Extensive Bone Involvement Research Articles

Lower Extremity Traumatic Wound Management: Relative Significance of Negative Pressure Wound Therapy in the Orthopedic Setting.

Significance: Lower extremity traumatic wounds are associated with numerous perioperative challenges. Their etiologies determine the characteristics and extent of the injury. The timing of subsequent surgical intervention and wound healing optimization after lower extremity trauma are integral to successful perioperative lower extremity wound management. Recent Advances: Managing trauma to the lower extremities uses a multidisciplinary surgical approach. The objective of this review is to summarize lower limb trauma assessment, advancements in lower extremity trauma management, and the clinical applications of advanced wound care in lower limb traumatic wounds. The advent of lower limb reconstruction and the development of advanced wound care modalities have helped to improve the management of these complex injuries. Critical Issues: The extensive involvement of bone, soft tissues, nerves, and blood vessels of severe lower extremity trauma wounds presents a challenge for clinicians in both the acute care setting and during patient rehabilitation. If not properly managed, these injuries may be subject to a decline in limb function and may possibly result in limb loss. To reveal developing limb-threatening conditions, serial examinations should be performed. Future Directions: The majority of lower limb traumatic wound will benefit from the perioperative administration of an appropriate negative pressure wound therapy (NPWT)-based system, which can help to promote granulation tissue and remove wound exudate before definitive closure and/or reconstruction. NPWT should be included as an important adjunct in the surgical management of lower limb traumatic wounds.

Maxillary Osteomyelitis: A Case Report Highlighting Diagnosis and Treatment Challenges

Osteomyelitis, a condition characterized by inflammatory bone infection involving the medullary cavity, haversian systems, and periosteum, is relatively rare but grave. Historically more prevalent prior to the antibiotic era, it remains a formidable challenge, particularly when comorbid with systemic illnesses such as diabetes mellitus. This case report details the presentation of a 70-year-old male with poorly controlled diabetes mellitus presenting with maxillary osteomyelitis, evidenced by tooth mobility, purulent discharge, and exposed bone areas. Radiographic assessment revealed extensive maxillary bone involvement, corroborated by histopathological examination confirming chronic osteomyelitis. Treatment entailed partial maxillectomy under local anesthesia, necessitated by financial constraints, followed by subsequent monitoring and prosthesis placement. This case underscores the significance of timely diagnosis, interdisciplinary management, and the complexities inherent in treating osteomyelitis complicated by systemic diseases.

Preclinical In Vivo Imaging of Multiple Myeloma with [ 18f]Fluorohomoleucine (FHL) PET/CT

