Ex Vivo Irradiation of Lung Cancer Stem Cells Identifies the Lowest Therapeutic Dose Needed for Tumor Growth Arrest and Mass Reduction In Vivo.

Radiotherapy represents a first-line treatment for many inoperable lung tumors. New technologies offer novel opportunities for the treatment of lung cancer with the administration of higher doses of radiation in smaller volumes. Because both therapeutic and toxic treatment effects are dose-dependent, it is important to identify a minimal dose protocol for each individual patient that maintains efficacy while decreasing toxicity. Cancer stem cells sustain tumor growth, promote metastatic dissemination, and may give rise to secondary resistance. The identification of effective protocols targeting these cells may improve disease-free survival of treated patients. In this work, we evaluated the existence of individual profiles of sensitivity to radiotherapy in patient-derived cancer stem cells (CSCs) using both in vitro and in vivo models. Both CSCs in vitro and mice implanted with CSCs were treated with radiotherapy at different dose intensities and rates. CSC response to different radiation doses greatly varied among patients. In vitro radiation sensitivity of CSCs corresponded to the therapeutic outcome in the corresponding mouse tumor model. On the other side, the dose administration rate did not affect the response. These findings suggest that in vitro evaluation of CSCs may potentially predict patients' response, thus guiding clinical decision.

Is video-assisted thoracoscopic lobectomy associated with higher overall costs compared with open surgery? Results of best evidence topic analysis.

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video-assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers.

Retroaortic closure of thoracic duct in the management of persistent chylothorax: a case report.

BACKGROUND: Chylothorax is a life-threatening pathological condition associated with significant morbidity and mortality. If chyle leakage does not close spontaneously with medical therapy, surgical treatment is inevitable. Herein, we reported a case of spontaneous persistent chylothorax from mediastinal seminoma that was successfully closed between the descending thoracic aorta, and the vertebral column through a left mini-thoracotomy. CASE PRESENTATION: A 24-year old man with mediastinal seminoma was referred to our attention for management of high output persistent chylothorax (> 800 ml/24 h for 30 days) that did not close with conservative treatment. As the leak was isolated within left upper chest cavity, we planned to close the thoracic duct via Poirier's triangle by uniportal thoracoscopy. However, the long conservative treatment favoured the formation of multiple, tenacious, and bleeding adhesions that made unfeasible thoracoscopy. A conversion to mini-thoracotomy was performed; by the incision of the posterior parietal pleura, the thoracic duct was isolated and ligated behind the thoracic aorta, in an anatomical space delimited by the 4th and the 5th posterior intercostal arteries and the vertebral column. CONCLUSIONS: Complete resolution of chylothorax was obtained the day after. Patient was discharged on post-operative day 5, and no recurrence was observed during the follow-up.

Uniportal Thoracoscopic Thoracic Duct Clipping in Poirier's Triangle for Postoperative Chylothorax.

Postoperative chylothorax is a rare but potentially life-threatening complication. Conservative treatment is usually unsuccessful in patients with high-output chylothorax, for whom early surgical thoracic duct ligation has been advocated to minimize morbidity and mortality. This report describes left uniportal thoracoscopic closure of persistent high-output chylothorax through Poirier's triangle in a patient undergoing thoracoscopic thymectomy. After resection of pleural adhesions, the mediastinal pleura was resected at the level of the aortic arch, left subclavian artery, and vertebral column, the anatomic limits of Poirier's triangle. The thoracic duct was then isolated from the esophagus and successfully clipped along its path.

Uniportal thoracoscopy combined with laparoscopy as minimally invasive treatment of esophageal cancer.

A 67-year-old man was referred to our attention for management of esophageal adenocarcinoma, localized at the level of the esophagogastric junction and obstructed the 1/3 of the esophageal lumen. Due to the extension of the disease (T3N1M0-Stage IIIA), the patient underwent neo-adjuvant chemo-radiation therapy and he was then scheduled for a minimally invasive surgical procedure including laparoscopic gastroplasty, uniportal thoracoscopic esophageal dissection and intrathoracic end-to-end esophago-gastric anastomosis. No intraoperative and post-operative complications were seen. The patient was discharged in post-operative day 9. Pathological study confirmed the diagnosis of adenocarcinoma (T2N1M0-Stage IIB) and he underwent adjuvant chemotherapy. At the time of present paper, patient is alive and well without signs of recurrence or metastasis. Our minimally approach compared to standard open procedure would help reduce post-operative pain and favours early return to normal activity. However, future experiences with a control group are required before our strategy can be widely used.

