Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

OBJECTIVES: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

[Comparison of mucosal reflux damage in remnant esophagus after esophagectomy and gastric interposition between Chinese and Canadian population].

OBJECTIVE: To compare the difference of mucosal damage in the remnant esophagus with similar postoperative reflux after esophagectomy and gastric interposition between Chinese and Canadian population. METHODS: A prospective 1 to 1 paired study based on the same surgical approach was performed in Medical Centre of University of Montreal and West China Hospital of Sichuan University during the period from September 2010 to October 2013. The patients were followed up and evaluated by reflux symptom scoring, endoscopic assessment of mucosal damage, pathologic examination of biopsies and proliferation index test of esophageal epithelium. RESULTS: Eighteen Han Chinese and 18 Caucasian Canadian patients with esophagectomy and gastric interposition were included in this study, with a follow-up period of 45 (28-67) months. There were no significant differences between the two groups in the incidence of postoperative reflux symptom, reflux symptom scoring, histological reflux esophagitis, erosion or stricture of remnant esophagus (all P>0.05). However, the incidence of mucosal metaplasia [44.4% (8/18) versus 11.1% (2/18), P=0.026], quantitative MUSE scoring [1.5 (1.0-2.0) versus 1.0 (0-2.0), P=0.042] and proliferation index [0.40 (0.30-0.45) versus 0.35 (0.30-0.50), P=0.038] of esophageal epithelium were significantly higher in Canadian patients than those in Chinese patients. CONCLUSION: Under similar reflux situation, esophageal mucosa of Canadian population is more sensitive to the gastroesophageal reflux damage compared with Chinese population, resulting in more severe reflux damage of remnant esophagus in Canadian patients.

Self-expanding metallic stent placement with an exaggerated 5-cm proximal tumor covering for palliation of esophageal cancer.

BACKGROUND: The study aimed to evaluate the short- and long-term outcomes with a technique of self-expanding metallic stent insertion in palliative esophageal cancer patients. We hypothesized that a systematic attempt at exaggerated (5 cm) proximal tumor covering could prevent both stent migration and tumor overgrowth/undergrowth. METHODS: We reviewed retrospectively all patients who underwent esophageal stenting for palliation of malignant dysphagia over a 24-month period. Consecutive patients were identified from a prospective thoracic surgery interventional endoscopy database. This technique consisted of endoscopic stent insertion with the aim of landing the proximal portion of the stent 5 cm cephalad to the proximal extent of the tumor. All patients were followed at one month post-procedure and every three months thereafter, until death. Short- and long-term complications associated with the procedure and mortality were evaluated. RESULTS: Forty seven patients underwent endoscopic insertion of an esophageal stent in the context of an inoperable esophageal cancer using this technique over a 24-month period. The mean age was 70.4±9.6 years. Four (8.5%) patients underwent re-stenting due to proximal tumor overgrowth. No stent migration, perforation, tumor ingrowth or stent occlusion was reported. The mean patient survival was 146±26.5 days. CONCLUSIONS: Esophageal stent insertion under endoscopic guidance with proximal tumor covering of 5 cm is effective and safe. No cases of stent migration and a low incidence of tumor overgrowth/undergrowth were observed with this technique.

Preoperative assessment of chest wall invasion in non-small cell lung cancer using surgeon-performed ultrasound.

