The Journal of Thoracic and Cardiovascular Surgery, Dec 14, 2017
Objective: To report the first analysis of long-term outcomes using near-infrared (NIR) image-gui... more Objective: To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC). Methods: Retrospective analysis of patients with NSCLC enrolled in 2 prospective phase 1 NIR-guided SLN mapping trials, including an indocyanine green (ICG) dose-escalation trial, was performed. All patients underwent NIR imaging for SLN identification followed by multistation mediastinal lymph node sampling (MLNS) and pathologic assessment. Disease-free (DFS) and overall survival (OS) were compared between patients with NIR þ SLN (SLN group) and those without (non-SLN group).
2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom), 2018
Mobile health (mHealth) apps have been adopted in areas of healthcare such as the management of d... more Mobile health (mHealth) apps have been adopted in areas of healthcare such as the management of diabetes, monitoring physical activities and the treatment of HIV. This paper provides three contributions to research on how the usability of an mHealth app impacts its frequency of use and adoption. First, we evaluate how different authentication approaches for mHealth apps impact their usability. Second, we present new metrics for evaluating mHealth app usage complexity in the context of four potential barriers to use: memory barriers, physical barriers, process barriers, and other barriers. Third, we evaluate the usability of two common authentication approaches for mHealth apps via several key process aspects and their impact on users. Based on the results, we propose a QR-Code based authentication approach for mHealth apps, which help overcome common impediments faced by mHealth apps that are used in acute care and other settings.
Advances in Electrical and Electronic Engineering, 2021
Mobile health (mHealth) apps are increasingly adopted in healthcare domains, such as diabetes man... more Mobile health (mHealth) apps are increasingly adopted in healthcare domains, such as diabetes management, physical activity monitoring, and HIV treatment. However, mHealth app development is restricted due to healthcare privacy regulations, which require apps to handle collected data securely. The advent of online platforms, such as REDCap, alleviates this problem by providing privacy-compliant databases, so that mHealth apps developed for research groups can securely handle stored inactive data (data-at-rest) with fewer privacy concerns. Unfortunately, the authentication architectures of many online platforms do not meet the needs of mHealth apps and provide insufficient integration support. Assumptions made in other types of mobile apps about how users operate, such as a user's ability to type or remember a password, therefore may not be valid in the mHealth domain. To address these problems this paper evaluates how authentication approaches impact the usability of mHealth apps. In particular, we present metrics to evaluate usability and show how the Proxy User Adapter pattern can integrate usability-enhanced authentication approaches to legacy secure database providers. We also propose a QR-Code authentication approach that applies the Proxy User Adapter pattern to help mHealth apps overcome common impediments, improve processing efficiency, and reduce potential mistakes caused by patients and providers alike.
Interactive CardioVascular and Thoracic Surgery, Jun 1, 2014
Objectives: To evaluate an intraoperative, minimally invasive near-infrared (NIR) image-guided ap... more Objectives: To evaluate an intraoperative, minimally invasive near-infrared (NIR) image-guided approach to sentinel lymph node (SLN) identification in lung cancer patients for initial safety and feasibility. Despite "curative" resection, recurrence rates are nearly 40% in early stage non-small-cell lung cancer (NSCLC) and five-year survival is less than 60%, outcomes largely attributable to missed nodal disease. The primary aim of SLN mapping in lung cancer is to identify the nodes at greatest risk for metastases (i.e. SLNs) for focused immunohistochemical and molecular analysis to improve staging and outcomes in this disease. Video description: In this pilot trial of 41 patients with suspected stage I/II NSCLC, peritumoural injection of NIR dye indocyanine green (ICG) was
The ability to produce rapid, cost-effective and human-relevant data has the potential to acceler... more The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood–retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using ind...
The Journal of thoracic and cardiovascular surgery, 2018
To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentine... more To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC). Retrospective analysis of patients with NSCLC enrolled in 2 prospective phase 1 NIR-guided SLN mapping trials, including an indocyanine green (ICG) dose-escalation trial, was performed. All patients underwent NIR imaging for SLN identification followed by multistation mediastinal lymph node sampling (MLNS) and pathologic assessment. Disease-free (DFS) and overall survival (OS) were compared between patients with NIR SLN (SLN group) and those without (non-SLN group). SLN detection, recurrence, DFS, and OS were assessed in 42 patients with NSCLC who underwent intraoperative peritumoral ICG injection, NIR imaging, and MLNS. NIR SLNs were identified in 23 patients (SLN group), whereas SLNs were not identified in 19 patients enrolled before ICG dose and camera optimization (non-SLN group). Median follow-up was 44.5 months. Path...