Purpose: Imaging of patients with multiple myeloma (MM) remains challenging due to its multi-focal nature affecting bone marrow, bone structures and soft tissue. As a result, current diagnostic methods like X-rays, CT and MRI scans only provide a partial understanding of disease activity and treatment response, lacking a comprehensive overview. Although 2-deoxy-2-[ 18F]fluoro-D-glucose (FDG) positron emission tomography (PET) has become the standard for detecting multifocal cancer spread, its use in MM patients is limited due to metabolic heterogeneity of MM and limited sensitivity in detecting extramedullary disease leading to false negative and false positive scans. To overcome these limitations, we developed a novel radiopharmaceutical L-[ 18F]Fluorohomoleucine (FHL) targeting LAT1 amino acid transporter. LAT1 has been significantly correlated with the proliferative activity of MM cells, poor prognosis and response to treatment in MM patients, presenting an appealing molecular target for assessing disease activity. Methods: FHL was synthesized as described by Nodwell et al. (J Nucl Med, 2019) and FDG was obtained from BC Cancer. LAT1 expression in multiple myeloma (MM) cell lines was confirmed by flow cytometry. Cell uptake assays were conducted using luciferase-transfected MM1S, L363, NCI H929 and AMO1 MM cells, and 2-amino-bicyclo[2.2.1]heptanes-2-carboxylic acid (BCH) was used as a blocking agent. For in vivo studies, male NRG mice were injected either with 1 x 10 6 MM cells intravenously (i.v.) via the caudal vein or subcutaneously (SQ) with 1 x 10 7 cells. Tumor engraftment was monitored weekly on an in vivo bioluminescence imager Perkin Elmer's IVIS Ilumina 5, starting at 2 weeks post-injection (p.i.). Biodistribution and PET/CT imaging studies were conducted at 4-6 weeks p.i. Results: All MM cells tested exhibited LAT1-specific FHL uptake in vitro with L363 and NCI H929 demonstrating the highest tracer uptake and average blocking efficacy over 83% and 93%, respectively. We were able to observe weekly progression of disease in the i.v. cohort using IVIS imaging. Biodistribution and PET imaging studies revealed FHL accumulation in the SQ xenografts, pancreas and excretion via the urinary tract. The SQ tumor uptake values were 4.53±0.82 %ID/g in AMO1 xenografts, 5.55±0.82 %ID/g in NCI H929, and 6.37±0.70 %ID/g in L363 tumors. In the i.v. cohort, the mouse intravenously injected with L363 cells demonstrated accumulation of radioactivity in the skull and vertebrae, as anticipated from the IVIS images. Furthermore, preliminary data suggests that FHL was able to detect a more extensive bone and lymphatic involvement than FDG in MM xenografts. Conclusion: We have demonstrated the ability of FHL for in vivo imaging of three human multiple myeloma tumors in SQ murine models, with the tumor uptake ranging from 4.53±0.82 %ID/g in AMO1 xenografts to 6.37±0.70 %ID/g in L363 tumors. Work is underway to establish the utility of this tracer in detecting disease dissemination in the orthotopic murine models of multiple myeloma, with promising preliminary results presented herein.

Outcome of Outpatient Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma and Relapsed and Refractory Hodgkin Lymphoma. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

Background: Autologous hematopoietic stem cell transplants (HSCT) is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM) and patients with relapsed and refractory Hodgkin lymphoma (R/R-HL) who achieve chemosensitivity after salvage therapy. Although autologous HSCT is routinely performed in an inpatient setting, the procedure can safely be performed in an outpatient setting. Methods and materials: A retrospective study of patients with MM and R/R- HL who received outpatient autologous HSCT at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia between the first of April 2017 and the 31st of January 2022 was performed. Results: Over the study period of 4 years and 10 months, a total of 90 outpatient autologous HSCTs were performed for 79 patients (54 patients with MM; 4 of them received planned tandem autografts and 7 other myeloma patients received second autologous HSCTs for relapsed or progressive disease; and 25 patients with R/R-HL) at our institution. The median ages of patients with MM and those with R/R-HL at HSCT were 50.4 years and 27.8 years respectively. At the presentation of their MM, the following high-risk (HR) features were encountered: stage II and III diseases according to the revised international scoring system (RISS) in 53.7%; adverse cytogenetics in 42.6% and extensive bone involvement in 53.7% of patients. In patients with HL at presentation, 48% of patients had stage IV disease according to Ann Arbor staging classification and 84% of patients had B symptoms. Survival for 100 days post-HSCT for all patients with MM and HL who received outpatient autologous transplants was 100%. For patients with MM, the overall survival (OS) rates at 3 years and 4 years post-HSCT were 80% and 67%, while the progression-free survival (PFS) rates over 3 years and 4 years were 58% and 38% respectively. For patients with HL, the OS at 6 years post-HSCT was 95% while the PFS rates at 3 years and 6 years post-HSCT were 84% and 62% respectively. Conclusion: Outpatient autologous HSCT for patients with MM and HL is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation performed in an inpatient setting. Additional benefits of outpatient autologous include saving beds and reducing hospital costs.

