FNA indication according to ACR-TIRADS, EU-TIRADS and K-TIRADS in thyroid incidentalomas at 18F-FDG PET/CT.

OBJECTIVE: Focal thyroid incidentaloma (TI) occurs in a 2% of 18F-FDG PET/CT and about one-third of TIs is cancer. Due to the lack of evidence on the optimal management of TI, current guidelines suggest performing fine-needle aspiration cytology (FNA). The study aim was to evaluate the reliability of ACR-TIRADS, EU-TIRADS, and K-TIRADS in indicating FNA in TIs. DESIGN: We retrospectively reviewed 18F-FDG PET/CT TIs recorded during the period 2016-2019. Enrolled were TIs with histologic outcome and autonomous nodules. Cases with uncertain matching between 18F-FDG PET/CT, US/scintiscan and histology were excluded. RESULTS: Eighty TIs at 18F-FDG PET/CT (median size 17 mm, median SUVmax 7.85) were included; a 26.2% was cancer. The percentage of nodules classified as high risk according to ACR-TIRADS, EU-TIRADS, and K-TIRADS was 20%, 30%, and 29.8%, respectively. The cancer prevalence in high-risk class was 56.2%, 66.7%, and 65.2% in ACR-TIRADS, EU-TIRADS, and K-TIRADS, respectively. ACR-TIRADS had the lowest number of cases with FNA indication (48%) and the K-TIRADS, the highest one (75%). Evaluating the reliability of the three systems in indicating FNA, we found a 100% sensitivity and NPV for EU-TIRADS and K-TIRADS; while all the three systems showed poor specificity and PPV. CONCLUSION: All TIRADSs were reliable to stratify the risk of cancer in focal TI. Comparing their reliability in indicating FNA, we found a good performance of EU-TIRADS and K-TIRADS. Considering the high cancer percentage expected in this setting of patients, those TIRADS with higher propensity to indicate FNA should be preferred.

Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

COPD and thyroid dysfunctions.

BACKGROUND: Chronic obstructive pulmonary (COPD) is one of the major causes of morbidity and mortality in the world. COPD is characterized by chronic inflammation in the pulmonary compartment and in the systemic circulation. This disorder is associated with clinically significant alterations in biochemistry and organ function; thyroid dysfunctions are common in chronic diseases, such as COPD. Several characteristics of COPD patients could increase their likelihood of developing hypothyroidism or hyperthyroidism. The purpose of our study was to assess the impact of thyroid dysfunction in patients with COPD. METHODS: We evaluated the pulmonary function tests, arterial blood gases, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and thyroid functions in patients with COPD, recruited between admissions in Respiratory Diseases Unit, Policlinico Umberto I, Rome, Italy, from June 2012 to May 2013. We selected patients with subclinical hypothyroidism (ScH), overt hypothyroidism, and hyperthyroidism, and a control group without thyroid disturbance. RESULTS: Our results indicate that patients with overt hypothyroidism have lower levels of pO2, MIP, and MEP compared with subjects with ScH, hyperthyroidism, and the control group. We also found a substantial tendency towards pCO2 levels increase in patients with hypothyroidism (p = 0.06). CONCLUSIONS: Patients with thyroid dysfunctions have a greater impairment of MIP and MEP and a negative correlation was observed between hypoxemia and TSH. Further studies are needed to investigate whether the treatment of thyroid disfunction could have a beneficial effect on COPD patients' lung function and prognosis.

Immune-related acute and lymphocytic gastritis in a patient with metastatic melanoma treated with pembrolizumab immunotherapy.

Here, we present a case of acute and lymphocytic gastritis related to therapy with pembrolizumab for metastatic melanoma. After an asymptomatic phase with moderate histological inflammation (observed at 9 months of immunotherapy), gastritis became symptomatic and severe on repeated biopsies (13 months after the beginning of pembrolizumab). Symptoms and histological lesions both improved with proton pump inhibitor and steroid therapy, as well as interruption of pembrozulimab. The interest of this case lays in the relative rarity of gastritis over small and large intestinal inflammatory lesions caused by immune checkpoint inhibitors as well as in the features of the inflammatory infiltrate, which may be purely lymphocytic (mainly T-cells, with a prevalence of CD8+ over CD4+ lymphocytes) or mixed lymphocytic and granulocytic, requiring the exclusion of other causes of disease. To our knowledge, only 7 cases of immune-related gastritis have been previously documented in the current literature, of which 4, included the current one, were exclusively associated with pembrozulimab therapy.