The Journal of Thoracic and Cardiovascular Surgery, 2017
Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-in... more Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). Methods: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR þ SLNs and adverse events were recorded. Results: Twelve patients underwent NB-guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR þ ''tattoo'' was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false-negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB-labeling or indocyanine green dye itself. Conclusions: NB-guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image-guided technique may permit the accurate localization and nodal staging of early stage lung cancers.
The Journal of Thoracic and Cardiovascular Surgery, 2016
Objective: To assess safety and feasibility of an intraoperative, minimally invasive near-infrare... more Objective: To assess safety and feasibility of an intraoperative, minimally invasive near-infrared (NIR) image-guided approach to lymphatic mapping in patients with esophageal cancer. Methods: Although local lymph nodes (LNs) are removed with the esophageal specimen, no techniques are available to identify the regional LNs (separate from the esophagus) during esophagectomy. We hypothesize that NIR imaging can identify regional LNs with the potential to improve staging and guide the extent of lymphadenectomy. Nine of the 10 patients enrolled had resectable esophageal adenocarcinoma and underwent NIR mapping following peritumoral submucosal injection of indocyanine green (ICG) alone or premixed in human serum albumin (ICG:HSA) before resection. NIR imaging was performed in situ and ex vivo. Results: In 6 of the 10 patients, intraoperative NIR imaging demonstrated an NIR signal at all tumors and in 2 to 6 NIR þ regional LNs. NIR þ LNs were not identified in 4 patients: 1 patient with occult stage IV disease, for whom further imaging was not performed and thus was excluded from analysis, and 3 patients in whom ICG was used without HSA. Identification of local LNs on the esophagus was obscured by a peritumoral background. Importantly, the pathological status of NIR þ regional LNs reflected overall regional nodal status. Conclusions: NIR lymphatic mapping is safe and feasible in patients with esophageal cancer and can identify regional LNs when ICG:HSA is used. Although more work is needed to improve background signals and local LN identification, intraoperative detection of regional NIR þ LNs allows an in-depth histological analysis of LN basins not commonly scrutinized as part of the specimen and may improve the detection of occult nodal disease.
End-stage renal disease is a significant negative predictor of limb salvage and patient survival ... more End-stage renal disease is a significant negative predictor of limb salvage and patient survival in patients with limb ischemia, but little is known of the overall effects of renal transplantation. Endovascular management may be less morbid than open surgery, but technical success and durability in these patients is not well established. All patients with functioning renal transplants and critical limb ischemia (CLI) treated with endovascular techniques between 2003 and 2010 were retrospectively reviewed for limb salvage, reintervention, pre- and postprocedure creatinine, and estimated glomerular filtration rate (eGFR), and overall survival. Contralateral common femoral access, low-profile techniques, and isosmolar contrast were standard for all interventions. Endovascular interventions were performed on 57 limbs in 28 patients with renal transplants. Mean age was 54 years, 78% were male, 85% were diabetic, 100% were hypertensive, and 64% had a positive smoking history. All patients were treated for CLI. Treated regions included 16 iliac, 19 superficial femoral, 16 popliteal, and 12 tibial arteries, as well as 1 bypass graft with initial technical success of 100% and 0% 30-day mortality. Of all lesions, 43% required reintervention during the follow-up period, the majority in the first year. There was no significant change in eGFR or creatinine comparing pre- and post-angiogram value. Limb salvage and 1-year survival were 83% and 82%, respectively. Endovascular management of CLI in renal transplant patients results in good technical success and can be accomplished without a measurable change in transplant kidney function, although it requires repeat interventions. Endovascular therapy is a reasonable first-line treatment option for this high-risk group.
The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co... more The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection a...
