Franca Melfi

Four-arm robotic lobectomy for the treatment of early-stage lung cancer

OBJECTIVES We investigated the feasibility and safety of four-arm robotic lung lobectomy in patients with lung cancer and described the robotic lobectomy technique with mediastinal lymph node dissection. METHODS Over 21 months, 54 patients underwent robotic lobectomy for early-stage lung cancer at our institute. We used a da Vinci Robotic System (Intuitive Surgical, Inc, Mountain View, Calif) with three ports plus one utility incision to isolate hilum elements and perform vascular and bronchial resection using standard endoscopic staplers. Standard mediastinal lymph node dissection was performed subsequently. Surgical outcomes were compared with those in 54 patients who underwent open surgery over the same period and were matched to the robotic group using propensity scores for a series of preoperative variables. RESULTS Conversion to open surgery was necessary in 7 (13%) cases. Postoperative complications (11/54, 20%, in each group) and median number of lymph nodes removed (17.5 robotic vs 17 open) were similar in the 2 groups. Median robotic operating time decreased by 43 minutes (P = .02) from first tertile (18 patients) to the second-plus-third tertile (36 patients). Median postoperative hospitalization was significantly shorter after robotic (excluding first tertile) than after open operations (4.5 days vs 6 days; P = .002). CONCLUSIONS Robotic lobectomy with lymph node dissection is practicable, safe, and associated with shorter postoperative hospitalization than open surgery. From the number of lymph nodes removed it also appears oncologically acceptable for early lung cancer. Benefits in terms of postoperative pain, respiratory function, and quality of life still require evaluation. We expect that technologic developments will further simplify the robotic procedure.

Mutational Analysis in Cytological Specimens of Advanced Lung Adenocarcinoma: A Sensitive Method for Molecular Diagnosis

Introduction: The discovery that somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with sensitivity to the EGFR tyrosine kinase inhibitors (TKIs) in lung adenocarcinomas, whereas Kras mutations are associated with resistance, has generated excitement among both clinicians and researchers studying non-small cell lung cancer (NSCLC). Mutational analysis may soon be very useful in choosing among a wide range of targeted therapies to individualize treatment to tumor characteristics. This analysis would be even more useful in patients with advanced NSCLC, in whom cytological specimens are often the only material available. Methods: We analyzed 23 archived cytologic specimens of advanced/metastatic lung adenocarcinomas for mutations in EGFR exons 18 to 21, and Kras exon 2. Results: Our data show that our cytological specimens were perfectly adequate for the molecular analysis of EGFR and Kras mutations. EGFR TK domain mutations were found in three cases (13.04%) and were associated with both female gender (p = 0.02) and a nonsmoking history (p = 0.008). Moreover, we explored the relationship between EGFR mutation status and the presence of Kras mutations. Kras mutations involving codon 12 in exon 2 were found in 5 (21.73%) of the 23 adenocarcinomas and were associated, where known, with smoking habits. We never found EGFR alterations in tumors with Kras mutations. Conclusions: Our results provide oncologists with a highly accurate laboratory method to identify biological predictors of the efficacy of different therapies, and they may have an important impact on clinical practice. This method may be particularly useful in patients with advanced/metastatic NSCLC.

A pilot study of the role of TC-99 radionuclide in localization of pulmonary nodular lesions for thoracoscopic resection

OBJECTIVE Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for diagnosis and treatment of peripheral pulmonary nodules. However, thoracoscopy has limits in the detection of small nodules, below the pleural surface, deep in the lung parenchyma, which cannot be seen as much as palpated. Methods to localize such lesions, including the methylene blue injection or the introduction of a hooked-wire under the radiological vision, have some advantages but a lot of limitations. We are developing a new technique for the detection of pulmonary nodules smaller than 2 cm, deep in the lung parenchyma. METHODS The technique consisted of a intra-lesional injection of 0.3 ml of solution of 99m Tc-labelled human serum albumin microspheres (5-10 MBq) under the CT-scan guide, 2 h before surgery. During thoracoscopy a 11 mm diameter-collimated probe connected to a gamma ray detector (Scinti Probe MR 100 - Pol. hi.tech., Aquila - Italy), is introduced by a 11.5 mm trocar and the pleural surface of the suspected area was scanned. A hot-spot indicated the presence of the injected nodule and as a consequence, the area to be resected. RESULTS from June 1997 to June 1999 we treated 39 patients with small pulmonary nodules. The patients were 27 men and 12 women with a mean age of 60.8 years (range: 13-80). In 19 cases the anamnesis was positive for synchronous or metachronous malignant neoplasm. The mean surgical procedure length was 50 min (range 20-100 min). In all the cases the nodule was resected and the resection margins were pathologically free of tumour. The mean post-operative hospital stay was 3 days (range 2-6 days). Histological examination showed 21 benign lesions and 18 malignant lesions (seven metastases and 11 primary lung cancers). Nine pts with primary lung carcinoma underwent a completion lobectomy by open surgery. CONCLUSIONS Radiolocalization by gamma-probe allows the detection and exeresis of small nodules in a easy and safe way. Future and predictable advances in radio-marked monoclonal antibodies, as well as in the development of endoscopic beta-detector probe, will offer a more effective method for detection of primary and metastatic tumours, targets of thoracoscopic resections.