CHILDHOOD ODONTOGENIC MYXOMA

Odontogenic myxoma is a benign odontogenic mesenchymal tumor. It is the third most frequent odontogenic tumor, with a recurrence rate of about 25%. An 11-year-old female patient referred to an infant hospital presented an asymptomatic facial asymmetry noticed 6 months earlier. Intraoral examination showed a lesion in the right posterior region of the maxilla, with an expansion of the vestibular bone board, without ulceration, mucosa-like in color. Computed tomography revealed a hypodense lesion, with extensive bone involvement, in the right maxillary region, with a displacement of the 18-dental germ, involving the maxillary sinus, orbital floor, and nasal cavity. A biopsy followed by histopathologic analysis revealed a benign nonencapsulated neoplasm, composed of spherical and spindle cells, in a myxoid stroma with varying amounts of collagen. The diagnosis was an odontogenic myxoma. Enucleation was performed with vigorous curettage of the lesion margins, with no recurrence observed in 2 years of postoperative follow-up.

Combined Orthoplastic Approach in Fracture-Related Infections of the Distal Tibia.

This series reports on the treatment of distal tibia (DT) fracture-related infections (FRI) with a combined orthoplastic approach. Thirteen patients were included. In eight patients with extensive bone involvement and in those with a non-healed fracture, the DT was resected (“staged approach”). In five cases, the DT was preserved (“single-stage approach”). A wide debridement was performed, and the cavity was filled with antibiotic-loaded PerOssal beads. All patients had a soft-tissue defect covered by a free vascularized flap (anterolateral thigh perforator flap in eight cases, latissimus dorsi flap in five). At the final follow-up (mean 25 months, range, 13–37), no infection recurrence was observed. In one patient, the persistence of infection was observed, and the patient underwent a repeated debridement. In two cases, a voluminous hematoma was observed. However, none of these complications impacted the final outcome. The successful treatment of FRI depends on proper debridement and obliteration of dead spaces with a flap. Therefore, when dealing with DT FRI, debridement of infected bone and soft tissues must be as radical as required, with no fear of the need for massive reconstructions.

Hyperostotic Invasive Meningioma of the Sphenoid Ridge Surgical Considerations: 2-Dimensional Operative Video.

Hyperostotic invasive sphenoid ridge meningiomas are a distinct and recognized entity.1-4 They are characterized by extensive bone involvement and expansive “en plaque” intradural extension.3,5 The goal of this surgery is improving and preserving the visual function and ocular motility while esthetically correcting and reconstructing the exophthalmos and temporal deformity.4,5 The surgery includes radical removal of the involved bone of the sphenoid ridge, orbital walls, and middle fossa floor, in addition to the “en plaque” dural and periorbital involvement and intradural extension.3,5,6 Early decompression of the optic nerve and orbital elements allows preventing visual function deterioration and yields frequent improvement. Thorough planned reconstruction can be achieved by molding a malleable mesh to the patient's skull before the extensive bone removal. Careful orbital wall reconstruction allows one to achieve a good postoperative cosmesis and prevent enophthalmos.4 We demonstrate the principles of this surgery through 2 cases of 46-year-old and 53-year-old women. The first case demonstrates the importance of middle fossa extensive drilling of involved bone and reconstruction while the second case demonstrates the visual decompression and postoperative improvement. The patients consented to the surgeries and publication of their images.

Dramatic radiotherapy response of a giant T4 cutaneous squamous cell carcinoma of the scalp with extensive bone destruction: a case report

BackgroundPatients with large cutaneous squamous cell carcinoma of the scalp are a treatment challenge. We report a case of dramatic radiotherapy response of a patient with a giant cutaneous squamous cell carcinoma of the scalp with extensive skull destruction and suspected infiltration of the dura mater and superior sagittal sinus. This case is the first report of this kind in the literature that shows that large bone defects can heal with the resolution of tumor and inflammation by secondary intention without surgical reconstruction. We want to put an end to concerns about radiocurability of tumors with extensive bone involvement, and show sustained complete response after definitive radiotherapy and programmed cell death protein-1 inhibiting antibody therapy.Case presentationA 74-year-old White man presented with a 7.2 × 6.8 × 5.5 cm painless tumor on the right parietal region of the scalp. Medical imaging revealed widespread destruction of the skull and suspected infiltration of the dura mater and superior sagittal sinus. Biopsies showed cutaneous squamous cell carcinoma (cT4a cN0 cM0, stage IVA). The patient was treated with a total dose of 60 Gy, at 2 Gy per daily fraction with volumetric modulated arc therapy using 6 megavoltage photons. The biologically effective dose (alpha/beta 10 Gy) was 72 Gy. The tumor response correlated with dose received. The patient had a massive tumor necrosis secondary to tumor shrinkage after 18 fractions (36 Gy, biologically effective dose 43.2 Gy). Leakage of cerebrospinal fluid did not occur. Radiotherapy did not hamper the patient’s quality of life. The patient had a clear regression of the initial tumor on the final day of radiotherapy. The bone defect healed by secondary intention without surgical interventions. The patient achieved a complete response with a good cosmetic result after 82 days follow-up. He started a programmed cell death protein-1 inhibiting antibody therapy with cemiplimab 2 months after radiotherapy, and is now at 10 months follow-up without evidence of recurrence.ConclusionDefinitive radiotherapy is a safe and highly effective therapy for giant tumors of the scalp with extensive bone destruction. We report a sustained complete response with a good cosmetic result after secondary wound healing.

