Massimo Castiglioni

Radiologic Evaluation of Small Lepidic Adenocarcinomas to Guide Decision Making in Surgical Resection

BACKGROUND The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of pulmonary adenocarcinomas identifies indolent lesions associated with low recurrence, superior survival, and the potential for sublobar resection. The distinction, however, is determined on the pathologic evaluation, limiting preoperative surgical planning. We sought to determine whether preoperative computed tomography (CT) characteristics could guide decisions about the extent of the pulmonary resection. METHODS We reviewed the preoperative CT scans for 136 patients identified to have adenocarcinomas with lepidic features on the final pathologic evaluation. The solid component on CT was substituted for the invasive component, and patients were radiologically classified as adenocarcinoma in situ, 3 cm or less with no solid component; minimally invasive adenocarcinoma, 3 cm or less with a solid component of 5 mm or less; or invasive adenocarcinoma, exceeding 3 cm or solid component exceeding 5 mm, or both. Analysis of variance, t test, χ(2) test, and Kaplan-Meier methods were used for analysis. RESULTS The radiologic classification identified 35 adenocarcinomas in situ (26%) and 12 minimally invasive (9%) and 89 invasive adenocarcinoma (65%) lesions. At a 32-month median follow-up, patient outcomes associated with the radiologic classification were similar to the pathologic-based classification: the radiologic classification identified 14 of 16 patients with recurrent disease and all 6 who died of lung cancer. In addition, patients with radiologic adenocarcinoma in situ and minimally invasive adenocarcinoma who underwent sublobar resections had no recurrence and 100% disease-free and overall survival at 5 years. CONCLUSIONS The radiologic classification of patients with lepidic adenocarcinomas is associated with similar oncologic and survival outcomes compared with the pathologic classification and may guide decision making in the approach to surgical resection.

Patients with multiple nodules and a dominant lung adenocarcinoma have similar outcomes and survival compared with patients who have a solitary adenocarcinoma

OBJECTIVES Lepidic growth pattern lung adenocarcinoma commonly presents as a dominant lesion (DL) with associated pulmonary nodules either in the ipsilateral or contralateral lung fields, posing a challenge in clinical decision-making. These tumours may be clinically upstaged compared with those who present with solitary lesions and, as a result, may be offered different therapies. The purpose of this study is to compare recurrence rates, the development of new lesions and survival in patients with adenocarcinoma with a lepidic component presenting with a DL with or without additional nodules. METHODS We performed a 13-year retrospective chart review of patients with lepidic growth pattern adenocarcinoma. Patients were grouped into a uninodular group (UG) if they presented with a solitary lesion and a multinodular group (MG) if they had a DL with additional nodules. Clinicopathological features, outcomes and survival between the two groups were analysed. RESULTS A total of 149 patients were identified: 62 (42%) in the UG and 87 (58%) in the MG. In addition to the DL, 217 nodules were preoperatively identified in the MG: 60 were resected concomitantly with the DL, while 157 were radiologically surveyed. Invasive adenocarcinoma was the predominant pathological cell type in both groups. The median time of follow-up was 3 years [interquartile range (IQR) 1.9-5.1]. Local (1 vs 2%), regional (1 vs 3%) and distant recurrences (7 vs 4%) were detected, respectively, in the UG and the MG. In the UG, 20 new lesions were identified, while in the MG there were 28. Only 4 of 157 (2.5%) surveyed pre-existing lesions were found to be malignant and required further treatment. No statistically significant differences were observed in 5-year disease-free and overall survival between the UG and the MG (82.3 vs 83.8%, P = 0.254 and 86.7 vs 93.8%, P = 0.096, respectively). CONCLUSIONS We observed that patients with lepidic growth pattern adenocarcinoma presenting with a DL with associated secondary nodules appear to behave similarly to patients with a solitary lesion. Multiple nodules including those that are malignant in this specific subset of non-small-cell lung cancer should not be upstaged as advanced disease and patients should be treated with the same curative intent as those presenting with uninodular disease.

The challenge of prognostic markers in pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a very aggressive tumor, highly resistant to chemo- and radio-therapy. Treatment of MPM patients is often disappointing, regardless of the modality used. Inter-individual variability of response to multimodal treatment remains a challenge and generally the MPM prognosis continues to be poor. Knowledge of predicting factors of outcome is currently insufficient; therefore, it would be highly desirable to find specific prognostic markers for MPM. Translational research projects are to be implemented.

