Pierluigi Novellis

Usefulness of Whole-Body Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Patients with Neurofibromatosis Type 1: A Systematic Review

Aim. To systematically review the role of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). Methods. A comprehensive literature search of published studies regarding FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit and language restriction were used; the search was updated until December 2011. Only those studies or subsets in studies including whole-body FDG-PET or PET/CT scans performed in patients with NF1 were included. Results. We identified 12 studies including 352 NF1 patients. Qualitative evaluation was performed in about half of the studies and semiquantitative analysis, mainly based on different values of SUV cutoff, in the others. Most of the studies evaluated the role of FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors (MPNSTs). Malignant lesions were detected with a sensitivity ranging between 100% and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG-PET seems to be an important imaging modality for predicting the progression to MPNST and the outcome in patients with MPNST. Two studies evaluated the role of FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are useful methods to identify malignant change in neurogenic tumors in NF1 and to discriminate malignant from benign neurogenic lesions.

Does myasthenia gravis influence overall survival and cumulative incidence of recurrence in thymoma patients? A Retrospective clinicopathological multicentre analysis on 797 patients

OBJECTIVE Aim of this study is to evaluate whether Myasthenia Gravis (MG) might influence Overall Survival (OS) and Cumulative Incidence of Recurrence (CIR) in thymoma patients. METHODS this is a multicenter retrospective study of patients operated in 6 high-volume Italian Institutions between 1990 and 2012. OS was estimated by the Kaplan-Meier method and CIR by considering death from any cause as a competing event. Crude and adjusted comparisons by MG for OS and CIR were performed using Cox and Fine&Gray models. Adjusted models included MG, age, gender, stage, histology, induction therapy, completeness of resection, adjuvant therapy. RESULTS Seven hundred ninety-seven patients were included: 375 (47%) had MG. MG patients were younger and more frequently female, with a B2-B3 thymoma. At the end of the study, 129 patients (54 with MG) developed a recurrence and 165 (66 with MG) died. At univariate analysis, MG showed a slight protective effect on OS, not confirmed by the multivariate model. Age, incomplete resection, advanced stages and thymic carcinoma were negative prognostic variables. Univariate analyses showed no evidence of MG protective effect on CIR. Advanced stages and induction therapy were significant negative predictors. CONCLUSION our study showed that MG was significantly associated with female, lower age and B2-B3 thymoma; it demonstrated a slight protective effect on OS at the univariate analysis which was not confirmed in multivariate as well as no impact on CIR. Advanced tumor stages and thymic carcinoma histology for OS and induction therapy and advanced stages for CIR were negative prognostic variables.

Chest wall tumors and prosthetic reconstruction: A comparative analysis on functional outcome

To address the question of how much chest‐wall (CW) resections and prosthetic reconstructions influence functional outcome.

Robotic lung cancer surgery: review of experience and costs

Use of robot-assisted techniques is growing fast in several surgical disciplines, now including thoracic surgery. The paper reviews experience of robotic surgery to resect lung cancer and in particular analyzes data on the costs of these procedures in comparison to open surgery and video-assisted thoracoscopic surgery (VATS). Retrospective studies published over 14 years show that robotic surgery for lung cancer has the advantages of minimally invasive surgery for patients, and some advantages over VATS for the surgeon. Limited data indicate that oncological outcomes are comparable with those of VATS and open surgery, while lymph node dissection may be more radical. Other studies indicate that robotic surgery for lung cancer offers no advantages either in terms of costs or outcomes. The high costs of purchase, maintenance and consumables are a concern and continue to limit uptake of robot systems in thoracic surgery. Most studies-but not all-indicate that robotic surgery for lung cancer is more expensive than VATS and open surgery. However limited data also indicate that hospitals can make a profit from robotic thoracic surgery, as costs seem to be lower than reimbursements from paying bodies. Nevertheless robotic thoracic surgery is still too expensive for many public hospitals, particularly in low income countries. Entry of new surgical robot manufacturers onto the market will bring much-needed competition that may also lead to cost reduction.

Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior.

OBJECTIVE Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors. METHODS From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors. RESULTS Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (∼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients. CONCLUSION BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis.

Thoracoscopic Nuss procedure or open Ravitch technique for pectus excavatum repair in young adult patients: a Hamlet's indecision.

We read with great interest the article by Hanna and collegues [1] about the use of the Nuss procedure in pectus excavatum (PE) repair for adult patients. Nuss and colleagues created a revolution in 1998 with their new, mini-invasive method to correct PE. A significant number of reports have been written to compare the two different techniques, but after 16 years, there is still no consensus about the best procedure to use. In our institution, we have performed a 170 Ravitch procedure. Only patients with aHaller index greater than 3.25 associatedwith one or more symptoms of dyspnea or pain underwent surgery. The current dominant theory to explain the development of PE is the overgrowth of costal cartilages, which pushes the sternal body inward and causes the deformity. The required force to elevate the nonmobilized sternum into the corrected position can be up to 250 N. Greater force is required for older patients. Chondrotomies and retrosternal dissection might reduce the needed force to 25 N [2]. Based on this consideration, the Ravitch technique is still preferred over the Nuss technique. We understand the choice not to use a computed tomographic (CT) examination, but the CT examination is important to define the gravity of PE and the sternal body introversion degree. Davis andWeinstein [3] confirmed that Ravitch used a safe and effective approach providing reliable results over a long period of time. Lam and colleagues [4] compared quality of life of different patients (mean age, 15.5 years) undergoing PE correction by Nuss or Ravitch procedure. The observation did not show any significant difference between the Nuss and Ravitch surgical approaches. Based on these considerations, we think that it is mandatory to develop a standard procedure for the PE correction for young adults.