An Unexplained Hyperphosphatemia in an Hispanic Woman , a Diagnosis Challenge

IntroductionHyperphosphatemia could be a finding in renal failure, tumor lysis syndrome, hypoparathyroidism, and ingestion of exogenous phosphate. We present the case of a woman with hyperphosphatemia in which we finally diagnosed multiple myeloma, serum phosphate level achieved normal range after chemotherapy started. Although hyperphosphatemia in multiple myeloma is a very rare finding, there are some reports. The proposed mechanisms include a large amount of paraproteins that interferes with phosphorus level determination showing a false increased level. When samples have been deproteinated before analysis, serum phosphorus level can decrease obtaining a true level. This case reminds clinicians the importance of seeking additional causes for abnormal phosphorus levels before starting treatments that could lead to hypophosphatemia.Case reportAn hispanic woman at the 7th decade of life that only suffered from controlled hypothyroidism, who assisted with complaints of axial pain mainly in thoracic and lumbar segments. She denied neurological and B symptoms. She had a CT scan performed and was referred to the hematology service.On clinical examination we didn't find any neurological signs, no megalies and no palpable nodes. The patient brought a CT spine scan showing thoracic images suggestive of mets with collapse of 50% in T12-L1 and a mass in S2.With these findings we decided to start intrahospitalary studies for excluding malignancy.Her relevant laboratories were: creatinine 0,7, BUN 25, Hemoglobin 9 gr/dl VCM 102 WBC 3330 Granulocytes 55% Platelet 222.000, UN 10,7, albumin 2.8, Lactate dehydrogenase 425. A series of labs seeking secondary causes of malignancy was made including plasmatic cell neoplasie.The hepatic function was normal but an unusually high Phosphorus level was detected (19,6) with normal calcemia (8.98), the tumoral biomarkers were in normal range (CEA, CA 19-9, Ca 125, AFP) and an elevated B2 microglobulin (8) was found. Additional labs included bence jones protein and PTH, both in normal range. A new Thoracic CT described mosaic infiltrates and an extensive bone involvement suggestive of lytic metastatic changes. The abdomen CT showed multiple lytic lesions in lumbo-sacral spine and pelvis, The skull radiography had lytic lesions too. The nephrology service was required by the Hyperphosphatemia and they asked about external intake of phosphorus finding that she was taking “hydrolyzed collagen”, so they started iv fluid and chelators (aluminium hydroxide and no calcium chelators).Because of unresponsive hyperphosphatemia, nephrology started hemodialysis.Hematology found high IgG levels (5500) concluding the need for bone marrow studies . Finally a the bone marrow study was performed and prescribed steroids on suspicion of Multiple myeloma. Until this day the Phosphorus level still remained in high levels (17,7) despite hemodialysis sessions. The bone marrow study revealed a plasmatic cell population of 28,9% with big and abundant cytoplasm, some of them with binucleations suggestive of infiltration by plasmatic cell neoplasie. The seric electrophoresis revealed a paraprotein (seric protein of 9,3 with a monoclonal peak of gamma region of 3,4 gr/dl), the seric immunofixation was positive for a monoclonal IgG lambda component. With this report we began chemotherapy treatment for Myeloma with CyBorD regimen (Cyclophosphamide, Bortezomib, dexamethasone). After treatment was initiated, phosphorus level began to lower and achieved normal range (4.28) in the first two weeks. Then she was discharged to continue outpatient management. Nowadays she is receiving her 3rd chemotherapy cycle without complications, her phosphorus level still remains within normality.ConclusionsSpurious hyperphosphatemia in patients with paraproteinemias like multiple myeloma can occur. The IgG monoclonal can interfere with the phosphomolybdate principle used in the assay of serum phosphate on most automated chemistry analysers. For labs which do not have a multilayered film technology based system, a serial dilution analysis of the suspected analyte could be performed. DisclosuresNo relevant conflicts of interest to declare.

Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients

BackgroundDespite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm “Bordier” core needle. We examined the feasibility of using a 2 mm “Jamshidi™” core needle as a more practical and less invasive technique. MethodsPatients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. ResultsTwelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. DiscussionOur results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.

Basal Cell Carcinoma with Disseminated Bone Metastization: An Unusual Outcome of the Most Common Malignancy

Basal cell carcinoma is the most common skin cancer, with a very low incidence of metastases, associated with high morbidity and mortality. The morpheaform clinical variant is uncommon, presenting an aggressive growth pattern. Early diagnosis and new targeted therapies for metastatic disease are important to improve survival rates. We present the case of a 29-year-old patient with morpheaform basal cell carcinoma in the right genian region. Due to local recurrences, he underwent surgery and adjuvant radiotherapy. For extensive metastatic bone involvement, the patient started vismodegib and, later, pembrolizumab, and also performed palliative radiotherapy. Despite several lines of systemic therapy, the disease progressed, and the patient died after 8 years of follow-up. This case shows how crucial it is to identify risk factors for metastatic basal cell carcinoma and highlights the need to improve target therapies and tailor them to the patient’s biological profile.

Rosai-Dorfman disease: a rare presentation of extranodal involvement of isolated bone. Case report

Introduction: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis, is a rare disorder characterized by histiocyte proliferation. Case presentation: A 33-year-old man consulted the emergency department of a tertiary care institution in Cartagena de Indias, Colombia, due to a 6-month history of progressive deformity in the frontal right side of the face, associated with pain of slow progression, without any other symptoms or dermatological involvement. There were no other major findings on physical examination and laboratory tests performed were negative. Imaging scans obtained showed extensive inflammatory involvement of the frontal bone, which led to suspect osteomyelitis as the first diagnostic possibility. A biopsy of the lesion was performed with negative cultures for bacteria, which allowed establishing a diagnosis of extranodal Rosai-Dorfman disease with isolated bone involvement. Treatment with systemic corticosteroids was indicated with poor response, so methotrexate was added, achieving an evident improvement after 2 months. Conclusions: Little is known about the manifestations of Rosai-Dorfman disease and its treatment in the adult population. The present case report contributes to expanding the literature on this topic, which can present with rare symptoms that may pose challenges for its diagnosis.

Open Treatment of Osteochondral Lesions of the Talus With Bone Grafting and Particulated Juvenile Cartilage Allografting.

Large cystic osteochondral lesions of the talus (OLT) are challenging pathological conditions to treat, but particulated juvenile cartilage allografts (PJCAs) supplemented with bone grafts are a promising therapeutic option. The purpose of this project was to further elucidate the role of PJCA with concomitant bone autografts for treating large cystic OLTs with extensive subchondral bone involvement (greater than 150 mm2 in area and/or deeper than 5 mm). We identified 6 patients with a mean OLT area of 307.2 ± 252.4 mm2 and a mean lesion depth of 10.85 ± 6.10 mm who underwent DeNovo PJCA with bone autografting between 2013 and 2017. Postoperative outcomes were assessed with radiographs, Foot and Ankle Outcome Scores (FAOS), and visual pain scale scores. At final follow-up (27.0 ± 12.59 weeks), all patients had symptomatic improvement and incorporation of the graft on radiographs. At an average of 62 ± 20.88 months postoperatively, no patients required a revision surgery. All patients contacted by phone in 2018 and 2020 reported they would do the procedure again in retrospect and reported an improvement in their symptoms relative to their preoperative state, especially with pain and in the FAOS activities of daily living subsection (91.93 ± 9.04 in 2018, 74.63 ± 26.86 in 2020). PJCA with concomitant bone autograft is a viable treatment option for patients with large cystic OLTs. Level IV.