Chest pain control with kinesiology taping after lobectomy for lung cancer: initial results of a randomized placebo-controlled study †

OBJECTIVES Kinesiology taping (KT) is a rehabilitative technique performed by the cutaneous application of a special elastic tape. We tested the safety and efficacy of KT in reducing postoperative chest pain after lung lobectomy. METHODS One-hundred and seventeen consecutive patients, both genders, age 18-85, undergoing lobectomy for lung cancer between January 2013 and July 2015 were initially considered. Lobectomies were performed by the same surgical team, with thoracotomy or video-assisted thoracoscopic surgery (VATS) access. Exclusion criteria (n = 25 patients) were: previous KT exposure, recent trauma, pre-existing chest pain, lack of informed consent, >24-h postoperative intensive care unit treatment. After surgery, the 92 eligible patients were randomized to KT experimental group (n = 46) or placebo control group (n = 46). Standard postoperative analgesia was administered in both groups (paracetamol/non-steroidal anti-inflammatory drugs, epidural analgesia including opioids), with supplemental analgesia boluses at patient request. On postoperative day 1 in addition, in experimental group patients a specialized physiotherapist applied KT, with standardized tape length, tension and shape, over three defined skin areas: at the chest access site pain trigger point; over the ipsilateral deltoid/trapezius; lower anterior chest. In control group, usual dressing tape mimicking KT was applied over the same areas, as placebo. Thoracic pain severity score [visual analogue scale (VAS) ranging 0-10] was self-assessed by all patients on postoperative days 1, 2, 5, 8, 9 and 30. RESULTS The KT group and the control group had similar demographics, lung cancer clinico-pathological features and thoracotomy/VATS ratio. Postoperatively, the two groups also resulted similar in supplemental analgesia, complication rate, mean duration of chest drainage and length of stay. There were no adverse events with KT application. After tape application, KT patients reported overall less thoracic pain than the control group, the difference being significant on postoperative day 5 [median VAS, 2 (interquartile range, 1-3) vs 3 (2-5), P < 0.01] and day 8 [median VAS, 1 (0-2) vs 2 (1-3), P < 0.05]. Moreover, on postoperative day 30 persistence of chest pain (VAS ≥3) was reported less frequently by the KT group than by the control group (7 vs 24%; P = 0.03). CONCLUSIONS KT after lung lobectomy is a safe and effective auxiliary technique for chest pain control. ISRCTN REGISTRY ISRCTN37253470.

Resection rate of lung cancer in Teesside (UK) and Varese (Italy): a comparison after implementation of the National Cancer Plan

Background In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations. Methods For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter ‘the 2010 cohort’), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate. Results In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p<0.001), performance status improved (p<0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I–II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p<0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I–II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0–1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64). Conclusions In Teesside the main independent predictor of resection was disease stage; in 2010–2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.

Management of Hypertension in Intrapericardial Paraganglioma

Functioning paraganglioma is extra-adrenal catecholamine-secreting tumours that may cause secondary hypertension. Primary intrapericardial paragangliomas are very rare and are located adjacent to the great vessels or heart, typically near the left atrium. These tumours are an exceptionally uncommon finding during the investigation of refractory hypertension. However, in recent years, intrapericardial paragangliomas have been diagnosed incidentally with increased frequency, due to the extensive use of radiologic chest imaging. The mainstay of treatment of functioning intrapericardial paraganglioma is surgical removal, which usually achieves blood pressure normalization. Due to the locations of these tumours, the surgical approach is through a median sternotomy or posterolateral thoracotomy, and manipulation-induced catecholamine release may cause paroxysmal hypertension. Typically in these patients, blood pressure fluctuates dramatically intra- and post-operatively, increasing the risk of cardiovascular complications. We review here the current modalities of perioperative fluid and hypotensive drug administration in the setting of surgery for functioning intrapericardial paraganglioma and discuss the recently proposed paradigm shift that omits preoperative preparation.

