ABSTRACT
BACKGROUND: Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. METHODS: One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. RESULTS: The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. CONCLUSION: Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. TRIAL REGISTRATION: retrospectively registered.
Subject(s)
Prostatic Neoplasms , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Testis , Humans , Male , Prostatic Neoplasms/radiotherapy , Retrospective Studies , Testis/radiation effects , Middle Aged , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Planning, Computer-Assisted/methods , Organs at Risk/radiation effects , Aged , Adult , Radiation Injuries/etiology , Fertility/radiation effectsABSTRACT
Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If single fraction sessions are routinely used for intracranial targets, their utilization for mobile extracranial lesions is a source of debate and apprehension. Single session treatments improve patient comfort, provide a medico-economic benefit, and have proven useful in the context of the SARS-CoV 2 pandemic. However, both technical and radiobiological uncertainties remain. Experience from intracranial radiosurgery has shown that the size of the target, its proximity to organs at risk, tumor histology, and the volume of normal tissue irradiated are all determining factors in the choice of fractionation. The literature on the use of single fraction for extracranial sites is still scarce. Only primary and secondary pulmonary tumors have been evaluated in prospective randomized trials, allowing the integration of these fractionation schemes in daily practice, for highly selected cases and in trained teams. The level of evidence for the other organs is mainly based on dose escalation or retrospective trials and calls for caution, with further studies being needed before routine use in clinical practice.
ABSTRACT
PURPOSE: Interstitial brachytherapy is indicated as part of a conservative strategy for children with bladder and/or prostate rhabdomyosarcoma (RMS), providing high local control probability with acceptable functional results. Vaginal and/or rectal complications were however reported, due to the close proximity to the implanted volume. We investigated the dosimetric impact of a vaginal spacer in terms of rectal and vaginal doses. METHODS AND PATIENTS: Medical records of 12 consecutive female patients with bladder neck RMS, median age 32 months (range: 1.3-6 years), were reviewed. Five patients were treated prior to 2017 without a vaginal spacer and seven patients treated after 2017 had their brachytherapy delivered with a vaginal spacer placed at time of implant. RESULTS: Minimal doses delivered to the most exposed 2cm3, 1cm3, and 0.5cm3 of the rectum were all statistically significantly lower among patients treated with a vaginal spacer, as compared to those treated without a spacer. Median rectal D2cm3 was 22GyEQD2 versus 38GyEQD2 (P=0.02), D1cm3 was 29GyEQD2 versus 51GyEQD2 (P=0.013), and D0.5cm3 was 32GyEQD2 versus 61GyEQD2 (P=0.017), with and without the vaginal spacer, respectively. The posterior vaginal wall D0.5cm3 dose was also significantly decreased, with median D0.5cm3 of 92GyEQD2 versus 54GyEQD2 (P<0.0001), with and without the spacer, respectively. Acute tolerance was excellent in all patients, with no need for replanning and no acute complication. CONCLUSIONS: The use of vaginal spacers in brachytherapy of female pediatric patients with bladder neck RMS resulted in significantly decreased doses to the rectum and the posterior vaginal wall. Though the clinical impact of such dose reduction remains undemonstrated, routine utilization of a vaginal spacer could be a method to decrease long-term morbidity in these patients.
Subject(s)
Brachytherapy , Pelvic Neoplasms , Rhabdomyosarcoma , Urinary Bladder Neoplasms , Brachytherapy/adverse effects , Brachytherapy/methods , Child , Child, Preschool , Female , Humans , Male , Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Rectum , Rhabdomyosarcoma/radiotherapy , Tomography, X-Ray Computed , Urinary BladderABSTRACT
Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.