Seminars in Thoracic and Cardiovascular Surgery, 2011
During the past few decades, particles of various compositions have been engineered in ever small... more During the past few decades, particles of various compositions have been engineered in ever smaller sizes to function in both diagnostic and therapeutic capacities. Nanoparticles are now available on a scale similar to many biological molecules and infectious agents, thereby opening the possibility of biological intervention on the molecular level. Several recent timely reports summarize nanoparticle properties and potential clinical applications in early-stage clinical trials.
Perioperative care of patients undergoing colon resection requires a multidisciplinary approach b... more Perioperative care of patients undergoing colon resection requires a multidisciplinary approach by the operating surgeon, residents, and nurses. Operations performed on Monday take full advantage of hospital resources throughout the week to meet expected discharge by Friday. In a current health care environment of diminishing means, improving the timing of surgery in relation to expected length of stay may play an important role in preserving health care resources. A retrospective review of a prospectively collected colorectal surgical database identified all patients who underwent segmental colon resection at a single tertiary care referral center from 2004 to 2010. Length of stay for patients undergoing elective open and minimally invasive segmental colectomy was compared for Monday versus Tuesday through the weekend. Patient and surgeon demographics were recorded as well as postoperative outcomes and complications. A total of 868 segmental colectomies were performed during the study period. Length of stay was significantly decreased by .73 days (P < .01) for all segmental colectomies performed on Monday compared with those performed Tuesday through Sunday. There was also a significant decrease in length of stay looking independently at right (.96 days, P < .01) and left or sigmoid colectomies (.56 days, P < .01). There was no significant difference in patient or surgeon demographics to account for this difference. Segmental colectomies have a significantly decreased length in stay when performed on Monday compared with the rest of the week. The decrease is independent of surgeon, comorbidities, and complications. This difference may be the result of patients' taking full advantage of hospital resources and ancillary support. Cost-effective measures may be evaluated and directed at adjustment of resources available throughout the week to reduce length of stay.
We present a case of a woman initially presenting with a neck mass and subsequently found to have... more We present a case of a woman initially presenting with a neck mass and subsequently found to have generalized lymphatic anomaly with diffuse lymphatic dilation and proliferation involving the mediastinum and pericardium. Intrathoracic involvement of generalized lymphatic anomalies can lead to recurrent pleural effusions, pericardial effusions, and severe respiratory infections. These anomalies cannot be cured and significantly impact quality of life. Multidisciplinary involvement is crucial to maximize symptom relief as surgery to remove lymphatics can be morbid and the disease is usually recurrent.
The Journal of Thoracic and Cardiovascular Surgery, 2013
Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year surviva... more Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year survival, particularly if lymph nodes are involved. Our objective was to perform a dose-escalation study to assess safety and feasibility of intraoperative near-infrared (NIR) fluorescence imaging to identify the first tumor-draining lymph nodes (ie, sentinel lymph nodes [SLNs] in patients with NSCLC). A-dose escalation phase 1 clinical trial assessing real-time NIR imaging after peritumoral injection of 3.8 to 2500 μg indocyanine green (ICG) was initiated in patients with suspected stage I/II NSCLC. Visualization of lymphatic migration, SLN identification, and adverse events were recorded. Thirty-eight patients underwent ICG injection and NIR imaging via thoracotomy (n = 18) or thoracoscopic imaging (n = 20). SLN identification increased with ICG dose, with fewer than 25% SLNs detected in dose cohorts of 600 μg or less versus 89% success at 1000 μg or greater. Twenty-six NIR(+) SLNs were identified in 15 patients, with 7 NIR(+) SLNs (6 patients) harboring metastatic disease on histologic analysis. Metastatic nodal disease was never identified in patients with a histologically negative NIR(+) SLN. No adverse reactions were noted. NIR-guided SLN identification with ICG was safe and feasible in this initial dose-escalation trial. ICG doses greater than 1000 μg yielded nearly 90% intrathoracic SLN visualization, with the presence or absence of metastatic disease in the SLN directly correlating with final nodal status of the lymphadenectomy specimen. Further studies are needed to optimize imaging parameters and confirm sensitivity and specificity of SLN mapping in NSCLC using this promising imaging technique.
Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, ... more Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin.
