Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma

VATS Right Middle Lobe Lobectomy in the Setting of Oligometastatic Lung Cancer

<p><strong>Background</strong></p><p>A 31-year-old woman who was a former ice hockey player, was in the military, and is a lifetime never-smoker presented with a medical history of asthma, migraine headaches, endometriosis, and recurrent sinus infections. She had a maternal grandfather with lung cancer and a paternal grandmother with colon cancer. During an initial evaluation for a breast abnormality, magnetic resonance imaging (MRI) of the breast was performed and revealed an incidental lung nodule. She then had a computed tomography (CT) scan of the chest, which showed a 3 cm spiculated lesion in the minor fissure on the right, without thoracic adenopathy (shown in video). The lesion was primarily located in the right middle lobe (RML) but extended focally into the right upper lobe (RUL) through the fissure. A 3.4 cm arterial-enhancing liver lesion was noted, but extended imaging determined that this lesion was benign focal nodular hyperplasia.</p><p><strong>Methods</strong></p><p>A positron emission tomography (PET)-CT scan showed flurodeoxyglucose (FDG) uptake in the right lung mass along with an FDG-avid subcentimeter right paratracheal lymph node. A video bronchoscopy-guided biopsy diagnosed adenocarcinoma, and further genetic testing revealed an exon 19 mutation. A brain MRI revealed two metastases, one in the left occipital lobe of the brain and one in the right parietal lobe (shown in video). She underwent an endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA), which revealed a station 4R lymph node (LN) positive for malignancy.</p><p>She underwent stereotactic body radiation (SBRT) to the two brain metastases. Her care was discussed in the multidisciplinary lung ablation tumor board (MDTB). The decision was made to treat her with erlotinib, an inhibitor of the epidermal growth factor receptor. After several months of treatment and SBRT to the brain, reimaging by PET scan showed only residual disease in the RML of the lung. There was no residual uptake in the mediastinum.</p><p>The decision was then made to remove the right mediastinal lymph nodes and the RML of the lung, extending the resection to the portions of the RUL that were contiguous with the tumor for a complete resection.<br><br><strong>Preference Card</strong> (shown in video)</p><ul><li>5 - 10 mm 30° camera and scope</li><li>3 long double-action ringed forceps</li><li>(1 sponge stick to stay on the back table at all times)</li><li>14" Metzenbaum scissors</li><li>Yankour suction tip and VATS suction tip</li><li>2 Weitlaner retractors or port protector</li><li>long protected bovie tip, bent at tip</li><li>long-handle double-action curved glover</li><li>large right angle double-action (larger more blunt tip)</li><li>VATS suture scissors</li><li>long-handled double-action right angle clamp</li><li>large EndoCatch™ bag</li><li>Mayo Clinic Scanlan™ VATS Pan (shown in video)</li><li>gray, tan, and purple endoscopic staplers</li><li>Hem-o-lok™ clips</li><li>optional energy device</li><li>Peanut and Tonsil sponges</li><li>30° operating thoracoscope and video system</li></ul><p><br><strong>Operative Steps</strong></p><p>Step One</p><ul><li>Bronchoscopy</li><li>Position and break table</li><li>Confirm DLETT</li><li>Prepare, drape, local anesthetic, incisions</li><li>Hilar LN dissection</li><li>Posterior dissection</li></ul><p>Step Two</p><ul><li>Posterolateral retraction of lobe </li><li>Remove LN between RUL and RML veins</li><li>Right angle clamp RML vein, then divide</li><li>Stapler to complete fissure between RUL and RML</li></ul><p>Step Three</p><ul><li>Retract RML superiorly</li><li>Remove lobar LN from artery in fissure</li><li>Divide RML bronchus</li></ul><p>Step Four</p><ul><li>Staple RML artery branches</li></ul><p>Step Five</p><ul><li>Staple fissure (RML and RUL)</li><li>Complete LN dissection</li><li>Bronchoscopy at end of case</li></ul><p><br><strong>Results</strong></p><p>The patient stayed in the hospital for five days after surgery. Her follow-up scans have shown no residual disease. She continues on erlotinib and has a rash from the therapy, but otherwise continues with daily activity and has no complications from her resection.</p><p><strong>Conclusions</strong></p><p>Patients with oligometastatic disease can be candidates for resection, but they require extensive preoperative evaluation, staging, and multidisciplinary discussion. Such complex patients may have even better survival in the face of novel therapies and minimally invasive surgery.</p><p><strong>Tips and Pitfalls</strong></p><ul><li>For RML video-assisted thoracoscopic surgery (VATS) lobectomy, watch for a third branch of the pulmonary artery that can exist.</li><li>When a tumor is in the fissure, take the adjacent lobe to complete the en bloc resection.</li><li>In patients with oligometastatic disease, the brain metastases should be controlled first and then fit patients with controllable disease should demonstrate response to targeted therapy if their disease is an unusual case (such as cases of N2 disease).</li><li>Extraordinary measures should be taken only after MDTB discussion in experienced centers.</li><li>Lung resection in patients with oligometastatic disease should only be considered for patients with good performance status and adequate lung function.</li><li>In the face of a negative CT and PET scan, invasive mediastinal staging (EBUS or video mediastinoscopy) is recommended in patients being considered for curative resection.</li><li>Intrathoracic lymph node disease (N1, N2, or N3) is associated with worse outcome in oligometastatic non-small cell lung cancer.</li><li>Primary lung cancer with synchronous solitary cranial or adrenal metastases should be evaluated for curative aggressive local therapy.</li><li>Curative intent for oligometastatic disease to organs other than lung, brain, or adrenal glands should be considered on a case-by-case basis.</li></ul><div>References and more: https://www.ctsnet.org/article/vats-right-middle-lobe-lobectomy-setting-oligometastatic-lung-cancer</div><p></p

