancreatic cancer are critical for discovery of effective therapeutics. Materials and Methods: Orthotopic mouse nude-mouse models of pancreatic cancer were established with the human pancreatic-cancer cell line Panc-1 expressing green fluorescent protein (GFP) by transplanting tumor fragments into the pancreas, using the procedure of surgical orthotopic implantation (SOI). Four weeks after establishment of the orthotopic models, the mice were imaged with the Analytik Jena UVP Biospectrum Advanced with a very-narrow-band-width excitation at 487 nm and peak emission at 513 nm. Results: Non-invasive fluorescence imaging of the mice implanted with Panc-1-GFP showed a very bright tumor in the area of the pancreas and peritoneal cavity. The skin background autofluorescence was absent. When a laparotomy was performed on the mouse for open imaging, the tumor on the pancreas was clearly imaged. There was very clear concordance of the non-invasive image and the image obtained during laparotomy. Conclusion: A precise orthotopic mouse model of pancreatic cancer was developed in which there was high concordance between non-invasive and invasive fluorescence imaging due to the ultra-bright signal and ultra-low background using very-narrow-band-width laser fluorescence excitation. This model can be used for high-throughput in vivo screening for improved therapeutics for pancreatic cancer.

Case report: Thyroid storm in a three-year-old girl presenting with febrile status epilepticus and hypoglycemia.

Thyroid storm, though extremely rare in toddlers, requires prompt diagnosis and treatment because it can be fatal if left untreated. However, thyroid storm is not often considered in the differential diagnosis of a febrile convulsion due to its rarity in children. Herein, we report the case of a 3-year-old girl with thyroid storm who presented with febrile status epilepticus. Although the seizure was stopped by diazepam administration, her tachycardia and widened pulse pressure persisted, and severe hypoglycemia was observed. Based on the findings of thyromegaly, a history of excessive sweating and hyperactivity, and a family history of Graves' disease, she was eventually diagnosed with a thyroid storm. The patient was successfully treated with thiamazole, landiolol, hydrocortisone, and potassium iodide. Propranolol, a non-selective ß-blocker, has been used to manage tachycardia during thyroid storm. However, a cardio-selective ß1-blockers, landiolol hydrochloride, was used in our case to avoid worsening hypoglycemia. Febrile status epilepticus is one of the most common medical emergencies in childhood; it is necessary to rule out treatable underlying critical diseases such as septic meningitis and encephalitis. Thyroid storm should be considered in children presenting with prolonged febrile convulsion accompanied by findings that are not usually observed with febrile convulsions.

Targeting Autophagy With the Synergistic Combination of Chloroquine and Rapamycin as a Novel Effective Treatment for Well-differentiated Liposarcoma.

BACKGROUND/AIM: Liposarcoma is a type of soft-tissue sarcoma arising from fat tissue. It is relatively common among soft-tissue sarcomas. Chloroquine (CQ), an antimalarial drug, can inhibit autophagy and induce apoptosis in cancer cells. Rapamycin (RAPA) is an inhibitor of mTOR. The combination of RAPA and CQ is a strong inhibitor of autophagy. Previously, we showed that the combination of RAPA and CQ was effective against a de-differentiated liposarcoma patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we investigated the mechanism of efficacy of the combination of RAPA and CQ to target autophagy in a well-differentiated liposarcoma (WDLS) cell line in vitro. MATERIALS AND METHODS: The human WDLS cell line 93T449 was used. The WST-8 assay was used to test the cytotoxicity of RAPA and CQ. Western blotting was used to detect microtubule-associated protein light chain 3-II (LC3-II) which is a component of autophagosomes. Immunostaining of LC3-II was also performed for autophagosome analysis. Τhe TUNEL assay was used to detect apoptotic cells, and apoptosis-positive cells were counted in three randomly selected microscopic fields for statistical validation. RESULTS: RAPA alone and CQ alone inhibited the viability of 93T449 cells. The combination of RAPA and CQ inhibited 93T449 cell viability significantly more than either drug alone and increased the number of autophagosomes which led to extensive apoptosis. CONCLUSION: The combination of RAPA and CQ increased the number of autophagosomes which led to apoptosis in 93T449 WDLS cells, suggesting novel effective treatment for this recalcitrant cancer by targeting autophagy.

Long-lasting Limb Salvage After Malignant Femoral-Bone Tumor Resection Reconstructed With a Thin-mantle Titanium Stem Fixated With Cement.

