scholarly journals Adipose-Derived Mesenchymal Stromal Cells Improve the Healing of Colonic Anastomoses Following High Dose of Irradiation Through Anti-Inflammatory and Angiogenic Processes

2017 ◽  
Vol 26 (12) ◽  
pp. 1919-1930 ◽  
Author(s):  
Dirk Van de putte ◽  
Christelle Demarquay ◽  
Elke Van Daele ◽  
Lara Moussa ◽  
Christian Vanhove ◽  
...  

Cancer patients treated with radiotherapy (RT) could develop severe late side effects that affect their quality of life. Long-term bowel complications after RT are mainly characterized by a transmural fibrosis that could lead to intestinal obstruction. Today, surgical resection is the only effective treatment. However, preoperative RT increases the risk of anastomotic leakage. In this study, we attempted to use mesenchymal stromal cells from adipose tissue (Ad-MSCs) to improve colonic anastomosis after high-dose irradiation. MSCs were isolated from the subcutaneous fat of rats, amplified in vitro, and characterized by flow cytometry. An animal model of late radiation side effects was induced by local irradiation of the colon. Colonic anastomosis was performed 4 wk after irradiation. It was analyzed another 4 wk later (i.e., 8 wk after irradiation). The Ad-MSC-treated group received injections several times before and after the surgical procedure. The therapeutic benefit of the Ad-MSC treatment was determined by colonoscopy and histology. The inflammatory process was investigated using Fluorine-182-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (18F-FDG-PET/CT) imaging and macrophage infiltrate analyses. Vascular density was assessed using immunohistochemistry. Results show that Ad-MSC treatment reduces ulcer size, increases mucosal vascular density, and limits hemorrhage. We also determined that 1 Ad-MSC injection limits the inflammatory process, as evaluated through 18F-FDG-PET-CT (at 4 wk), with a greater proportion of type 2 macrophages after iterative cell injections (8 wk). In conclusion, Ad-MSC injections promote anastomotic healing in an irradiated colon through enhanced vessel formation and reduced inflammation. This study also determined parameters that could be improved in further investigations.

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Tine N. Christensen ◽  
Seppo W. Langer ◽  
Gitte Persson ◽  
Klaus Richter Larsen ◽  
Annemarie G. Amtoft ◽  
...  

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.


Radiographics ◽  
2021 ◽  
Vol 41 (7) ◽  
pp. 2071-2089
Author(s):  
Jordan A. Lang ◽  
Sanjeev Bhalla ◽  
Dhakshinamoorthy Ganeshan ◽  
Gabriel J. Felder ◽  
Malak Itani

2012 ◽  
Vol 20 (1-2) ◽  
pp. 17-23
Author(s):  
Antonija Balenovic ◽  
Slobodanka Ostojic-Kolonic ◽  
Jasna Mihailovic

Lymphoproliferative diseases include a wide range of malignant diseases with various histological characteristics, clinical presentation and therapeutic possibilities. Reliable assessment of the spread of the disease and the knowledge of the biological characteristics of the tumor are the prerequisites of a successful patient treatment. In most patients with lymphoma, positron emission tomography (PET) with fluorodeoxyglucose ( 18 F-FDG) proved to be a useful imaging method which contributes to the assessment of the spread of the disease by identifying increased glycolysis in tumor cells. In the initial phases of the clinical implementation of FDG PET, the method was mostly used to determine the stage of the disease. At present, FDG PET is being increasingly used to assess the effects of therapy and to determine prognostic factor. Today, the treatment of lymphoma patients implies an individualized approach aiming at maximum disease control with the smallest possible risk of late side effects. Numerous prospective studies in patients with lymphoma have contributed to a better understanding of the metabolic changes. FDG PET performed after only 1 or 2 cycles of chemotherapy can assess tumor sensitivity to the therapy. Thus, the long-term response to therapy can be predicted at the very early stage of treatment. Many studies are being conducted in order to assess the potential usefulness of this prognostic information so that the therapy protocols can be altered and the long term administration of drugs that will not result in a sustained response be stopped. It is expected that this approach might result in avoiding late side effects and toxicity. The degree of metabolic activity assessed by interim FDG PET at the very beginning of chemotherapy administration serves as a biomarker of tumor responsiveness to chemotherapy. Because of that, more precise criteria are needed to answer the question ?what is a positive interim FDG PET finding?. Our understanding of lymphoproliferative diseases and the effects which some therapeutic procedures have on the metabolism of tissue contribute significantly to the accurate interpretation of FDG-PET/CT findings. For successful utilization of FDG PET/CT, a multidisciplinary team which includes hematology, radiation oncology, diagnostic radiology and nuclear medicine specialists is necessary.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3414-3414
Author(s):  
Douglas A. Stewart ◽  
Peter Duggan ◽  
Nizar J Bahlis ◽  
Andrew Daly ◽  
Michelle Geddes ◽  
...  

