Preliminary study of CT features of intermediate- and high-grade alimentary lymphoma and adenocarcinoma in cats

Case series summary The ultrasonographic findings of many feline intestinal tumours are similar. This study evaluated the CT features of intermediate- and high-grade alimentary lymphoma and adenocarcinoma in cats. CT was performed on six cats with adenocarcinoma and 14 cats with lymphoma. Comparisons between tumour types were conducted, focusing on CT features, including obstruction (present or absent), growth patterns of lesions (symmetry or asymmetry), layering enhancement (present or absent), location of the lesion, number of lesions (solitary or multiple), lymphadenopathy (present or absent), location of lymphadenopathy, pulmonary metastasis (present or absent) and maximum thickness (mm) of the lesion. The cats with adenocarcinoma (n = 5/6 [83%]) experienced intestinal obstruction significantly more often than cats with lymphoma (n = 0/14 [0%]; P = 0.0004). Layering enhancement was observed significantly more often in cats with adenocarcinoma (n = 6/6 [100%]) than in cats with lymphoma (n = 1/14 [7%]; P = 0.0002). Lymphadenopathy was detected significantly more often in cats with lymphoma (n = 14/14 [100%]) than in cats with adenocarcinoma (n = 2/6 [33%]) ( P = 0.003). In cats with lymphoma, the intestine (12.1 ± 3.9 mm) was significantly thicker than that in cats with adenocarcinoma (6.4 ± 2.3 mm; P = 0.005). Relevance and novel information To the best of our knowledge, no reports have described the characteristics of feline intestinal tumours using CT. Layering enhancement was observed in cats with intestinal adenocarcinomas. No layering enhancement was observed in alimentary lymphoma in cats, but enlarged regional nodes were noted. Lesions with lymphoma were thicker than those with adenocarcinoma. These findings may help differentiate between adenocarcinomas and lymphomas.

CSF Levels of CXCL12 and Osteopontin as Early Markers of Primary Progressive Multiple Sclerosis

Background and ObjectivesTo evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS).MethodsLevels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness.ResultsHigher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34–11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01–4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09–0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS.ConclusionsAt the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS.Classification of EvidenceThis study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study.

Mean Brain Dose Remains Uninfluenced by Lesion Number for Gamma Knife Stereotactic Radiosurgery for Ten+ Metastases

Purpose:Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with ten or more brain metastases (BM). However, the clinical and dosimetric consequences of this practice are not well established.Methods: We performed a single institution, retrospective analysis of 30 patients who received GK SRS for ten or more BM in one session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. Results: Our cohort had a median number of 13 treated lesions (range 10 to 26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70 to 3.8 Gy). Mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r=0.23, p=0.21), but was closely associated with tumor volume (Pearson r=0.95, p<0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and six patients (20%) underwent WBRT a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier WBRT.Conclusion: The mean dose to the whole brain in patients treated with GK SRS for 10 or more BM remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent WBRT.

Characteristics of patients with osteonecrosis of the jaw with oral versus intravenous bisphosphonate treatment

Purpose This retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP). Materials and methods This retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared. Results Total 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group. Conclusion IV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.

Differential association of cortical, subcortical and spinal cord damage with multiple sclerosis disability milestones: A multiparametric MRI study

Background: In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases. Purpose: To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones. Methods: Multi-centre 3T brain and cervical cord T2- and three-dimensional (3D) T1-weighted images were acquired from 198 MS patients (139 relapsing-remitting (RR) MS, 59 progressive (P) MS) and 67 healthy controls. Brain/cord lesion burden, cortical thickness (CTh), DGM and cerebellar volumetry and cord cross-sectional area (CSA) were quantified. Random forest analyses identified predictors of expanded disability status scale (EDSS) disability milestones (EDSS = 3.0, 4.0 and 6.0). Results: MS patients had widespread atrophy in all investigated compartments versus controls ( p-range: ⩽0.001–0.05). Informative determinants of EDSS = 3.0 were cord CSA, brain lesion volume, frontal CTh and thalamic and cerebellar atrophy (out-of-bag (OOB) accuracy = 0.84, p-range: ⩽0.001–0.05). EDSS = 4.0 was mainly predicted by cerebellar and cord atrophy, frontal and sensorimotor CTh and cord lesion number (OOB accuracy = 0.84, p-range: ⩽0.001–0.04). Cervical cord CSA ( p = 0.001) and cord lesion number ( p = 0.003) predicted EDSS = 6.0 (OOB accuracy = 0.77). Conclusion: Brain lesion burden, cortical and thalamic atrophy were the main determinants of EDSS = 3.0 and 4.0, while cord damage played a major contribution to EDSS = 6.0.