Subject(s)
Sarcoma/radiotherapy , Soft Tissue Neoplasms/radiotherapy , Combined Modality Therapy , Extremities , Humans , Postoperative Period , Preoperative Period , Sarcoma/surgery , Soft Tissue Neoplasms/surgeryABSTRACT
The prognosis of patients with rectal cancer and synchronous liver metastasis has improved thanks to chemotherapy and rectal and liver surgery progresses. However, there is no consensus about optimal management and practices remain heterogeneous. A curative treatment may be considered for 20 to 30% of patients with complete resection of metastasis and primary tumor after induction chemotherapy. To this end, a primary optimal evaluation by a multidisciplinary board including hepatic and colorectal surgeons is crucial. The therapeutic strategy associates chemotherapy, radiotherapy, hepatic and rectal surgery. The most threatening site guides the sequence of treatments. If hepatic resectability is uncertain, a "liver first" strategy associating induction chemotherapy and hepatic surgery is preferred. In non-resectable metastatic cases, chemotherapies with targeted therapies might lead to secondary resection for 30% of patients (conversion). This has changed our practice and triggers reconsidering resectability after chemotherapy. When metastases remain non-resectable, additional treatment focusing on primary tumor should control pelvic symptoms otherwise hardly impacting quality of life. Rectal surgery, short-course radiotherapy (5×5Gy), conformational long-course chemoradiotherapy or intensity-modulated radiation therapy with dose escalation are options discussed in this review.
Subject(s)
Liver Neoplasms/secondary , Liver Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Combined Modality Therapy , HumansABSTRACT
BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in airway hyperresponsiveness (AHR) and inflammation. However, the role of nociceptin at modulating the inflammatory immune microenvironment in asthma is still unclear. OBJECTIVE: To understand the role of N/OFQ in the regulation of a Th2-like environment, we used a conventional murine model of AHR. METHODS: Balb/c and CD1 mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. A group of Balb/c mice were killed at 7 and 14 days from the first sensitization for the inflammatory profile evaluation while a group of Balb/c and CD1 mice were aerosol-challenged from day 21 to 23 with OVA and killed 24 h later for functional evaluations. RESULTS: In OVA-sensitized mice, N/OFQ significantly reduced IL-4+ CD4+ T cells in lymph nodes (LN) and IL-13 in the lungs, while it induced IFN-γ increase in the lung. The efflux of dendritic cells (DCs) to the mediastinic LN and into the lung of OVA-sensitized mice was reduced in N/OFQ-treated and sensitized mice. N/OFQ reduced the expression of CD80 on DCs, indicating its ability to modulate the activation of DCs. In a less prone Th2-like environment mice strain, such as CD1 mice, N/OFQ did not modify lung resistances as observed in BALB/c mice. Finally, spectroscopic data showed the N/OFQ was able to interact onto the membrane of DCs obtained from Balb/c rather than CD1 mice, indicating its ability to modulate AHR in a Th2-like environment with a direct activity on DCs. CONCLUSIONS AND CLINICAL RELEVANCE: Our data confirmed the capability of N/OFQ to modulate the immune microenvironment in the lung of Th2-biased, OVA-sensitized Balb/c mice, suggesting N/OFQ-NOP axis as a novel pharmacological tool to modulate the inflammatory immune microenvironment in asthma.
Subject(s)
Cellular Microenvironment/immunology , Opioid Peptides/metabolism , Respiratory Hypersensitivity/immunology , Respiratory Hypersensitivity/metabolism , Animals , Apoptosis/drug effects , Biomarkers , Cellular Microenvironment/drug effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Disease Models, Animal , Female , Immunization , Immunophenotyping , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Mice , Mice, Inbred BALB C , Opioid Peptides/pharmacology , Ovalbumin/immunology , Phenotype , Respiratory Hypersensitivity/drug therapy , Respiratory Hypersensitivity/pathology , Th2 Cells/immunology , Th2 Cells/metabolism , NociceptinABSTRACT
BACKGROUND AND PURPOSE: Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. EXPERIMENTAL APPROACH: BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. KEY RESULTS: S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper-reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T-cells harvested from S1P-treated mice presented all the features elicited by S1P in the lung. CONCLUSIONS AND IMPLICATIONS: S1P triggers a cascade of events that sequentially involves T-cells, IgE and mast cells reproducing several asthma-like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently-used drugs as well as in the development of new therapeutic approaches for asthma-like diseases.