An "alternative" clinical course of COPD exacerbation and pulmonary embolism.

Patients with chronic diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and diabetes mellitus, are exposed to particular complications that require a careful diagnostic algorithm. Pulmonary Embolism (PE) in COPD patients often demands an accurate differential diagnosis and a prompt therapeutic intervention. Aspergillus spp. infection comprises a large spectrum of pathological manifestations, depending on immune status and the presence of underlying lung disease. These manifestations may range from invasive pulmonary aspergillosis (IPA) in gravely immunocompromised patients, to chronic necrotizing aspergillosis (CNA) in patients with chronic lung diseases and moderately compromised immune systems. Aspergilloma is generally observed in patients with cavitary lung diseases, and allergic bronchopulmonary aspergillosis (ABPA) is reported in patients with hypersensitivity to Aspergillus antigens. We report a case with pulmonary aspergillosis arisen on a pulmonary infarction after PE in a patient with COPD and diabetes mellitus. To date, report with this clinical evolution was not reported in literature. This report is intended to describe an accurate diagnostic path in a complex overlap of different pathological conditions, highlighting the great importance of differential diagnosis and an appropriate diagnostic algorithm. In addition, open issues on the real diagnostic value of clinical, radiological, and laboratory features for COPD exacerbation, PE and aspergillosis have been discussed.

A woman with a solitary pulmonary nodule: is it a lung cancer?

BACKGROUND: Solitary pulmonary nodules present a real challenge for physicians. Due to the clinical implications and prognosis of a certain diagnosis, it should be pursued with any cost; a clear definition is not always simple and further investigations are often necessary to exclude the possibility of a malignancy. A diagnostic path must be followed and the clinical hypothesis should be reconsidered on the basis of the new information provided by the tests, always keeping in mind their limits! Sometimes only the surgical resection permits a definitive diagnosis. A 68 year-old non-smoker female with a pulmonary solitary nodule highly suspicious to be malignant at the chest CT, performed a FBS with BAL, negative for neoplastic cells and for infective agents, and a CT guided pulmonary biopsy that was inconclusive. The patient underwent then a video-thoracoscopic atypical lung resection that demonstrated the reactive nature of the lesion, definitely excluding the presence of a malignancy.

Human neutrophil peptides sputum levels in symptomatic smokers and COPD patients.

BACKGROUND AND OBJECTIVES: Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of airway inflammation and progression towards pulmonary functional impairment, and correlate with the degree of airways obstruction. MATERIALS AND METHODS: We measured, by ELISA tests, HNP concentrations from 37 symptomatic smokers and 34 COPD patients. All participants underwent pulmonary function tests. Sputum samples were collected at the enrolment, and 6 months after smoking cessation. Differences between groups and correlation coefficients between variables were determined using non parametric tests. RESULTS: Sputum HNP concentrations were higher in COPD patients as compared to symptomatic smokers (14 +/- 1.5 microg/ml vs 1.6 +/- 0.4 microg/ml; p < 0.0001). Among COPD patients HNP concentrations were higher in individuals with severe obstruction than in patients with mild to moderate COPD (19.9 +/- 2.3 microg/ml vs 10.3 +/- 0.8 microg/ml, p = 0.003). A negative correlation was observed between HNP levels and FEV1 (rho = -0.38, p = 0.02), and FEV1/FVC (rho = -0.42, p = 0.01). No differences were found in HNP levels before and after 6 months of smoking withdrawal (1.1 microg/ml +/- 0.3 vs 1.1 microg/ml +/- 0.3 for symptomatic smokers, p = 0.9, and 14.4 microg/ml +/- 1 vs 16 microg/ml +/- 1.1 for COPD, p = 0.6). DISCUSSION: Sputum levels of HNP may represent a marker of severity of functional impairment in COPD. Our data support the hypothesis that HNP may have a role in smoking- and COPD-related lung inflammation.

Serum CA 15-3 is increased in pulmonary fibrosis.