Abstract Abstract 3414 Poster Board III-302 Purpose Approximately 50-55% of patients (pts) with stage 3-4 DLBCL and elevated serum LDH achieve long-term event-free survival (EFS) following R-CHOP chemotherapy. A prospective, multicentre, phase II clinical trial was designed to evaluate the use of high dose sequential therapy with RDICEP then RBEAM/ASCT for such pts who have positive interim restaging FDG-PET/CT scans after 2 cycles of RCHOP. Patients and Methods Pts were eligible if they were HIV-, 18-65 years of age, and had stage 3-4 DLBCL with elevated serum LDH. An FDG-PET/CT scan was performed 10-15 days following the second cycle of R-CHOP. Pts with negative interim restaging PET scans completed 4 further cycles of RCHOP, whereas pts with positive PET scans (more than 1 site with uptake more intense than background liver) received one cycle of RDICEP (Rituximab 375mg/m2 day 1 and 8, C 1.75g/m2 d2-4, E 350mg/m2 d2-4 P 35mg/m2 d2-4, G-CSF d15-21 and autologous blood stem cell collection by apheresis d21or 22) followed by one cycle of RBEAM/ASCT (Rituximab 375mg/m2 day -6 and +14, BCNU 300mg/m2 d-6, E 200mg/m2 d-5to-2, A 400mg/m2 d-5to-2, M 140mg/m2 d-1). Results Of the 36 pts who have been accrued from 5/2007-7/2009, 33 pts have undergone interim PET/CT restaging following 2 cycles RCHOP. All 33 pts had IPI scores 3-5, the median age was 55 years (range19-65) with 7 pts (21%) older than 60 years, 20 (61%) had ECOG status 2-4, 28 (85%) had stage 4, 22 (67%) >1 extranodal site. At a median follow-up of 12mo, the 1 year OS and EFS rates for all 33 pts are 82% (95%CI = 66-98%) and 76% (95%CI = 58-83%), respectively. Interim restaging PET/CT was positive for 16 pts and negative for 17 pts. The EFS rates for PET+ and PET- pts are 78% (95%CI = 57-100%) and 66% (95%CI = 36-99%), respectively (logrank p=0.97). To date, 4 pts have died, 3 from lymphoma at 6, 10, 11 months post-RCHOP1, and 1 from sepsis and necrotic bowel on day 5 post-ASCT. Conclusions Preliminary results of this phase II study are encouraging, and suggest that high dose induction therapy with RDICEP and RBEAM/ASCT might improve EFS for poor prognosis DLBCL with positive interim restaging PET/CT. Accrual will continue to target ≥ 35 PET+ and ≥35 PET- pts. Disclosures Stewart: Hoffmann La Roche: Advisory Board, Honoraria, Research Funding. Off Label Use: Rituximab with High Dose Chemotherapy and Autologous Stem Cell Transplantation for DLBCL. Bence-Bruckler:Hoffmann La Roche: Honoraria, Research Funding.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4128-4128
Author(s):  
Takafumi Koyama ◽  
Kan-ichi Iwama ◽  
Masayuki Yamakura ◽  
Masami Takeuchi ◽  
Kosei Matsue