Subject(s)
Bronchial Hyperreactivity/immunology , Lysophospholipids/immunology , Pneumonia/immunology , Sphingosine/analogs & derivatives , Animals , Bronchial Hyperreactivity/blood , CD4-Positive T-Lymphocytes/immunology , Immunoglobulin E/blood , Interleukin-13/immunology , Interleukin-4/immunology , Mast Cells/immunology , Mice, Inbred BALB C , Mice, Knockout , Mice, Nude , Pneumonia/blood , Prostaglandin D2/blood , Sphingosine/immunologyABSTRACT
PURPOSE: The aim of this study was to evaluate the efficacy of endovascular treatment of isolated iliac artery aneurysms (IIAA) and compare our data with those reported in the literature. MATERIALS AND METHODS: From May 2005 to December 2010, 32 patients (31 men and one woman; mean age 73±12 years) with a total of 40 IIAAs underwent endovascular treatment at our institute. We evaluated technical success, long-term patency, early and late complications and overall mortality. RESULTS: At a median follow-up of 36 months, we achieved a technical success of 100%, a primary patency of 95% and a secondary patency of 100%, with complete exclusion of the aneurysm in 84.6% of cases. In 12.8% of cases, there was a reduction in aneurysm sac volume, with an incidence of type II endoleak of 12.8%. Overall survival at 1, 2, 3, and 6 years was 96.8%, 84.2%, 66.6% and 64%, respectively. CONCLUSIONS: Our study documents the effectiveness of endovascular treatment of iliac aneurysms, which has become the first-choice treatment at our institute. This finding is consistent with the most recent literature and confirms the safety and long-term patency of stent-graft placement.
Subject(s)
Endovascular Procedures , Iliac Aneurysm/surgery , Aged , Angiography , Blood Vessel Prosthesis Implantation , Female , Follow-Up Studies , Humans , Iliac Aneurysm/diagnostic imaging , Iliac Aneurysm/mortality , Male , Radiography, Interventional , Stents , Survival Rate , Tomography, X-Ray Computed , Treatment Outcome , Vascular PatencyABSTRACT
PURPOSE: We sought to assess the effectiveness of endovascular abdominal aortic aneurysm (AAA) repair (EVAR) through a retrospective review of 6 years' experience at a single centre. MATERIALS AND METHODS: From April 2005 to August 2011, 222 patients affected by abdominal aortic aneurysms underwent EVAR. We evaluated primary technical success, postprocedural mortality, intraprocedural and postprocedural complications with contrast-enhanced computed tomography (CT) and contrast-enhanced ultrasound (US) follow-up at 1, 6 and 12 months and annually thereafter. RESULTS: The procedures were elective in 75.7% and urgent due to symptomatic or ruptured aneurysm in 24.3%. Technical success was 98.6%; three patients (1.4%) required conversion to open surgery. Postoperative mortality rate was 24% for urgent and 2.3% for elective procedures. During a mean follow-up period of 29.6 months, no cases of stent-graft migration were observed; the overall incidence of endoleaks was 27% (60/222) and comprised four type I (1.8%) and one type III (0.45%), all treated by stent-graft extension, and 55 type 2 (24.8%), eight of which (14.5%) were treated by percutaneous injection of thrombin. In 10/222 cases (4.5%), thrombotic occlusion of the iliac extension was detected, which was successfully treated by transcatheter intra-arterial thrombolysis. One patient developed stent-graft infection requiring surgical explantation. Average hospital stay was 4 days, and average time in intensive care was 2 days. CONCLUSIONS: Consistent with the literature data, our study confirms the safety and long-term efficacy of EVAR for treating AAA.
Subject(s)
Aneurysm, Ruptured/surgery , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/methods , Aged , Aged, 80 and over , Angiography , Aortic Aneurysm, Abdominal/diagnostic imaging , Comorbidity , Contrast Media , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , Treatment Outcome , UltrasonographyABSTRACT
PURPOSE: We evaluated the effectiveness of endovascular treatment with percutaneous transluminal balloon angioplasty (PTA)/stenting of transplanted renal artery stenosis (TRAS). MATERIALS AND METHODS: Between January 2005 and December 2010, 17 patients (4 women, 13 men; mean age 60.9 years) with TRAS underwent PTA/stenting. The parameters analysed were: technical success, pre- and post-treatment serum creatinine (SCr) and blood pressure (BP), average number of antihypertensive drugs administered before and after treatment and vessel patency on colour Doppler ultrasound (CDUS) at 1, 3, 6 and 12 months and once a year thereafter. RESULTS: Technical success was 100%. During a mean follow-up of 28.3±18.7 months, there was a statistically significant reduction in SCr and BP values. In 18 % of cases, moderate (<60%) restenosis was observed on CDUS without renal failure and not requiring new treatment. There was a reduction in antihypertensive drugs from an average of 3.5±0.5 to 1.5±0.5. CONCLUSIONS: Consistent with the literature data, our experience shows that endovascular treatment with PTA/stenting is a safe and effective option for managing TRAS and can thus be considered the method of choice.