BACKGROUND: Chest wall invasion in operable lung cancer upgrades the stage and can affect operative planning. Diagnosing chest wall invasion preoperatively is important in patient consent, in the choice of operative incision placement, and can be helpful in choosing an operative approach (open vs thoracoscopic). The objectives of this study were to determine the diagnostic accuracy of preoperative, surgeon-performed ultrasound (US) in assessing tumoral chest wall invasion (T3) in non-small cell lung cancer (NSCLC) patients and to compare its accuracy vs preoperative computed tomography (CT). METHODS: This study was a prospective clinical trial (ClinicalTrials.gov: NCT01206894) that prospectively enrolled patients between September 2010 and January 2013. Eligible patients included those with NSCLC abutting the parietal pleura or invading the chest wall on preoperative CT scan of the chest and who were planned for surgical resection. Criteria for chest wall invasion on US included (1) disruption of the parietal pleura, (2) invasion of the ribs, or (3) impairment of pleural movement with respiration. The US chest wall examination was performed by the thoracic surgical team immediately before the surgical intervention. Sensitivity and specificity for CT scan and US in assessing chest wall invasion were calculated using definitive chest wall invasion on final pathologic analysis as the gold standard for chest wall invasion. RESULTS: During a 28-month period, 28 patients (15 men and 13 women) patients were prospectively enrolled. Mean age was 62 ± 11 years, and mean body mass index was 25.3 ± 4.5 kg/m(2). The average time for surgeon-performed US assessment looking for chest wall invasion was 5.3 ± 5 minutes. The sensitivity of US in evaluating chest wall invasion was 90.9% and the specificity was 85.7%. CT scan was associated with a sensitivity of 61.5% and a specificity of 84.6%. The positive and negative predictive values of surgeon-performed US for tumoral chest wall invasion were 83.3% and 92.3%, respectively, compared with 80% and 68.8% for CT scan. CONCLUSIONS: Surgeon-performed preoperative chest wall US can reliably diagnose tumoral chest wall invasion in patients with NSCLC. CT scan has poor sensitivity in predicting chest wall invasion preoperatively. Surgeon-performed US can be considered as a complementary adjunct to preoperative imaging in patients with pulmonary lesions abutting the chest wall to improve preoperative diagnosis, staging, and operative planning.

Endosonographic mediastinal lymph node staging of lung cancer.

BACKGROUND: It is unclear whether endoscopic mediastinal lymph node (LN) staging techniques are equivalent to surgical mediastinal staging (SMS) techniques in patients with potentially operable non-small cell lung cancer (NSCLC). METHODS: A total of 166 patients with confirmed or suspected NSCLC who required SMS based on current guidelines were enrolled in this prospective controlled trial comparing endosonographic mediastinal LN staging with SMS. Each patient served as his or her own control. All patients underwent endobronchial ultrasound (EBUS), endoscopic ultrasound (EUS), and SMS during a single procedure. Results of EBUS, EUS, and combined EBUS/EUS were compared with SMS (gold standard) and in patients with negative LN staging results, with LN sampling at pulmonary resection. RESULTS: EBUS, EUS, combined EBUS/EUS, and SMS sampled a mean of 2.2, 1.7, 3.9, and 3.1 LN stations, respectively. The prevalence of mediastinal nodal disease (N2/N3) was 32% (53 of 166 patients). The sensitivity, negative predictive value, and diagnostic accuracy of the endoscopic staging modalities, respectively, were EBUS, 72% (95% CI, 0.58-0.83), 88% (0.81-0.93), and 91% (0.85-0.95); EUS, 62% (0.48-0.75), 85% (0.78-0.91), and 88% (0.82-0.92); and combined EBUS/EUS, 91% (0.79-0.97), 96% (0.90-0.99), and 97% (0.93-0.99). Endosonography was diagnostic for N2/N3/M1 disease in 24 patients in whom SMS findings were negative, preventing futile thoracotomy in an additional 14% of patients. CONCLUSIONS: The combined EBUS/EUS procedure can replace surgical mediastinal staging in patients with potentially resectable NSCLC. Additionally, endosonography leads to improved staging compared with SMS because it allows the biopsy of LNs and metastases unattainable with SMS techniques. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01011595; URL: www.clinicaltrials.gov.

Pleural ultrasound as an adjunct to physical examination in the preoperative evaluation of lung cancer patients.