Abstract Abstract 4128 Background; Intravascular large B-cell lymphoma (IVL) is characterised by proliferation of lymphoma cells only in the lumina of small vessels in various organs, a high incidence of neurological symptoms associated with central nervous system (CNS) involvement has been reported, but its association with peripheral nerve involvement (neurolymphomatosis, NL) has rarely described previously. We recently encountered 2 patients with IVL who relapsed as a NL shortly after the completion of chemotherapy. Because both NL and IVL is extremely rare clinical condition, its occurrence led us to explore the predilection of NL in patients with IVL. Method; We reviewed the medical records of patients with diagnosis of IVL over the past 4 years. Diagnosis of IVL was made by the definition of WHO classification of hematopoietic tumours. The diagnosis of NL required: 1) clinical symptoms and neurological findings related to the peripheral neuropathy of cranial or spinal nerves; and 2) histological confirmation of lymphoma cells within the peripheral nerve, nerve root/plexus, or cranial nerve; or 3) CT/MRI demonstration of nerve enhancement and/or enlargement of peripheral nerve(s) that were also demonstrated by accumulation of FDG by FDG-PET/CT. Results; We identified 5 patients of NL among 12 IVL patients. NL occurred as an initial manifestation in one patient and relapse disease in the remaining 4 patients. All 5 patients had neurologic symptoms corresponding to the NL of cranial and/or peripheral nerve. Comparison of clinical and laboratory features could not disclose the difference in IVL patients with or without NL in terms of presence or absence of haemophagocytosis, bone marrow infiltration, neurological symptoms, cytopenia, soluble interleukin 2 receptor level, and skin lesions. All of the 4 patients with NL as a relapse disease occurred during or shortly after R-CHOP chemotherapy. Brain MRI and whole-spine MRI with thin sliced coronal image could reveal the nerve infiltration by gadolinium enhancement and enlargement of nerve structure, it might not always sensitive enough for its detection because of patchy distribution and small lesion. In contrast, FDG-PET/CT successfully revealed the involved lesions as a linear or nodular FDG-uptake which was anatomically correlated with cranial nerves, nerve plexus, spinal nerve root, or peripheral nerves in all of the 5 cases. In addition FDG-PET/CT was useful for evaluating the therapeutic responses. Treatment with high-dose methotrexate with or without systemic chemotherapy appeared beneficial, however one of the 5 patient needed additional localized irradiation for relapse disease. Conclusion; Considering the extreme rarity of both IVL and NL, there may be a strong predilection of NL in patients with IVL. As IVL has a high frequency of CNS involvement, it may also have a high frequency of peripheral nerve involvement. Early recognition and familiarity of the disease and prompt institution of aggressive chemotherapy incorporating high-dose MTX with or without involved field radiation might be useful, although further studies are still warranted. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 47 (6) ◽  
pp. 1552-1563 ◽  
Author(s):  
G. L. Poli ◽  
L. Torres ◽  
M. Coca ◽  
M. Veselinovic ◽  
M. Lassmann ◽  
...  

