Lung cancer screening, what has changed after the latest evidence?

Lung cancer(LC)is still one of the most frequent cancers with a high related mortality.Their prognosis is directly proportional to the stage at the time of diagnosis.Seventy percent are currently diagnosed in advanced or locally advanced stage(higher than stage III),making a cure unlikely for the majority of patients.Developments in LC treatment are significant however they do not seem to be enough to reverse the current situation,at least,in a short period of time.Despite recent advances in treatment,primary prevention and early diagnosis appear to be the key to reduce the incidence and mortality of this disease.Many countries have developed LC screening programs based on the results of clinical trials published in recent years.The aim of this paper is to review the latest results of the NEderlands Leuvens Longkanker Screenings Onderzoek and compare them with the findings of the National Lung Screening Trial.We address the question whether it is necessary to continue discussing the evidence regarding LC screening.In both trials,there is a clear impact on LC mortality but,with a modest reduction in over all mortality.Undoubtedly,the benefit of screening can be expected to grow as low-dose computed tomographys are performed over longer periods of time.

Does manual thrombus aspiration help optimize stent implantation in ST-segment elevation myocardial infarction?

AIM: To evaluate the impact of thrombus aspiration(TA) on procedural outcomes in a real-world ST-segment elevation myocardial infarction(STEMI) registry.METHODS: From May 2006 to August 2008, 542 consecutive STEMI patients referred for primary or rescue percutaneous coronary intervention were enrolled and the angiographic results and stent implantation characteristics were compared according to the performance of manual TA.RESULTS: A total of 456 patients were analyzable and categorized in TA group(156 patients; 34.2%) and non-TA(NTA) group(300 patients; 65.8%). Patientstreated with TA had less prevalence of multivessel disease(39.7% vs 54.7%, P = 0.003) and higher prevalence of initial thrombolysis in myocardial infarction flow < 3(P < 0.001) than NTA group. There was a higher rate of direct stenting(58.7% vs 45.5%, P = 0.009), with shorter(24.1 ± 11.8 mm vs 26.9 ± 15.7 mm, P = 0.038) and larger stents(3.17 ± 0.43 mm vs 2.93 ± 0.44 mm, P < 0.001) in the TA group as compared to NTA group. The number of implanted stents(1.3 ± 0.67 vs 1.5 ± 0.84, P = 0.009) was also lower in TA group. CONCLUSION: In an "all-comers" STEMI population, the use of TA resulted in more efficient procedure leading to the implantation of less number of stents per lesion of shorter lengths and larger sizes.

Clinical and prognostic implications of delirium in elderly patients with non–ST-segment elevation acute coronary syndromes

Background Elderly patients with non-ST-segment elevation acute coronary syndromes(NSTE-ACS)may present delirium but its clinical relevance is unknown.This study aimed at detennining the clinical associated factors,and prognostic implications of delirium in old-aged patients admitted for NSTE-ACS.Methods LONGEVO-SCA is a prospective multicenter registry including unselected patients with NSTE-ACS aged>80 years.Clinical variables and a complete geriatric evaluation were assessed during hospitalization.The association between delirium and 6-month mortality was assessed by a Cox regression model weighted for a propensity score including the potential confounding variables.We also analysed its association with 6-month bleeding and cognitive or functional decline.Results Among 527 patients included,thirty-seven(7%)patients presented delirium during the hospitalization.Delirium was more frequent in patients with dementia or depression and in those from nursing homes(27.0%vs.3.1%,24.3%vs.11.6%,and 11.1%V5.2.2%,respectively;all P<0.05).Delirium was significantly associated with in-hospital infections(27.0%vs.5.3%,P<0.001)and usage of diuretics(70.3%vs.49.8%,P=0.02).Patients with delirium had longer hospitalizations[median 8.5(5.5-14)vs.6.0(4.0-10)days,P=0.02]and higher incidence of 6-month bleeding and mortality(32.3%vs.10.0%and 24.3%vs.10.8%,respectively;both P<0.05)but similar cognitive or functional decline.Delirium was independently associated with 6-month mortality(HR=1.47,95%CI:1.02-2.13,P=0.04)and 6-month bleeding events(OR=2.87;95%CI:1.98-4」6,P<0.01).Conclusions In-hospital delirium in elderly patients with NSTE-ACS is associated with some preventable risk factors and it is an independent predictor of 6-month mortality.