Background. The presence of lymph node metastasis is the most important prognostic factor in earl... more Background. The presence of lymph node metastasis is the most important prognostic factor in early non-small cell lung cancer. Our objective was to develop a rapid, simple, and reliable method for thoracic sentinel lymph node (SLN) identification using near-infrared fluorescence imaging and clinically available contrast agents.
Locoregional recurrence significantly impacts survival and quality of life in patients with ovari... more Locoregional recurrence significantly impacts survival and quality of life in patients with ovarian carcinoma. We hypothesize that local administration of paclitaxel-loaded expansile nanoparticles (pax-eNP) at the time of cytoreductive surgery decreases local tumor recurrence. In vitro cytotoxicity of pax-eNP was assessed against both the OVCAR-3 human ovarian cancer cell line and tumor cells isolated from a malignant pleural effusion from a patient with multidrug-resistant ovarian cancer. A murine xenogenic model involving surgical cytoreduction of established OVCAR-3 intra-abdominal tumor was used to evaluate in vivo efficacy of intraoperative intraperitoneal (IP) injection of 10 mg/kg of paclitaxel either as pax-eNP or paclitaxel in Cremophor EL/ethanol solution (pax-C/E) versus empty eNP controls. Cytoreductive surgery and intraoperative treatment were performed 4 weeks after established tumor. All animals were sacrificed when empty eNP controls displayed extensive evidence of disease progression. Labeled-eNP entered tumor cells in vitro within 4 h and specifically accumulated at sites of tumor in vivo. Pax-eNP exhibited dose-dependent cytotoxicity in both OVCAR-3 and patient tumor cells isolated from a malignant pleural effusion and effectively prevented tumor recurrence following debulking (p = 0.003 vs. empty eNP). Furthermore, pax-eNP-treated animals did not develop severe recurrent carcinomatosis compared with 43 % of the pax-C/E-treated cohort, suggesting that single-dose intracavitary pax-eNP is more effective than an equivalent dose of pax-C/E. Expansile nanoparticles readily enter human ovarian tumor cells and localize to sites of tumor in vivo with pax-eNP cytotoxicity resulting in superior inhibition of locoregional tumor recurrence following cytoreductive surgery.
The Journal of Thoracic and Cardiovascular Surgery, Dec 14, 2017
Objective: To report the first analysis of long-term outcomes using near-infrared (NIR) image-gui... more Objective: To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC). Methods: Retrospective analysis of patients with NSCLC enrolled in 2 prospective phase 1 NIR-guided SLN mapping trials, including an indocyanine green (ICG) dose-escalation trial, was performed. All patients underwent NIR imaging for SLN identification followed by multistation mediastinal lymph node sampling (MLNS) and pathologic assessment. Disease-free (DFS) and overall survival (OS) were compared between patients with NIR þ SLN (SLN group) and those without (non-SLN group).
2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom), 2018
Mobile health (mHealth) apps have been adopted in areas of healthcare such as the management of d... more Mobile health (mHealth) apps have been adopted in areas of healthcare such as the management of diabetes, monitoring physical activities and the treatment of HIV. This paper provides three contributions to research on how the usability of an mHealth app impacts its frequency of use and adoption. First, we evaluate how different authentication approaches for mHealth apps impact their usability. Second, we present new metrics for evaluating mHealth app usage complexity in the context of four potential barriers to use: memory barriers, physical barriers, process barriers, and other barriers. Third, we evaluate the usability of two common authentication approaches for mHealth apps via several key process aspects and their impact on users. Based on the results, we propose a QR-Code based authentication approach for mHealth apps, which help overcome common impediments faced by mHealth apps that are used in acute care and other settings.
Advances in Electrical and Electronic Engineering, 2021
Mobile health (mHealth) apps are increasingly adopted in healthcare domains, such as diabetes man... more Mobile health (mHealth) apps are increasingly adopted in healthcare domains, such as diabetes management, physical activity monitoring, and HIV treatment. However, mHealth app development is restricted due to healthcare privacy regulations, which require apps to handle collected data securely. The advent of online platforms, such as REDCap, alleviates this problem by providing privacy-compliant databases, so that mHealth apps developed for research groups can securely handle stored inactive data (data-at-rest) with fewer privacy concerns. Unfortunately, the authentication architectures of many online platforms do not meet the needs of mHealth apps and provide insufficient integration support. Assumptions made in other types of mobile apps about how users operate, such as a user's ability to type or remember a password, therefore may not be valid in the mHealth domain. To address these problems this paper evaluates how authentication approaches impact the usability of mHealth apps. In particular, we present metrics to evaluate usability and show how the Proxy User Adapter pattern can integrate usability-enhanced authentication approaches to legacy secure database providers. We also propose a QR-Code authentication approach that applies the Proxy User Adapter pattern to help mHealth apps overcome common impediments, improve processing efficiency, and reduce potential mistakes caused by patients and providers alike.