BACKGROUND AND AIM OF THE WORK: Carbohydrate antigen CA 15-3 is a glycoprotein whose expression, aberrant intracellular localization and changes in glycosylation have been associated with a wide range of cancers. Pulmonary fibrosis represents the final evolution of a chronic inflammation and is defined by the overgrowth of fibroblasts and exaggerated extracellular matrix deposition. The aim of the present study was to evaluate the possible diagnostic role of CA 15-3 in fibrosis in different idiopathic interstitial pneumonias. METHODS: CA 15-3 was measured in serum samples from healthy subjects (n=25) and patients affected with idiopathic pulmonary fibrosis (IPF/UIP) (n=20), sarcoidosis (n=22) at different stages (I, II, and III) and systemic sclerosis (n=25). CA 15-3 protein expression was also evaluated by immunohistochemistry in 21 lung biopsies and in 6 primary lung fibroblasts cell lines. RESULTS: The CA 15-3 serum levels were significantly higher in patients with IPF/UIP and with clinically advanced sarcoidosis (stage III). Serum CA 15-3 levels were slightly increased in patients with systemic sclerosis. No difference was observed between serum CA 15-3 levels in patients with sarcoidosis at stages I and II compared with control subjects. In IPF/UIP and in sarcoidosis at stage III elevated CA 15-3 serum levels significantly correlated with decreased total lung capacity, decreased diffusing capacity of carbon monoxide and high resolution computed tomography findings. Immunohistochemical analysis showed an intense specific CA 15-3 staining in fibroblasts within fibroblastic foci, surrounding sarcoid granulomas and in all cell cultures of lung fibroblasts from IPF/UIP lungs. CONCLUSIONS: Our results indicate that increased CA 15-3 levels are associated with pulmonary interstitial damage, fibroblast activity and progression to fibrosis of the lung. Therefore, CA-15-3 may be considered a sensitive marker useful in the identification of patients with advanced fibrosis and more severe prognosis.

A prospective study of the effects of carbocysteine lysine salt on frequency of exacerbations in COPD patients treated with or without inhaled steroids.

OBJECTIVE: COPD is one of the major causes of morbidity and mortality worldwide and represents one of the most important issues for public health. Frequent exacerbations induce a faster decline in lung function and poorer quality of life, increase mortality, and have a socio-economic impact with a high burden in terms of resources and healthcare costs. The clinical trials evaluated the effect of mucolytics in COPD and showed that the long-term carbocysteine, associated with bronchodilators, anticholinergics, and steroids, reduces the frequency of exacerbations and improves the quality of life. PATIENTS AND METHODS: The aim of this prospective real-life study was to evaluate the long-term impact on exacerbations (at 1 year) in COPD patients treated with carbocysteine lysine salt (single dose of 2.7 g once a day) in addition to background therapy with or without inhaled steroids. RESULTS: In a total of 155 evaluable patients, our study showed that the addition of a single dose of carbocysteine lysine salt to background therapy determines a statistically significant reduction of the average number of exacerbations vs. the number observed in the previous year (from 1.97±0.10 to 1.03±0.11; p<0.01), irrespective of treatment with or without inhaled steroids. In particular, in patients with ≥2 exacerbations in the previous year, the addition of carbocysteine lysine salt resulted in a statistically significant reduction in the exacerbations rate from 69% to 33% and from 58% to 25%, respectively (p<0.01) in patients with or without inhaled steroids. CONCLUSIONS: In summary, our data highlighted the efficacy of long-term administration of a single daily dose of carbocysteine lysine salt (2.7 g/day) in reducing the number and rate of exacerbations in COPD patients, independently from the use of inhaled steroids.

18F-FDG-PET/CT Imaging in Advanced Glottic Cancer: A Tool for Clinical Decision in Comparison with Conventional Imaging.

This study assessed the role of 18F-FDG PET-CT (PET/CT) to detect the cartilage and paraglottic infiltration in advanced glottic cancer comparing the results with those of conventional imaging (CI) (contrast-enhanced computed tomography and/or magnetic resonance). In addition, we assessed the prognostic value of quantitative parameters, measured on baseline PET/CT, in terms of event-free survival (EFS) and overall survival (OS). We retrospectively analyzed 27 patients with glottic squamous cell carcinoma stage III and IVA, treated in our institute between 2010 and 2016, comparing PET/CT, performed for staging and radiotherapy planning, and CI findings. Cohen's K was used to compare concordance between PET/CT and CI. Imaging findings were correlated with endoscopic evaluation and histological reports (gold standard (GS)). All lesions shown by CI were also detected by PET/CT imaging, and in 5 cases, a better definition of local infiltration was achieved with PET/CT than CI (5 CT). Sensitivity, specificity, and accuracy of PET/CT and CT were 95%, 86%, and 93% and 70%, 86%, and 74% for, respectively. MRI showed sensitivity and specificity of 100%. One false-negative (FN) cases and 1 false-positive (FP) case were observed with PET/CT with no difference compared to MRI (10 cases). Six FN cases and 1 FP case were observed with CT. Cohen's K was 0.60 (PET vs. CI) and 0.80 (PET vs. GS). Patients were followed-up for at least 24 months to calculate EFS and OS. 13 local recurrence and 7 deaths were recorded. Among quantitative PET parameters, baseline MTV was the most powerful predictor of outcome. Our data suggest a reliable sensitivity and accuracy of PET/CT in the evaluation of local extension, proving a useful method for initial local staging in addition to the well-established role in lymph-node and distant sites assessment. Furthermore, pretreatment MTV provides better prognostic information than other PET/CT parameters.

