Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).

The Italian Association of Medical Oncology recommendations on thymic epithelial tumors, which have been drawn up for the first time in 2020 through an evidence-based approach, report indications on all the main aspects of clinical management of this group of rare diseases, from diagnosis and staging, to new available systemic treatments, such as targeted therapies and immunotherapies. A summary of key recommendations is presented here and complete recommendations are reported as Supplementary Materials, available at https://doi.org/10.1016/j.esmoop.2021.100188.

Exploratory Analysis on Overall Survival after Either Surgery or Stereotactic Radiotherapy for Lung Oligometastases from Colorectal Cancer.

AIMS: Lung metastasectomy and, more recently, stereotactic body radiotherapy (SBRT), are frequently proposed to stage IV oligometastatic colorectal cancer (CRC) patients. In the absence of a randomised comparison between the two treatments, we aimed to retrospectively explore the effect on overall survival and progression-free survival (PFS) in a comparative cohort study. MATERIALS AND METHODS: We included patients who consecutively underwent surgery (n = 142) or SBRT (n = 28) as first local therapy at the time of lung progression, between 2005 and 2012. Both overall survival and PFS functions according to treatment were calculated using the Kaplan-Meier method and compared using the Log-rank test. The effect of treatment on overall survival and PFS was estimated by Cox models using different adjustment methods. RESULTS: Patients receiving SBRT were older and were treated more recently, whereas the two cohorts were similar for most baseline prognostic factors. Overall survival at 1 and 2 years was 0.89 and 0.77 for SBRT and 0.96 and 0.82 for surgery (P = 0.134), respectively. Multivariable analyses did not highlight a clear treatment effect on overall survival (adjusted hazard ratioSBRT versus surgery = 1.71; 95% confidence interval 0.82-3.54; P = 0.149) and even smaller differences using the inverse probability treatment weighting method (hazard ratioSBRT versus surgery = 1.28, 95% confidence interval 0.58-2.82; P = 0.547). The results of PFS were unreliable because different follow-up protocols were applied in the two cohorts. CONCLUSION: With limitations consisting in the retrospective observational design and different sample sizes, the results of this explorative analysis indicate that overall survival probability after SBRT is similar to surgery for the first 2 years from treatment. This finding supports the need for high-quality trials comparing different treatment modalities for lung oligometastases from CRC.

Lung abscess in a child secondary to Mycoplasma pneumoniae infection.

We present a case of a lung abscess in a child 6-year-old admitted with a history of right hemithorax pain lasting for 15 days and the onset of mild fever in the last two days. Etiological research showed positivity of IgM antibodies to Mycoplasma pneumoniae after seven days of admission. The child has been successfully treated with antibiotic therapy, without the use of macrolides, for a duration of 4 weeks. Our study suggests that the Mycoplasma pneumoniae infection may predispose to severe infections, such as lung abscess, caused by typical respiratory pathogens. The reported case of lung abscess is one of the few reported in the literature in the modern antibiotic era and is the first preceded by Mycoplasma pneumoniae infection.

Two cases of neonatal adrenal hemorrhage presenting with persistent jaundice.

The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.

Lung volume reduction surgery 10 years later.

AIM: The purpose of this study was to evaluate whether favorable short-term results in term of functional outcome and survival following lung volume reduction surgery persist for longer periods. Composite preoperative and early postoperative variables were analysed. METHODS: This study was conducted on 52 emphysematous patients who underwent lung volume reduction surgery (LVRS) from 1993 to 2000, through a delayed retrospective analysis that has allowed us to evaluate a long-term follow-up (10 years or more); lung function and other variables were considered with respect to survival; 11 patients submitted to lung transplantation were also evaluated. RESULTS: Upper lobe distribution of emphysema (P=0.02, HR:2.43) and systolic PAP (P=0.04, HR=2.11) were significantly correlated to survival in a multivariate analysis; these variables seem to identify a small subgroup of 14 patients with longer survival (more than 10 years). Lung transplantation performed in some worsening patients (mean FEV1%:17±4) showed a trend of better survival when we compared the observed survival (55±47 months) with expected survival (39.5±15 months) (P=ns). CONCLUSION: We conclude that LVRS can lead to a very long survival (10 years or more) in a small subgroup of patients, with improvement of pulmonary functional data. Some preoperative data (upper lobe distribution of emphysema and pulmonary arterial pressure) appear to predict survival. Lung transplantation can be offered to these patients, showing a trend to improved life expectancy.

Lung volume reduction surgery 10 years later.