Resection of esophageal diverticulum through uniportal video-assisted thoracoscopic surgery.

Open surgery remains the standard strategy for management of esophageal diverticulum in symptomatic patients. However, in the last years an increasing number of minimally invasive approaches have been proposed for this issue in order to reduce the surgical trauma and favor a fast return to daily activity. Herein, we describe a novel technique as uniportal video-assisted thoracoscopic surgery (VATS) for performing resection of esophageal diverticulum. This procedure was successfully carried out in three consecutive patients with giant mid-esophageal diverticulum (mean size: 6.5±0.5 cm). The mean post-operative time was 121±10 minutes. The chest drain was removed 48 hours later in all cases and the mean length of hospital stay was 9±1 days. No intraoperative neither postoperative complications were found in all patients but one. He had a small fistula 15 days later that was successfully treated with stent insertion. No recurrence of diverticulum was seen in all cases. Uniportal VATS is a feasible procedure that in theory could reduce the surgical trauma compared to standard open approach. However, future prospective studies should corroborate our impression before it can be recommended as acceptable therapy.

Uniportal video-assisted lobectomy through a posterior approach.

We propose a technique of uniportal VATS lobectomy using a posterior approach. The main differences of our technique versus standard anterior uniportal VATS are the following: (I) the surgical incision is performed in the auscultatory triangle instead of in the posterior axillary line and (II) the surgeon is placed posteriorly to the patient rather than anteriorly. For thoracic surgeons who are familiar with posterolateral thoracotomy, our technique allows to replicate the same maneuvers performed in the open approach. This strategy was applied with success in 19 consecutive patients for anatomical resection of neoplastic (n=17) and benign (n=2) diseases.

Uniportal bilateral video-assisted sequential thoracoscopic extended thymectomy.

Standard video-assisted thoracoscopic surgery has been reported as a minimally invasive approach alternative to sternotomy for management of myasthenia gravis (MG) associated with thymoma or thymic hyperplasia. Uniportal video-thoracoscopy is an evolution of standard multi-portal video-thoracoscopy for management of several thoracic diseases but its role for resecting mediastinal tumor remains under-evaluated. Herein, we describe our experience with bilateral uniportal thoracoscopic sequential extended thymectomy with case and video illustrations.

Tubeless tracheal resection and reconstruction for management of benign stenosis.

BACKGROUND: We reported a tubeless tracheal resection and reconstruction for the management of benign posttracheostomy tracheal stenosis. METHODS: A 34-year-old man with stridor, severe respiratory distress, and recurrent pneumonia was referred to our attention for treatment of benign posttracheostomy tracheal stenosis. As he refused general anesthesia, the procedure was performed while he was under local anesthesia and spontaneous ventilation. RESULTS: Sedation was started with infusion of dexmedetomidine 0.7 mg/kg/min and of remifentanil 0.5 mg/kg/h; also, 40%-50% oxygen was delivered using a laryngeal mask at a rate of 3.5 mL/min. An additional dose of 2% lidocaine was injected into the surgical site during the operation to achieve an adequate level of anesthesia. A standard resection and reconstruction of trachea was carried out and no recurrence was found in the follow-up of 41 months. CONCLUSION: Tubeless tracheal surgery seems to be a feasible and safe procedure. Larger prospective series should validate our results.

Uniportal Video-Assisted Thoracoscopic Surgery Resection of a Giant Midesophageal Diverticulum.

We describe a new video-assisted technique for the management of a giant midesophageal diverticulum using a single 5-cm port. It maintained the same principles of the traditional open technique as diverticulectomy, myotomy, and fundoplication. The better visualization of the main esophageal body, diverticulum, and esophagogastric junction and the better alignment of the stapler cartridge to the longitudinal axis of the esophagus are all technical factors supporting our procedure. Heavily calcified mediastinal lymph nodes and diffuse pleural adhesions are the main contraindications. However, future experiences are needed before this technique can be recommended as acceptable treatment.

Trans-tracheostomy repair of tracheo-esophageal fistula under endoscopic view in a 75-year-old woman.

