Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression.

Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]. The patient developed BP with increasing serum titres of anti-BP180 IgG autoantibodies and increasing disease severity during pembrolizumab therapy. High doses of corticosteroids and methotrexate were needed to control the BP. Following the termination of pembrolizumab therapy, imaging showed complete regression of all metastatic sites. This result may indicate a crucial role for T-cell suppressive activity in controlling and preventing BP.

Relationship between history of smoking, metabolic and inflammatory markers, parameters of body composition and muscle strength.

The objective of this study was to investigate the relationship between smoking history expressed by pack-years, metabolic and inflammatory markers, parameters of body composition (BC) and muscle strength among heavy smokers. A detailed smoking history was obtained from 49 heavy smokers (age = 44 ± 12, pack-years = 31 ± 23). Blood samples were analyzed for levels of glucose, lipids, liver enzymes and C-reactive protein (CRP). Anthropometric measurements included waist circumference and assessment of BC by dual energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA). Muscle strength was assessed by handgrip dynamometry and predicted one-repetition maximum (p1RM) tests. Positive correlations were found between pack-years of smoking, fasting glucose, alkaline phosphatase and CRP levels. Pack-years were also positively correlated with waist circumference, body mass index (BMI), whole-body and trunk fat mass measured by both DEXA and BIA. A negative correlation was found between pack-years of smoking and muscle strength measured by p1RM for the leg press exercise. After adjustment for age, sex and BMI, a positive correlation remained between pack-years of smoking and CRP levels. In conclusion, after controlling for possible confounders, smoking history was found to be positively associated with CRP levels among heavy smokers.

Body composition in heavy smokers: comparison of segmental bioelectrical impedance analysis and dual-energy X-ray absorptiometry.

Smokers tend to have lower body mass index, on one hand, and increased abdominal obesity, on the other hand. Also, low levels of lean mass (LM) and bone mineral content (BMC) were found among older smokers compared with non-smokers. This altered body composition and its consequences raise the need for simple and reliable methods for assessment of body composition in smokers. This study aimed to compare body composition assessment by segmental bioelectrical impedance analysis (sBIA) with the reference method, dual energy X-ray absorptiometry (DEXA). Body composition was measured by sBIA (Tanita BC-545) and DEXA (Hologic) in 49 heavy smokers (>15 cigarettes/day, mean age 43.8±12.0). The comparison included correlations and differences between measurements obtained using the two methods as well as the Blande-Altman analysis. Whole-body fat mass (FM) and LM measured by the two methods were found to be highly correlated (r>0.9, p<0.001). Compared with DEXA, sBIA significantly overestimated whole-body LM and BMC (1,126 g and 382 g, respectively, p<0.01). The Bland-Altman analysis revealed a good agreement for whole-body FM and LM, but a poor agreement for BMC. The segmental FM percentage and LM were also highly correlated (r>0.9, p<0.001). However, sBIA significantly overestimated LM of the trunk and legs and underestimated the appendicular FM percentage. Verified by DEXA, sBIA provides reliable measures of whole-body LM, FM, and trunk FM in heavy smokers. A lesser degree of agreement was found for BMC, appendicular LM, and FM.

FDG-PET for the detection of infected vascular grafts.

Graft infection following prosthetic vascular reconstruction is an uncommon but severe complication. The clinical presentation is often subtle and non-specific and may occur long after surgery. While defining a prosthetic vascular graft infection can be difficult, early diagnosis and treatment are essential for the correct choice of treatment in order to prevent further complications as well as the high morbidity and mortality associated with repeat surgery and removal of infected grafts. False positive results may lead to unnecessary surgery while failure to diagnose graft infection may have life-threatening sequels. Scarce literature that is currently available regarding the role of fluorodeoxyglucose (FDG) imaging for assessment of vascular graft infection suggests that this modality may represent reliable non-invasive imaging modality in this specific clinical setting. Hybrid positron emission tomography (PET)/computed tomography (CT), combining CT with PET, increases the test specificity and thus improves diagnostic accuracy. The precise anatomic localization of increased FDG uptake provided by PET/CT enables accurate differentiation between graft and adjacent soft tissue infection leading to more accurate diagnosis and subsequent optimized therapeutic strategy.

Multimodality imaging of direct ureteric involvement in non-Hodgkin's lymphoma using PET/CT, CT urography and antegrade CT pyelography.

Positron emission tomography/computed tomography (PET/CT), CT urography (CTU) and antegrade CT pyelography (ACTP) findings of ureteric involvement in non-Hodgkin's lymphoma (NHL) are presented. PET/CT performed for restaging in a patient with a 2-year history of Stage 4 NHL showed increased 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) activity in a distended ureteric segment. CTU and ACTP, performed to further evaluate PET/CT findings, demonstrated diffuse, irregular and concentric thickening of the affected ureteric walls, accompanied by severe irregular narrowing of affected ureteric lumen. Tissue sampling using percutaneous CT-guided biopsy revealed NHL involvement of the ureter. To the best of our knowledge, this is the first report of PET/CT, CTU and ACTP findings of ureteric NHL.

CZT gamma camera for scintimammography.

