Calcium pyrophosphate crystal deposition with rotator cuff tear-A case report.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear.

Gliadin intake induces oxidative-stress responses in Caenorhabditis elegans.

Clinical attention to gluten-related disorders, such as celiac disease and nonceliac gluten sensitivity, is on the rise. However, identifying the pathophysiological mechanisms of gluten-related disorders remains elusive. Gliadin, a component of gluten, is known to play a major role in gluten toxicity. Caenorhabditis elegans has been widely used as the predominant experimental animal model to study toxicity and stress response in biomedical research. We investigated the stress response induced by gliadin intake in C. elegans to evaluate its toxicity and found brood size, body bending, and pumping rates to be significantly altered in response to gliadin. Notably, reactive oxygen species (ROS) production and Pgst-4::GFP transgene expression, an indicator of the oxidative-stress response, were significantly increased after gliadin intake. Reduced pumping rates were most likely caused by gliadin-induced oxidative stress, since pumping rates in oxidative stress-sensitive mev-1 mutants were more severely reduced than in oxidative stress-resistant daf-2 mutants following gliadin intake. Our results indicated that gluten/gliadin intake in C. elegans triggered ROS production and induced an oxidative stress response that reduced pumping rates and decreased brood size. We suggest C. elegans to be a useful model system for studying gluten/gliadin toxicity.

BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status.

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.

Clinical Significance of Substaging and HER2 Expression in Papillary Nonmuscle Invasive Urothelial Cancers of the Urinary Bladder.

The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.

Expression of Peroxisome Proliferator Activated Receptor gamma in Prostatic Adenocarcinoma.

Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-γ ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-γ expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-γ antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-γ and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-γ except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-γ was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-γ mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-γ mRNA expression between low (≤7) and high (>7) Gleason score groups. There was no association of PPAR-γ mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-γ. Further studies are needed to assess the functional role of PPAR-γ and to validate its therapeutic implication in prostate cancer.

Imaging mass spectrometry in papillary thyroid carcinoma for the identification and validation of biomarker proteins.

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2.

Primary ductal adenocarcinoma of the lacrimal gland, associated with abundant intracytoplasmic lumens containing some eosinophilic hyaline globules: cytological, histological and ultrastructural findings.

A primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare distinct subtype of an epithelial tumor arising in the lacrimal gland. PDA is the counterpart of salivary duct carcinoma (SDC) resembling an invasive ductal carcinoma (IDC) of the breast. In our case, PDA revealed histopathological and immunohistochemical results corresponding to SDC. Interestingly, the tumor cells showed intracytoplasmic vacuoles containing dense eosinophilic hyaline globules at light microscopy. Ultrastructurally, the tumor cells exhibited microvilli-lined intracytoplasmic lumen containing homogenous electron-dense secretory products. A previous study demonstrated that numerous intracytoplasmic lumens of tumor cells are favored breast malignant tumor, similar to the histopathology of PDA, rather than benign lesion. This characteristic finding may be meaningful to diagnose high grade epithelial tumors including PDA.

An Autopsy-proven Case-based Review of Autoimmune Encephalitis.

Autoimmune encephalitis (AIE) is a type of immunoreactive encephalitic disorder and is recognized as the most prevalent noninfectious encephalitis. Nevertheless, the rarity of definitive AIE diagnosis through biopsy or autopsy represents a significant hurdle to understanding and managing the disease. In this article, we present the pathological findings of AIE and review the literature based on a distinct case of AIE presenting as CD8+ T-lymphocyte predominant encephalitis. We describe the clinical progression, diagnostic imaging, laboratory data, and autopsy findings of an 80-year-old deceased male patient. The patient was diagnosed with pulmonary tuberculosis 6 months before death and received appropriate medications. A week before admission to the hospital, the patient manifested symptoms such as a tendency to sleep, decreased appetite, and confusion. Although the patient temporally improved with medication including correction of hyponatremia, the patient progressed rapidly and died in 6 weeks. The brain tissue revealed lymphocytic infiltration in the gray and white matter, leptomeninges, and perivascular infiltration with a predominance of CD8+ T lymphocytes, suggesting a case of AIE. There was no detectable evidence of viral infection or underlying neoplasm. The autopsy revealed that this patient also had Alzheimer's disease, atherosclerosis, arteriolosclerosis, and aging-related tau astrogliopathy. This report emphasizes the pivotal role of pathological examination in the diagnosis of AIE, especially when serological autoantibody testing is not available or when a patient is suspected of having multiple diseases.