Robotic renal transplantation: first European case

A kidney from a 56‐year‐old mother was transplanted to her 37‐year‐old daughter laparoscopically using the daVinci HDSi surgical system. The kidney was introduced into the abdomen through a 7‐cm suprapubic incision used also for the uretero‐vescical anastomosis. Vascular anastomoses were carried out through a total of three additional ports. Surgery lasted 154 min, including 51 min of warm ischemia of the graft. Urine production started immediately after graft reperfusion. Renal function remains optimal at the longest follow‐up of 3 months. The technique employed in this case is discussed in comparison with the only other two contemporary experiences, both from the USA. Furthermore, possible advantages and disadvantages of robotics in kidney transplantation are discussed extensively. We conclude that the daVinci surgical system allows the performance of kidney transplantation under optimal operative conditions. Further experience is needed, but it is likely that solid organ transplantation will not remain immune to robotics.

Robotically Assisted Lobectomy: Learning Curve and Complications

The past two decades have witnessed a revolutionary transition in surgical technique and technology with the development of minimally invasive approaches. Many advantages were obtained by using video-assisted thoracoscopic surgery: less surgical trauma and pain, shorter hospital stay, and satisfactory cosmetic results. Limitations still remain, however, because of impaired vision, restricted instrument-maneuverability, unstable camera platform, and poor ergonomics for the surgeon. Some of the more prominent limitations involve the technical and mechanical nature of the equipment. This article describes technical aspects, learning curve, and complications in the field of robotic lobectomy.

Robot-aided thoracoscopic thymectomy for early-stage thymoma: A multicenter European study

OBJECTIVE Minimally invasive thymectomy for stage I to stage II thymoma has been suggested in recent years and considered technically feasible. However, because of the lack of data on long-term results, controversies still exist on surgical access indication. We sought to evaluate the results after robot-assisted thoracoscopic thymectomy in early-stage thymoma. METHODS Data were collected from 4 European centers. Between 2002 and 2011, 79 patients (38 men and 41 women; median age, 57 years) with early-stage thymoma were operated by left-sided (82.4%), right-sided (12.6%), or bilateral (5%) robotic thoracoscopic approach. Forty-five patients (57%) had associated myasthenia gravis. RESULTS Average operative time was 155 minutes (range, 70-320 minutes). One patient needed open conversion, in 1 patient a standard thoracoscopy was performed after robotic system breakdown, and in 5 patients an additional access was required. No vascular and nervous injuries were recorded, and no perioperative mortality occurred. Ten patients (12.7%) had postoperative complications. Median hospital stay was 3 days (range, 2-15 days). Median diameter of tumor resected was 3 cm (range, 1-12 cm), and Masaoka stage was stage I in 30 patients (38%) and stage II in 49 patients (62%). At a median follow-up of 40 months, 74 patients were alive and 5 had died (4 patients from nonthymoma-related causes and 1 from a diffuse intrathoracic recurrence), with a 5-year survival rate of 90%. CONCLUSIONS Our data indicate that robot-enhanced thoracoscopic thymectomy for early-stage thymoma is a technically sound and safe procedure with a low complication rate and a short hospital stay. Oncologic outcome seems good, but a longer follow-up is needed to consider this as a standard approach definitively.