Subject(s)
Angioplasty , Kidney Transplantation , Postoperative Complications/therapy , Renal Artery Obstruction/therapy , Stents , Adult , Aged , Angiography , Antihypertensive Agents/administration & dosage , Contrast Media , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Renal Artery Obstruction/diagnostic imaging , Treatment Outcome , Triiodobenzoic AcidsABSTRACT
PURPOSE: Popliteal artery aneurysms (PAAs) are a rare condition with an incidence <0.1%. The objective of this study was to evaluate the effectiveness of endovascular treatment of PAA with a covered stent-graft. MATERIALS AND METHODS: Between January 2009 and July 2010, ten patients (nine men and one woman, mean age 69 ± 12 years) with PAA were treated by endovascular placement of a heparin-coated stent-graft. All procedures were evaluated in terms of technical success, patency at 1, 6 and 12 months as assessed by colour Doppler ultrasound, complications, procedure duration and length of postoperative hospital stay. RESULTS: We obtained 100% technical success, with no peri- or postprocedural complications. Average duration of the procedure was 40 min, and mean hospital stay was 3 days. Primary and secondary patency rates at 1, 6 and 12 months were 100% and 100%, 90% and 100%, and 90% and 100%, respectively. Only one case of endoleak occurred. DISCUSSION: In keeping with the literature, our study demonstrates the effectiveness of endovascular repair of PAA, with short- and mid-term patency rates comparable to those of open surgery. Larger series and longer follow-up periods are needed to confirm these preliminary results.
Subject(s)
Aneurysm/surgery , Blood Vessel Prosthesis Implantation , Popliteal Artery , Stents , Aged , Aneurysm/diagnostic imaging , Angiography , Female , Humans , Length of Stay/statistics & numerical data , Male , Operative Time , Postoperative Complications/diagnostic imaging , Treatment Outcome , Ultrasonography, Doppler, Color , Vascular PatencyABSTRACT
PURPOSE: The authors compared the immediate, mid-term and long-term effectiveness of cryoplasty and conventional angioplasty for treating stenotic-occlusive lesions of the femoropopliteal arteries in diabetic patients. MATERIALS AND METHODS: From October 2006 to November 2009, 48 patients with non-insulin-dependent diabetes mellitus (DM) and an indication for percutaneous revascularisation of the femoropopliteal arteries were randomly assigned to treatment with angioplasty or cryoplasty. The following parameters were analysed and compared between the two groups: immediate technical success (residual stenosis <30%) and distal run-off as assessed on postprocedural angiography, and degree of restenosis and distal run-off at 6 and 12 months, as assessed with either colour Doppler ultrasound (CDUS) or digital subtraction angiography (DSA). RESULTS: Treatment with angioplasty revealed a significant superiority in procedural technical success (p=0.04), a significant reduction in the degree of restenosis at 6 months (p=0.02) and a significant increase in the distal run-off at 6 (p=0.005) and 12 (p=0.01) months. CONCLUSIONS: Conventional angioplasty is more effective than cryoplasty for treating stenotic-occlusive lesions of the femoropopliteal arteries in diabetic patients and provides better immediate, mid-term and long-term results.
Subject(s)
Angioplasty/methods , Arterial Occlusive Diseases/therapy , Cryotherapy/methods , Diabetes Mellitus, Type 2/complications , Femoral Artery/pathology , Leg/blood supply , Popliteal Artery/pathology , Aged , Angiography, Digital Subtraction , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , Female , Humans , Male , Treatment Outcome , Ultrasonography, Doppler, ColorABSTRACT
BACKGROUND: Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly belonging to the Th1, Th17 and Th22 lineage. OBJECTIVE: To identify whether treatment with the anti-tumour-necrosis-factor antagonist etanercept is able to induce significant modulations in transcription factor and cytokine mRNA gene expressions related to the different T cell immune response polarization (Th1, Th2, Th17 and regulatory T cells, Treg and to correlate them with clinical response. METHODS: The study population included 19 psoriasis patients treated with etanercept and 19 healthy subjects. Blood samples were collected at baseline and every 4 weeks during treatment. Taqman quantitative real-time polymerase chain reaction was applied to analyse the expression of: Stat-4, T-bet, IL-12p35 and IFN-γ (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, RORγt, IL-23p19 (Th17-related); Foxp3, IL-2 (Treg-related). Flow cytometry was applied to analyse CD4+CD25+(bright)Foxp3+ cells in peripheral blood. RESULTS: Upregulation of Th1 and Th17 and downregulation of Treg subsets was found at baseline. The response to etanercept could be associated with a significant reversal of the Th1/Th17 activation, and a concomitant upregulation of Th2 and Treg subsets. CONCLUSION: Our data may contribute to a better understanding of the mechanisms underlying the achievement of clinical response in psoriasis and could be helpful for the identification of early predictive markers of response.