Whole Body Low Dose Computed Tomography (WBLDCT) Can Be Comparable to Whole-Body Magnetic Resonance Imaging (WBMRI) in the Assessment of Multiple Myeloma

Aim of the study is to compare the agreement between whole-body low-dose computed tomography (WBLDCT) and magnetic resonance imaging (WBMRI) in the evaluation of bone marrow involvement in patients with multiple myeloma (MM). Patients with biopsy-proven MM, who underwent both WBLDCT and WBMRI were retrospectively enrolled. After identifying the presence of focal bone involvement (focal infiltration pattern), the whole skeleton was divided into five anatomic districts (skull, spine, sternum and ribs, pelvis, and limbs). Patients were grouped according to the number and location of the lytic lesions (<5, 5–20, and >20) and Durie and Salmon staging system. The agreement between CT and MRI regarding focal pattern, staging, lesion number, and distribution was assessed using the Cohen Kappa statistics. The majority of patients showed focal involvement. According to the distribution of the focal lesions and Durie Salmon staging, the agreement between CT and MRI was substantial or almost perfect (all κ > 0.60). The agreement increased proportionally with the number of lesions in the pelvis and spine (κ = 0.373 to κ = 0.564, and κ = 0.469–0.624), while for the skull the agreement proportionally decreased without reaching a statistically significant difference (p > 0.05). In conclusion, WBLDCT showed an almost perfect agreement in the evaluation of focal involvement, staging, lesion number, and distribution of bone involvement in comparison with WBMRI.

Correlation of cortical lesions of multiple sclerosis at double inversion recovery with cognition screening scores

Background Multiple sclerosis is a chronic inflammatory disease affecting both white and gray matters of the central nervous system. It has been approved that the degree of gray matter involvement is closely associated with the degree of physical disability and the extent of cognitive impairment. Thus, it is necessary to incorporate widely available simple methods for neurocognitive evaluation and gray matter detection in the periodic assessment of MS patients that will influence treatment decisions. Objectives To assess the correlation of cortical lesions of multiple sclerosis (MS) at double inversion recovery (DIR) with cognition screening scores Methods This study was conducted on 30 patients with MS with an average age of 31.3±13.6 years. All of them underwent MRI and clinical assessment with the calculation of Expanded Disability Status Scale (EDSS), Montreal Cognitive Assessment (MoCA), and Symbol Digit Modality Test (SDMT) scores. The image analysis was performed by 2 reviewers for cortical lesion number, shape, and subtypes, and total lesion load. Results Both MoCA and SDMT scales had a significant inverse correlation with cortical lesions number (r=− 0.68, − 0.72) respectively and total lesion load (r=− 0.53, − 0.65) respectively. Besides, there was a significant inverse correlation between the MoCA test, varied cortical subtypes: leukocortical, juxtacortical, and intracortical subtypes (r = − 0.63, − 0.56, − 0.52) respectively, and different cortical lesion shapes: oval, wedge, and curvilinear shaped (r = − 0.62, − 0.69, − 0.49) respectively. As well, the SDMT scale showed a significant inverse correlation with varied cortical subtypes: intracortical, leukocortical, and juxtacortical subtypes (r = − 0.63, − 0.61, − 0.57) respectively, and different cortical lesion shapes: oval, curvilinear, and wedge shaped (r = − 0.61, − 0.59, − 0.46) respectively. Interestingly, there was an excellent inter-observer correlation of cortical lesion number (r = 0.96), total lesion load (r = 0.95), subtypes of cortical lesion (r = 0.94), and cortical lesion shapes (r = 0.77). Conclusion We concluded that DIR can detect cortical lesions of MS, and MRI findings were well-correlated with cognitive dysfunction in these patients.

Baseline lesion number as an efficacy predictive and independent prognostic factor and its joint utility with TMB for PD-1 inhibitor treatment in advanced gastric cancer

Background: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. Methods: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. Results: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. Conclusions: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.

A community-based validation of the International Alliance for the Control of Scabies Consensus Criteria by expert and non-expert examiners in Liberia

Background The International Alliance for the Control of Scabies (IACS) recently published expert consensus criteria for scabies diagnosis. Formal validation of these criteria is needed to guide implementation. We conducted a study to provide detailed description of the morphology and distribution of scabies lesions as assessed by dermatologists and validate the IACS criteria for diagnosis by both expert and non-expert examiners. Methods Participants from a community in Monrovia, Liberia, were independently assessed by two dermatologists and six non-expert examiners. Lesion morphology and distribution were documented based on the dermatologist examination. Diagnoses were classified by IACS criteria and the sensitivity and specificity of non-expert examiner assessments calculated. Results Papules were the most common lesions (97.8%). Burrows were found in just under half (46.7%) and dermatoscopy was positive in a minority (13.3%). Scabies lesions were found in all body regions but more than 90% of patients could have been diagnosed by an examination of only the limbs. Severity of itch was associated with lesion number (p = 0.003). The sensitivity of non-expert examiners to detect typical scabies ranged between 69–83% and specificity 70–96%. The sensitivity of non-expert examiners was higher in more extensive disease (78–94%). Conclusions The IACS criteria proved a valid tool for scabies diagnosis. For the purposes of implementation papules and burrows represent truly ‘typical’ scabies lesions. Non-expert examiners are able to diagnose scabies with a high degree of accuracy, demonstrating they could form a key component in population-level control strategies.

PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis

Introduction [177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy. Methods A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions. Results Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value. Conclusion PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.