Does phosphorylation of cofilin affect the progression of human bladder cancer?

BACKGROUND: We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. METHODS: We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. RESULTS: The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. CONCLUSIONS: These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

Genetic alteration and immunohistochemical staining patterns of ovarian high-grade serous adenocarcinoma with special emphasis on p53 immnnostaining pattern.

We evaluated p53, KRAS, BRAF and CTNNB1 mutation and p53, WT1, p16 and beta-catenin expression in 31 ovarian high-grade serous adenocarcinoma. Twenty-five (80.6%) tumors contained functional mutations of p53; three frameshift, four nonsense and 19 missense mutations. None of the tumors showed KRAS, BRAF or CTNNB1 mutation. In all 18 tumors with missense mutations, ≥60% of tumor cells were strongly positive for p53 immunostaining whereas all tumors with frameshift or nonsense mutations were completely negative. Missense mutation was correlated with diffuse and strong imunoreaction and frameshift/nonsense mutation was correlated with completely negative immunoreaction (P = 0.000). Tumors with wild-type p53 revealed a wide range of immunostaining patterns. In 27 (87.1%) and 18 (58.1%) tumors, ≥50% of tumor cells were moderate to strongly positive for WT1 and p16, respectively. A considerable intratumoral heterogeneity for p16 expression was present. None of the tumors demonstrated nuclear beta-catenin expression. p53 mutations appear to be a powerful molecular marker for ovarian high-grade serous adenocarcinoma. Using p53 with an appropriate interpretation criteria together with WT1, p16 and beta-catenin, most of the high-grade serous adenocarcinoma could be distinguished from other ovarian tumors.

Surgical corner. Evaluation of the wound healing response after deep dermal heating by fractional micro-needle radiofrequency device.

BACKGROUND: Fractional Radiofrequency Microneedles (FRM) are minimally invasive devices that use inserting bipolar radiofrequency for deep dermal heating, has been introduced. We investigated the tissue response after FRM according to different energy levels in porcine skin. METHODS: Porcine back skin was used in the study. A FRM device was composed of 49 insulated needles. Needles were vertically inserted with 1.5mm depth and four different energy levels were used to examine wound healing response chronologically. Histologic evaluation was done by hematoxylin & eosin (H&E) and heat shock proteins (HSP) 47 staining for immediately after, 2 days after, 14 days after, 28 days after and 10 weeks after the procedure. RT-PCR was done for various cytokines including HSP47, HSP72, metalloproteinase (MMP), and extracellular matrix (ECM) proteins. RESULTS: FRM treatment generated a thermally coagulated zone localized in the reticular dermis, without damaging the epidermis. The coagulation necrosis zone in H&E staining was replaced by new collagen tissue over 10 weeks. RT-PCR studies revealed an increase in HSP, MMPs, and ECM proteins. In the high energy level procedure, an increased number of fibroblasts were found. CONCLUSION: FRM treatment induced a dermal remodeling process including neocollagenesis in the deep dermis. From this result, FRM is expected to provide a good and positive efficacy for skin rejuvenation.

Chronologic change in the growth plate after radiofrequency-induced thermal injury: MRI-histologic correlation.

OBJECTIVE: The purposes of this study were to assess chronologic changes in normal growth plate after radiofrequency-induced thermal injury and to evaluate the feasibility of MRI for revealing alteration of the growth plate. MATERIALS AND METHODS: Radiofrequency ablation was performed on the right proximal tibia of 13 8-week-old New Zealand White rabbits. An 18-gauge cooled-tip electrode with a 5-mm active tip was placed distal to the physis under fluoroscopic guidance. MRI, including T1- and T2-weighted images, gradient-recalled echo images, and contrast-enhanced T1-weighted images, was performed 2, 4, and 12 weeks after ablation. Rabbits were sacrificed 2 (n = 4), 4 (n = 4), and 12 weeks (n = 5) after ablation. The sequential changes in the ablated zone, the injured physis, and the nonablated portion of the physis were correlated between MRI features and histologic results. RESULTS: Diameter of the nonenhancing lesion on MR images strongly correlated with the size of the region of coagulation necrosis at gross examination. The intraclass correlation coefficients were 0.98 and 0.94 for the long and short axes (p < 0.001). On gradient-recalled echo images, physial conspicuity was less in the injured physis than in the nonablated portion and less in the ablated than the control tibia. Physial conspicuity was graded for comparison with physial thickness at microscopic examination. The thickness of the physis was less in the ablated than in the control tibia 4 and 12 weeks after treatment (p < 0.05, paired Student t test). The cartilage column of the injured physis was delaminated 2 weeks after treatment, and a bone bridge through the injured physis was detected at 4 weeks. CONCLUSION: Radiofrequency-induced thermal injury causes early closure of the physis. MRI can depict the extent of radiofrequency-induced thermal injury and alterations in the physis that lead to early closure.