Interactive CardioVascular and Thoracic Surgery, Jun 1, 2014
Objectives: To evaluate an intraoperative, minimally invasive near-infrared (NIR) image-guided ap... more Objectives: To evaluate an intraoperative, minimally invasive near-infrared (NIR) image-guided approach to sentinel lymph node (SLN) identification in lung cancer patients for initial safety and feasibility. Despite "curative" resection, recurrence rates are nearly 40% in early stage non-small-cell lung cancer (NSCLC) and five-year survival is less than 60%, outcomes largely attributable to missed nodal disease. The primary aim of SLN mapping in lung cancer is to identify the nodes at greatest risk for metastases (i.e. SLNs) for focused immunohistochemical and molecular analysis to improve staging and outcomes in this disease. Video description: In this pilot trial of 41 patients with suspected stage I/II NSCLC, peritumoural injection of NIR dye indocyanine green (ICG) was
The ability to produce rapid, cost-effective and human-relevant data has the potential to acceler... more The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood–retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using ind...
The Journal of thoracic and cardiovascular surgery, 2018
To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentine... more To report the first analysis of long-term outcomes using near-infrared (NIR) image-guided sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC). Retrospective analysis of patients with NSCLC enrolled in 2 prospective phase 1 NIR-guided SLN mapping trials, including an indocyanine green (ICG) dose-escalation trial, was performed. All patients underwent NIR imaging for SLN identification followed by multistation mediastinal lymph node sampling (MLNS) and pathologic assessment. Disease-free (DFS) and overall survival (OS) were compared between patients with NIR SLN (SLN group) and those without (non-SLN group). SLN detection, recurrence, DFS, and OS were assessed in 42 patients with NSCLC who underwent intraoperative peritumoral ICG injection, NIR imaging, and MLNS. NIR SLNs were identified in 23 patients (SLN group), whereas SLNs were not identified in 19 patients enrolled before ICG dose and camera optimization (non-SLN group). Median follow-up was 44.5 months. Path...
The Journal of Thoracic and Cardiovascular Surgery, 2017
Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-in... more Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). Methods: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR þ SLNs and adverse events were recorded. Results: Twelve patients underwent NB-guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR þ ''tattoo'' was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false-negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB-labeling or indocyanine green dye itself. Conclusions: NB-guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image-guided technique may permit the accurate localization and nodal staging of early stage lung cancers.
The Journal of Thoracic and Cardiovascular Surgery, 2016
Objective: To assess safety and feasibility of an intraoperative, minimally invasive near-infrare... more Objective: To assess safety and feasibility of an intraoperative, minimally invasive near-infrared (NIR) image-guided approach to lymphatic mapping in patients with esophageal cancer. Methods: Although local lymph nodes (LNs) are removed with the esophageal specimen, no techniques are available to identify the regional LNs (separate from the esophagus) during esophagectomy. We hypothesize that NIR imaging can identify regional LNs with the potential to improve staging and guide the extent of lymphadenectomy. Nine of the 10 patients enrolled had resectable esophageal adenocarcinoma and underwent NIR mapping following peritumoral submucosal injection of indocyanine green (ICG) alone or premixed in human serum albumin (ICG:HSA) before resection. NIR imaging was performed in situ and ex vivo. Results: In 6 of the 10 patients, intraoperative NIR imaging demonstrated an NIR signal at all tumors and in 2 to 6 NIR þ regional LNs. NIR þ LNs were not identified in 4 patients: 1 patient with occult stage IV disease, for whom further imaging was not performed and thus was excluded from analysis, and 3 patients in whom ICG was used without HSA. Identification of local LNs on the esophagus was obscured by a peritumoral background. Importantly, the pathological status of NIR þ regional LNs reflected overall regional nodal status. Conclusions: NIR lymphatic mapping is safe and feasible in patients with esophageal cancer and can identify regional LNs when ICG:HSA is used. Although more work is needed to improve background signals and local LN identification, intraoperative detection of regional NIR þ LNs allows an in-depth histological analysis of LN basins not commonly scrutinized as part of the specimen and may improve the detection of occult nodal disease.