Subject(s)
Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Psoriasis/drug therapy , Receptors, Tumor Necrosis Factor/therapeutic use , T-Lymphocytes, Regulatory/metabolism , Th1 Cells/metabolism , Th17 Cells/metabolism , Th2 Cells/metabolism , Adult , Case-Control Studies , Cytokines/genetics , Etanercept , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Psoriasis/immunology , RNA, Messenger/metabolism , Transcription Factors/metabolism , Treatment OutcomeABSTRACT
Evaluation of BK virus replication is a fundamental tool in the monitoring of renal transplant recipients. Herein, we investigated the role of urine VP1 messenger RNA (mRNA) quantification and combined measurement of serum DNA and urine VP1 mRNA in 428 kidney allograft recipients. BK viremia and viruria were detected in 24 (5.6%) and 54 (12.6%) patients, respectively. A diagnosis of BKV-associated nephropathy (BKVAN) was established in 2 patients, both within the first year posttransplantation. Based on urine VP1 mRNA measurement, BKV replication was observed in 10 (2.1%) patients, 2 of whom displayed BKVAN. Urine VP1 mRNA was detected in all cases in association with viremia except 5 and in all cases with viruria. No difference among VP1 mRNA levels was noted between the 2 BKVAN patients and the highest values in patients without BKVAN. The urine VP1 mRNA result by analysis using the operating characteristics was not superior to viremia, despite the improvement obtained with the combined measurement of viremia (cut-off, 16,000 copies/mL) and urine VP1 mRNA (>10,000 copies/10(3) cells). In conclusion, VP1 mRNA measurements may complement viremia and viruria to monitor BKV replication, although its use is limited by its technical complexity in comparison with DNA detection.
Subject(s)
BK Virus/genetics , Capsid Proteins/genetics , DNA, Viral/blood , Kidney Transplantation/adverse effects , Polyomavirus Infections/diagnosis , RNA, Messenger/urine , Virus Replication , Aged , BK Virus/pathogenicity , Biomarkers/blood , Biomarkers/urine , Female , Humans , Italy , Male , Middle Aged , Polyomavirus Infections/virology , Predictive Value of Tests , Prospective Studies , ROC Curve , Time Factors , Treatment Outcome , Viral LoadABSTRACT
In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10(4) copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10(5) ± 2.4 × 10(5) copies/ml versus 7.9 × 10(3) ± 1.4 × 10(4) (P=.02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease.
Subject(s)
Cytomegalovirus Infections/virology , Cytomegalovirus/immunology , Immunity, Cellular/drug effects , Lung Transplantation/immunology , Adult , Aged , Antiviral Agents/therapeutic use , Bronchoalveolar Lavage Fluid/virology , Chi-Square Distribution , Cytomegalovirus/genetics , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/prevention & control , DNA, Viral/blood , DNA, Viral/isolation & purification , Enzyme-Linked Immunospot Assay , Female , Humans , Immunosuppressive Agents/therapeutic use , Italy , Male , Middle Aged , Monitoring, Immunologic/methods , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Viral LoadABSTRACT
AIM: The aim of this study was to report most recent data regarding the occurrence of influenza A virus H1N1v in the lower respiratory tract from a cohort of hospitalized adult patients during the winter season 2009/2010 and investigated the main clinical features and outcomes. METHODS: A total of 130 consecutive BAL specimens (collected from October 2009-March 2010) of 101 patients were retrospectively analyzed for influenza A virus H1N1v positivity using a commercial kit. RESULTS: Overall, 19/130 (14.6%) BAL specimens from 17/101 (16.8%) patients were positive for the novel influenza A H1N1v virus. H1N1v resulted significantly more prevalent in immunocompetent subjects. As regards clinical features, H1N1v resulted more prevalent in respiratory insufficiency or acute respiratory illness. Thirteen patients died during the analytic period; three of them (23.1%) resulted positive to H1N1v but no direct association has been made. CONCLUSION: Our cohort study of influenza A H1N1v detection in BAL from hospitalized adult patients confirms the overall moderate clinical impact of this virus, as reported in most reports worldwide. It remains to be evaluated the role of reassortment with influenza virus strains circulating in the winter season 2010/2011 and its potential pathogenicity.