Metastatic Epithelioid Angiosarcoma of the Spine, Hip, and Femur

Epithelioid Angiosarcoma (EA) is an extremely rare and highly aggressive malignant tumor. It comprises <1 % of all soft tissue sarcomas and is associated with a poor prognosis. In this case report, we are reporting an 85-years-old male who presented with lower back and left hip pain. A computerized tomography (CT) of the lumbar spine and left hip showed a significant fracture of lumbar spine L3 and osteolytic lesions involving the left hip and femur. The patient underwent L1-L5 fusion with cement augmentation and biopsy of L3. Surgical pathology showed a metastatic undifferentiated tumor of unknown primary origin. Histologic analysis of the specimen and immunohistochemistry confirmed EA. Given extensive diffuse bone involvement, our patient was not a candidate for definitive surgical treatment.

The Prognostic Value of Quantitative Bone SPECT/CT Before 223Ra Treatment in Metastatic Castration-Resistant Prostate Cancer.

Radiolabeled bisphosphonates such as 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) typically show intense uptake in skeletal metastases from metastatic castration-resistant prostate cancer (mCRPC). Extensive bone involvement is regarded as a risk factor for mCRPC patients treated with 223Ra-dichloride (223Ra). The aim of this study was to quantify 99mTc-DPD uptake by means of SPECT/CT before 223Ra and compare the results with the feasibility of treatment and overall survival (OS). Methods: Sixty consecutive mCRPC patients were prospectively included in this study. SPECT/CT of the central skeleton covering the skull to the mid-femoral level was performed before the first cycle of 223Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation, and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, U test, and Cox regression analysis were used for statistics. Results: Total 99mTc-DPD uptake of the central skeleton varied between 11% and 56% of injected dose (%ID) or between 1.8 and 10.5 %ID/1,000 mL of bone volume (%ID/L). SUVmean ranged from 1.9 to 7.4, whereas the SUVmax range was 18-248. Patients unable to complete 223Ra treatment because of progression and/or cytopenia (n = 23) showed significantly higher uptake (31.9 vs. 25.4 %ID and 6.0 vs. 4.7 %ID/L; P < 0.02). OS after 223Ra (median, 15.2 mo) was reduced to 7.3 mo in cases of skeletal uptake that was 26 %ID or higher, as compared with 30.8 mo if lower than 26 %ID (P = 0.008). Similar results were obtained for %ID/L and SUVmean SUVmax did not correlate with survival. %ID/L was identified as an independent prognostic factor for OS (hazard ratio, 1.381 per unit), along with number of previous treatment lines. Conclusion: Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival in mCRPC patients treated with 223Ra.

MANDIBULAR OSTEONECROSIS AFTER 40 YEARS OF ORAL ALENDRONATE: CASE REPORT

One of the adverse effects of the use of bisphosphonates is osteonecrosis of the jaw. The present study aims to report a clinical case of an 89-year-old female patient, who had used alendronate for more than 40 years, and was diagnosed with symptomatic osteonecrosis in the mandible after dental implants rehabilitation. In 2017 on clinical examination, hyperemia and persistent infection were observed. Radiographically, extensive bone involvement was found in the mandibular body, although clinical bone exposure did not reveal the complexity of the case. The proposed treatment was the association between pentoxifylline and tocopherol, laser, and conservative surgical approach. Currently, the patient has been asymptomatic for 4 months. Although the presence of osteonecrosis by the use of oral bisphosphonates is not common, the dental surgeon must be aware of this condition so the professional can diagnose and conduct the treatment in order to improve the quality of life of the patient.