OBJECTIVES: Preoperative evaluation of patients with suspected or confirmed lung cancer consists of clinical and radiological staging. Malignant pleural effusion is a poor prognosticator in non-small-cell lung cancer. Pleural ultrasound (PU) allows for the assessment of pleural effusion, providing real-time guidance for its aspiration and cytological analysis. Pleural Ultrasonography in Lung Cancer (PULC) as an adjunct to physical examination has the potential to improve preoperative staging of non-small-cell lung cancer during first surgical encounter by allowing the evaluation of previously unassessed pleural effusion. METHODS: This study consisted of a prospective trial of surgeon-performed PU in the preoperative evaluation of lung cancer patients. All patients evaluated in the thoracic surgery clinic with the new or presumed diagnosis of lung cancer were eligible. A portable ultrasound machine was used to evaluate pleural fluid in the bilateral costophrenic sulci with pleural fluid aspiration for cytological analysis. RESULTS: Forty-five patients were prospectively enrolled over a 3-month period. Thirteen patients had ultrasound evidence of a pleural effusion, of which 3 were significant enough for aspiration. Cytological analysis of these effusions yielded malignant cells in 1 patient. Positive PULC evaluation led to a change in clinical staging (M0 to M1a) in 10 patients and a change in pathological staging (pleural fluid cytology positive) in 1 patient. The time required for PULC examination was 15 ± 7 min. There were no complications related to the procedures. CONCLUSIONS: Preoperative pleural ultrasonography is a rapid and effective way to improve precision of staging in patients with lung cancer. More precise staging may allow for more appropriate testing, patient prognostication and operative planning.

Endobronchial ultrasonography added to endoscopic ultrasonography improves staging in esophageal cancer.

BACKGROUND: The gold standard for staging the local extension (T stage) and lymph node (LN) status (N stage) of esophageal cancer is endoscopic ultrasonography (EUS). When biopsy of the peritumoral LNs is performed using EUS, there is a risk of specimen contamination secondary to piercing the primary tumor; this shortcoming can be circumvented with endobronchial ultrasonography (EBUS). Moreover, EBUS allows for biopsy of LN stations not accessible with EUS. METHODS: The study consisted of a prospective clinical trial. Fifty-two consecutive patients with potentially resectable esophageal cancer referred for endoscopic staging were prospectively enrolled. Radial and convex EUS followed by convex EBUS were performed during a single staging procedure. The LNs not accessible by EUS were biopsied using EBUS. Results of the EBUS procedure were compared to those of EUS in terms of the addition of staging information, upstaging, and confirmation of stage. RESULTS: The combined EBUS-EUS procedure was performed in 42 patients. Ten patients were excluded. In all, 54 LNs were biopsied under EUS guidance and 48 LNs were biopsied under EBUS guidance. The EUS results were positive for metastatic esophageal cancer in 29 LNs (54%), and EBUS was positive in 10 LNs (21%). The addition of EBUS to EUS in the staging of esophageal cancer led to nodal and patient upstaging in 5 patients (12%) and confirmed the EUS stage with additional negative or positive LN sampling in 29 patients (69%). Positive EBUS that led to upstaging (5 patients) changed the treatment plan from potentially resectable to palliative. There was no morbidity related to EBUS. CONCLUSIONS: A combined EBUS-EUS staging procedure improves precision in staging, leads to upstaging, and can change the treatment plan in patients with esophageal cancer.

Initial experience with a new technique of endoscopic and ultrasonographic access for biopsy of para-aortic (station 6) mediastinal lymph nodes without traversing the aorta.

OBJECTIVES: All lymph node stations but the para-aortic are accessible by a combination of endoscopic ultrasound and endobronchial ultrasound. We recently described an echographic-endoscopic technique for the biopsy of para-aortic (station 6) lymph nodes without traversing the thoracic aorta. This study reviewed our initial experience with this new technique. METHODS: This first-in-human evaluation of the biopsy of station 6 mediastinal lymph nodes with curvilinear endoscopic ultrasound without arterial puncture used a retrospective case series design to study 12 consecutive patients who underwent this new technique. Station 6 lymph nodes were approached with a long fine needle aspiration approach (6-8 cm) through the proximal esophagus. The needle was passed through the esophagus into the mediastinum just medial to the left subclavian artery. It was then directed toward the para-aortic location (6-8 cm trajectory) to reach and enter the para-aortic lymph nodes without piercing the aorta or great vessels. RESULTS: Successful cytologic diagnoses of station 6 lymph nodes were obtained in all cases (lymphocytes in all samples). No morbidity resulted from the procedure, nor was any observed at 30 days after the procedure. Patient anatomy may preclude safe access in certain situations. CONCLUSIONS: Endoscopic ultrasound access of para-aortic (station 6) lymph nodes allows complete, minimally invasive mediastinal lymph node staging and diagnosis without traversal of the aorta. This technique, the final piece of the puzzle required for complete staging of the mediastinum with nonsurgical endoscopic techniques, is reproducible and safe.

