Gary S. Schwartz

Timely Airway Stenting Improves Survival in Patients With Malignant Central Airway Obstruction

BACKGROUND The survival of patients with malignant central airway obstruction is very limited. Although airway stenting results in significant palliation of symptoms, data regarding improved survival after stenting for advanced thoracic cancer with central airway obstruction are lacking. METHODS Fifty patients received a total of 72 airway stents for malignant central airway obstruction over a two-year period at a single institution. The Medical Research Council (MRC) dyspnea scale and Eastern Cooperative Oncology Group (ECOG) performance status were used to divide patients into a poor performance group (MRC = 5, ECOG = 4) and an intermediate performance group (MRC ≤ 4, ECOG ≤ 3). The SPSS version 16.0 (SPSS Inc, Chicago, IL) and Microsoft Excel (Microsoft, Redmond, WA) were used to analyze the data. Survival curves were constructed using the Kaplan-Meier survival analysis method and a log-rank test was used to compare the survival distributions among different groups. RESULTS Successful patency of the airway was achieved in all patients with no procedure-related mortality. Stenting resulted in significant improvement in MRC and ECOG performance scores (p < 0.01). Significantly improved survival was observed only in patients in the intermediate performance group compared with patients in the poor performance group (p < 0.05). CONCLUSIONS Airway stenting resulted in significant palliation of symptoms in both groups as evaluated by MRC dyspnea scale and ECOG performance status. Compared with historic controls, a significant survival advantage was seen only in the intermediate performance group. We postulate that timely stenting of the airway, before the morbid complications of malignant central airway obstruction have set in, results in improved survival.

The role of gender in coronary surgery

Gender-based outcome data in coronary artery bypass graft (CABG) surgery has been the focus of extensive research over the last two decades. Increased awareness in gender-specific health and advancements in scientific research have produced evidence that risk profiles vary between genders and alter operative mortality after CABG. Some of these data remain controversial, emphasizing the complexity of gender as an independent variable and questioning processes of care that are intimately associated with outcome. Although patient gender cannot be changed, understanding gender-specific risks and modifying surgical practice may be helpful in improving patient outcomes.

Dietary Flaxseed Protects Against Lung Ischemia Reperfusion Injury Via Inhibition of Apoptosis and Inflammation in a Murine Model

BACKGROUND The hallmark of lung ischemia-reperfusion injury (IRI) is the production of reactive oxygen species (ROS), and the resultant oxidant stress has been implicated in apoptotic cell death as well as subsequent development of inflammation. Dietary flaxseed (FS) is a rich source of naturally occurring antioxidants and has been shown to reduce lung IRI in mice. However, the mechanisms underlying the protective effects of FS in IRI remain to be determined. METHODS We used a mouse model of IRI with 60 min of ischemia followed by 180 min of reperfusion and evaluated the anti-apoptotic and anti-inflammatory effects of 10% FS dietary supplementation. RESULTS Mice fed 10% FS undergoing lung IRI had significantly lower levels of caspases and decreased apoptotic activity compared with mice fed 0% FS. Lung homogenates and bronchoalveolar lavage fluid analysis demonstrated significantly reduced inflammatory infiltrate in mice fed with 10% FS diet. Additionally, 10% FS treated mice showed significantly increased expression of antioxidant enzymes and decreased markers of lung injury. CONCLUSIONS We conclude that dietary FS is protective against lung IRI in a clinically relevant murine model, and this protective effect may in part be mediated by the inhibition of apoptosis and inflammation.

Morbidity and mortality after hepatic and pancreatic resections: results from one surgeon at a low-volume urban hospital over thirty years

BACKGROUND Recent reviews of state and national databases suggest that hospital volume is inversely proportional to morbidity after hepatic and pancreatic resection. Volume may be a surrogate marker for factors such as coordination of care and surgeon training. The authors hypothesized that low-volume centers can obtain acceptable outcomes if these requirements are satisfied. METHODS A retrospective review was performed of all hepatic and pancreatic resections performed from 1978 to 2008 by 1 surgeon at 1 low-volume institution. The etiology of disease, type of resection, and 30-day morbidity and mortality were assessed. RESULTS One hundred sixty-eight hepatic resections were performed for malignant (76%) or benign (24%) etiologies. Major resections included extended lobectomy (n = 19), lobectomy (n = 58), and segmentectomy (n = 62); minor resections consisted of wedge resections (n = 29). Overall 30-day mortality was 1.8%, and major morbidity was 17.9%; for major hepatic resections, mortality and morbidity were 1.4% and 20.1%, respectively. One hundred fourteen pancreatic resections were performed for malignant (76.3%) or benign (23.7%) etiologies. Major resections included pancreaticoduodenectomy (n = 91), central pancreatectomy (n = 1), and total pancreatectomy (n = 4); minor resections consisted of distal pancreatectomy (n = 18). Overall 30-day mortality was 2.6%, and major morbidity was 27.2%; for major pancreatic resections, mortality and morbidity were 3.1% and 31.3%, respectively. CONCLUSIONS Hepatic and pancreatic resections can be performed safely at a low-volume hospital with adequate surgeon training and perioperative systems of care.