PB1685 RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA MIMICKING MIKULICZ SYNDROME DURING BLINATUMUMAB TREATMENT: A CASE REPORT

Background:Mikulicz syndrome is a rare immune mediated condition characterized by tumor‐like swelling, lymphoplasmacytic infiltrate and fibrosis of salivary and lacrimal glands of poorly understood etiology. Its clinical presentation in the course of treating acute leukemia can be hard to differentiate from progression of the disease. We present a challenging diagnostic case of extramedullary acute lymphoblastic leukemia (ALL) relapse in the course of blinatumumab.Aims:Case report that aims to remember that AAL relapse can mimic any clinical picture.Methods:A 42‐year‐old woman was diagnosed in May 2017 with acute pro‐B lymphoblastic leukemia Ph negative, EGIL B‐II. Treatment with intensive multiagent chemotherapy according to PETHEMA high risk group was started. After induction, patient achieved complete response (CR) with negative minimal residual disease (MRD). Four additional courses of chemotherapy were completed following the PETHEMA high risk schedule. First relapse occurred and salvage therapy with Fludarabine, Ara‐C and Idarubicin was started achieving 2nd CR. Unfortunately, the patient relapsed three months later in the bone marrow and blinatumumab was decided. Two cycles were administered without neurological toxicities achieving CR with MRD of 0.31% and 0.11% after 1st and 2nd cycles, respectively. On 26th day of the 3rd cycle, acute swelling of both submandibular glands, swelling of right parotid gland and right monocular diplopia were observed. Cervical and cranial magnetic resonance was performed (Image 1) showing significant enlargement of the right lacrimal gland and bilateral submandibular glands. Bone marrow aspiration (BMA) showed CR with improved MRD of 0.02%. Cytological and cytometric cerebrospinal fluid analysis did not find ALL infiltration. With no evidence of disease progression and given the characteristics of the clinical and radiological picture, Mikulicz Syndrome was raised as a probable diagnostic possibility. However, a submandibular glandular tru‐cut biopsy showed glandular infiltration by ALL cells. One week later, a body PET/CT found significant metabolic uptake activity in the glands, regional lymph nodes and extensive bone involvement. Then, a new BMA (performed 10 days after de previous one) demonstrated ALL massive medullar relapse.Results:Relapsed/refractory (R/R) ALL is a bad condition with poor survival. Isolated extramedullary ALL relapse occurs in up to 6% of ALL according to literature and is often hard to demonstrate. In our case, the picture started as neck and head glandular swelling and diplopia. In the absence of medullar disease, Mikulicz Syndrome was suspected. Mikulicz Syndrome is a rare immune chronic benign condition characterized of swelling of neck and head glands where diplopia is often the first clinical sign. It has been related with several diseases including sarcoidosis, lymphoma and acute lymphoblastic leukemia. In this scenario, a biopsy of the involved glands is strongly recommended to rule out leukemia progression. In our case, tru‐cut biopsy of one of the involved glands demonstrated AAL extramedullary relapse despite absence of medullar involvement. Unfortunately, massive medullar relapse was confirmed a week later.Summary/Conclusion:Mikulicz syndrome is a diagnostic challenge for clinicians. In the setting of patients with ALL under blinatumumab treatment, clinicians should rule out ALL relapse before confirming this rare condition.image

Imaging analysis of 18F-FDG PET/CT in patients with multiple myeloma

Objective To analyze the imaging characteristics of 18F-fluorodeoxyglucose (FDG) PET/CT in patients with multiple myeloma (MM). Methods Sixty-eight patients (41 males, 27 females, age (61.5±17.2) years) with pathologically proven MM were retrospectively reviewed between January 2011 and August 2016. Imaging characteristics of 18F-FDG PET/CT in patients were analyzed. Maximum standardized uptake value (SUVmax), score of the bone involvement (bones of whole body were classified into 10 groups, and when 1 group was involved, the score was 1), the number of bone lesions and soft tissue swelling around bone lesions were investigated. Results A total of 1 310 lesions were detected in 68 MM patients. The SUVmax varied widely and mild metabolic activity (2.5≤SUVmax<5.0) was observed in the highest proportion of MM patients (49.8%, 652/1 310). The SUVmax of MM patients was 6.63±3.02. The score of bone involvement was 4.49±3.01. The number of bone lesions was 10.50(3.00, 33.00), and soft tissue swelling around bone lesions was observed in 22 patients. Conclusions There are special imaging characteristics of 18F-FDG PET/CT in MM patients, such as multiple osteolytic lesions with mild to moderate metabolic activity, clear boundary and extensive bone involvement, and lesions usually limit to the skeletal system. The characteristics are of certain value in the diagnosis and differential diagnosis of MM. Key words: Multiple myeloma; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Two stage management of Cierny-Mader type IV chronic osteomyelitis of the long bones