BACKGROUND/AIM: The purpose of the present study was to review and report clinical outcomes of the Kyocera Modular Limb Salvage System (KMLS) using a thin-mantle titanium stem fixated with cement, for reconstruction after resection of malignant femoral-bone tumors. PATIENTS AND METHODS: Twenty consecutive patients who had undergone reconstruction using the KMLS with cemented thin-mantle titanium stem fixation between July 2010 and December 2019 at Ryukyu University Hospital were included. We retrospectively collected the following data: age, sex, follow-up period, tumor location, histological diagnosis, stem size, overall implant survival, radiolucency, postoperative complications, overall survival, and oncological survival. RESULTS: The median follow-up period was 63 months (range=10.7-261 months). The bone tumors were in the proximal part of the femur in 9 patients and in the distal part of the femur in 11 patients. The 5-year overall implant survival rate was 90.9% among surviving patients. A revision surgery was required for only one patient (5%), due to infection. Radiolucency, due to an instability of the implant, was observed in 7 out of 20 patients: 6 patients with distal femoral reconstruction, and 1 patient with proximal femoral reconstruction. However, none of the patients complained of any symptoms or required revision surgeries at the last follow-up. The 5-year overall patient-survival rate was 67.6%. CONCLUSION: The KMLS with cemented thin-mantle titanium stem fixation for femoral bone reconstruction after resection for bone malignancy resulted in long-term patient benefit.

Meckel's Diverticulum Carcinoma Is Arrested by Oxaliplatinum and Eradicated by 5-Fluorouracil in a PDX Mouse Model Indicating Candidate First-line Treatment for a Rare Cancer.

BACKGROUND/AIM: Meckel's diverticulum carcinoma (MDCa) is extremely rare. It is often advanced when found, and the prognosis is poor. Effective treatment for this cancer has not yet been developed. We previously established a patient-derived xenograft (PDX) nude-mouse model of MDCa. In the present study, we investigated the efficacy of oxaliplatinum (L-OHP) and 5-fluorouracil (5-FU) on an MDCa PDX nude-mouse model. MATERIALS AND METHODS: PDX mouse models of MDCa were divided into three groups (five mice per group): untreated control; L-OHP-treated; and 5-FU-treated. Tumor volumes of the three groups were compared after 2 weeks. RESULTS: L-OHP arrested tumor growth (p=0.038) and 5-FU apparently eradicated the tumor (p=0.007). CONCLUSION: L-OHP and 5-FU are candidates for clinical first-line therapy of MDCa.

Intraoperative cone-beam computed tomography-guided curettage for osteoid osteoma.

Recently, cone-beam computed tomography (CBCT)-guided surgeries have been developed for bone and soft tissue tumors. The present study aimed to evaluate the efficacy of CBCT-guided curettage for osteoid osteoma. Our study population included 13 patients who underwent primary curettage for osteoid osteoma using intraoperative CBCT in a hybrid operating room between April 2019 and November 2022. We collected the following data: sex, age, follow-up period, symptom onset to time of surgery, tumor size and location, length of skin incision, operating time, radiation dose, recurrence, postoperative complications, and visual analog scale for pain during the last follow-up. There were 10 male and 3 female patients, and the mean age was 25.0 years (range, 9-49 years). The mean follow-up period was 10.6 months (range, 0.4-24.0 months). The locations of the tumors were the proximal femur in 6 patients, the acetabular region in 2 patients, and the ilium, tibial shaft, calcaneus, cuboid, and talus in 1 patient each. The mean time of symptoms onset to surgery was 18.7 months (range, 2.3-69.9 months). The mean maximum diameter of the tumor was 5.9 mm (range, 3.5-10.0 mm). The mean length of the skin incision was 2.2 cm (range, 1.5-3.5 cm). The mean operating time was 96.9 minutes (range, 64-157 minutes). The mean dose of radiation was 193.2 mGy (range, 16.3-484.0 mGy). No recurrences, postoperative complications, and reoperation were observed in this study. All the patients reported 0 mm on the visual analogue scale for pain on the last follow-up. CBCT-guided curettage for osteoid osteoma was minimally invasive and reliable. This procedure can be effective for the treatment of lesions found in deep locations such as the pelvic bone and proximal femur or an invisible lesion that cannot be detected by regular fluoroscopy.