Acquired C1-inhibitor deficiency due to splenic marginal zone lymhoma: Case Report.

We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the face and larynx. After thorough biochemical investigations, an acquired deficiency of C1-INH was suspected. To evaluate a potential underlying malignancy, a whole-body FDG-PET/CT was performed and showed solely a marked splenomegaly pointing towards a splenic marginal zone lymphoma, which was confirmed by pathological examination.With this case, we discuss the pathophysiology, diagnosis and management of recurrent acquired angioedema attacks as the first presentation of an underlying lymphoproliferative disease.

Granulomatosis with polyangiitis with breast involvement mimicking metastatic cancer: Case report and literature review.

Granulomatosis with polyangiitis (GPA) is a systemic inflammatory disease, characterized by the presence of necrotizing vasculitis of small and medium-sized vessels, granulomatous inflammation and anti-neutrophil cytoplasmic antibodies (ANCAs). The diagnosis can be challenging due to the variable clinical presentation and possible involvement of virtually all organ systems. A correct diagnosis is indispensable for a timely start of medical treatment and to avoid unnecessary surgery. Therefore, cooperation with and the input of the pathologist is crucial. We report a case of a woman presenting with suspected metastatic cancer. The diagnosis of GPA was made mainly based on breast biopsy, and the patient was treated accordingly, with full recovery. This report provides a case description and a brief review of the literature.

Anatomical mapping of lymph nodes in patients receiving salvage lymphadenectomy based on a positive 11C-choline positron emission tomography/computed tomography scan.

INTRODUCTION: This paper aims to assess the diagnostic accuracy of an 11C-choline positron emission tomography/computed tomography (PET/CT) scan in the detection of lymph node (LN) metastases in patients with biochemical recurrence after radically treated prostate cancer (PCa), as compared to histology. The secondary goal is to depict spreading patterns of metastatic LNs in recurrent PCa. MATERIAL AND METHODS: A single center retrospective study comprising of 30 patients who underwent retroperitoneal and/or pelvic salvage lymph node dissection (LND) due to 11C-choline PET/CT-positive nodal recurrences after radical treatment (median Prostate Specific Antigen (PSA) 1.5 ng/ml, range 0.2-11.4). Positive nodes on the preoperative PET/CT scans were mapped and compared to post-operative pathology results.LNs were marked as true positive, false positive, true negative and false negative and a patient- and a region-based analysis was performed. Sensitivity, specificity and positive/negative predictive value (PPV/NPV) were calculated. RESULTS: Sixty positive LNs were detected on PET/CT with a median number of two positive nodes per patient (range 1-6). In 29 patients, a super-extended pelvic LND (PLND) was performed combined with a retroperitoneal LND (RPLND) in 13 of those cases. One patient underwent an inguinal LND. One hundred thirty-seven of 644 resected LNs contained metastases. The 11C-choline PET/CT scan correctly predicted 31 positive nodes (55%) while 25 nodes were falsely positive (45%). One hundred and six histologically proven metastatic nodes were not detected on the 11C-choline PET/CT scan (77%). Sensitivity, specificity, PPV and NPV of the 11C-choline PET/CT were 23%, 95%, 55% and 82%, respectively. CONCLUSIONS: 11C-choline PET/CT has a relatively low detection rate and a moderate PPV for metastatic LNs in patients with biochemical recurrence after radically treated PCa.

Role of 18F-FDG PET/CT in Restrictive Allograft Syndrome After Lung Transplantation.

BACKGROUND: Differential diagnosis of phenotypes of chronic lung allograft dysfunction (CLAD) remains troublesome. We hypothesized that F-fluorodeoxyglucose positron emission tomography with computed tomography (F-FDG PET/CT) may help in differential diagnosis of CLAD phenotypes, as it showed promising results regarding diagnosis and prognosis in interstitial lung diseases. METHODS: A monocentric, retrospective study was performed including all lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) who underwent F-FDG PET/CT scan, in comparison with stable lung transplant recipients. Maximum standardized uptake value (SUVmax) was associated with pulmonary function and survival. Proof-of-concept microCT and glucose transporter-1 staining served as morphologic validation for regions with different SUVmax. RESULTS: Maximum standardized uptake value was higher in RAS (median, 2.6; n = 29) compared with BOS (median, 1.0; n = 15) and stable patients (median, 0.59; n = 8) (P < 0.0001). In RAS, high SUVmax was associated with worse survival after F-FDG PET/CT (P = 0.0004; hazard ratio, 1.82). Forced vital capacity at F-FDG PET/CT inversely correlated with SUVmax (R = -0.40, P = 0.03). MicroCT analysis revealed extensive fibrosis in regions of high SUVmax, with an increased number of glucose transporter-1-positive cells. CONCLUSIONS: F-fluorodeoxyglucose positron emission tomography with CT may noninvasively differentiate RAS from BOS. RAS patients with areas of increased lung metabolism have worse outcome, demonstrating the potential use of F-FDG PET/CT during follow-up after lung transplantation.

Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series.

Pirfenidone may attenuate the decline of pulmonary function in restrictive allograft syndrome (RAS) after lung transplantation. We retrospectively assessed all lung transplant recipients with RAS who were treated with pirfenidone for at least 3 months (n = 11) in our lung transplant center and report on their long-term outcomes following initiation of pirfenidone. Main outcome parameters included evolution of pulmonary function and overall survival. Pirfenidone appears to attenuate the decline in forced vital capacity and forced expiratory volume in 1 second. Notably, 3 patients were bridged to redo-transplantation with pirfenidone for 11 (5-12) months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function after 26.6 (range 18.4-46.6) months of treatment. Median overall 3-year survival after RAS diagnosis was 54.5%. Subjective intolerance, mainly anorexia and nausea, necessitating pirfenidone dose de-escalation in 55% of patients, as well as calcineurin dose increase requirements with about 20% are important complications during pirfenidone treatment after lung transplantation. Our findings provide further evidence that pirfenidone appears to be safe and may attenuate the rate of decline in lung function in patients with RAS, but the actual clinical benefit cannot be assessed in the context of this study design and requires further investigation in a larger randomized trial.

On the optimal z-score threshold for SISCOM analysis to localize the ictal onset zone.

BACKGROUND: In epilepsy patients, SISCOM or subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging has become a routinely used, non-invasive technique to localize the ictal onset zone (IOZ). Thresholding of clusters with a predefined number of standard deviations from normality (z-score) is generally accepted to localize the IOZ. In this study, we aimed to assess the robustness of this parameter in a group of patients with well-characterized drug-resistant epilepsy in whom the exact location of the IOZ was known after successful epilepsy surgery. Eighty patients underwent preoperative SISCOM and were seizure free in a postoperative period of minimum 1 year. SISCOMs with z-threshold 2 and 1.5 were analyzed by two experienced readers separately, blinded from the clinical ground truth data. Their reported location of the IOZ was compared with the operative resection zone. Furthermore, confidence scores of the SISCOM IOZ were compared for the two thresholds. RESULTS: Visual reporting with a z-score threshold of 1.5 and 2 showed no statistically significant difference in localizing correspondence with the ground truth (70 vs. 72% respectively, p = 0.17). Interrater agreement was moderate (κ = 0.65) at the threshold of 1.5, but high (κ = 0.84) at a threshold of 2, where also reviewers were significantly more confident (p < 0.01). CONCLUSIONS: SISCOM is a clinically useful, routinely used modality in the preoperative work-up in many epilepsy surgery centers. We found no significant differences in localizing value of the IOZ using a threshold of 1.5 or 2, but interrater agreement and reader confidence were higher using a z-score threshold of 2.

Correlation of neuropsychological and metabolic changes after epilepsy surgery in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Epilepsy surgery often causes changes in cognition and cerebral glucose metabolism. Our aim was to explore relationships between pre- and postoperative cerebral metabolism as measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological test scores in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), who were rendered seizure-free after epilepsy surgery. RESULTS: Thirteen patients were included. All had neuropsychological testing and an interictal FDG-PET scan of the brain pre- and postoperative. Correlations between changes in neuropsychological test scores and metabolism were examined using statistical parametric mapping (SPM). There were no significant changes in the neuropsychological test scores pre- and postoperatively at the group level. Decreased metabolism was observed in the left mesial temporal regions and occipital lobe. Increased metabolism was observed in the bi-frontal and right parietal lobes, temporal lobes, occipital lobes, thalamus, cerebellum, and vermis. In these regions, we did not find a correlation between changes in metabolism and neuropsychological test scores. A significant negative correlation, however, was found between metabolic changes in the precuneus and Boston Naming Test (BNT) scores. CONCLUSIONS: There are significant metabolic decreases in the left mesial temporal regions and increases in the bi-frontal lobes; right parietal, temporal, and occipital lobes; right thalamus; cerebellum; and vermis in patients with left MTLE-HS who were rendered seizure-free after epilepsy surgery. We could not confirm that these changes translate into significant cognitive changes. A significant negative correlation was found between changes in confrontation naming and changes in metabolism in the precuneus. We speculate that the precuneus may play a compensatory role in patients with postoperative naming difficulties after left TLE surgery. Understanding of these neural mechanisms may aid in designing cognitive rehabilitation strategies.