IntroductionCierny-Mader (C-M) type IV chronic osteomyelitis represents a complex clinical challenge with permeation of extensive bone and soft tissue involvement. Aggressive debridement through viable tissue margin includes en bloc resection improves the odds of eradication of infection, which creates large bone and soft tissue loss in treating this type of osteomyelitis. The potentially large defects increase reconstruction problems with traditional reconstruction technique. The newly staged induced membrane technique presents length-independent, potential as an alternative reconstruction method for segmental bone defects due to type IV chronic osteomyelitis. The purpose of this study was to assess the result and related factors of C-M type IV chronic osteomyelitis treated with staged methods of aggressive debridement and induced membrane technique. MethodsFrom January 2012 to January 2014, 36 consecutive adult patients of C-M type IV chronic osteomyelitis were treated by this staged method in our clinical center with a minimum of 2-years follow-up. The clinical and imaging results were retrospectively analyzed. ResultsFive patients had a second debridement and eight needed a local flap transfer to cover the wound in the first stage. Patients formed a mean of 5.5cm (range: 2–10.9) segmental bone defect; Sixteen patients had autograft and twenty had autograft mixed allograft in the second stage. The mean follow-up time was 29.5 months (range: 24–45). No patients required amputation. Bone union was achieved in all patients. Clinical eradication of osteomyelitis was achieved in 35 (97%) patients, 35 (97%) patients were able to walk independently, and 31patients (86%) returned to work. Patients returned to a mean of 82% (46.3%–100%) lower extremity function. Bone union time was not dependent on the length of bone defect, but associated with the infection site (p=0.005) and age (p=0.005). ConclusionsStaged methods of aggressive debridement and induced membrane technique seems to be a simple, reliable and effective for the treatment of C-M type IV chronic osteomyelitis. Advanced age and poor soft tissue envelope may have adverse affects and are relative contraindications. The combined assessment and management of such patients with a plastic surgeon are advocated.

Inhibition of Activin A Ameliorates Skeletal Muscle Injury and Rescues Contractile Properties by Inducing Efficient Remodeling in Female Mice

Activin A, a member of the transforming growth factor-β superfamily, provides pleiotropic regulation of fibrosis and inflammation. We aimed at determining whether selective inhibition of activin A would provide a regenerative benefit. The introduction of activin A into normal muscle increased the expression of inflammatory and muscle atrophy genes Tnf, Tnfrsf12a, Trim63, and Fbxo32 by 3.5-, 10-, 2-, and 4-fold, respectively. The data indicate a sensitive response of muscle to activin A. Two hours after cardiotoxin-induced muscle damage, local activin A protein expression increased by threefold to ninefold. Neutralization of activin A with a specific monoclonal antibody in this muscle injury model decreased the muscle protein levels of lymphotoxin α and Il17a by 32% and 42%, respectively. Muscle histopathological features showed that activin A antibody-treated mice displayed an increase in muscle degradation, with the concomitant 9.2-fold elevation in F4/80-positive cells 3 days after injury. At the same time, the number of Pax7/Myod1-positive cells also increased, indicative of potentiated muscle precursor activation. Ultimately, activin A inhibition resulted in rapid recovery of muscle contractile properties indicated by a restoration of maximum and specific force. In summary, selective inhibition of activin A with a monoclonal antibody in muscle injury leads to the early onset of tissue degradation and subsequent enhanced myogenesis, thereby accelerating muscle repair and functional recovery.