A simple size-tailored algorithm for the removal of chest drain following minimally invasive lobectomy: a prospective randomized study.

BACKGROUND: The pleural space can resorb 0.11-0.36 ml/kg of body weight/hour (h) per hemithorax. There are only a limited number of studies on thresholds for chest drain removal (CDR) and all are based on arbitrary amounts, for example, 300 ml/day. We studied an individualized size-based threshold for CDR-specifically 5 ml/kg, a simple, easily applicable measure. METHODS: This is a single-center prospective randomized trial enrolling 80 patients undergoing VATS lobectomy. There were two groups: an experimental (E) group, in which once the daily output went down to 5 ml/kg the chest drain was removed and a control (C) group, with chest drain removal as per our current practice of less than 250 ml/day. RESULTS: The groups did not differ in pre- and peri- and postoperative characteristics, except for chest drain duration (mean, SD 2.02 ± 0.97 vs. 3.25 ± 1.39 days, p < 0.001) and length of hospital stay (median, IQR 4.5; 3 vs. 6; 2.75 days, p = 0.008) in favor of E group. The re-intervention rate was the same in both groups (once in each group). CONCLUSION: The new threshold for chest drain removal following thoracoscopic lobectomy of 5 ml/kg/d leads to both shorter chest drainage and hospital stay without apparent increase in morbidity. (Clinical registration number: DRKS00014252).

Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade.

AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (i) externally validate the prognostic role of pleomorphic features in E-MPM and (ii) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared to those without (5.4 versus 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 versus 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting: An External Validation Study of 563 Cases.

Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P<0.001 except 2-tier nuclear grade, P=0.001). In the scenario of a single- site biopsy with tissue dimension ≤10 mm, none but age (P=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum tissue dimension of at least 20 mm from a single site is optimal for nuclear grade assessment. In conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy cohort provided the tissue sample met minimum dimensional criteria.

Management of Progressive Pulmonary Nodules Found during and outside of CT Lung Cancer Screening Studies.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk. This is also endorsed by many major medical societies and advocacy group stakeholders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.

Increasing frequency of non-smoking lung cancer: Presentation of patients with early disease to a tertiary institution in the UK.

BACKGROUND: Never-smokers with lung cancer often present late as there are no established aetiological risk factors. The aim of the study is to define the frequency over time and characterise clinical features of never-smokers presenting sufficiently early to determine if it is possible to identify patients at risk. METHODS: We retrospectively analysed data from a prospectively collected database of patients who underwent surgery. The frequency was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were collated as frequency. RESULTS: A total of 2170 patients underwent resection for lung cancer from March 2008 to November 2014. The annual frequency of developing lung cancer in never-smokers increased from 13% to 28%, attributable to an absolute increase in numbers and not simply a change in the ratio of never-smokers to current and ex-smokers. A total of 436 (20%) patients were never-smokers. The mean age was 60 (16 SD) years and 67% were female. Presenting features were non-specific consisting of cough in 34%, chest infections in 18% and haemoptysis in 11%. A total of 14% were detected on incidental chest film, 30% on computed tomography, 7% on positron-emission tomography/computed tomography and 1% on MRI. CONCLUSIONS: We observed more than a double of the annual frequency of never-smokers in the last 7 years. Patients present with non-specific symptoms and majority were detected on incidental imaging, a modality that is likely to play an increasingly important role for early detection in this cohort that does not have any observable clinical risk factors.

Follicular dendritic cell tumour/sarcoma: a commonly misdiagnosed tumour in the thorax.

AIMS: Follicular dendritic cell sarcoma is a rare tumour reported to occur occasionally in association with the hyaline-vascular type of Castleman's disease (HVCD). Most cases arise in lymph nodes, although extranodal presentation is described. METHODS AND RESULTS: Clinical, radiological and histological characteristics, including diagnosis on pre-resection material, were assessed in seven intrathoracic cases from five males and two females with a median age of 38 years. Clinical symptoms were related to mass location, six cases presenting within central and/or posterior mediastinal compartments and one within the lungs. Positron emission tomography-computed tomography demonstrated marked fluoro-deoxy-glucose avidity and the prominent vessels traversing the lesions. Four of six cases (67%) were misdiagnosed initially. HVCD was present in three cases. Two cases with high mitotic rates recurred after resection. All were positive for at least one of the follicular dendritic cell markers (CD21, CD35 and CD23). Six of seven cases (86%) show cyclin D1 expression ranging from 5% to 90%. CONCLUSIONS: Follicular dendritic cell sarcoma is often misdiagnosed on biopsy and pathologists need to be aware of the tumour to request the relevant immunohistochemistry, especially in masses presenting in the central/posterior mediastinum with high vascularity and standardized uptake values. Background HVCD appears more common than previously thought.

Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model.

BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I.

Adult lung tumours of childhood origin.

The remit of this article is principally to explore the risk of malignancy developing in a congenital cystic adenomatoid malformation (CCAM) in adulthood.

The Rationale for Treatment of Postresectional Bronchopleural Fistula: Analysis of 52 Patients.

BACKGROUND: Bronchopleural fistulas are a major therapeutic challenge. We have reviewed our experience to establish the best choice of treatment. METHODS: From January 2001 to December 2013, the records of 3,832 patients who underwent pulmonary anatomic resections were retrospectively reviewed. RESULTS: The overall incidence of bronchopleural fistulas was 1.4% (52 of 3,832): 1.2% after lobectomy and 4.4% after pneumonectomy. Pneumonectomy vs lobectomy, right-sided vs left-sided resection, and hand-sewn closure of the stump vs stapling showed a statistically significant correlation with fistula formation. Primary bronchoscopic treatment was performed in 35 of 52 patients (67.3%) with a fistula of less than 1 cm and with a viable stump. The remaining 17 patients (32.7%) underwent primary operation. The fistula was cured with endoscopic treatment in 80% and with operative repair in 88.2%. Cure rates were 62.5% after pneumonectomy and 86.4% after lobectomy. The cure rate with endoscopic treatment was 92.3% in very small fistulas, 71.4% in small fistulas, and 80% in intermediate fistulas. The cure rate after surgical treatment was 100% in small fistulas, 75% in intermediate fistulas, and 100% in very large fistulas. Morbidity and mortality rates were 5.8% and 3.8%, respectively. CONCLUSIONS: The bronchoscopic approach shows very promising results in all but the largest bronchopleural fistulas. Very small, small, and intermediate fistulas with a viable bronchial stump can be managed endoscopically, using mechanical abrasion, polidocanol sclerosing agent, and cyanoacrylate glue. Bronchoscopic treatment can be repeated, and if it fails, does not preclude subsequent successful surgical treatment.

Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours.

Positron emission tomography-CT (PET-CT) is one of the initial mediastinal staging modality for non-small cell lung cancer; however, the clinical utility in carcinoid tumours is uncertain. We sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. We collated data from seven institutions, performing a retrospective search on pathological databases for a consecutive series of patients who underwent thoracic surgery (with lymph nodal dissection) for carcinoid tumours with preoperative PET-CT staging. PET-CT results were compared with the reference standard of pathologic results obtained from lymph node dissection and test performance reported using sensitivity and specificity. From November 1999 to January 2013, 247 patients from seven institutions underwent surgery for carcinoid tumours with a corresponding preoperative PET-CT scan. The mean age of the patients was 61 (SD 15, range 73) and 84 were male patients (34%). The pathologic subtype was typical carcinoid in 217 patients (88%) and atypical carcinoid in 30 patients (12%). Results from lymph node dissection were obtained in 207 patients. The calculated sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 33% (95% CI 4% to 78%) and 94% (95% CI 89% to 97%), respectively. Our results indicate that PET-CT has a poor sensitivity but good specificity to detect the presence of mediastinal lymph node metastases in pulmonary carcinoid tumours. Mediastinal lymph node metastases cannot be ruled out with negative PET-CT uptake, and if the absence of mediastinal lymph node disease is a prerequisite for directing management, tissue sampling should be undertaken.

Type A and AB thymomas: histological features associated with increased stage.

AIMS: The current WHO classification of thymic epithelial neoplasms describes type A and type AB thymomas as behaving 'like benign neoplasms'. However, recent published data suggest that rare cases may show more aggressive behaviour. The aim of this study was to assess the frequency of atypical cases, and to determine whether atypia is associated with more advanced disease. METHODS AND RESULTS: One hundred and twenty-one thymomas (type A, n = 68; type AB, n = 53) were retrospectively reviewed for 'atypical' features (nuclear pleomorphism, mitotic activity, and necrosis). Logistic regression was used to ascertain the association with increasing Masaoka-Koga stage. Where available, follow-up data were also reviewed. There were 72 stage I, 42 stage II, five stage III and two stage IV tumours. Only the presence of necrosis showed a significant association with increased stage in univariate and multivariate analysis. Nuclear atypia and increased mitotic activity were not associated with increasing stage of disease. CONCLUSIONS: Our data support the concept of there being more aggressive atypical variants of both type A and type AB thymoma, and suggest that the presence of necrosis could be used to predict aggressive behaviour.