Targeting Coagulase Activity in Staphylococcus aureus Bacteraemia: A Randomized Controlled Single-Centre Trial of Staphylothrombin Inhibition.

BACKGROUND: Staphylococcus aureus (S. aureus) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection. OBJECTIVE: A single-centre, randomized, controlled feasibility and safety trial of staphylothrombin inhibition with DTIs in patients with S. aureus bacteraemia. PATIENTS AND METHODS: Consecutive eligible adult patients with S. aureus positive blood cultures in the University Hospitals Leuven (Belgium) were randomized 1:1 to DTI (oral dabigatran 110 mg twice daily or intravenous argatroban according to activated partial thromboplastin time [aPTT]) for 7 to 10 days, or subcutaneous enoxaparin 40 mg once daily. Primary outcomes were feasibility and safety of DTI in patients with S. aureus bacteraemia. Secondary outcomes include D-dimer evolution (day 0-4) as marker of coagulation activation; inflammatory and microbiological parameters; and clinical outcomes including metastatic infections. RESULTS: Thirty-one percent (94/303) of screened patients were enrolled. Dabigatran plasma levels inhibited staphylothrombin. Clinically relevant bleeding (5/47 vs. 5/47) and thrombotic (7/47 vs. 7/47) complications were similar in both groups. Coagulase inhibition with DTIs was associated with a trend towards faster D-dimer decrease at day 4 (-662 ± 249 ng/mL vs. -40 ± 213 ng/mL for DTI-treated patients vs. control; p = 0.06) and a numerically lower number of persistently positive blood cultures. No differences in inflammatory parameters or other clinical outcomes were observed. CONCLUSION: Targeting staphylothrombin with DTIs is feasible in a subset of S. aureus bacteraemic patients, with comparable safety to standard thromboprophylaxis. In future studies of staphylothrombin inhibition, feasibility can be further improved by rapid diagnostics and by strategies without concomitant anticoagulant effect.

Phase 2 Study of 99mTc-Trofolastat SPECT/CT to Identify and Localize Prostate Cancer in Intermediate- and High-Risk Patients Undergoing Radical Prostatectomy and Extended Pelvic LN Dissection.

99mTc-trofolastat (99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen, shows high potential to detect prostate cancer (PCa) noninvasively using SPECT. We therefore wanted to assess the performance of 99mTc-trofolastat SPECT/CT in a phase 2 multicenter, multireader prospective study in patients with intermediate- and high-grade PCa, before radical prostatectomy and extended pelvic lymph node (LN) dissection, with histopathology as the gold standard. Methods: PCa patients (n = 105) with an increased risk of LN involvement (LNI) underwent pelvic 99mTc-trofolastat SPECT/CT before radical prostatectomy with extended pelvic LN dissection. The sensitivity of 99mTc-trofolastat for detection of PCa on a patient and lobe basis, using visual and semiquantitative (tumor-to-background ratio [TBR]) scores, and of LNI was evaluated as well as the correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of 99mTc-trofolastat uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared with tumor-negative lobes. Receiver-operating characteristic analysis showed that visual scores more accurately discriminated lobes with GS ≤ 3 + 3 from ≥ 3 + 4, whereas TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. 99mTc-trofolastat SPECT/CT detected LNI with a sensitivity of 50% and specificity of 87%, and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion:99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared with histology. It has the potential to be used as a surrogate marker for GS and predict LNI.

Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography versus bone marrow biopsy.

Detecting bone marrow involvement (BMI) in lymphoma is important as it adversely affects stage. Bone marrow biopsy (BMB) remains the standard to detect BMI but is prone to sampling error. We retrospectively investigated whether (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) could identify BMI in patients with post-transplant lymphoproliferative disorder (PTLD) with sufficient accuracy in comparison with staging BMB. Twenty-five patients diagnosed with PTLD who underwent (18)F-FDG-PET/CT and BMB within one month were evaluated. Based on our criteria, six patients (24%) were considered positive for BMI on (18)F-FDG-PET/CT compared to one by BMB. Although we cannot completely exclude false positive results on (18)F-FDG-PET/CT, our data indicate a significantly higher sensitivity of (18)F-FDG-PET/CT compared to BMB (100% vs 17%) but similar specificity. These data confirm the high diagnostic performance of (18)F-FDG-PET/CT for detecting BMI, but prospective studies are needed to determine whether (18)F-FDG-PET/CT could indeed replace staging BMB in PTLD.