End-stage renal disease is a significant negative predictor of limb salvage and patient survival ... more End-stage renal disease is a significant negative predictor of limb salvage and patient survival in patients with limb ischemia, but little is known of the overall effects of renal transplantation. Endovascular management may be less morbid than open surgery, but technical success and durability in these patients is not well established. All patients with functioning renal transplants and critical limb ischemia (CLI) treated with endovascular techniques between 2003 and 2010 were retrospectively reviewed for limb salvage, reintervention, pre- and postprocedure creatinine, and estimated glomerular filtration rate (eGFR), and overall survival. Contralateral common femoral access, low-profile techniques, and isosmolar contrast were standard for all interventions. Endovascular interventions were performed on 57 limbs in 28 patients with renal transplants. Mean age was 54 years, 78% were male, 85% were diabetic, 100% were hypertensive, and 64% had a positive smoking history. All patients were treated for CLI. Treated regions included 16 iliac, 19 superficial femoral, 16 popliteal, and 12 tibial arteries, as well as 1 bypass graft with initial technical success of 100% and 0% 30-day mortality. Of all lesions, 43% required reintervention during the follow-up period, the majority in the first year. There was no significant change in eGFR or creatinine comparing pre- and post-angiogram value. Limb salvage and 1-year survival were 83% and 82%, respectively. Endovascular management of CLI in renal transplant patients results in good technical success and can be accomplished without a measurable change in transplant kidney function, although it requires repeat interventions. Endovascular therapy is a reasonable first-line treatment option for this high-risk group.
The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co... more The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection a...
Seminars in Thoracic and Cardiovascular Surgery, 2011
During the past few decades, particles of various compositions have been engineered in ever small... more During the past few decades, particles of various compositions have been engineered in ever smaller sizes to function in both diagnostic and therapeutic capacities. Nanoparticles are now available on a scale similar to many biological molecules and infectious agents, thereby opening the possibility of biological intervention on the molecular level. Several recent timely reports summarize nanoparticle properties and potential clinical applications in early-stage clinical trials.
Perioperative care of patients undergoing colon resection requires a multidisciplinary approach b... more Perioperative care of patients undergoing colon resection requires a multidisciplinary approach by the operating surgeon, residents, and nurses. Operations performed on Monday take full advantage of hospital resources throughout the week to meet expected discharge by Friday. In a current health care environment of diminishing means, improving the timing of surgery in relation to expected length of stay may play an important role in preserving health care resources. A retrospective review of a prospectively collected colorectal surgical database identified all patients who underwent segmental colon resection at a single tertiary care referral center from 2004 to 2010. Length of stay for patients undergoing elective open and minimally invasive segmental colectomy was compared for Monday versus Tuesday through the weekend. Patient and surgeon demographics were recorded as well as postoperative outcomes and complications. A total of 868 segmental colectomies were performed during the study period. Length of stay was significantly decreased by .73 days (P < .01) for all segmental colectomies performed on Monday compared with those performed Tuesday through Sunday. There was also a significant decrease in length of stay looking independently at right (.96 days, P < .01) and left or sigmoid colectomies (.56 days, P < .01). There was no significant difference in patient or surgeon demographics to account for this difference. Segmental colectomies have a significantly decreased length in stay when performed on Monday compared with the rest of the week. The decrease is independent of surgeon, comorbidities, and complications. This difference may be the result of patients' taking full advantage of hospital resources and ancillary support. Cost-effective measures may be evaluated and directed at adjustment of resources available throughout the week to reduce length of stay.