Surgical approaches for lung volume reduction in emphysema.

Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) is recommended in both British and international guidelines because trials have shown improvement in survival in selected patients with poor baseline exercise capacity and upper lobe-predominant emphysema. Despite this, few procedures are carried out, possibly because of historical concerns about high levels of morbidity and mortality associated with the operation. The authors reviewed data on lung volume reduction procedures at their institution between January 2000 and September 2012. There were no deaths within 90 days of unilateral LVRS (n = 81), bullectomy (n = 20) or intracavity drainage procedures (n = 14). These data suggest that concerns about surgical mortality should not discourage LVRS in selected patients with COPD, provided that it is undertaken within a multidisciplinary team environment involving appropriate patient selection.

Pure bronchoplastic resections of the bronchus without pulmonary resection for endobronchial carcinoid tumours.

OBJECTIVES: Bronchopulmonary carcinoid tumours are relatively uncommon primary lung neoplasms. A small proportion of these lesions are predominantly endobronchial and do not extend beyond the bronchial wall. Endoscopic resection can be performed, but carries around a one in three risk of local recurrence and, therefore, mandates long-term surveillance. An alternative is complete surgical resection via bronchoplastic resection. We present our experience of surgical resection in patients with endobronchial carcinoids. METHODS: From 2000 to 2010, 13 patients (age 45±16 years, 10 males) underwent pure bronchoplastic resection, including systematic nodal dissection, for endobronchial carcinoid tumours, without the resection of lung parenchyma. RESULTS: There was no significant operative morbidity or mortality. This is a retrospective review of a consecutive case series. The last follow-up for all patients was obtained in 2011. The mean maximum tumour size was 18±8 mm. No lymph node invasion was observed. The median follow-up was 6.3±3.3 years, with no regional recurrence. In 1 case, a tumourlet was identified at 5 years in the contralateral airway and viewed as a metachronous new lesion. CONCLUSIONS: Bronchial sleeve resection is a safe procedure for suitably located endobronchial carcinoid tumours. Endoscopic resection should be reserved for patients who decline, or are unfit, for surgery.

Prognostic significance of predominant histologic pattern and nuclear grade in resected adenocarcinoma of the lung: potential parameters for a grading system.

INTRODUCTION: Currently, no agreed histologic grading system exists for lung adenocarcinomas (ADCs). With a recently updated consensus classification, the aim of this study was to assess potential prognostic factors identifiable on routine histology, which might be used as grading parameters. METHODS: A retrospective study of resected pulmonary ADCs (n = 238) in patients with stage IA to IIIB disease was carried out in which various histopathological parameters were correlated with survival data. The relationship between these factors and patient survivability was analyzed using Cox proportional hazards regression. RESULTS: Mitotic rate was found to be a highly significant prognostic marker (p = 0.008), as was overall nuclear grade (p < 0.001). ADC subtyping was also found to be potentially important, as lepidic predominant (hazard ratio 0.99, p = 0.023) and solid predominant (hazard ratio 1.01, p = 0.003) subtypes were found to be independent (to age and tumor, node, metastasis category) prognostic predictors. Vessel invasion within tumor approached significance as a negative prognostic factor (p = 0.067). CONCLUSIONS: This study showed not only that histologic subtype and mitotic rate are important prognostic factors in lung ADCs, but also that other criteria described previously may not be useful in our specific patient population.

Pulmonary sequestration with haemoptysis and an unsuspected carcinoid tumour.

We report the case of a fit and healthy 41-year-old man, who presented with significant haemoptysis without a history of recurrent infections. His computed tomography scan showed a dense lesion in the left lower lobe with a feeding vessel arising from the abdominal aorta, characteristic for an intra-pulmonary sequestration. To prevent possible further haemoptysis or infections, a left lower lobectomy was performed. The histological examination showed the typical features of a sequestration. However, within the sequestration, a carcinoid tumour without atypical features was found. There was no lymph node involvement. Sequestrations are congenital lesions without communication with the bronchial tree and with a systemic blood supply. They commonly cause recurrent infection. Fatal haemoptysis has also been described, but is rare. There are very few reports of neoplastic lesions in sequestrations. This case illustrates two unusual aspects of sequestrations. Surgery offers definitive treatment for both pathologies, as opposed to embolisation.