Robotic Brachytherapy and Sublobar Resection for T1 Non-Small Cell Lung Cancer in High-Risk Patients

BACKGROUND Sublobar lung resection and brachytherapy seed placement is gaining acceptance for T1 non-small cell lung cancer (NSCLC) in select patients with comorbidities precluding lobectomy. Our institution first reported utilization of the da Vinci system for robotic brachytherapy developed experimentally in swine and applied to high-risk patients 5 years ago. We now report seed dosimetrics and midterm follow-up. METHODS Eleven high-risk patients with stage IA NSCLC who were not candidates for conventional lobectomy underwent limited resection of 12 primary tumors. To reduce locoregional recurrence, (125)I brachytherapy seeds were robotically sutured intracorporeally over resection margins to deliver 14,400 cGy 1 cm from the implant plane. Patients were followed with dosimetric computed tomography scans at 30 +/- 16 days. Survival and sites of recurrence were documented. RESULTS Resected tumor size averaged 1.48 +/- 0.38 cm (range, 1.1 to 2.1 cm). Perioperative mortality was 0% and recurrence was 9% (1 of 11 [margin recurrence at 6 months with resultant mortality at 1 year]). Follow-up duration was 31.82 +/- 17.35 months. Dosimetrics confirmed 14,400 cGy delivery using 24.21 +/- 4.6 (125)I seeds (range, 17 to 30 seeds) over a planning target volume of 10.29 +/- 2.39 cc(3). Overall, 84.1% of the planning target volume was covered by 100% of the prescription dose (V100), and 88.2% was covered by 87% of the prescription dose (V87), comparable to open dosimetric data at our institution. Follow-up imaging confirmed seed stability in all patients. CONCLUSIONS Robotic (125)I brachytherapy seed placement is a feasible adjuvant procedure to reduce the incidence of recurrence after sublobar resection in medically compromised patients. Tailored robotic seed placement delivers an exact dosing regimen in a minimally invasive fashion with equivalent precision to open surgery.

Uncommon etiology of an anterior chest wall mass.

A rare but important constellation of musculoskeletal and cutaneous symptoms, including synovitis, acne, pustulosis, hyperostosis, and osteitis, has recently been designated the SAPHO syndrome. The exact etiology is unknown, although various infectious agents have been proposed. The most common site of osteoarticular involvement is the sternoclavicular joint, and therefore, recognition of this syndrome and appropriate workup and management is crucial in the differential diagnosis of an anterior chest wall mass.

The effect of metallic tracheal stents on radiation dose in the airway and surrounding tissues.

BACKGROUND Metallic airway stents are often used in the management of central airway malignancies. The presence of a metallic foreign body may affect radiation dose in tissue. We studied the effect of a metallic airway stent on radiation dose delivery in a phantom and an in vivo porcine model. METHODS A metallic tracheal stent was fitted onto a support in a water phantom. Point dosimeters were positioned in the phantom around the support and the stent. Irradiation was then performed on a linear accelerator with and without the stent. Metallic tracheal stents were deployed in the trachea of three pigs. Dosimeters were implanted in the tissues near (Group 1) and away (Group 2) from the stent. The pigs were then irradiated, and the dose perturbation factor was calculated by comparing the actual dose detected by the dosimeters versus the planned dose. RESULTS The difference in the dose detected by the dosimeters and the planned dose ranged from 1.8% to 6.1% for the phantom with the stent and 0%-5.3% for the phantom without the stent. These values were largely within the manufacturers specified error of 5%. No significant difference was observed in the dose perturbation factor for Group 1 and Group 2 dosimeters (0.836 ± 0.058 versus 0.877 ± 0.088, P = 0.220) in all the three pigs. CONCLUSIONS Metallic airway stents do not significantly affect radiation dose in the airway and surrounding tissues in a phantom and porcine model. Radiation treatment planning systems can account for the presence of the stent. External beam radiation can be delivered without concern for significant dose perturbation.