AIM:The purpose of this study was to evaluate whether favorable short-term results in term of functional outcome and survival following lung volume reduction surgery persist for longer periods. Composite preoperative and early postoperative variables were analysed. METHODS: This study was conducted on 52 emphysematous patients who underwent lung volume reduction surgery (LVRS) from 1993 to 2000, through a delayed retrospective analysis that has allowed us to evaluate a long-term follow-up (10 years or more); lung function and other variables were considered with respect to survival; 11 patients submitted to lung transplantation were also evaluated. RESULTS:Upper lobe distribution of emphysema (P=0.02, HR:2.43) and systolic PAP (P=0.04, HR=2.11) were significantly correlated to survival in a multivariate analysis; these variables seem to identify a small subgroup of 14 patients with longer survival (more than 10 years). Lung transplantation performed in some worsening patients (mean FEV1%:17±4) showed a trend of better survival when we compared the observed survival (55±47 months) with expected survival (39.5±15 months) (P=ns). CONCLUSION: We conclude that LVRS can lead to a very long survival (10 years or more) in a small subgroup of patients, with improvement of pulmonary functional data. Some preoperative data (upper lobe distribution of emphysema and pulmonary arterial pressure) appear to predict survival. Lung transplantation can be offered to these patients, showing a trend to improved life expectancy.

[Proper antibiotic therapy. From penicillin to pharmacogenomic]. / Terapia antibiotica appropriata: dalla penicillina alla farmacogenomica.

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical judgment, and clinical discretion is always required in their application. Genome studies have identified hundreds of genetic polymorphism important determinants of the efficacy of therapy and several trial demonstrated the successful use of pharmacogenomic testing to reduce the incidence of hypersensitivity reactions in patients. Knowing the phenotype of a patient prior to therapy, optimal dose and type drugs can be prescribed to achieve better management of patients.

Chronic massive fetomaternal hemorrhage in a newborn from immigrants. Clinical and organizational implications.

Fetomaternal hemorrhage (FMH) refers to the entry of fetal blood into the maternal bloodstream before or during delivery. FMH of more than 30 mL occurs with the frequency of about 1/300. Fetal outcomes may be compromised by still births, hydrops fetalis, cardiac complications, and increased rates of postpartum infant death. In most cases, the cause is not identified. Clinical manifestations of FMH depend on the volume of blood lost and the rate that it occurred. We report a case of chronic massive FMH in a newborn of an immigrant mother with a favorable outcome. Medical visits and tests during pregnancy, including ultrasound scans, were not performed. The baby was hemodynamically stable after birth, manifesting only pallor. The complete blood count revealed severe hypochromic anemia (hemoglobin 3,8 g/dl, hematocrit 14,4%) and reticulocytosis (reticulocyte 25,2%). There was no ABO blood type incompatibility and the result of direct Coomb's test was negative. The Kleihauer-Betke test revealed 5% of fetal erythrocytes in the maternal bloodstream equivalent to 180 mL. The fact that FMH can occur without prior risk factors, and the diagnosis is often postnatal, underscores the importance of heightened of medical suspicion particularly in infants born to immigrants where there is often the lack of prenatal visits.

Preliminary results of a new small-bore percutaneous pleural catheter used for treatment of malignant pleural effusions in ECOG PS 3-4 patients.

BACKGROUND: In cancer patients with malignant pleural effusions(MPEs),the commonest procedure to treat them with palliative intention is talc pleurodesis (TP) which can be obtained with talc slurry (TS) using small-bore catheters(SBC)or with thoracoscopic poudrage. SBC use is therefore rapidly increasing. The aim of this paper is to present our preliminary TP results using a new percutaneous chest drainage system(UNICO®, Redax, Mirandola Modena, Italy). METHODS: In the period 1st March-20th of July 2011,seven consecutive ECOG PS 3-4 patients(4 females, mean age 73.2 ± 12.1 years),unfit for thoracoscopic talc poudrage, were enrolled in our study. All patients received many thoracentesis before the placement of a chest drainage(median thoracentesis number:4.42 ± 1.13).UNICO® was bedside placed in all cases and TS was administered through the drainage when the overall fluid amount didn't exceed 150-200 ml/24 h and the lung was correctly re-expanded at the chest X-ray control. RESULTS: There were no clinical complications following the placement of the drainage: its placement was easy, safe and well-tolerated by all patients. The median chest tube stay, before TS, was 7.2 ± 2.7 days while the median chest tube stay after TS was 1.5 ± 0.7 days. A satisfactory radiological lung expansion was achieved in all cases; PL effectiveness and dyspnea relief were complete in 6 and 4 cases, respectively. No patients required any further thoracentesis. CONCLUSIONS: TS through UNICO® is safe and efficient. The drainage was well-tolerated by all patients, even in case of its long-term stay. We may conclude that bedside TS through this new small-bore percutaneous drainage should be proposed as a viable clinical solution for MPEs in ECOG PS 3-4 patients, unfit for a thoracoscopic procedure. Moreover, with this device, we believe that TS might be an accessible procedure for pulmonologists and oncologists too.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

Patient's home care management in persistent air leaks and chronic pneumothorax using a new drainage system.