Robotic resection of Stage III lung cancer: an international retrospective study

OBJECTIVES Minimally invasive surgery is accepted for early-stage lung cancer, but its role in locally advanced disease is controversial, especially using a robotic platform. The aim of this retrospective study was to assess the safety and effectiveness of robot-assisted resection in patients with Stage IIIA non-small-cell lung cancer (NSCLC) or carcinoid tumours in the series as a whole and in different subgroups according to adjuvant treatment. METHODS This was a retrospective multicentre study of consecutive patients with clinically evident or occult N2 disease (210 NSCLC and 13 carcinoid) who, in 2007-2016, underwent robot-assisted resection at 7 high-volume centres. Perioperative outcomes, recurrences and overall survival were assessed. RESULTS N2 disease was diagnosed preoperatively in 72 (32%) patients and intraoperatively in 151 (68%) patients. Surgical margins were negative in 98.4% of cases with available data. Thirty-four (15.2%) patients received neoadjuvant treatment, 140 (63%) patients received postoperative treatment, and 49 (22%) patients underwent surgery only. There were 22 (9.9%) conversions to thoracotomy, 23 (10.3%) had serious (Grades III-IV) postoperative morbidity and the mean hospital stay was 5.3 days. Complications and outcomes did not differ significantly between treatment groups. Of the 34 patients who were given neoadjuvant chemotherapy, all had R0 resection, 5 (15%) patients required conversion but none required conversion because of bleeding and 4 (12%) patients had Grade III or IV postoperative complications. After a median of 18 (interquartile range 8-33) months, 3-year overall survival in NSCLC patients was 61.2% and 60.3% (P = 0.6) of patients in the subgroup were given induction treatment. However, overall survival was significantly better (P = 0.012) in NSCLC patients with ≤2 positive nodes (vs >2). Nineteen (8.5%) patients developed local recurrence. CONCLUSIONS Robot-assisted lobectomy is safe and effective in patients with Stage III NSCLC or carcinoid tumours with low conversions and complications. Among patients with NSCLC, including those who were given induction chemotherapy, survival was similar to that reported for open surgery.

FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression

Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade. FLNA silencing reduces cyclin D1 levels (-51±5, p<0.001) and cell proliferation in PNT cells (-37±4, p<0.05), colony formation and VEGF expression (-39±9%, p<0.01) in H727 cells. FLNA and Rap1 co-localize in cellular protrusions and FLNA silencing up-regulates Rap1 expression (+73±18%, p<0.01). Rap1 silencing prevents cell adhesion increase (+43%±18%, p<0.01) and cell migration decrease (-56±7%, p<0.01) induced by FLNA silencing, without affecting cell proliferation reduction. In conclusion, FLNA is implicated in PNT progression, in part through Rap1, thus providing a potential diagnostic and therapeutic target.

Robot-assisted surgery for lung cancer: State of the art and perspectives.

The robotic surgical system is the result of a long process of development aimed at producing a natural extension of the surgeons eyes and hands via the intermediation of a computer. In this way, the ease of movement obtained with open surgery is summated with the advantages of the minimally invasive technique. Since 2000, when the first robotic system for surgery was introduced, robot-assisted thoracic surgery (RATS) has been adopted by an increasing number of centres around the world, and today is used in ∼10% of lobectomies in the US. Here, we review the characteristics and function of the robotic system available today (namely, Intuitive Surgical Inc.s da Vinci Surgical System), outline the different techniques for major lung resection via RATS, compare RATS with video-assisted thoracoscopic surgery (VATS) and thoracotomy, and speculate on future developments. To date, no randomized trials have reported comparative data on RATS vs. VATS/thoracotomy for lung cancer. Retrospective analysis comparing RATS vs. thoracotomy have revealed advantages for the former, especially shorter hospital stays and a lower complication rate, but RATS produces similar or only slightly better results to VATS, the two being minimally invasive techniques with no need for rib separation. A few studies have reported RATS to be safer than VATS, with less conversions for bleeding, less complications; in others, it was associated with lower postoperative consumption of pain killers and quicker return of patients to normal activity. In addition, lymphnode upstaging has been shown to be higher with RATS than with VATS, with a similar rate as thoracotomy. The main disadvantage of RATS is the higher costs of instrumentation. Nevertheless, the future will probably see reductions in the costs and improvements in the instrumentation, integration with 3D imaging to improve virtual reality, and more patients benefitting from minimally invasive procedures for lung malignancies.

Surgical Treatment in Patient with Non–Small-Cell Lung Cancer with Fissure Involvement: Anatomical versus Nonanatomical Resection

Objective: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non–small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. Methods: From January 2000 to January 2010, the clinical data of 40 non–small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, &khgr;2, and log-rank tests, Kaplan–Meier method, and Cox and logistic regression analyses were used for the statistical analysis. Results: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (−24.9% ± 13.5%) when compared with that in group B (−19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). Conclusions: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in “frail” patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life.