Subject(s)
Bronchoalveolar Lavage , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/virology , Seasons , Adult , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/classification , Influenza, Human/epidemiology , Italy/epidemiology , Lung Transplantation/statistics & numerical data , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/virology , Retrospective Studies , Young AdultABSTRACT
The newly discovered polyomaviruses KI and WU (KIV and WUV) were isolated from secretions of patients with respiratory symptoms as well as in blood, spleen, lymphoid tissues, and stools, especially in immunocompromised conditions. The aim of this work was to evaluate the prevalence of KIV and WUV in bronchoalveolar lavage (BAL) from lung transplant recipients. We also examined potential correlations between these viruses and occurrences of pneumonia, acute respiratory insufficiency, or other acute respiratory conditions and acute rejection episodes. Discharge diagnosis was based on the International Classification of Diseases-Italian version 2002, based on the 9th-revision clinical modification. A rejection episode was diagnosed by transbronchial lung biopsy in accordance with the 2007 International Society for Heart and Lung Transplantation Working Formulation. Overall, we analyzed 53 BALs obtained from 24 transplant recipients. Positive polymerase chain reaction results were observed in 6 samples (11.3%) from 6 patients (25%), versus 7 samples (13.2%) from 7 patients (29.2%) for KIV and WUV, respectively. Regarding the diagnosis of pneumonia, the prevalence was 22.2% and 33.3% for KIV and WUV, respectively. In cases of acute respiratory insufficiency or other acute respiratory conditions, 2 out of 9 samples were positive for KIV (22.2%) and 4 out of 9 for WUV (44.4%). An Acute rejection episode (ARE) was diagnosed in 7 instances among 6 lung transplant patients: The corresponding BAL specimens showed positive results for KIV in 3 out of 7 (42.8%) cases with ARE vs 3 out of 46 (6.5%) without an ARE (P < .05), and for WUV in 3 out of 7 (42.8%) vs 4 out of 46 (8.7%) (P < .05), respectively. Although the small number of specimens limits the statistical analysis, our results showed a higher prevalence of WUV compared with KIV. The compromised pulmonary environment in the lung allograft may cause reactivation of these viruses. Their roles in this context need to be further evaluated.
Subject(s)
Lung Transplantation , Polyomavirus Infections/epidemiology , Polyomavirus/isolation & purification , Adult , Aged , Bronchoalveolar Lavage Fluid/virology , Female , Graft Rejection/epidemiology , Graft Rejection/virology , Humans , Immunosuppressive Agents/therapeutic use , Lung Transplantation/adverse effects , Lung Transplantation/immunology , Male , Middle Aged , Opportunistic Infections/prevention & control , Opportunistic Infections/virology , Polyomavirus/genetics , Postoperative Complications/virology , Prevalence , Respiratory Tract Infections/virology , Retrospective Studies , Viral Load , Young AdultABSTRACT
AIM: The recently described polyomaviruses KI and WU have been detected in respiratory samples, stools, tonsils, and blood, particularly in immunocompromised conditions, although little is known about tissue tropism. Herein we investigated the occurrence of KIV and WUV in non-malignant tonsillar specimens by Real-time quantitative PCR; the presence of polyomaviruses BK, JC and SV40-DNA was also evaluated. METHODS: Twenty-nine non-malignant tonsil specimens obtained from children and adults admitted for tonsillectomy were prospectively studied. Real-time quantitative TaqMan PCR for polyomaviruses KI, WU, BK, JC, and SV40 were performed. RESULTS: KI-DNA was positive in 2/29 tonsillar specimens (6.9%), while BK- DNA, JC-DNA, SV-40 DNA, and WU-DNA sequences were not identified. CONCLUSION: Few studies have investigated the prevalence of polyomaviruses in tonsil specimens, with varying results, and data are particularly scant as regards the newly discovered KIV and WUV. Two major questions remain to be definitely answered at this regard: the possibility that human tonsils represent the initial site of infection and/or a latency site and the biological and clinical meaning of KIV and WUV in different contexts and groups of patients, in that it is not clear whether they are simple bystanders or play a role in tonsil disease.