Imaging parameters of high grade gliomas in relation to the MGMT promoter methylation status: the CT, diffusion tensor imaging, and perfusion MR imaging.

INTRODUCTION: We hypothesized that methyl-guanine methyl transferase (MGMT) promoter methylation status, a predictor of the chemosensitivity for high grade gliomas (HGGs), may be associated with computed tomography (CT)/magnetic resonance (MR) imaging variables. METHODS: Out of 38 consecutive patients with HGGs, 24 patients whose MGMT promoter methylation status was available [12 men and 12 women; median age, 49 years; age range, 22-79 years; WHO grade III (n = 7), WHO grade IV (n = 17)] were enrolled retrospectively. CT attenuation, apparent diffusion coefficient (ADC), fractional anisotropy (FA), and relative cerebral blood volume (rCBV) were measured for enhancing tumors. Qualitative imaging features were also analyzed. Mann-Whitney and Fisher's exact tests were used to evaluate relationships between MGMT promoter methylation status and imaging variables. RESULTS: Maximum CT attenuation was significantly lower in the methylated MGMT promoter group than that in the unmethylated MGMT promoter group (30.3 ± 9.5 HU versus 39.2 ± 4.7 HU, respectively, p = 0.009). While ADC values tended to be higher in the methylated group than in the unmethylated group (p = 0.055), ADC ratio was significantly higher, and the FA and FA ratios were significantly lower in the methylated group than in the unmethylated group (p = 0.032, p = 0.006 and p = 0.007, respectively). In contrast, rCBV ratio did not differ between the two groups (p = 0.380). Regarding imaging features, only ill-defined margin was seen more frequently in the methylated group than in the unmethylated group (45.5% versus 7.7%, respectively, p = 0.048). CONCLUSION: Preoperative imaging can predict MGMT promoter methylation status, which is of paramount importance for predicting treatment response to chemotherapy with an alkylating agent.

Effects of epidural TNF-α inhibitor injection: analysis of the pathological changes in a rat model of chronic compression of the dorsal root ganglion.

OBJECTIVES: To evaluate the efficacy of a single direct epidural injection of tumor necrosis factor (TNF)-α inhibitor to reduce the pathological changes in nerve fiber injuries in a rat model of chronic compression of the dorsal root ganglion (CCD). MATERIALS AND METHODS: A surgical procedure for CCD was performed in 17 adult male F-344 rats. The effects of the epidural TNF-α inhibitors on CCD-induced pathological changes were investigated. Three groups of rats (n = 17) were used: (1) CCD + saline (n = 4), (2) CCD + triamcinolone (n = 5), and (3) CCD + TNF-α inhibitors (n = 8). Their dorsal root ganglia and nerve roots were removed on postoperative day 14. The intraneural edema, demyelination, and Wallerian degeneration of all 17 rats were scored pathologically. RESULTS: The pathology scores of the rats in the TNF-α inhibitor treatment group (1.38 ± 0.74) indicated a mild degree of intraneural edema compared to the saline treatment group (2.25 ± 0.50, p = 0.041). In addition, rats in the TNF-α inhibitor treatment group (2.13 ± 0.35) had a mild degree of demyelination compared to the saline treatment group (2.75 ± 0.50, p = 0.038) and the triamcinolone treatment group (2.80 ± 0.45, p = 0.019). The differences in the pathology scores for Wallerian degeneration were not statistically significant in all three study groups (p = 0.658). CONCLUSION: The epidural injection of a TNF-α inhibitor was more effective than a placebo and comparable to triamcinolone in reducing pathological nerve injury progression.