ALK Rearrangement in a Large Series of Consecutive Non–Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment

CONTEXT Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application. OBJECTIVE To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC. DESIGN We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. RESULTS Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. CONCLUSIONS Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

Neoadjuvant Chemotherapy for Stage III and IVA Thymomas: A Single-Institution Experience with a Long Follow-up

Background: Since 1989 we have enrolled patients with clinical-radiological stage III-IVA thymomas, independent of the surgeons judgment of resectability, into a prospective study of neoadjuvant chemotherapy–surgery and postoperative radiotherapy. In this article, we review our long-term experience of neoadjuvant chemotherapy of advanced stage (III-IVA) thymomas. Methods: From 1989 to 2004, 30 patients with Masaoka stage III and IVA thymomas underwent neoadjuvant chemotherapy, surgery, and postoperative radiotherapy. The neoadjuvant and adjuvant chemotherapy consisted of three courses of cisplatin, epidoxorubicin, and etoposide every 3 weeks. Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections. Results: The preoperative diagnosis of invasive thymomas was obtained for 16 patients: five by mediastinotomy, seven by video-assisted thoracic surgery, and four by fine needle aspiration. For 14 patients, no histological diagnosis was available, but a thymus-related syndrome was present in all. Twenty-seven patients are still alive (25 disease-free) and three have died (one disease-free). The 10-year survival rates were 85.7% and 76.1% for stage III and IVA thymomas, respectively (difference not significant). Only the World Health Organization pathological diagnosis significantly affected the survival, with type B3 having a worse prognosis than type AB, B1, and B2 thymomas (p = 0.02). Conclusion: The multimodality treatment of stage III and IVA thymomas by means of neoadjuvant chemotherapy provides good long-term outcomes in both stages of the disease.

Intraoperative radioguided sentinel lymph node biopsy in non-small cell lung cancer

OBJECTIVES The aim of this study was to determine the accuracy and the role of the sentinel lymph node (SLN) technique in patients with early non-small cell lung cancer (NSCLC). METHODS This study was carried out on 29 consecutive patients (M/F = 24:5, mean age 65.9 +/- 7.1 years) with resectable NSCLC (Stage IA-IB). Intraoperative injection with a (99m)Tc-nanocolloid suspension was performed in the first ten patients; the following patients were injected under computed tomography scan guidance. A total dose of 37 MBq (1 ml) was administered in two to four divided aliquots (depending on the size), injected in the periphery of the tumour. Intraoperative radioactivity counting started a mean of 1 h (range 50-70 min) after the injection. The SLN was defined as the node with the highest count rate using a handheld gamma probe counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic and immunohistochemistry (IHC) examination. RESULTS Three of the 29 patients did not have NSCLC (two benign lesions, and one metastatic breast tumour) and were excluded. The SLN was identified in 25/26 (96.1%) patients (a total of 31 SLNs); 7/31 (22.5%) of the SLNs were positive for metastatic involvement after histologic and IHC examination. One inaccurately identified SLN was encountered (3.8%). CONCLUSIONS These preliminary results demonstrate the feasibility of this procedure in identifying the first site of potential nodal metastases of NSCLC. The actual clinical impact of this procedure remains to be elucidated by further investigation in larger groups of patients.

Surgical treatment of non-small cell lung cancer in octogenarians

As the European population ages, surgeons are regularly faced with octogenarians with resectable early stage non-small cell lung cancer (NSCLC). We compared our experience with those reported in the literature to comprehend the feasibility, outcomes and lessons learned regarding surgical treatment. We reviewed octogenarians who underwent lung resection for NSCLC in the past nine years in our Department. The purpose of this paper is to retrospectively analyse postoperative surgical and oncological outcomes of our series, trying to find possible correlations between mortality, morbidity, survival and preoperative oncological and functional assessment, surgical approach and extent of resection. Eighty-two patients (M/F = 63/19), with a mean age 81.0 years (range 80-87 years) underwent lung resection for NSCLC: 63 lobectomies, one inferior bilobectomy, three segmentectomies, and 15 wedge resections. There were two perioperative deaths (2.4%). The overall complication rate was 30.0%, with a major complication rate of 2.5%. Actuarial cancer-related survival rates at one, three and five years were 90%, 44% and 36%, respectively, with a statistically-significant correlation with pathological stage. Octogenarians may benefit from surgical treatment of NSCLC with an acceptable morbidity and mortality rate, if an accurate preoperative selection is pursued.