Tracheo-esophageal fistula is a life-threatening condition for fatal pulmonary complications. Surgery is the treatment of choice. Unfortunately, the most of patients are unfit for surgery and in these cases there is no a standardized management. Herein, we reported a clinical case of a 75-year-old-woman with a tracheoesophageal fistula related to tracheostomy. The fistula was localized 3.5 cm below the vocal folds and extended 3 cm distally. The patient's poor clinical condition contraindicated surgery while the characteristics of fistula prevented any successfully endoscopic repair with standard methods as application of fibrin glue, clipping, or stenting. Thus, we performed a minimally invasive procedure as trans-tracheotomy closure of the fistula under endoscopic view. Under general anesthesia, the patient was intubated with a rigid bronchoscopy. The cannula was removed and a standard needle-holder was inserted through the tracheotomy. The tear was closed from the distal to the proximal ends with interrupted stitch. Following, a Montgomery T tube was inserted to protect the suture and maintain the air-way patency. At the last follow-up (7 months after the procedure), the patient was alive and tolerated a full diet.

Mediastinal syndrome from plasmablastic lymphoma in human immunodeficiency virus and human herpes virus 8 negative patient with polycythemia vera: a case report.

BACKGROUND: Plasmoblastic lymphoma is a rare and aggressive subtype of diffuse large B cell lymphoma, which occurs usually in the jaw of immunocompromised subjects. CASE PRESENTATION: We describe the occurrence of plasmoblastic lymphoma in the mediastinum and chest wall skin of an human immunodeficiency virus-negative 63-year-old Caucasian man who had had polycytemia vera 7 years before. At admission, the patient showed a superior vena cava syndrome, with persistent dyspnoea, cough, and distension of the jugular veins. Imaging findings showed a 9.7 × 8 × 5.7 cm mediastinal mass. A chest wall neoformation biopsy and ultrasound-guided fine-needle aspiration biopsy of the mediastinal mass allowed diagnosis of plasmoblastic lymphoma and establishment of an immediate chemotherapeutic regimen, with rapid remission of compression symptoms. CONCLUSIONS: Plasmoblastic lymphoma is a very uncommon, difficult to diagnose, and aggressive disease. The presented case represents the first rare mediastinal plasmoblastic lymphoma in a human immunodeficiency virus-/human herpesvirus-8-negative patient. Pathologists should be aware that this tumor does appear in sites other than the oral cavity. Fine-needle aspiration biopsy is a low-cost, repeatable, easy-to-perform technique, with a high diagnostic accuracy and with very low complication and mortality rates. Fine-needle aspiration biopsy could represent the right alternative to surgery in those patients affected by plasmoblastic lymphoma, being rapid and minimally invasive. It allowed establishment of prompt medical treatment with subsequent considerable reduction of the neoplastic tissue and resolution of the mediastinal syndrome.

Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma: A Novel Mini-Invasive Technique.

We report a novel less-invasive extrapleural pneumonectomy for early-stage malignant pleural mesothelioma without rib spreading. Our approach is unique and differed from the previously reported cases, because we used one skin incision and two small intercostal incisions with videothoracoscopic viewing without rib spreading. The pleural dissection and approach to the hilum for pneumonectomy were performed through a 4- to 5-cm port incision in the sixth intercostal space. Another 4- to 5-cm port was made in the eight intercostal space through the same skin incision and was used for diaphragm resection and reconstruction. At the end of the surgery, the skin incision was enlarged to 8 cm; through which and the first port in the sixth intercostal space, the resected specimen was retrieved. Three cycles of adjuvant chemotherapy followed by radiation therapy were administered. Eleven-month follow-up showed no recurrence.

A new technique to repair huge tracheo-gastric fistula following esophagectomy.

We reported the management of a life-threatening condition as a large tracheo-gastric fistula involved the carina, the left and the right bronchus that complicated Ivor Lewis esophagogastrectomy for esophageal cancer. An urgent right thoracotomy was performed and the tracheal defect was covered with a reversed pedicled pericardial patch reinforced with an intercostal muscle flap. Cervical esophagostomy and a feeding jejunostomy completed the operation. Five months later, the continuity of gastrointestinal tract was restored using a transverse colon.

Bilateral single-port thoracoscopic extended thymectomy for management of thymoma and myasthenia gravis: case report.