Abstract LB-200: Potent antitumor activity of MLN0128, an investigational selective mTORC1/2 kinase inhibitor, in preclinical models of rhabdomyosarcoma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) axis regulates growth and homeostasis, and is often dysregulated in rhabdomyosarcoma. Agents that target mammalian target of rapamycin complex 1 (mTORC1), one of the two multi-protein complexes comprising the serine-threonine kinase mTOR, have been disappointing in clinical trials, and novel therapeutics are urgently needed to treat patients with relapsed, refractory, or metastatic alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. It is hypothesized that modest clinical results with mTORC1 only inhibitors may be attributed to the lack of inhibition of the second mTOR complex, mTORC2, and its downstream effectors, as well as release of mTOR-mediated negative feedback of the pathway that leads to activation of receptor tyrosine kinases and feedback activation of AKT. In the present preclinical study, MLN0128, a selective and highly potent inhibitor of both mTORC1 and mTORC2, was tested for its antitumor activity in vitro and in a mouse xenograft model. Data suggest that the anti-proliferative effect of MLN-0128 was superior to rapamycin, a selective mTORC1 inhibitor, in a broad panel of ERMS and ARMS cell lines where it was found to be highly effective at low concentrations from 5 to 175 nanomolar. Western immunoblot analysis of treated cells showed inhibition of phosphorylation of mTORC1 and mTORC2 targets including phosphorylated S6 ribosomal protein (pS6), phospho-p70-S6K, phospho-AKT-S473, phospho-AKT-T308, and phospho-4E-BP1. Apoptosis in both ERMS and ARMS cell lines was confirmed by the presence of cleaved poly ADP ribose. Additionally, MLN0128 was found to have superior anti-tumor effect in a xenograft model of rhabdomyosarcoma without significant toxicity when compared with rapamycin. These pre-clinical studies support further research of MLN0128 as a potential therapeutic approach for patients with ARMS and ERMS. Citation Format: Emily Slotkin, Parag Patwardhan, Shyamprasad Vasudeva Deraje, Gary Schwartz, Tap William. Potent antitumor activity of MLN0128, an investigational selective mTORC1/2 kinase inhibitor, in preclinical models of rhabdomyosarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-200. doi:10.1158/1538-7445.AM2014-LB-200

Hyperthermic Intrathoracic Chemotherapy for Metastatic Ovarian Cancer

Introduction: Ovarian serous carcinoma is an aggressive malignancy, often with metastases at presentation. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy has been studied as a treatment option for intraperitoneal spread of ovarian cancer. Hyperthermic intrathoracic chemotherapy, the thoracic counterpart to hyperthermic intraperitoneal chemotherapy, is emerging as a treatment option for both primary and secondary pleural cancers but has not previously been reported for treatment of ovarian metastases. The use of minimally invasive thoracoscopic techniques, including robotic assistance, for intrathoracic chemotherapy is rare. We present a case report of a patient with pleural metastasis of ovarian serous carcinoma treated with cytoreductive surgery and intrathoracic chemotherapy. Case Description: In a 55-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingooophorectomy with cytoreduction in July 2011 for ovarian cancer, a right-sided pleural effusion developed on postoperative radiographs. After chemotherapy treatment, she had a 7-month remission until positron emission tomography/ computed tomography scan identified an isolated pleural metastasis. The findings of diagnostic laparoscopy were negative for occult abdominal disease. We performed robotic-assisted right-sided video-assisted thoracoscopic surgery, partial pleurectomy, and resection of pleural, diaphragmatic, mediastinal, and pericardial nodules, followed by perfusion with heated cisplatinum for 60 minutes. The surgical procedure was uncomplicated, and the patient was discharged on postoperative day 3. The serum creatinine level remained normal. The pathologic specimens showed poorly differentiated/high-grade adenocarcinoma consistent with the patient’s ovarian primary. At 10 months postoperatively, she had no evidence of early recurrence and had a normal Karnofsky performance score (100). Conclusion: We report the first case of robotic-assisted hyperthermic intrathoracic chemotherapy to treat ovarian carcinoma. Intrathoracic chemotherapy may be an important tool in the treatment of ovarian metastases in the chest.

Internal mammary silicone lymphadenopathy diagnosed by robotic thoracoscopic lymphadenectomy

Internal mammary lymphadenopathy can be caused by a variety of disease processes and is a difficult diagnostic dilemma. We report a case of internal mammary lymphadenopathy, in a patient with a significant history of malignancy, requiring a tissue diagnosis. Robotic thoracoscopic lymphadenectomy was used to facilitate excisional biopsy. Pathology was significant for silicone granulomatous lymphadenitis secondary to silicone breast implants inserted after mastectomy for breast cancer.