Subject(s)
Palatine Tonsil/virology , Polyomavirus/isolation & purification , Adolescent , Adult , BK Virus/isolation & purification , Child , Child, Preschool , DNA, Viral/isolation & purification , Female , Humans , JC Virus/isolation & purification , Male , Middle Aged , Polymerase Chain Reaction/methods , Polyomavirus/classification , Polyomavirus Infections/virology , Simian virus 40/isolation & purification , Tonsillectomy , Young AdultABSTRACT
AIM: Human Cytomegalovirus (HCMV) is a relevant pathogen in transplant recipients, particularly in the first three months post-transplantation. The use of antiviral prophylaxis and pre-emptive therapy is able to reduce incidence of HCMV infection and disease. The incidence of HCMV infection and disease in renal transplant recipients in the first 100 days post-transplantation was investigated, in relation with HCMV serological matching and therapeutic management. METHODS: Incidence of HCMV infection in the first 100 days post-transplantation was evaluated by pp65-antigenemia in 165 patients on a total number of 1241 clinical samples. Patients were divided in four groups according to donor/recipient serological matching: D(-)/R(-) (low risk of HCMV disease), D(-)/R+ and D+/R+ (intermediate risk) and D+/R(-) (high risk). Antiviral strategy (prophylaxis in high risk group; pre-emptive therapy in intermediate risk group, no therapy in low risk group) and immunosuppressive protocol were recorded. RESULTS: Incidence of antigenemia-positivity was as follows: 0/3 D(-)/R(-) patients; 59/130 (45.4%) D+/R+; 5/16 (31.3%) D(-)/R+; 4/16 D+/R(-). No significative difference was found between the four groups in terms of incidence of antigenemia-positivity in the first 100 days following transplantation. Antigenemia values >50 pp65-positive/2x10(5) peripheral blood leukocytes (used to start pre-emptive therapy) were present in 18/130 (13.8%) D+/R+; 1/16 (6.2%) D+/R(-); 0/16 D(-)/R+. Viral kinetics in patients with HCMV infection was described. CONCLUSION: No significative difference was found in terms of incidence of HCMV infection in the first 100 days post-transplantation in relation to immunosuppressive protocol and serological matching, suggesting the appropriateness of antiviral strategies and viral monitoring adopted in this setting.
Subject(s)
Cytomegalovirus Infections/epidemiology , Kidney Transplantation , Phosphoproteins/immunology , Viral Matrix Proteins/immunology , Viremia/epidemiology , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Female , Humans , Incidence , Leukocyte Count , Male , Middle Aged , Time Factors , Viremia/diagnosisABSTRACT
PURPOSE: Percutaneous vertebroplasty (PVP), first described by Hervè Deramond in 1984, is an interventional procedure for the treatment of aggressive vertebral angioma. The aim of this study was to evaluate magnetic resonance imaging (MRI) patterns in the affected vertebrae before and after vertebroplasty by determining changes in signal intensity and size and distribution of bone cement within the vertebra at follow-up carried out at 1 week, 6 months and 12 months. MATERIALS AND METHODS: Fourteen patients were examined using MRI, for a total of 41 treated vertebrae; MRI was performed with a 0.5-Tesla (T) superconductive magnet (SIGNA GE). RESULTS: MRI patterns following vertebroplasty are mainly characterised by the signal produced by the areas surrounding the cement and by the cement itself. There is little effect on the size of the treated vertebra. Acrylic cement appears as an intraspongy focal area of T1 and T2 hypointensity that is mostly oval (34%) or rounded (26.8%); this appearance tends to become stable 6 months after treatment. The area surrounding the cement appears hypointense on T1 and hyperintense on T2, a likely expression of bone marrow oedema; this signal alteration tends to disappear gradually. CONCLUSIONS: In pre- and post-vertebroplasty imaging, MRI is regarded as the reference standard for correct evaluation of both container and content. Awareness of cement changes over time and of the reaction of the surrounding bone tissue is crucial for correct assessment of post-vertebroplasty images.