Osler-Rendu-Weber syndrome: congenital arteriovenous intrapulmonary fistula treated using a percutaneous Amplatzer plug.

Pulmonary arteriovenous fistulas (PAVFs) are rare vascular malformations (PAVMs) of the lung that could lead to severe hypoxiemia due to right-to-left intrapulmonary shunts. They may occur as isolated entities or associated with Osler-Rendu-Weber syndrome or hereditary haemorrhagic telangiectasia (HHT). We report a case of a 70 years old woman with Rendu-Osler-Weber disease and a large arteriovenous malformation involving the left pulmonary artery. We describe the successful transcatheter occlusion of the PAVF using an Amplatzer vascular plug. This work is an attempt to focus the attention on pulmonary arteriovenous malformations and on percutaneous treatment as an alternative to surgery, that consists of a conservative lung resection.

Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens.

STUDY OBJECTIVES: In this study we evaluated the role of three currently available therapeutic regimens in the treatment of early stages of idiopathic pulmonary fibrosis (IPF). PATIENTS: The study population consisted of 57 consecutive suspected individuals with IPF. Patients with interstitial pneumonias other than IPF and subjects with advanced disease or contraindication to therapy were excluded. We evaluated 30 subjects with mild-moderate IPF, homogeneous baseline characteristics and prognostic parameters that were assigned to 3 treatment regimens: group 1 (n = 11): prednisone 1 mg/kg/ day; group 2 (n = 9): prednisone 0.5 mg/kg/day plus cyclophosphamide 100 mg/day; group 3 (n = 10): prednisone 0.5 mg/kg/day plus colchicine 1 mg/day. We analysed response to therapy by analysis of a clinical-radiographic-physiologic (CRP) score before treatment and at 6 months intervals for 18 months. Side effects and three years survival rate were also investigated. RESULTS: Although our study was performed in a subset of patients with early disease's stages, these data showed that none of the regimens was able to interfere with IPF's course. However treatment with colchicine plus prednisone resulted in fewer side effects and re-evaluation parameters showed a significant decrease of dyspnoea (p < 0.01). No significant differences were observed in survival rate among the three groups. CONCLUSIONS: None of the regimens analyzed was effective even in the treatment of the early stages of IPF. The association colchicine/corticosteroids could be considered a safe and not expensive regimen that may be used in the treatment of IPF, especially in patients who have experienced adverse effects from immunosuppressive agents, while waiting for newer therapeutic strategies.

[18-Fluoro-deoxy-glucose (15FDG) positon emission tomography (PET) for the evaluation of malignant pleural disease]. / La tomographie par émission de positons (TEP) au 18-fluoro-déoxy-glucose (18FDG) dans l'évaluation de la pathologie pleurale maligne.

Use of 18FDG-PET for malignant tumors of the pleura raises certain technical difficulties because of the small size of the tumors and their diffuse distribution, but hybrid PET/CT machines offer a better localization of FDG uptake. FDG-PET can discriminate between malignant and benign pleural tumors FDG uptake in the pleura is the best diagnostic criteria of malignancy. The presence of FDG uptake in pleural effusion is less discriminate between benign and malignant disease. For mesotheliomas, FDG-PET can difference malignant tumors from benign tumors of the pleura on the basis of the SUV value ( 2). It does not enable detection of mediastinal node involvement and regional extension but is effective in detecting extra-thoracic regional spread not identified with other imaging methods. FDG-PET can thus affect the therapeutic strategy. The intensity of uptake has prognostic value. SUV<4 associated with an epithelial tumor is a sign of good prognosis at three years. SUV > 4 associated with a non-epithelial tumor is a sign of poor prognosis. For mesotheliomas, FDG uptake can be used to assess the effect of chemotherapy and determine whether patients are good responders or not.

Holmium Intraductal Laser Lithotripsy of Biliary Stones in Liver Grafts.

