Nivolumab increases pulmonary artery pressure in patients treated for non-small cell lung cancer.

PURPOSE: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). METHODS: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated. RESULTS: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p < 0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1. CONCLUSION: Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.

Subsolid Lung Nodule Classification: A CT Criterion for Improving Interobserver Agreement.

Purpose To evaluate an objective computed tomographic (CT) criterion for distinguishing between part-solid (PS) and nonsolid (NS) lung nodules. Materials and Methods This study received institutional review board approval, and patients gave informed consent. Preoperative CT studies in all patients who underwent surgery for subsolid nodules between 2008 and 2015 were first reviewed by two senior radiologists, who subjectively classified the nodules as PS or NS. A second reading performed 1 month later used predefined classification criteria and involved a third senior radiologist as well as three junior radiologists. Subsolid nodules were classified as PS if a solid portion was detectable in the mediastinal window setting (nonmeasurable, < 50%, or > 50% of the entire nodule) and were otherwise classified as NS (subclassified as pure or heterogeneous). Interreader agreement was assessed with κ statistics and the intraclass correlation coefficient (ICC). Results A total of 99 nodules measuring a median of 20 mm (range, 5-47 mm) in lung window CT images were analyzed. Senior radiologist agreement on the PS/NS distinction increased from moderate (κ = 0.54; 95% confidence interval [CI]: 0.37, 0.71) to excellent (κ = 0.89; 95% CI: 0.80, 0.98) between the first and second readings. At the second readings, agreement among senior and junior radiologists was excellent for PS/NS distinction (ICC = 0.87; 95% CI: 0.83, 0.90) and for subcategorization (ICC = 0.82; 95% CI: 0.77, 0.87). When a solid portion was measurable in the mediastinal window, the specificity for adenocarcinoma invasiveness ranged from 86% to 96%. Conclusion Detection of a solid portion in the mediastinal window setting allows subsolid nodules to be classified as PS with excellent interreader agreement. If the solid portion is measurable, the specificity for adenocarcinoma invasiveness is high. © RSNA, 2017 Online supplemental material is available for this article.

Prognostic factors after pulmonary metastasectomy of colorectal cancers: a single-center experience.

BACKGROUND: Surgical resection has been widely admitted as the treatment of choice for pulmonary metastases of colorectal cancer (CRC). Nevertheless, this practice is not supported by high level of evidence and patients' eligibility remains controversial. Aim of this study was to evaluate long terms results and factors influencing survival after lung metastasectomy of CRC. METHODS: A single-center retrospective analysis of patients with pathologically proven colorectal metastasis, operated from 2004 to 2013, was performed. Patients were treated with a multidisciplinary approach and selected for surgery if complete resection was considered feasible. RESULTS: Three hundred and six patients were considered for analysis. Mean number of lesions at CT scan was 2.6±2.3. Ratios of each largest resection type at first side surgery were: segmentectomy 20.6%, lobectomy 12.9%, bilobectomy 1.2%, pneumonectomy 1.2% and sub-lobar resection 64.1%, respectively. No in-hospital death occurred. At pathology, mean number of resected metastasis was 2.6±2.3, ranging from 1 to 12. Resection was complete in 92.5% of patients. Nodal involvement was proven in 40 (12.9%) patients. The initially planned complete resection could not be achieved in 23 (7.5%) cases. Mean follow-up was 3.06±2.36 years. Kaplan-Meier analysis revealed that recurrence-free survival (RFS) was 76.3% [95% confidence interval (95% CI), 71-80.7%], 38.9% (95% CI, 33-44.7%), 28.3% (95% CI, 22.5-34.4%) and 22.7% (95% CI, 16.5-29.5%) at 1, 3, 5 and 7 years, respectively. Overall survival (OS) estimates were 77.8% (95% CI, 72.7-82.7%), 59.0% (95% CI, 51.2-66.4%), and 56.9% (95% CI, 48.4-65.0%) at 3, 5 and 7 years, respectively. Multivariate analysis, including pT parameter of the primary tumor, number of lesions, one-sided versus bilateral lung disease, and body mass index (BMI) (all significant at univariate analysis), showed that bilateral disease (P<0.001) and pT4 primary (P=0.005) were independent pejorative predictors of OS, whereas BMI ≥25 was protective (P=0.028). CONCLUSIONS: Bilateralism and primary tumor local extension influence the prognosis of patients surgically treated for pulmonary colorectal metastases. Specifically designed randomized trials are necessary.

Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer.

BACKGROUND: Hypothesizing that morphometric measurements are reliable markers of fitness in patients with lung cancer requiring aggressive surgical intervention, the purpose of this study was to assess their impact on postoperative outcome and long-term survival in patients with non-small cell lung cancer (NSCLC) requiring pneumonectomy. METHODS: Height, weight, and body mass index (BMI), as well as usual clinical, laboratory (including C-reactive protein [CRP] concentrations), and pathologic data were retrospectively retrieved from files of 161 consecutive patients treated by pneumonectomy for NSCLC, whose preoperative computed tomographic (CT) scans were available in the Picture Archive and Communication System (PACS) of the hospital. Cross-sectional areas of right and left psoas areas (measured by CT scan at the L3 level), perirenal fat thickness, and anterior subcutaneous tissue thickness at the left renal vein level were also assessed. RESULTS: BMI and total psoas area were strongly and directly correlated (p = 0.0000001), whereas BMI was inversely related to CRP levels. Sarcopenia (total psoas area ≤33rd percentile) was associated with high CRP levels (>20 mg/L) (p = 0.010). Factors associated with 90-day mortality included older age (p = 0.000045), lower body weight (p = 0.032), and BMI less than or equal to 25 kg/m2 (p = 0.013). At univariate analysis, long-term outcome was negatively affected by a nonsquamous cell histologic type (p = 0.011), pathologic stage IIIB-IV (p =0.026), CRP levels greater than 20 mg/L (p = 0.017), BMI less than or equal to 25 kg/m2 (p = 0.010), and total psoas area less than or equal to the 33rd percentile (p = 0.029). Multivariate analysis showed the independent prognostic value of both BMI and total psoas area. CONCLUSIONS: BMI less than or equal to 25 kg/m2 and total psoas cross-sectional area less than or equal to the 33rd percentile are prognostic determinants in patients with NSCLC requiring pneumonectomy.