Emerging glioneuronal and neuronal tumors: case-based review.

Glioneuronal and neuronal tumors (GNTs) are rare heterogeneous central nervous system tumors characterized by slow growth and favorable outcomes, but are often associated with diagnostic difficulties. A thorough analysis of three rare and recently recognized GNTs was performed in the context of clinicopathological features and molecular genetic characterization. The current spinal diffuse leptomeningeal glioneuronal tumor (DLGNT) was characterized with oligodendroglioma-like tumor with chromosome 1p/19q codeletion without IDH mutations and KIAA1549:BRAF fusion. The current occipital multinodular and vacuolating neuronal tumor (MVNT) was characteristic of the variable-sized vague nodules consisted of gangliocytic tumor cells with intracytoplasmic and pericellular vacuolation and the next-generation sequencing (NGS) revealed MAP2K1 p.Q56_V60del. A diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) of the amygdala was characterized by oligodendroglia-like cells and nuclear clusters, and monosomy 14. From the current cases and literature review, we found that DLGNT commonly occurs in the spinal cord and can make mass and more commonly have KIAA1549:BRAF fusion; MVNT is a neoplasm rather than malformation and MAP2K1 deletion is one of the hallmarks of this tumor; although DGONC may require a methylation profile, we can reach a diagnosis through its unique histology, monosomy 14, and exclusion diagnosis without a methylation profile.

Fatty acid synthetase expression in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism-related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. METHODS: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2-3+ FASN staining as high-grade FASN. RESULTS: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups. CONCLUSIONS: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Overexpression of FRAT1 protein is closely related to triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.

BACKGROUND/AIM: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). PATIENTS AND METHODS: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. RESULTS: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. CONCLUSION: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.

Osteochondroma of the calcaneus presenting as Haglund's deformity.

Haglund's deformity is a symptomatic osseous prominence of the posterosuperior corner of the calcaneus creating posterior heel pain and swelling around the insertion of the Achilles tendon. We have experienced an exceptionally huge Haglund's deformity in a 22-year-old female who initially presented to us with a large painful bony heel mass that had developed over the last decade. We performed the surgical resection of the prominence and the pathology confirmed the diagnosis of calcaneal osteochondroma. To our best knowledge, such a gigantic Haglund's deformity caused by calcaneal osteochondroma has never been reported in any medical literature.

Unusual clinicopathological presentation of nontraumatic cerebral fat embolism: Two-case report.

RATIONALE: Fat embolism syndrome (FES) is characterized by the classical triad of cerebral, respiratory, and cutaneous manifestations. In contrast, cerebral fat embolism (CFE), corresponding to incomplete pure type FES, is much rarer and usually follows trauma. CFE typically shows a "starfield" pattern on diffusion-weighted magnetic resonance imaging due to the involvement of multiple small arteries. We report 2 unusual cases of CFE that showed a nontraumatic etiology and the involvement of a single dominant cerebral artery. PATIENT CONCERNS: Case 1 was a 33-year-old woman without a history of trauma who visited the emergency room due to hemiparesis and hemisensory deficits. She was a heavy smoker and had used oral contraceptives for several years. Most importantly, she had 2 experiences of autologous fat grafting 2 months previously. Magnetic resonance angiography (MRA) revealed acute occlusion of the right middle cerebral artery. Case 2 was an 80-year-old man suddenly presented with dizziness, ataxia, and left-sided sensorimotor dysfunction. He had a history of hypertension, untreated atrial fibrillation, and chronic alcoholism. MRA demonstrated the occlusion of the distal basilar artery. DIAGNOSIS: Case 1: Microscopic findings demonstrated variable sized fat vacuoles intermixed with moderate amounts of thrombi. Case 2: Histologically, mature adipocytes were intermingled with fibrin, blood cells, and a fragment of entrapped soft tissue resembling the vessel wall. INTERVENTION: Case 1 and 2 underwent aspirational thrombectomy guided by transfemoral cerebral angiography. OUTCOME: Case 1 recovered well but Case 2 still suffers from gait ataxia. LESSONS: CFE can rarely occur in various nontraumatic conditions, with or without evident etiology. Furthermore, it may not show characteristic clinicopathological manifestations. Therefore, careful follow up of those who have undergone procedures that are likely to trigger FES or who have hemodynamic or hypercoagulable risk factors is needed.