The management of persistent air leaks (PALs) is one of the most common problems in general thoracic surgery, especially after elective pulmonary resections. The statistically most frequent air leak is caused by alveolar-pleural fistula (APF), which is defined as a link between the pulmonary parenchyma distal to a segmental bronchus, and the pleural space. Prolonged air leaks result in an increase in patient's hospital length of stay with possible infectious complications, aside from an overall hospitalization cost increase. The ability to discharge a patient who would otherwise depend on continuous aspiration, because chronic PALs represent a very important clinical and technological improvement. We describe the case of a patient with chronic PALs and pneumothorax due to pulmonary fibrosis secondary to rheumatoid arthritis, with diffuse pulmonary nodules, in which surgical attempts to manage air leaks were ineffective. He was successfully home-assisted with a new chest drainage system with automatic constant negative suction pressure.

Digital air leak monitoring after lobectomy for primary lung cancer in patients with moderate COPD: can a fast-tracking algorithm reduce postoperative costs and complications?

AIM: Prolonged air leaks remain one of the most important complication after pulmonary resection. The aim of this study was to test a new fast-track chest tube removal protocol using a new drainage system, which digitally records postoperative air leaks, compared to the traditional one, with subjective visual air leak assessment. METHODS: Patients with moderate COPD undergoing lobectomy for primary lung cancer at the Department of Thoracic Surgery of the University of Torino were randomised in two groups with different chest drainage systems and different removal protocols: in Group A the drainage was removed after digitally recordered measurement of air leaks; in Group B the tube was removed according to the air leaks visualization by bubbling in the water column. The following variables were evaluated: first and second drainage removal day; overall hospital length of stay; overall hospitalization costs. RESULTS: First and second drainages were removed sooner in those patients with the digital drainage system. An earlier drainage removal is associated with significative reduction in hospital length of stay and overall hospitalization costs. CONCLUSION: The digital and continuous air leak measurement reduces the hospital length of stay by a more accurate and reproductive air leaks measurement. Further studies are mandatory to corroborate our preliminary results.

Combined prophylaxis decreases incidence of CMV-associated pneumonia after lung transplantation.

Among solid-organ recipients, those with lung transplants are at highest risk of cytomegalovirus (CMV) infection or to die of CMV-associated disease. We evaluated the effect of combined CMV antiviral prophylaxis and CMV-immunoglobulin prophylaxis on CMV-associated pneumonia diagnosed in 303 follow-up transbronchial biopsy (TBB) specimens from lung transplant recipients. At our center, 24 recipients (control group; 1999-2002) received acyclovir for 24 months and 33 recipients (study group; 2003-2008) received combined CMV prophylaxis consisting of CMV immunoglobulin on days 1, 4, 8, 15, and 30 and monthly for 12 months plus gancyclovir or valgancyclovir from postoperative day 21 for 3 weeks followed by acyclovir for up to 24 months. The percentage of pneumonia-positive TBB specimens at 1-month follow-up was similar in the study and control groups: 9.1% (3 of 33 specimens) vs 8.3% (2 of 24) (P = .90). However, after the first month, the percentage of pneumonia-positive TBB specimens was significantly lower in the study group in the first year (months 3, 6, 9, and 12) of follow-up, at 1% (1 of 99) vs 6.4% (5 of 78) (P = .048), and in the first 2 years (months 3, 6, 9, 12, 18, and 24), at 0.8% (1 of 122) vs 6.5% (8 of 124) (P = .02). These data suggest the efficacy of combined prophylaxis to decrease the incidence of CMV-associated pneumonia after the first month in lung transplant recipients. The effect of combined prophylaxis after transplantation seems useful to prevent CMV-associated pneumonia not only in the first year after lung transplantation but also in the second year, which suggests a long-lasting immunologic role of prophylaxis.

Chest wall and hemidiaphragm reconstruction with Gore-Tex mesh and omolateral latissimus dorsi flap. A case report.