Thoracoscopic localization of intraparenchymal pulmonary nodules using direct intracavitary thoracoscopic ultrasonography prevents conversion of VATS procedures to thoracotomy in selected patients.

OBJECTIVES: To investigate the feasibility, accuracy, and effect on conversion rates of intracavitary video-assisted thoracoscopic surgery ultrasonography (VATS-US) for localization of difficult to visualize pulmonary nodules. METHODS: The study consisted of a prospective cohort of VATS-US for localization of intraparenchymal peripheral pulmonary nodules. Patients with pulmonary nodules not touching the visceral pleura on the computed tomography scan, who were scheduled for VATS wedge resection, were prospectively enrolled. The lobe of interest was examined: visually, using finger palpation when possible, and using the instrument sliding method. The nodule was then sought using a sterile ultrasound transducer. The primary outcome measure was the prevention of conversion to thoracotomy or lobectomy secondary to positive VATS-US findings in patients with nodules that were not identifiable using standard VATS techniques. RESULTS: Four different surgeons performed 45 individual VATS-US procedures during a 13-month period. Intracavitary VATS-US was able to detect 43 of 46 nodules. The sensitivity of VATS-US was 93%, and the positive predictive value was 100%. The lung nodules were visualized by thoracoscopic lung examination in 12 cases (27%), palpable by finger in 18 cases (40%), and palpable using the instrument sliding technique in 17 cases (38%). In 20 cases, lung nodules were not identifiable using any of the traditional techniques and were identified only with VATS-US. VATS-US, therefore, prevented conversion to thoracotomy or lobectomy without tissue diagnosis in 43% (20/46) of cases. CONCLUSIONS: Intracavitary VATS-US is a real-time, feasible, reliable, and effective method of localization of intraparenchymal pulmonary nodules during selected VATS wedge resection procedures and can decrease the conversion rates to thoracotomy or lobectomy.

Developing academic surgery in a socialized health care system: a 35-year experience.

The most important benefit of a socialized health care system is the elimination of the threat of personal financial ruin to pay for medical care. Serious disadvantages of a socialized health care system, particularly in a university hospital setting, include restricted financial resources for education and patient care, limited working facilities, and loss of physician-directed decision making in planning and prioritizing. This article describes how a group practice model has supported clinical and academic activities within the faculty of medicine of our university and offers this model as a possible template for other surgical and medical disciplines working in an academic socialized environment.

Cervical video-assisted thoracoscopic surgery using a flexible endoscope for bilateral thoracoscopy.

Video-assisted thoracoscopic surgery (VATS) has become the standard of care for pleural evaluation, drainage, and pleurodesis. The major limitations to standard VATS techniques include intercostal pain and the unilateral nature of the procedure. We report on a cervical VATS approach for bilateral thoracoscopy, pleural biopsy, and talc pleurodesis using a flexible video endoscope without any intercostal incision. A 64-year old male with peritoneal carcinomatosis was noted to have significant bilateral pleural effusions. A cervical video-assisted thoracoscopic surgery (C-VATS) procedure was performed through a 2-cm cervical incision using a sterile flexible gastroscope. Bilateral thoracoscopy, pleural drainage, pleural biopsies, lung biopsy, and talc pleurodesis were performed. No thoracic intercostal incisions were performed. Total operative time was 48 minutes. The procedure was successful and the recovery was uneventful. The patient was discharged 4 days after the procedure. C-VATS is an extremely minimally invasive procedure. It avoids intercostal incisions and allows for bilateral pleural procedures through a single small cervical incision.

Prospective trial evaluating sonography after thoracic surgery in postoperative care and decision making.