Inflammatory bowel disease in travelers:Choosing the right vaccines and check-ups

The majority of patients with inflammatory bowel disease (IBD) achieve good control of the inflammatory activity using available therapies. When remission is achieved and quality of life recovered, a considerable proportion of IBD patients express their desire to travel abroad, be it for business, academic or leisure purposes. Their physicians should help and encourage them whenever possible. However, preventive measures are warranted to minimize the risk, since IBD patients are exposed to the same infections affecting the general population, plus opportunistic infections (OI) related to the immunosuppression. There are a large number of potential OI that might affect patients with IBD. The true prevalence of these infections is unknown, and can vary from country to country. Therefore, reactivation or de novo acquisition of infections such as tuberculosis, malaria, and viral hepatitis will be much more frequent in endemic areas. Therefore, physicians should beaware of these aspects when planning specific preventive measures for patients traveling to a particular country. This includes good control of environmental exposure, chemoprophylaxis when indicated, and the use of a specific vaccination program to prevent endemic infections. In addition, it should be noted that, though the risk of acquiring an infectious disease is probably greater for IBD patients traveling from a developed to a developing country, the inverse situation can also occur; it depends on the previous acquired immunity of the host against infections in any particular environment.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma(NSCLC)has undergone major changes in recent years.On the one hand,improved sensitivity of diagnostic tests,both radiological and endoscopic,has altered the way patients are staged.On the other hand,the arrival of new drugs with antitumoral activity,such as targeted therapies or immunotherapy,has changed the prognosis of patients,improving disease control and prolonging survival.Finally,the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body.All of these advances have impacted the treatment of patients with advanced lung cancer,especially in a subgroup of these patients in which all of these treatment modalities converge.This poses a challenge for physicians who must decide upon the best treatment strategy for each patient,without solid evidence for one optimal mode of treatment in this patient population.The aim of this article is to review,from a practical and multidisciplinary perspective,published evidence on the management of oligometastatic NSCLC patients.We evaluate the different alternatives for radical ablative treatments,the role of primary tumor resection or radiation,the impact of systemic treatments,and the therapeutic sequence.In short,the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Pure motor stroke as the most frequent lacunar syndrome: A clinical update

Pure motor stroke(PMS), also known as pure motor hemiparesis, is the most common of any lacunar form(between one half and two thirds of cases, depending on the series). In an acute stroke registry, 733 patients presented a lacunar infarct and PMS accounted for 12.7%(n = 342) of all first-ever stroke patients and for 48% of all lacunar syndromes. The posterior limb of the internal capsule, corona radiata, and pons are the most frequent brain topographies. Infarcts in the mesencephalus or medullary pyramid have been exceptionally reported. This present update is focused on the clinical evidence and mechanisms underlying the relationship between PMS and different stroke etiologies.

Emergency Short-Stay Unit as an Effective Alternative to In-Hospital Admission for Acute Exacerbation of Chronic Heart Failure

Study Objective: To determine whether a new emergency department short-stay unit (EDSSU) was an effective alternative to conventional hospital units (HU) for acute exacerbation of chronic heart failure patients. Methods: Design: A comparative analysis was used to identify differences among patients admitted to EDSSU (n = 1546) and those admitted to the internal medicine (n = 552) or cardiology wards (n = 336) during the period of the study (January 1, 2008 to December 31, 2012). Setting: The study was performed at Sant Pau Hospital, a 500-bed teaching tertiary care referral center in Barcelona, Spain. The ED attends about 144,000 emergency visits per year. Participants: We studied retrospectively the characteristics of patients hospitalized with an acute exacerbation of chronic heart failure between January 1, 2008 and December 31, 2012 (n = 2434). We chose charts of patients from the hospital discharge database and selected according to the 9th revision of the International Classification of Diseases Codes. We used the computerized database to obtain outcome data on all patients. Results: Statistically significant differences were found in terms of mean age (HU: 77.38 (14.44) years versus EDSSU: 82.43 (8.72) years;p p p p = 0.998). There were statistically significant differences regarding sex (HU women = 60.6%;EDDSU women = 67.7%;p p < 0.001). Conclusion: The EDSSU proved to be an effective and safe measure in emergency care of patients with acute heart failure (AHF).

Short-Stay Surgery: Impact of Opening a New Unit in a Tertiary Urban Hospital

Objective: The number of procedures considered suitable for short-stay surgery has experienced a remarkable increase. The objective of the study was to determine whether a new short-stay surgical unit (SSSU) was an effective alternative to conventional Hospital Units (HU) for selected elective and urgent surgical conditions. Methods: A comparative analysis (Mann-Whitney test) was used to identify differences between patients admitted to HU (n = 2873) and those admitted to the SSSU (n = 544) during the following months (January 1, 2014 to August 31, 2014, and January 1, 2015 to August 31, 2015, respectively). Results: Statistically significant differences were found in terms of mean length of stay (HU: 4.8 days versus SSSU: 2.2 days;P P = 0.02). There were no statistically significant differences regarding age and sex. Conclusions: We conclude that selected surgical patients with elective or acute conditions can be effectively treated in the SSSU.

Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients

AIM: To determine the clinical reasons for conversion to everolimus(EVL) and long-term outcomes in heart transplant(HT) recipients.METHODS: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT recipients.RESULTS: Two hundred and twenty-two patients were included(mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity(30%), chronic allograft vasculopathy(20%) and neoplasms(17%). The doses and mean levels of EVL at baseline(conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors(CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d(P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL(P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL(P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min(P < 0.001). There were 37 episodes of acute rejection in 24 patients(11%). The most frequent adverse events were oedemas(12%), infections(9%) and gastrointestinal problems(6%). EVL was suspended in 44 patients(20%). Since the database was closed at the end of the study, no further followup data is available.CONCLUSION: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

Classical and Non-Classical Celiac Disease Comparison: Ten Years of Study

Objective: Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten. It has a variable combination of clinical manifestations and changes that have been occurring in recent decades however they are not known in detail. The purpose of the article is to compare Classical and Non-Classical CD cases in terms of demographic characteristics, duodenal biopsy, extraintestinal manifestations, and associated comorbidities. Materials and Methods: A comparative retrospective cohort study from January 2008 to December 2018. Results: A total of 128 cases were included: 84 Classical (66%) and 44 Non-Classical CD (34%). The family history of CD was identified in 14% of cases without differences between groups. The age at diagnosis was distinct for Classical and Non-Classical CD (4.9 ± 4 and 8.3 ± 4 years old;p 0.001), respectively. Important changes were found within the classical presentation, including mono symptoms and a significantly higher rate of intestinal atrophy;p = 0.04. The main Non-Classical CD symptom was recurrent abdominal pain. The extraintestinal manifestations (EIM) were identified in 42% and occurred in both groups. The comparison between groups showed differences in rates of migraine and vitamin D deficiency and was higher for Non-Classical CD (p 0.05). Associated diseases occurred in 10.9%, and type 1 diabetes was significant for the Non-Classical CD group (p = 0.04). Conclusion: The classical CD was the most prevalent profile and presented a decrease in the severity of symptoms however remain a higher rate of intestinal atrophy. Recurrent abdominal pain was the main symptom of Non-Classical CD. Extraintestinal manifestations and associated diseases presented an increasing trend of occurrence among cases of Non-Classical CD.

Prognostic value of increased carbohydrate antigen in patients with heart failure

AIM:To study the prognostic value of carbohydrateantigen 125(CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide(NT-proBNP) in stable heart failure(HF) patients.METHODS:The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011.Patients were included in the study if they had a previous documented episode of HF and received HF treatment.CA125 and NT-proBNP concentrations were measured.The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis,and their combined predictive ability was tested by the integrated discrimination improvement(IDI) index.RESULTS:The mean age of the 156 patients was 72 ± 12 years.During follow-up(17 ± 8 mo),27 patients died,1 received an urgent heart transplantation and 106 required hospitalization for HF.Higher CA125 values were correlated with outcomes:58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not(P < 0.05),and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors(P < 0.01).After adjusting for propensity scores,the highest risk was observed when both biomarkers were elevated vs not elevated(HR = 8.95,95%CI:3.11-25.73; P < 0.001) and intermediate when only NT-proBNP was elevated vs not elevated(HR = 4.15,95%CI:1.41-12.24; P < 0.01).Moreover,when CA125 was added to the clinical model with NT-proBNP,a 4%(P < 0.05) improvement in the IDI was found.CONCLUSION:CA125 > 60 KU/L identified patients in stable HF with poor survival.Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.

Failed medial patellofemoral ligament reconstruction:Causes and surgical strategies

Patel ar instability is a common clinical problem encountered by orthopedic surgeons specializing in the knee. For patients with chronic lateral patellar instability, the standard surgical approach is to stabilize the patella through a medial patellofemoral ligament(MPFL) reconstruction. Foreseeably, an increasing number of revision surgeries of the reconstructed MPFL will be seen in upcoming years. In this paper, the causes of failed MPFL reconstruction are analyzed:(1) incorrect surgical indication or inappropriate surgical technique/patient selection;(2) a technical error; and(3) an incorrect assessment of the concomitant risk factors for instability. An understanding of the anatomy and biomechanics of the MPFL and cautiousness with the imaging techniques while favoring clinical over radiological findings and the use of common sense to determine the adequate surgical technique for each particular case, are critical to minimizing MPFL surgery failure. Additionally, our approach to dealing with failure after primary MPFL reconstruction is also presented.

Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know

External beam radiotherapy(EBRT) is one of the principal curative treatments for patients with prostate cancer(PCa). Risk group classification is based on prostate-specific antigen(PSA) level, Gleason score, and T-stage. After risk group determination, the treatment volume and dose are defined and androgen deprivation therapy is prescribed, if appropriate. Traditionally, imaging has played only a minor role in T-staging due to the low diagnostic accuracy of conventional imaging strategies such as transrectal ultrasound, computed tomography, and morphologic magnetic resonance imaging(MRI). As a result, a notable percentage of tumours are understaged, leading to inappropriate and imprecise EBRT. The development of multiparametric MRI(mp MRI), an imaging technique that combines morphologic studies with functional diffusion-weighted sequences and dynamic contrastenhanced imaging, has revolutionized the diagnosis and management of PCa. As a result, mpM RI is now used in staging PCa prior to EBRT, with possible implications for both risk group classification and treatment decisionmaking for EBRT. mpM RI is also being used in salvageradiotherapy(SRT), the treatment of choice for patients who develop biochemical recurrence after radical prostatectomy. In the clinical context of biochemical relapse, it is essential to accurately determine the site of recurrence-pelvic(local, nodal, or bone) or distant-in order to select the optimal therapeutic management approach. Studies have demonstrated the value of mpM RI in detecting local recurrences-even in patients with low PSA levels(0.3-0.5 ng/m L)-and in diagnosing bone and nodal metastasis. The main objective of this review is to update the role of mpM RI prior to radical EBRT or SRT. We also consider future directions for the use and development of MRI in the field of radiation oncology.

Cytokine production in patients with cirrhosis and TLR4 polymorphisms

AIM:To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.METHODS:The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms,and 10 wild-type patients matched for age,sex and degree of liver failure.TLR4 polymorphisms were determined by sequence-based genotyping.Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide(LPS)and lipoteichoic acid(LTA)stimulation.RESULTS:Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients(78%vs 20%,P=0.02).Spontaneous production of interleukin(IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients[IL-6:888.7(172.0-2119.3)pg/m L vs 5540.4(1159.2-26053.9)pg/m L,P<0.001;IL-10:28.7(6.5-177.1)pg/m L vs 117.8(6.5-318.1)pg/m L,P=0.02].However,the production of tumor necrosis factor-α,IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups.CONCLUSION:TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients,suggesting that they play a role in the development of cirrhosis complications.

Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2

The 2004 discovery of EGFR mutations,followed by ALK rearrangements,ushered in a targeted therapy era for advanced non-small cell lung cancer(NSCLC).Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC.In the last decade,rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies.Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets,including RET,NTRK fusions,c-MET alterations,and activating mutations in KRAS,BRAF,and HER2,all with frequencies greater than 1%.Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development.This review updates the therapeutic arsenal that especially targets those genes.

Anemia in patients with high-risk acute coronary syndromes admitted to Intensive Cardiac Care Units

Background Little information exists about the role of anemia in patients with acute coronary syndromes(ACS)admitted to Intensive Cardiac Care Units(ICCU).The aim of this study was to assess the prevalence of anemia and its impact on management and outcomes in this clinical setting.Methods All consecutive patients admitted to eight different ICCUs with diagnosis of non-ST segment elevation ACS(NSTEACS)were prospectively included.Anemia was defined as hemoglobin<130 g/L in men and<120 g/L in women.The association between anemia and mortality or readmission at six months was assessed by the Cox regression method.Results A total of 629 patients were included.Mean age was 66.6 years.A total of 197 patients(31.3%)had anemia.Coronary angiography was performed in most patients(96.2%).Patients with anemia were significantly older,with a higher prevalence of comorbidities,poorer left ventricle ejection fraction and higher GRACE score values.Patients with anemia underwent less often coronary angiography,but underwent more often intraaortic counterpulsation,non-invasive mechanical ventilation and renal replacement therapies.Both ICCU and hospital stay were significantly longer in patients with anemia.Both the incidence of mortality(HR=3.36,95%CI:1.43–7.85,P=0.001)and the incidence of mortality/readmission were significantly higher in patients with anemia(HR=2.80,95%CI:2.03–3.86,P=0.001).After adjusting for confounders,the association between anemia and mortality/readmission remained significant(P=0.031).Conclusions Almost one of three NSTEACS patients admitted to ICCU had anemia.Most patients underwent coronary angiography.Anemia was independently associated to poorer outcomes at 6 months.

Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical resection.Neoadjuvant chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease.Treatment with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies.These immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term benefits.Importantly,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications.However,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival outcomes.Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

Advances and controversies in the management of early stage nonsmall cell lung cancer

Complete resection continues to be the gold standard for the treatment of earlystage lung cancer.The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer,as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy.There is a growing tendency to perform sublobar resection in selected cases,as,depending on factors such as tumor size,histologic subtype,lymph node involvement,and resection margins,it can produce similar oncological results to lobectomy.Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse surgery.