Multifocal Lung Cancer Discussion and Case Presentation

<p><strong>Introduction</strong></p><p>Multifocal lung cancer is an increasingly common clinical scenario, but there is a lack of high-level evidence for its optimal treatment [1]. Staging is an important first step in the management of such pathologies. As many as six percent of patients may present with unsuspected cranial metastases [2]. Minimally invasive resections, parenchymal-sparing approaches, and multidisciplinary care are the central themes emphasized in this case report and review of the literature.</p> <p><strong>Case</strong></p><p>A 69-year-old woman who was an active tennis player presented with a prior history of right upper lobe lung cancer that was discovered incidentally on low dose screening chest CT scan. She is a former smoker with a 25-30 pack year history, but quit 25 years ago. Once removed, her previous tumor was pathologically staged as a well-differentiated adenocarcinoma, stage IIB, N0, M0. She underwent a right posterolateral open thoracotomy with right upper lobectomy in 2013, with postoperative adjuvant chemotherapy. Four years later, she presented with multiple foci of new suspicious lesions on surveillance scans, predominantly located in the left lower lobe of the lung. There were no new lesions that were suspicious on the right lung. The results of her pulmonary lung function tests showed adequate pulmonary reserve for another lobectomy. The authors discussed her care in their Multidisciplinary Lung Ablation Tumor Board. The left lower lobe predominant lesion gave an intermediate probability of invasive adenocarcinoma based on her Canary analysis (the predicted probability of the nodule being adenocarcinoma). Her positron emission tomography scan was negative for extrathoracic or mediastinal disease. Brain magnetic resonance imaging was negative for malignant lesions. She underwent endobronchial ultrasound fine needle aspiration, and all mediastinal lymph nodes were negative for malignant disease. </p><p><strong>Results</strong></p><p>The left lower lobe resection was uncomplicated (Video 1). Lymph node stations 5, 7, 9L, 10L, 11L, and multiple intrapulmonary peribronchial lymph nodes were negative for tumor, with a total of 22 nodes sampled during the surgery. Within the left lower lobe of the lung, the pathologic assessment revealed adenocarcinoma forming 10 nodules that ranged in size from 0.4 - 1.0 cm, with each tumor having a negative margin. The patient was discharged on postoperative day three.</p><p><strong>Conclusion</strong></p><p>The management of patients with multifocal lung cancer can be difficult due to several factors. Discriminating between metastatic disease and separate primary lesions is important, and published criteria may guide oncologic care planning [3-5]. When technically resecting a left lower lobe of the lung, it is possible to take the lung sequentially from a bottom-up approach, if safe: dividing the vein, followed by the bronchus, and finally the artery. One should make sure the superior segmental branch of the pulmonary artery has been taken, as well as the bronchus, when dividing these branches.<br><br>In the setting of multifocal lesions, the approach should be to resect the least amount of lung in the least invasive manner the first time, but with the best cancer resection to preserve lung. This will provide the patient with better options in the setting of the other ground glass opacities or nodules progressing. In patients with adequate pulmonary reserve, another parenchymal-sparing approach should then be considered, if they present with new cancers. Extraordinary measures should be taken only after multidisciplinary thoracic tumor board discussions in experienced centers [6-9].</p><p><strong>References</strong></p><ol><li>Leventakos K, Peikert T, Midthun DE, et al. Management of multifocal lung cancer: results of a survey. <a href="https://doi.org/10.1016/j.jtho.2017.05.013"><em>J Thorac Oncol</em>. 2017;12(9):1398-1402</a>. </li><li>Leventakos K, Mansfield AS, Blackmon S, et al. 88P: Use of brain imaging in the management of patients with lymph node negative multifocal lung cancer. <a href="https://doi.org/10.1016/S1556-0864(16)30201-5"><em>J Thorac Oncol</em>. 2016;11(4 suppl):S93-S94</a>.</li><li>Martini N, Melamed MR. Multiple primary lung cancers. <a href="https://www.ncbi.nlm.nih.gov/pubmed/170482"><em>J Thorac Cardiovasc Surg</em>. 1975;70(4):606-612</a>.</li><li>Antakli T, Schaefer RF, Rutherford JE, Read RC. Second primary lung cancer. <a href="https://www.ncbi.nlm.nih.gov/pubmed/7695410"><em>AnnThorac Surg</em>. 1995;59(4):863-867</a>.</li><li>Shen KR, Meyers BF, Larner JM, Jones DR, American College of Chest Physicians. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). <a href="https://doi.org/10.1378/chest.07-1382"><em>Chest</em>. 2007;132(3 suppl):290S-305S</a>.</li><li>Deschamps C, Pairolero PC, Trastek VF, Payne WS. Multiple primary lung cancers. Results of surgical treatment. <a href="https://www.ncbi.nlm.nih.gov/pubmed/2329815"><em>J Thorac Cardiovasc Surg</em>. 1990;99(5):769-777</a>.</li><li>Yang J, Liu M, Fan J, et al. Surgical treatment of metachronous second primary lung cancer. <a href="https://doi.org/10.1016/j.athoracsur.2014.05.050"><em>Ann Thorac Surg</em>. 2014;98(4):1192-1198</a>.</li><li>Taioli E, Lee DS, Kaufman A, et al. Second Primary Lung Cancers Demonstrate Better Survival with Surgery than Radiation. <a href="https://doi.org/10.1053/j.semtcvs.2016.02.010"><em>Semin Thorac Surg</em>. 2016;28(1):195-200</a>. </li><li>Rice D, Kim HW, Sabichi A, et al. The risk of second primary tumors after resection of stage I nonsmall cell lung cancer. <a href="https://www.ncbi.nlm.nih.gov/pubmed/14529975"><em>Ann Thorac Surg</em>. 2003;76(4):1001-1008</a>.</li></ol