OBJECTIVE: Following thoracic surgery, daily chest X-rays (CXRs) are performed to assess patient evolution and to make decisions regarding chest tube removal and patient discharge. Sonography after thoracic surgery (SATS) has the potential to be an effective, convenient, inexpensive and easy to learn tool in the post-operative management of thoracic surgery patients. We hypothesized that SATS could alleviate the need for repetitive CXRs, thus reducing the related risks, costs and inconvenience. METHODS: This study consisted of a prospective cohort trial. All patients scheduled to undergo thoracic surgery at a single academic medical centre were eligible. Post-operative bedside pleural ultrasound was performed whenever a CXR was ordered by the treating team. Investigators specifically assessed patients with the goals of identifying pleural effusions and pneumothoraces. Study investigators were blinded to CXR results. SATS findings were compared with CXRs, which were considered the gold standard in routine post-operative pleural space evaluation. RESULTS: One hundred and twenty patients were prospectively enrolled over a 5.5-month period. Three hundred and fifty-two ultrasound examinations were performed (mean = 3.0 ± 2.4 exams per patient). The time interval between the ultrasound and the comparative CXR was 166 ± 149 min. The mean time required to perform SATS was 11 ± 6 min per exam. In the detection of pleural effusion, SATS yielded a sensitivity of 83.1% and a specificity of 59.3%. In the detection of pneumothoraces, a sensitivity of 21.2% and a specificity of 94.7% were obtained. CONCLUSIONS: Post-operative ultrasound may alleviate the need to perform routine CXR in patients with a previously ruled out pneumothorax. SATS used selectively may be able to reduce the number of routine CXRs performed; however, it does not have high enough accuracy to replace CXRs.

Phenotypic characterization of chronic inflammation in a rare case of endobronchial carcinoma.

This report presents a phenotypical characterization of the immune cell infiltrate in a rare case of endobronchial carcinoma. A patient initially treated for an adenocarcinoma of the esophagus developed an endobronchial carcinoma surrounded by gastric metaplasia distal to a suspected gastrobronchial fistula, 11 years after esophagectomy. Our hypothesis is that the sustained exposure of the bronchial mucosa to a mixed acid and pancreatobiliary refluxate led to chronic inflammation and promoted malignant transformation. We performed an immunohistochemical study of the tumor microenvironment evaluating the density of CD3(+), CD8(+) T lymphocytes, CD20(+) B lymphocytes, CD68(+) macrophages and FoxP3(+) regulatory T cells. Quantification of immune cell density was completed using a novel software-based analysis method. Our results suggest that, within all the tissues analyzed, FoxP3(+) regulatory T cells were present at their highest density in the malignant and metaplastic tissues. The endobronchial metaplasia biopsied several years prior to the detection of the endobronchial adenocarcinoma was already densely infiltrated by B cells and macrophages, when compared to the immune cell infiltrate of the endobronchial carcinoma. Altogether, these observations support the current understanding of carcinogenesis promoted by chronic inflammation.

Lateral mediastinal tracheostomy in benign disease: an uncommon procedure for a rare indication.

Tracheostomy is sometimes required for long-term ventilation in patients with a challenging cervical anatomy. We present a case of a patient requiring prolonged mechanical ventilation with prohibitive cervical anatomy for standard tracheostomy secondary to severe ankylosing spondylitis and a cervical spine fracture.

Major airway laceration secondary to endobronchial ultrasound transbronchial lymph node biopsy.

A 48-year-old woman underwent complete mediastinal lymph node staging for non-small-cell lung cancer. After convex endobronchial ultrasound (EBUS)-guided transbronchial biopsy of the subcarinal lymph node station (station no. 7), it was noted that a laceration had occurred in the left mainstem bronchus. The tear occurred at the medial cartilaginous-membranous junction, seemed to be full thickness into the mediastinum, and was approximately 1.5cm long. The cytologic results of all lymph node biopsies were negative and the patient underwent right upper and middle lobe bilobectomy 12 hours after the EBUS procedure. This is the first report of a serious airway injury occurring during convex EBUS lymph node biopsy.