There are various method of reconstruction when chest wall resection is performed for the treatment of tumors of the chest wall. In this case a chest wall resection and reconstruction was performed using an omolateral latissimus dorsi flap, together with Gore-Tex mesh. A 42-year-old woman was diagnosed as having a huge low grade chondrosarcoma and underwent surgical resection which interested the anterior chest wall from the level of the IV to X rib and the right hemidiaphragm. Gore-Tex mesh was fixed to the residual chest wall and an ipsilateral pedicled latissimus dorsi muscle flap was placed on the alloplastic mesh. The patient was discharged from the hospital 17 days postoperatively. The postoperative course was uneventful and the wound was fine.

Urinary tract infection caused by Kluyvera ascorbata in a child: case report and review of the kluyvera infections in children.

Kluyvera species are described infrequently in association with clinically significant infections, and infections caused by these gram negative rods are rare in children. The spectrum of disease due to Kluyvera infection in children includes urinary tract infections, enteritis, soft tissue infections, sepsis, central venous catheter infections and peritonitis. The authors report a case of Kluyvera ascorbata urinary tract infection in a 3-month-old female baby, and they review the literature on Kluyvera infections in children.

Single versus double lung transplantation in pulmonary fibrosis: a debated topic.

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

Combined cytomegalovirus prophylaxis in lung transplantation: effects on acute rejection, lymphocytic bronchitis/bronchiolitis, and herpesvirus infections.

Lung transplantation recipients are at high risk for herpesvirus infections. We evaluated the effect of combined cytomegalovirus (CMV) prophylaxis on CMV pneumonia, acute rejection episodes (ARE), lymphocytic bronchitis/bronchiolitis (LB), and obliterans bronchiolitis (OB) diagnosed in 180 transbronchial biopsies (TBB) of lung transplant recipients. At our center, 25 patients (control group; 1999-2002) received acyclovir for 12 months and 21 recipients (study group; 2003-2007) received combined CMV prophylaxis consisting of CMV-IG (Cytotect Biotest) for 12 months and ganciclovir or valganciclovir from postoperative day 21 for 3 weeks. Among the study group (since 2005), CMV shell vial viral culture and Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and HHV-7 DNA were determined on BAL specimens. In the study group, the number of LB was significantly lower than in the control group (2% vs 11%; P= .04). Similar results were obtained for ARE (6% vs 17%; P= .04). No difference was observed in OB (5% vs 5%; P= .53, NS). A reduction trend was found in CMV pneumonia (2% vs 7%; P= .23, NS). Logistic regression analysis showed a relationship between prophylaxis and a reduced prevalence of ARE (odds ratio [OR] 3.25, confidence interval [CI] 1.12-9.40; P= .03). Finally, in the study group, BAL EBV-DNA positivity and EBV-CMV coinfections were low (6% and 0%, respectively) compared with other herpesviruses and with the literature. Our data suggested the efficacy of combined CMV prophylaxis to prevent ARE and LB, 2 risk factors for chronic rejection, and a possible role to reduce the trend toward CMV pneumonia and EBV infections.

Glucose and leucine metabolism in lung tranplanted patients on low dose of steroids for immunosuppressive therapy.

BACKGROUND: This study examined the metabolic effects of lung transplantation in patients with end-stage respiratory failure on low dose of steroids for immunosuppressive therapy. METHODS: We examined 6 patients, including 2 women and 4 men of overall mean age 53 +/- 15 years and age at transplantation 34 +/- 12 months, receiving cyclosporine 5.73 +/- 1.43 mg/kg/d or tacrolimus (FK 506) 4.67 +/- 0.58 mg/d, azathioprine 0.47 +/- 0.29 mg/kg/d, and prednisone 8.25 mg/d for comparison with 6 healthy subjects, who were selected to be comparable to the recipients in terms of anthropometric features and age. A euglycemic hyperinsulinemic clamp (1 mU/kg/min) associated with infusion of glucose and leucine isotopes was performed with indirect calorimetry. RESULTS: Lung transplanted patients showed postabsorptive leucine and free fatty acid metabolism similar to controls. In contrast, there was peripheral insulin resistance with respect to glucose metabolism namely, higher values of glucose and insulin vs controls (P < .03 and P < .02, respectively). During the clamp the metabolic picture was characterized by a relative insulin resistance with respect to glucose metabolism (P = .07). Lipid and protein metabolism in the basal and insulin-stimulated conditions were similar to the control group. CONCLUSIONS: In the basal condition insulin resistance is evident with respect to glucose metabolism. The metabolic picture in lung transplanted patients on low-dose steroid therapy was characterized by normal insulin-stimulated glucose, leucine, and free fatty acid metabolism. The minimal metabolic alterations in these patients were not due to transplantation itself but probably mainly attributable to immunosuppressive therapy.