We present a case of a woman initially presenting with a neck mass and subsequently found to have... more We present a case of a woman initially presenting with a neck mass and subsequently found to have generalized lymphatic anomaly with diffuse lymphatic dilation and proliferation involving the mediastinum and pericardium. Intrathoracic involvement of generalized lymphatic anomalies can lead to recurrent pleural effusions, pericardial effusions, and severe respiratory infections. These anomalies cannot be cured and significantly impact quality of life. Multidisciplinary involvement is crucial to maximize symptom relief as surgery to remove lymphatics can be morbid and the disease is usually recurrent.
The Journal of Thoracic and Cardiovascular Surgery, 2013
Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year surviva... more Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year survival, particularly if lymph nodes are involved. Our objective was to perform a dose-escalation study to assess safety and feasibility of intraoperative near-infrared (NIR) fluorescence imaging to identify the first tumor-draining lymph nodes (ie, sentinel lymph nodes [SLNs] in patients with NSCLC). A-dose escalation phase 1 clinical trial assessing real-time NIR imaging after peritumoral injection of 3.8 to 2500 μg indocyanine green (ICG) was initiated in patients with suspected stage I/II NSCLC. Visualization of lymphatic migration, SLN identification, and adverse events were recorded. Thirty-eight patients underwent ICG injection and NIR imaging via thoracotomy (n = 18) or thoracoscopic imaging (n = 20). SLN identification increased with ICG dose, with fewer than 25% SLNs detected in dose cohorts of 600 μg or less versus 89% success at 1000 μg or greater. Twenty-six NIR(+) SLNs were identified in 15 patients, with 7 NIR(+) SLNs (6 patients) harboring metastatic disease on histologic analysis. Metastatic nodal disease was never identified in patients with a histologically negative NIR(+) SLN. No adverse reactions were noted. NIR-guided SLN identification with ICG was safe and feasible in this initial dose-escalation trial. ICG doses greater than 1000 μg yielded nearly 90% intrathoracic SLN visualization, with the presence or absence of metastatic disease in the SLN directly correlating with final nodal status of the lymphadenectomy specimen. Further studies are needed to optimize imaging parameters and confirm sensitivity and specificity of SLN mapping in NSCLC using this promising imaging technique.
Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, ... more Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin.
Background. The presence of lymph node metastasis is the most important prognostic factor in earl... more Background. The presence of lymph node metastasis is the most important prognostic factor in early non-small cell lung cancer. Our objective was to develop a rapid, simple, and reliable method for thoracic sentinel lymph node (SLN) identification using near-infrared fluorescence imaging and clinically available contrast agents.
Locoregional recurrence significantly impacts survival and quality of life in patients with ovari... more Locoregional recurrence significantly impacts survival and quality of life in patients with ovarian carcinoma. We hypothesize that local administration of paclitaxel-loaded expansile nanoparticles (pax-eNP) at the time of cytoreductive surgery decreases local tumor recurrence. In vitro cytotoxicity of pax-eNP was assessed against both the OVCAR-3 human ovarian cancer cell line and tumor cells isolated from a malignant pleural effusion from a patient with multidrug-resistant ovarian cancer. A murine xenogenic model involving surgical cytoreduction of established OVCAR-3 intra-abdominal tumor was used to evaluate in vivo efficacy of intraoperative intraperitoneal (IP) injection of 10 mg/kg of paclitaxel either as pax-eNP or paclitaxel in Cremophor EL/ethanol solution (pax-C/E) versus empty eNP controls. Cytoreductive surgery and intraoperative treatment were performed 4 weeks after established tumor. All animals were sacrificed when empty eNP controls displayed extensive evidence of disease progression. Labeled-eNP entered tumor cells in vitro within 4 h and specifically accumulated at sites of tumor in vivo. Pax-eNP exhibited dose-dependent cytotoxicity in both OVCAR-3 and patient tumor cells isolated from a malignant pleural effusion and effectively prevented tumor recurrence following debulking (p = 0.003 vs. empty eNP). Furthermore, pax-eNP-treated animals did not develop severe recurrent carcinomatosis compared with 43 % of the pax-C/E-treated cohort, suggesting that single-dose intracavitary pax-eNP is more effective than an equivalent dose of pax-C/E. Expansile nanoparticles readily enter human ovarian tumor cells and localize to sites of tumor in vivo with pax-eNP cytotoxicity resulting in superior inhibition of locoregional tumor recurrence following cytoreductive surgery.
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Papers by Denis Gilmore