BACKGROUND: Biliary stones after liver transplantation (LT) rarely occur but a focus on those complications and their treatment is needed. PATIENTS AND METHODS: In total, 390 adult patients who underwent an LT from July 2004 to July 2014 entered the study. Biliary complications and notably biliary stones after LT were identified. RESULTS: In total, 365 LT were analyzed. Biliary stones were identified in 14 patients (3.8%). Predictive factors for the onset of biliary stones after LT were hepatocellular diseases (P = .038; OR = 9.7) and biliary stenosis (P = .000; OR = 11.9). Treatments consisted of percutaneous transhepatic procedures (4 patients), endoscopic retrograde procedures (9 patients), and in open surgery (1 case); in 2 cases, due to a failure of previous treatments, holmium intraductal laser lithotripsy (HILL) was used: the first patient, a 35-year-old woman developed multiple intrahepatic biliary stones after LT. Percutaneous transhepatic cholangiography (PTC) was ineffective and a HILL was performed, clearing the right common bile duct but leaving residual stones in the left duct. The patient underwent a retransplantation due to recurrent hepatitis C virus infection but died 3 months later because of graft failure. The second patient, a 42-year-old 14 years after retransplantation, developed biliary sludge and stones; after several attempts with PTC and endoscopic retrograde cholangiopancreatography, a HILL was performed. All stones except one big one were treated. The patient is alive and well. CONCLUSIONS: When usual treatments are unsuccessful and biliary stones are large, their fragmentation and treatment could be done with HILL, a promising procedure after LT.

Blood and sputum biomarkers in COPD and asthma: a review.

Chronic obstructive pulmonary disease (COPD) and asthma are lung inflammatory diseases that represent major public health problems. The primary, and often unique, method to evaluate lung function is spirometry, which reflects disease severity rather than disease activity. Moreover, its measurements strictly depend on patient's compliance, physician's expertise and data interpretation. The limitations of clinical history and pulmonary function tests have encouraged focusing on new possible tracers of diseases. The increase of the inflammatory response in the lungs represents an early pathological event, so biological markers related to inflammation may play key roles in earlier diagnosis, evaluation of functional impairment and prognosis. Biomarkers are measurable indicators associated with the presence and/or severity of a biological or pathogenic process, which may predict functional impairment, prognosis and response to therapy. The traditional approach based on invasive techniques (bronchoalveolar lavage and biopsies) may be replaced, at least in part, by using less invasive methods to collect specimens (sputum and blood), in which biomarkers could be measured. Proteomics, by the association between different protein profiles and pathogenic processes, is gaining an important role in pulmonary medicine allowing a more precise discrimination between patients with different outcomes and response to therapy. The aim of this review was to evaluate the use of biomarkers of airway inflammation in the context of both research and clinical practice.

Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology.

PURPOSE: To evaluate the role of (18)F-flurodeoxiglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in predicting malignancy of thyroid nodules with indeterminate cytology. PATIENTS AND METHODS: We analysed 87 patients who have been scheduled to undergo surgery for thyroid nodule with indeterminate cytology. All patients underwent (18)F-FDG-PET/CT, multiparametric neck ultrasonography (MPUS), and (99m)Tc-methoxyisobutylisonitrile scintigraphy ((99m)Tc-MIBI-scan). Histopathology was the standard of reference. We compared the sensitivity (SE), specificity (SP), accuracy (AC), positive (PPV) and negative predictive (NPV) values of (18)F-FDG-PET/CT with those of (99m)Tc-MIBI-scan and MPUS in detecting cancer. Univariate and multivariate analyses evaluated the association between each diagnostic tool and histopathology. RESULTS: On histopathology, 69 out of 87 nodules were found to be benign and 18 to be malignant. The SE, SP, AC, PPV and NPV of (18)F-FDG-PET/CT were 94, 58, 66, 37 and 98% respectively. The SE, AC and NPV of (18)F-FDG-PET/CT were significantly higher than those of MPUS and (99m)Tc-MIBI-scan. The association of both positive (18)F-FDG-PET/CT and MPUS (FDG+/MPUS+) showed significantly lower SE (61% vs 94%) and NPV (88% vs 98%) than (18)F-FDG-PET/CT alone, but significantly higher SP (77% vs 58%). On univariate analysis, (18)F-FDG-PET/CT and the combination of FDG+/MPUS+ and of FDG+/MIBI- were all significantly associated with histopathology. On multivariate analysis, only FDG+/MIBI- was significantly associated with histopathology. CONCLUSION: The AC of (18)F-FDG-PET /CT in detecting thyroid malignancy is higher than that of (99m)Tc-MIBI-scan and MPUS. A negative (18)F-FDG-PET/CT correctly predicts benign findings on histopathology. The association of FDG+/MPS+ is significantly more specific than (18)F-FDG-PET/CT alone in identifying differentiated thyroid cancer. A positive (18)F-FDG-PET/CT is significantly associated with malignancy when qualitative (99m)Tc-MIBI-scan is rated as negative.