Abstract Purpose The International Atomic Energy Agency (IAEA) decided to initiate a survey to evaluate the current status of the practice of paediatric nuclear medicine worldwide, with the focus mainly on low and middle-income countries specifically in Latin America, Eastern Europe, Africa and Asia. This investigation sought to determine if the practice in paediatric nuclear medicine in these countries differed from that indicated by the survey of the Nuclear Medicine Global Initiative (NMGI) and if nuclear medicine practitioners were following established paediatric nuclear medicine guidelines. Methods A total of 133 institutes took part in the survey from 62 different IAEA member states within Africa (29), Asia (39), Europe (29) and Latin America (36). The four most frequent conventional (single-photon) nuclear medicine procedures were 99mTc labelled MDP, DSMA, MAG3 and pertechnetate thyroid scans. In addition, 46 centres provided data on FDG PET/CT, including exposure data for the CT component. Nearly half of the sites (48%) perform less than 200 paediatric nuclear medicine studies per year, while 11% perform more than 1000 such studies per year. Results Administered activities largely exceeded the recommendations for most of the sites for DMSA, MAG3 and pertechnetate, while compliance with international standards was somehow better for MDP studies. For FDG PET, the results were more uniform than for conventional nuclear medicine procedures. However, the use of CT in PET/CT for paediatric nuclear medicine revealed a high variability and, in some cases, high, dose-length product (DLP) values. This observation indicates that further attention is warranted for optimizing clinical practice in FDG PET/CT. Conclusions Overall, in most parts of the world, efforts have been undertaken to comply either with the EANM dosage card or with the North American Consensus Guidelines. However, variability in the practice of paediatric nuclear medicine still exists. The results of this survey provide valuable recommendations for a path towards global standardization of determining the amount of activity to be administered to children undergoing nuclear medicine procedures.


Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 879
Author(s):  
Natasja Justesen ◽  
Michael Hansen ◽  
Mads Jensen ◽  
Oliver Klefter ◽  
Jane Brittain ◽  
...  

: Giant cell arteritis (GCA) is the most common form of large vessel vasculitis. GCA is a medical and ophthalmological emergency, and rapid diagnosis and treatment with high-dose corticosteroids is critical in order to reduce the risk of stroke and sudden irreversible loss of vision. GCA can be difficult to diagnose due to insidious and unspecific symptoms—especially if typical superficial extracranial arteries are not affected. In these cases, verification of clinical diagnosis using temporal artery biopsy is not possible. This example illustrates the diagnostic value of hybrid imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT), and the limitations of the temporal artery biopsy in bilateral vertebral GCA, causing transient ischemic attack in the visual cortex. In addition it indicates that inflammation in the artery wall can be visualized on 2-[18F]FDG PET/CT despite long term and ongoing high dose glucocorticoid treatment.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
C. Pisani ◽  
L. Vigna ◽  
F. Mastroleo ◽  
G. Loi ◽  
V. Amisano ◽  
...  

Abstract Objective To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). Methods and materials From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, “Marginal recurrence” or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. Results We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6–28.9 cc), while the mean MTVrec was 4.3 cc (1.1–12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61–91%) and 4 recurrences were marginal to MTVpre (1–33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5–69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). Conclusion Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.


2019 ◽  
Vol 20 (5) ◽  
pp. 1049 ◽  
Author(s):  
Francesca Rossi ◽  
Chiara Tortora ◽  
Giuseppe Palumbo ◽  
Francesca Punzo ◽  
Maura Argenziano ◽  
...  

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction, with a complex and unclear pathogenesis. The impaired immunosuppressive capacity of mesenchymal stromal cells in ITP patients (ITP-MSCs) might play a role in the development of the disease. Correcting the MSC defects could represent an alternative therapeutic approach for ITP. High-dose dexamethasone (HD-Dexa) is the mainstay of the ITP therapeutic regimen, although it has several side effects. We previously demonstrated a role for cannabinoid receptor 2 (CB2) as a mediator of anti-inflammatory and immunoregulatory properties of human MSCs. We analyzed the effects of CB2 stimulation, with the selective agonist JWH-133, and of Dexa alone and in combination on ITP-MSC survival and immunosuppressive capacity. We provided new insights into the pathogenesis of ITP, suggesting CB2 receptor involvement in the impairment of ITP-MSC function and confirming MSCs as responsive cellular targets of Dexa. Moreover, we demonstrated that CB2 stimulation and Dexa attenuate apoptosis, via Bcl2 signaling, and restore the immune-modulatory properties of MSCs derived from ITP patients. These data suggest the possibility of using Dexa in combination with JWH-133 in ITP, reducing its dose and side effects but maintaining its therapeutic benefits.


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