A high performance prototype gamma camera based on the semiconductor radiation detector Cd(Zn)Te is described. The camera features high spatial resolution, high-energy resolution, a reduced dead space on the edge of the field of view, and a compact format. The camera performance was first examined by comparison of small field of view examinations with those from an Elscint SP6HR standard clinical gamma camera. The new camera was found to give equal or improved image quality. The camera was then used for a systematic phantom study of small lesions in a background as would be found in breast cancer imaging. In this study the camera was able to systematically detect smaller, deeper, and fainter lesions. The camera is presently being used in a clinical trial aimed to assess its value in scintimammography where previous limitations of image quality and detector size have restricted the use of the functional imaging techniques. Preliminary results from 40 patients show high sensitivity and specificity with respect to X-ray mammography and surgery.

The new technology of combined transmission and emission tomography in evaluation of endocrine neoplasms.

UNLABELLED: The clinical value of a novel technology of combined transmission and emission tomography (TET) was assessed in patients with endocrine tumors. METHODS: TET technology, which combines simultaneous acquisition of SPECT and CT images, using the same imaging device, allows correct fusion of images of both modalities. TET was performed on 27 patients with known or suspected endocrine tumors. The radiopharmaceuticals used for the emission part of the study were chosen according to the tumor type: (111)In-octreotide for patients with neuroendocrine tumors (n = 10), (99m)Tc-sestamibi for patients with primary hyperparathyroidism (n = 8), (131)I for patients with thyroid cancer (n = 4), and (123)I-metaiodobenzylguanidine and (75)Se-cholesterol for patients with adrenal masses (n = 3 and n = 2, respectively). The additional information provided by TET compared with scintigraphy was assessed for both image interpretation and clinical utility. RESULTS: TET did not provide any additional data in 16 patients (59%), including 5 patients with normal scintigraphy. In 11 patients (41%) with abnormal SPECT findings, TET improved image interpretation by providing a better anatomic localization of SPECT-detected lesions. It showed unsuspected bone involvement in 4 patients, it identified the organs involved and the relationship of the lesions to neighboring structures in 5 patients, and it differentiated physiologic uptake from tumor uptake in 2 patients. TET provided additional information of clinical value in 9 patients (33%). It assisted in better planning of surgery in 2 patients with neuroendocrine tumors and in 2 patients with ectopic parathyroid adenomas. It changed the treatment approach in 2 patients with neuroendocrine tumors and 1 patient with thyroid carcinoma, and it altered prognosis in 2 patients with thyroid malignancy. CONCLUSION: TET enhances the already unique role of nuclear medicine procedures in the assessment and management of patients with endocrine neoplasms.

The fusion of anatomic and physiologic imaging in the management of patients with cancer.

Imaging is of major clinical importance in the noninvasive evaluation and management of patients with cancer. Computed tomography (CT) and other anatomic imaging modalities, such as magnetic resonance imaging (MRI) or ultrasound, have a high diagnostic ability by visualizing lesion morphology and by providing the exact localization of malignant sites. Nuclear medicine provides information on the function and metabolism of cancer. Over the last decade, there have been numerous attempts to combine data obtained from different imaging techniques. Fused images of nuclear medicine and CT (or to a lesser extent, MRI) overcome the inherent limitations of both modalities. Valuable physiologic information benefits from a precise topographic localization. Coregistered data have been shown to be useful in the evaluation of patients with cancer at diagnosis and staging, in monitoring the response to treatment, and during follow up, for early detection of recurrence. Time-consuming and difficult realignment and computation for fusion of independent studies have, until now, limited the use of registration techniques to pilot studies performed in a small number of patients. The development of the new technology of single photon emission computed tomography/CT and positron emission tomography/CT that allows for combined functional and anatomic data acquisition has the potential to make fusion an everyday clinical tool.

Large cell lymphoma of bone presented by limp.

We present a rare case of anaplastic large cell lymphoma of the bone in the leg of a child. The patient initially presented with suspected osteomyelitis of the fibula and was treated by antibiotics without apparent success. Thereafter, an open biopsy of the lesion was performed and the correct diagnosis was established. This rare case demonstrates the difficulties that a treating physician meets in establishing the correct diagnosis in a child presenting with limping. A review of the pertinent literature is introduced.

Quantitative bone single-photon emission computed tomography for prediction of pain relief in metastatic bone disease treated with rhenium-186 etidronate.