Long-term outcome of right split in situ grafts in adults.

In situ split liver transplants represent a technical progression from ex situ split procedures conceived to retrieve grafts for pediatric recipients. The transection line runs along the falciform ligament, so the main artery to the right graft is the right proper artery, whereas the left graft retains the main arterial axis with the celiac trunk. Although the major advantages are for pediatric recipients, due to the expanded pool of grafts available, for adult recipients the results of right split in situ grafts must be compared with whole grafts. We considered two groups of consecutive grafts transplanted since 1993 as first grafts: 20 of the former and 261 of the latter. Groups were comparable for donor gender, recipient age and gender, perfusion solution, ischemia time, and follow-up time, but not for donor age and for the number of arterial anastomoses. Although there were more major surgical complications in the former compared with the latter group (40% vs 25%), the only statistically significant difference was found in retransplantation rate for arterial complications (15% vs 2.2%). No statistical difference was observed in graft or patient actuarial survival rates at 1, 3, or 6 years after transplantation; for right split grafts these were 85%, 69%, and 69% and 95%, 79%, and 79%, respectively.

A "steroid-free" tacrolimus and low-dose mycophenolate mofetil primary immunosuppression does not prevent early acute rejection after liver transplantation.

To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus (Tac) and low-dose mycophenolate mofetil (MMF) without steroids and to determine the exposure to mycophenolic acid (MPA) in the early postoperative period, we performed a single-center, randomized 1:1, open-label, controlled study planned to be 60 liver transplantation patients randomized into 2 groups: group A, tacrolimus + MMF (750 mg orally twice a day); and group B, tacrolimus + MMF (750 mg orally twice a day) + steroids. After an interim analysis by the ethical committee patient enrollment was stopped. Data from 30 patients (12 in group A and 18 in group B with a mean follow-up period of 31 +/- 7 months) showed a patient survival rate of 91.7% in group A and 100% in group B and a graft survival rate of 91.7% and 88.9%, respectively. Nine patients (75%) in group A suffered an acute rejection episode, whereas in group B only 3 patients (16.7%) showed acute rejection (P = .002). All rejection episodes occurred in both groups at 1 week after transplantation. The difference in histological grading was statistically significant (P = .021). The toxicity profiles were similar in both groups. A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival.

Back-table arterial reconstructions in liver transplantation: single-center experience.

Anatomic variations of the arterial supply to donor liver grafts often require complex hepatic artery reconstructions on the back table. Therefore, because of the additional anastomoses, there is a greater risk of arterial thrombosis and graft loss. Among the 620 orthotopic liver transplantations (OLT) in 549 adult and pediatric patients performed from June 1983 through August 2004, the rates and types of donor hepatic artery variations (HAV) and the type of reconstructions were reviewed as well as the 1- and 5-year grafts and patient survival rates after OLT. At least 1 HAV was present in 133 liver grafts (21.4%). The most frequent variations were as follows: right hepatic artery (RHA) from superior mesenteric artery (SMA) (44 cases); RHA from aorta (4 cases); and RHA from SMA, combined with a left hepatic artery (LHA) from left gastric artery (3 cases). No graft was discarded. Fifty-six of 133 (42%) HAV required arterial reconstructions, generally a termino-terminal (TT) anastomosis between RHA and splenic artery (26 cases, 46.4%). Less frequently performed anastomoses were the "fold-over" technique (15 cases, 26.8%) and the anastomosis between the RHA and the gastro-duodenal artery (6 cases, 10.6%); rare reconstructions were performed in 9 cases (16.0%). The rate of hepatic artery thrombosis was 5.4% (3 of 56 OLT) in complex hepatic artery reconstructions and 2.2% in other grafts. One- and 5-years graft and patient actuarial survival rates have been respectively 73.2%- 71.4% in hepatic artery reconstructions and 78.6%-76.8% in the absence of an artery reconstruction, respectively.

A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.