Indications and Results of Reconstructive Techniques with Flaps Transposition in Patients Requiring Complex Thoracic Surgery: A 12-Year Experience.

BACKGROUND: Flap transposition is an infrequent but far from exceptional thoracic surgical procedure. The aim of this retrospective study was to report our experience in a referral unit of general thoracic surgery analyzing the early results after flap transposition. METHODS: We retrospectively analyzed the clinical records, surgical notes, and postoperative results of a cohort of patients who underwent flap transposition in our unit from November 2000 to February 2013. RESULTS: Overall, a surgical approach adopting flap reconstruction techniques was performed in 81 patients (54 males, 27 females) with a median age of 62 years (range 20-87). Flap transposition was necessary to reconstruct chest wall after resection for malignancy (27 patients), to repair intrathoracic viscera perforation (15 patients), and to fill residual cavities secondary to pulmonary/pleural infection (39 patients). A pedicle muscle flap was transposed in most of cases (64 pts, 79 %), while in the remaining 17 cases (11 %), an omental flap was used. There were no immediate postoperative complications, while three in-hospital deaths occurred due to respiratory or multiorgan failure. Among patients undergone flap transposition to fill a residual cavity, we observed a recurrent bronchopleural fistula in three patients (7.7 %); such patients were treated by repeat flap transposition (2 cases) and by repeat cavernostomy (1 case). CONCLUSION: Flap transposition may be indicated as part of a multimodal treatment for severely ill patients requiring complex thoracic surgery.

A case of variant scimitar syndrome.

Scimitar syndrome is one of the large congenital pulmonary venolobar syndromes and is defined as hypogenetic lung associated with partial anomalous pulmonary venous return. We report the case of a 25-year-old man with complex and exceptional variant scimitar syndrome. A chest CT scan with three-dimensional (3-D) reconstruction led us to identify hypoplastic right lung with homolateral hemidiaphragm agenesis and hypogenetic right pulmonary artery. There was a large and sinuous systemic arterial supply and anomalous venous return directed into the left atrium (venous return being usually directed into the right atrium or inferior vena cava in scimitar syndrome). Hyperoxia test showed no shunt. This variant scimitar syndrome has been previously reported and anomalous venous return called "meandering" pulmonary vein. Diagnosis and management of these patients with complex congenital anomalies are difficult because of their exceptional condition. Chest CT scan with 3-D reconstruction offers an accurate noninvasive diagnosis.

Alternatives to resectional surgery for infectious disease of the lung: from embolization to thoracoplasty.

Surgical treatment of lung diseases is based on removal of the affected lung tissue, achieved by atypical or anatomic lung resection. Infectious lung diseases are generally treated by medical therapy, including medications, chest physiotherapy, bronchoscopic toilet, and respiratory rehabilitation. Surgical management of infectious disease of the lung is integrated in the multispecialty care. This article focuses exclusively on nonresectional surgery and other alternatives to lung resection and addresses bacterial infection and fungal disease of the lung.

Comparison of coronal and axial computed tomography measurements of mediastinal nodes before primary surgery for non-small cell lung cancer.

OBJECTIVE: To assess computed tomography (CT) evaluation of mediastinal nodes in non-small cell lung cancer to predict metastatic involvement by measurement of their axis and surface area in the coronal plane, as compared to standard short-axis measures in the axial plane. METHODS: Evaluation of mediastinal nodes was retrospectively performed on CT scans of 100 patients before thoracotomy. In all patients, mediastinal dissection was performed in the appropriate stations (n=264) according to the side (59 right, 41 left) of the tumor. Measurements of short axis and surface area of the largest node in each dissected station were performed on axial and coronal planes. RESULTS: By using the standard threshold of axial short axis ≥10 mm, sensitivity and specificity were 25% and 98%, respectively. Areas under receiver operating characteristic curves were 0.828 and 0.821 for axial short axis and axial surface area data. For comparison, areas under receiver operating characteristic curves were 0.843 and 0.845 for coronal short axis and coronal surface area data, respectively. So, for a specificity of 98%, sensitivity was 29% for coronal short axis ≥11 mm and 33% for coronal surface area ≥123 mm(2). When using axial short axis ≥10 mm or coronal surface area ≥120 mm(2), sensitivity was 45%, whereas specificity remained at 96%. CONCLUSION: Coronal measurements of mediastinal nodes give a slightly albeit non-significant improvement of diagnostic accuracy over axial ones. If both axial short axis and coronal surface area are taken into account, accuracy is improved.