PURPOSE: To calculate radiation doses of rhenium-186 ((186)Re) etidronate in painful bone metastases using quantitative bone single-photon emission computed tomography (SPECT) and to determine the threshold dose for predicting pain relief. We also wanted to determine whether technetium-99m ((99m)Tc) methylene diphosphonate (MDP) concentrations predict radiation doses of (186)Re etidronate in painful lesions. MATERIALS AND METHODS: Forty-eight patients with breast and prostate cancer were evaluated. Patients received therapeutic doses of (186)Re etidronate. The area under the pain over time curve (AUPC) was measured for 8 weeks after treatment. Response was calculated as the percentage of change in AUPC. Quantitative bone SPECT (QBS)-measured concentration of (186)Re etidronate was used for calculating radiation doses. Receiver operating characteristics curve analysis determined the radiation dose threshold that best separated responders from nonresponders. SPECT-measured concentration of (186)Re etidronate in the urinary bladder was correlated with its concentration in the voided urine. Concentration of (99m)Tc MDP was compared with radiation doses to painful metastases. RESULTS: The radiation dose threshold was 2.10 Gy. For a decrease of 50% in the AUPC, the positive predictive value (PPV) of this value was 75% and the negative predictive value (NPV) was 88%. For a decrease in pain of 33%, the PPV was 84% and the NPV was 81%. In prostate cancer patients only, the PPV was 81% and the NPV was 92%. The correlation between in vivo/in vitro measured urine concentration was 0.90. The correlation between (99m)Tc MDP concentration and radiation doses of (186)Re etidronate was 0.92. CONCLUSION: QBS-measured radiation doses of (186)Re etidronate in painful metastases are a good predictor of pain relief. Bone SPECT using (99m)Tc MDP predicts radiation doses delivered by (186)Re etidronate.

October 17, 2000 8:30-8:45. The New Technology of Combined Transmission and Emission F-18 FDG Tomography (FDG-TET) in the Diagnosis and Management of Cancer Patients.

The purpose of the study was to evaluate a new technology of simultaneous transmission and F-18 FDG emission tomography (FDG-TET) in tumor imaging and its impact on patient management.Emission and transmission devices were installed on the same gantry. 167 patients with histologically proven malignancy were evaluated at diagnosis or during follow up. Eight mCi of FDG were injected for PET and a low dose X-ray tube was used for CT. The FDG and CT were first interpreted independently, without knowledge of findings in other imaging modality. Subsequently fusion images were analyzed.FDG-TET changed the interpretation of PET or CT in 75 patients (45%). In 60 patients TET allowed for correct localization of lesions on the PET studies. In 15 patients, FDG uptake was found in sites of physiologic activity. In 12 patients lesions previously missed on CT were retrospectively identified. In 21 patients, TET detected 34 previously unknown sites of disease.FDG-TET changed the clinical management of 29 patients (17%). The stage of disease was changed in 9 patients. Early diagnosis of recurrence was made in 8 patients. Seven patients were referred for previously unplanned surgery. In 6 patients surgery was cancelled. Fifteen patients received additional chemo- or radiotherapy.Diagnosis of cancer on CT is based on a change in size or attenuation of a mass. PET shows the metabolic status of a lesion but lacks anatomical landmarks. FDG-TET improves the diagnostic accuracy in cancer and may have a significant impact on patient management.

Acute oliguric renal failure associated with unilateral renal embolism: a successful treatment with iloprost.

A 66-year-old woman presented with acute-onset rapid atrial fibrillation and right upper quadrant pain which had appeared 24 h prior to admission. The patient also manifested acute oliguric renal failure (serum creatinine 6.9 mg/dl). Selective renal angiography revealed total occlusion of the right renal artery with normal visualization of the left kidney vasculature. The patient was treated with intra-arterial urokinase and intravenous heparin, with no response. Intravenous administration of the prostacyclin analogue, iloprost, resulted in rapid resolution (within hours) of the oliguric acute renal failure, in spite of the continuing presence of a nonfunctioning right kidney. We conclude that the etiology of the acute renal insult in this patient is probably related to unilateral renal arterial embolization accompanied by arterial spasm of the unaffected kidney. The contralateral vasospasm can be reversed by iloprost, which then leads to a rapid recovery from acute renal failure. We are unaware of prior reports documenting the beneficial effect of iloprost in a clinical setting as described here.

Bone mineral density and turnover in children with systemic juvenile chronic arthritis.

OBJECTIVE: To assess bone mineral status in a group of children with systemic type juvenile chronic arthritis (JCA), which places them at high risk to develop osteoporosis. METHODS: Bone mineral density (BMD) was measured in 17 children aged 6-18 yrs (mean 14.9 +/- 4.5) with systemic JCA and in 18 matched controls by dual energy x-ray absorptiometry. Bone turnover was determined by quantitative bone scintigraphy, using quantitative single photon emission computed tomography based on skeletal uptake of methylene diphosphonates (MDP uptake). Serum concentrations of minerals, osteocalcin, and bone alkaline phosphatase were determined. Nutrient intake was assessed by a 24 hour dietary recall. RESULTS: Patients with systemic JCA who received corticosteroid therapy had significantly reduced BMD in both the lumbar spine (p < 0.05) and the femoral neck (p < 0.05) compared to controls, whereas BMD values of the non-steroid systemic JCA patients were not different from controls. Bone turnover measurement by MDP uptake showed no difference between patients with JCA and controls. Levels of calcium, phosphorus, alkaline phosphatase. and osteocalcin were within normal limits in all patients. CONCLUSION: Patients with systemic JCA receiving longterm steroid treatment may develop a significant decrease in BMD. The normal MDP uptake values together with normal osteocalcin levels that we observed in our patients indicate that their disease is not associated with enhancement of bone turnover rates. These observations might have therapeutic implications for prevention and management of osteoporosis in JCA.