Management of a LC2 Carinal Carcinoid Tumor Through a Minimally Invasive Parenchymal-Sparing Approach

<p><strong>Objectives</strong></p><p>Bronchial neuroendocrine tumors are an uncommon neoplasm of the lungs characterized by an endobronchial mass that mostly arise in the proximal airways. This video demonstrates successful management of an LC2 carinal carcinoid tumor through a minimally invasive, parenchymal-sparing approach.</p><div><p><strong>Methods</strong></p><p>A 34-year-old welder presented with a two- to three-year history of wheezing with progressive shortness of breath requiring multiple visits to the emergency room. The preliminary evaluation included a computed tomography scan and flexible bronchoscopy, which demonstrated a lumen-obstructing mass at the LC2 carina with complete left lower lobe collapse. He underwent a bronchoscopic debulking of the tumor with pathology consistent with a carcinoid. A ⁶⁸Ga DOTA-TATE scan did not demonstrate any distant metastatic disease. The patient underwent a video-assisted thoracoscopic resection of the left superior segment of the lower lobe, resection of the left LC2 carina, and bronchoplasty with pleural flap buttressing. Bronchoscopic guidance was employed during the surgery to optimize resection.</p><p><strong>Results</strong></p><p>The patient was dismissed on postoperative day six with an uneventful hospital course. A bronchoscopy before dismissal demonstrated an intact bronchoplasty. Final pathology confirmed a pT1aN0 typical carcinoid tumor with negative margins.</p><p><strong>Conclusion</strong></p><p>This video demonstrates a successful parenchymal-sparing LC2 carina resection and bronchoplasty using a VATS approach for a typical carcinoid tumor.</p></div><div>This educational content was originally presented during the STSA 64th Annual Meeting. This content is published with the permission of the <a href="https://stsa.org/">STSA</a>. For more information on the STSA and its next Annual Meeting, please click <a href="http://stsa.org/annualmeeting/">here</a>.<br></div

Safety in Minimally Invasive Thoracic Surgery

Filmed at the 2016 EACTS Annual Meeting in Barcelona, Joel Dunning and Shanda Blackmon discuss safety in minimally invasive general thoracic surgery. They focus on the importance of preparation, such that a surgical team knows its course of action for potential critical events ahead of their occurance. Mr Dunning and Dr Blackmon also discuss surgical videos of VATS bleeding events, with the intention of fostering a culture of openness where surgeons and trainees are able to learn to better manage such events

Treatment of Sternoclavicular Joint Osteomyelitis with Debridement and Delayed Resection with Muscle Flap Coverage Improves Outcomes

The objective of this study was to evaluate the efficacy of various treatment options for sternoclavicular joint osteomyelitis. We evaluated patients with a diagnosis of sternoclavicular joint osteomyelitis, treated at our hospital from 2002 to 2012. Four treatment options were compared. Three out of twelve patients were successfully cured with antibiotics alone (25%). Debridement with or without negative pressure therapy was successful for one of three patients (33%). Simultaneous debridement, bone resection, and muscle flap coverage of the acquired defect successfully treated one of two patients (50%). Debridement with delayed bone resection and muscle flap coverage was successful in five of five patients (100%). Osteomyelitis of the sternoclavicular joint is a rare disease that has become more prevalent in recent years and can be associated with increasing use of long-term indwelling catheters. Initial debridement with delayed bone resection and pectoralis major muscle flap coverage can effectively treat sternoclavicular joint osteomyelitis