BACKGROUND: Video-assisted thoracoscopy is become a widely accepted approach for the resection of anterior mediastinal masses, including thymoma. The current trend is to reduce the number of ports and minimize the length of incisions to further decrease postoperative pain, chest wall paresthesia, and length of hospitalization. Herein, we reported an extended resection of thymoma in a patient with myasthenia gravis through an uniportal bilateral thoracoscopic approach. CASE PRESENTATION: A 74 years old woman with myasthenia gravis was referred to our attention for management of a 3.5 cm, well capsulate, thymoma. All laboratory and cardio-pulmonary tests were within normal; thus, she was scheduled for thymoma resection through an uniportal bilateral thoracoscopic approach. Under general anaesthesia and selective intubation, the patient was placed in a 60° right lateral decubitus. A 3 cm skin incision was performed in the fourth right intercostal space and, through that a 30° video-camera and working instruments were inserted without rib spreading. After complete dissection of the thymus and mediastinal fat, the contralateral pleura was opened, and, through that the specimen was pushed into the left pleural cavity. Then, the patient was placed in the left lateral decubitus. Similarly to the right side procedure, a 3-cm incision was performed in the fourth left intercostal space to complete thymic dissection and retrieve the specimen. No intraoperative and post-operative complications were found. The patient was discharged four days later. Pathological examination revealed a type A thymoma (Masaoka stage I). No recurrence was found at 18 months of follow-up CONCLUSIONS: Bilateral single-port thoracoscopy is an available procedure for management of thymoma associated with myasthenia gravis. The less post-operative pain, the reduction of hospital stay and the better esthetic results are all potential advantages of this approach over traditional technique. Obviously, our impression should be validated by larger studies in terms of long-term oncological outcomes.

Bilateral thoracoscopic extended thymectomy versus sternotomy.

BACKGROUND: Complete open surgical resection is the standard treatment for thymoma and myasthenia gravis. We evaluated the feasibility of bilateral video-assisted thoracoscopic extended thymectomy, and compared it to surgery via sternotomy. METHODS: From 2011 to 2014, 43 patients undergoing thymectomy were divided into 2 groups: 23 underwent video-assisted thoracoscopic extended thymectomy, and 20 had thymectomy via sternotomy. The primary outcomes were postoperative pain score (visual analog scale) at 6, 12, 24, 48, and 72 h, and 1-month postoperatively, and morphine consumption in the first 48 h. Secondary outcomes were surgical and clinical results. RESULTS: There were no significant differences between the 2 groups in terms of demographics and preoperative clinical data. Compared to the sternotomy group, the video-assisted thoracoscopic thymectomy group had lower pain scores and morphine consumption at all time points, significantly less operative blood loss and chest drainage volume, and shorter hospital stay. The rates of improvement in myasthenia gravis were 85% and 86% in the video-assisted thoracoscopic thymectomy and sternotomy groups, respectively. No recurrence of thymoma was found in either group (median follow-up 27 months). CONCLUSIONS: Our results seem to confirm that in selected cases, video-assisted thoracoscopic thymectomy allows complete resection of thymus and perithymic tissue, similar to sternotomy but with the known advantages of minimally invasive surgery including less pain and a good cosmetic result.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Reconstruction with a pectoralis major myocutaneous flap after left first rib and clavicular chest wall resection for a metastasis from laryngeal cancer.

We presented a case of recurrent metastasis from epidermoid cancer that occurred in the left clavicle of a patient with a history of laryngeal cancer treated on April 2005 with extended hemilaryngectomy, neck dissection and chemoradiation therapy. On September 2008, he developed a left clavicular metastasis. The disease was initially well controlled by chemoradiotherapy but it recurred 17 months later. The optimal treatment plan was established by several multidisciplinary meetings and the patient subsequently underwent an en bloc resection of the left clavicle, first rib and all the other involved structures. Coverage of the thoracic defect was achieved using pectoralis major myocutaneous flap. The patient had a successful surgical outcome. At 1-year follow-up, he had no evidence of disease, a good cosmetic result and returned to normal daily activity. He died for bone metastasis with an overall 21 months post-surgical survival.

A persistent tracheocutaneous fistula closed with two hinged skin flaps and rib cartilage interpositional grafting.

Persistent tracheal fistula after tracheostomy decannulation is a recognized sequel to long-term tracheostomy use, causing important morbidity including difficult to vocalization and control of air secretions, recurrent pulmonary infections, and cosmetic and social problems. Herein, we reported a new method for closure of persistent tracheocutaneous fistula with rib cartilages. Compared to other techniques previously reported, the variations of our strategy were the use of temporary metal-covered tracheal stent and the hinged turnover skin bi-flaps reinforced with rib cartilage grafts. Rib cartilages were useful in order to reconstruct the trachea and prevent stenosis. Since it become difficult to obtain the maintenance of the trachea stability until healing of suture was well established, a covered metallic stent was also inserted to avoid flap collapse. The stent was removed 3 months later. Six months follow-up showed normal tracheal patency.