Surveillance of the Remaining Nodules after Resection of the Dominant Lung Adenocarcinoma is an Appropriate Follow-Up Strategy

Introduction: Adenocarcinomas, commonly present as a dominant lesion (DL) with additional nodules in the ipsilateral or contralateral lung. We sought to determine the fate and management of the secondary nodules and to assess the risk of these nodules using the Lung CT Screening Reporting and Data System (Lung-RADS) criteria and the National Comprehensive Cancer Network (NCCN) Guidelines to determine if surveillance is an appropriate strategy. Methods: We retrospectively evaluated patients with lepidic growth pattern adenocarcinoma and secondary nodules from 2000 to 2013. Risk assessment of the additional lesions was completed with a simplified model of Lung-RADS and NCCN-Guidelines. Results: Eighty-seven patients underwent resection of 87 DLs (Group 1) concurrently with 60 additional pulmonary nodules (Group 2), while 157 non-DLs were radiologically surveyed over a median follow-up time of 3.2 years (Group 3). Malignancy was found in 29/60 (48%) nodules in Group 2. Whereas, only 9/157 (6%) of the lesions in Group 3 enlarged, 4 of which (2.5% of total) were found to be malignant, and then treated, while the remaining nodules continued surveillance. After applying the Lung-RADS and NCCN simplified models, nodules in Group 2 were at higher risk for lung cancer than those in Group 3. Conclusion: In patients with lepidic growth pattern adenocarcinoma associated with multiple secondary nodules, surveillance of the remaining nodules, after resection of the DL, is a reasonable strategy since these nodules exhibited a slow rate of growth and minimal malignancy. In contrast, nodules resected from the ipsilateral lung at the time of the DL, harbor malignancy in 48%. Risk assessment models may provide a useful and standardized tool for clinical assessment of pulmonary nodules.

Assessment of the aggregate risk score to predict mortality after surgical biopsy for interstitial lung disease

OBJECTIVES An aggregate risk score (range 0-6 points) for predicting mortality after surgical biopsy for interstitial lung disease (ILD) was recently developed from four independent variables: intensive care unit treatment (2 points), age >67 years (1.5 points), immunosuppression (1.5 points), open biopsy (1 point). In the development cohort, patients were grouped in four classes of aggregate score (A, B, C, D) showing incremental risk of death within 90 days from biopsy. We tested this mortality risk model in an independent cohort. METHODS The aggregate risk score and the corresponding class of 90-day mortality risk was retrospectively determined in 151 consecutive patients undergoing biopsy for uncertain ILD at the Center for Thoracic Surgery, University of Insubria (Varese, Italy) in 1997-2012. We evaluated, by Spearmans ρ test, the correlation between aggregate risk score and mortality rate in the development cohort and in our cohort. Fishers exact test was used for comparison of overall mortality rate between the two cohorts. RESULTS The mortality rate correlation with risk score differed in our cohort (ρ = 0.127; P = 0.06) compared with the development cohort (ρ = 0.352; P < 0.0001). In our dataset mortality polarized: it was minimal in Classes A and B (2% and 0%, respectively), 33% in Classes C and D. This skewed mortality distribution was possibly contributed by significantly lower overall mortality rate in our cohort than in the development cohort (2.6% vs 10.6%; P = 0.0017). Despite the difference in mortality distribution, in our dataset, we confirmed that ILD patients with aggregate score >2 (Classes C and D) were at exceedingly high risk of postoperative mortality. CONCLUSIONS The aggregate score is a simple and useful risk score for ILD. Our dataset confirms that lung biopsy is reasonably safe in Class A and B patients while, in Class C and D patients, it is indicated only if histology would substantially change management and prognosis.

Thoracoscopic or robotic surgery? No matter, as long as they have good results

Despite the encouraging results, minimally invasive thoracic surgery is still used in a minority of non-small cell lung cancer (NSCLC) patients, currently in about one third of all major pulmonary resections (1). Since the 1990s video-assisted thoracic surgery (VATS) has gradually become more and more popular and, over the past two decades, it has been gradually accepted as an alternative option to open thoracotomy for selected patients. Compared with thoracotomy, VATS lobectomy is associated with less pain, shorter chest tube duration, fewer cardiac complications (especially atrial fibrillation), lower rate of infectious complications (i.e., pneumonia), lower incidence of blood transfusion, shorter length of hospitalization and faster recovery (2-4). Another significant advantage of VATS has been reported in high risk patients, particularly in those with preoperative poor pulmonary function (5).