S100A4 alters metabolism and promotes invasion of lung cancer cells by up-regulating mitochondrial complex I protein NDUFS2.

It is generally accepted that alterations in metabolism are critical for the metastatic process; however, the mechanisms by which these metabolic changes are controlled by the major drivers of the metastatic process remain elusive. Here, we found that S100 calcium-binding protein A4 (S100A4), a major metastasis-promoting protein, confers metabolic plasticity to drive tumor invasion and metastasis of non-small cell lung cancer cells. Investigating how S100A4 regulates metabolism, we found that S100A4 depletion decreases oxygen consumption rates, mitochondrial activity, and ATP production and also shifts cell metabolism to higher glycolytic activity. We further identified that the 49-kDa mitochondrial complex I subunit NADH dehydrogenase (ubiquinone) Fe-S protein 2 (NDUFS2) is regulated in an S100A4-dependent manner and that S100A4 and NDUFS2 exhibit co-occurrence at significant levels in various cancer types as determined by database-driven analysis of genomes in clinical samples using cBioPortal for Cancer Genomics. Importantly, we noted that S100A4 or NDUFS2 silencing inhibits mitochondrial complex I activity, reduces cellular ATP level, decreases invasive capacity in three-dimensional growth, and dramatically decreases metastasis rates as well as tumor growth in vivo Finally, we provide evidence that cells depleted in S100A4 or NDUFS2 shift their metabolism toward glycolysis by up-regulating hexokinase expression and that suppressing S100A4 signaling sensitizes lung cancer cells to glycolysis inhibition. Our findings uncover a novel S100A4 function and highlight its importance in controlling NDUFS2 expression to regulate the plasticity of mitochondrial metabolism and thereby promote the invasive and metastatic capacity in lung cancer.

Failure to operate on resectable gastric cancer: implications for policy changes and regionalization.

BACKGROUND: A significant proportion of patients never receive curative-intent surgery for resectable gastric cancer (GC). The primary aims of this study were to identify disparities and targetable risk factors associated with failure to operate in the context of national trends in surgical rates for resectable GC. METHODS: The National Cancer Database was used to identify patients with resectable GC (adenocarcinoma, clinical stage IA-IIIC, 2004-2013). Multivariate modeling was used to identify predictors of resection and to analyze the impact of surgery on overall survival (OS). RESULTS: Of 46,970 patients with resectable GC, 18,085 (39%) did not receive an appropriate operation. Among unresected patients, 69% had no comorbidities. Failure to resect was associated with reduced median OS (44.4 versus 11.8 mo, hazard ratio [HR]: 2.09, P < 0.001). In the multivariate analysis, the most critical factors affecting OS were resection (HR: 2.09) and stage (reference IA; HR range: 1.16-3.50, stage IB-IIIC). Variables independently associated with no surgery included insurance other than private or Medicare (odds ratio [OR]: 1.60/1.54), nonacademic/nonresearch hospital (OR: 1.16), non-Asian race (OR: 1.72), male (OR: 1.19), older age (OR: 1.04), Charlson-Deyo score >1 (OR: 1.17), residing in areas with median income <$48,000 (OR: 1.23), small urban populations <20,000 (OR: 1.41), and stage (reference IA; OR range: 1.36-3.79, stage IB-IIIC, P < 0.001). CONCLUSIONS: Over one-third of patients with resectable GC fail to receive surgery. Suitable insurance coverage and treatment facility are the most salient (and only modifiable) risk factors for omitting surgery. To mitigate national disparities in surgical care, policymakers should consider improving insurance coverage in underserved areas and regionalization of gastric cancer care.

Video-Assisted Thoracoscopic versus Open Lobectomy: Costs and Outcomes.

OBJECTIVES: Video-assisted thoracoscopic (VATS) lobectomy is considered a promising surgical therapy for the diagnosis and treatment of non-small-cell lung carcinoma. The issue of whether VATS is superior to open thoracotomy remains controversial, however. We sought to determine whether the use of VATS lobectomy for diagnosing and treating non-small-cell lung carcinoma would improve patient outcomes at our institution. METHODS: A retrospective review of electronic and paper medical charts identified 109 consecutive operations for all patients undergoing thoracotomy or VATS lobectomy performed at the University of Kentucky Chandler Medical Center for fiscal years 2013 and 2014. Variables of interest included operative procedure (thoracotomy vs VATS) and operative findings (pathologic stage, operative time, postoperative length of stay [LOS], time spent in the intensive care unit, postoperative complications, direct cost). RESULTS: The demographic characteristics of the patients of both groups were similar in terms of sex (64.6% vs 44.3% male) and age (62.4 vs 61.6 years), but not stage, which was higher in the thoracotomy group. The overall operative procedure time (170.6 vs 196.3 minutes), postoperative LOS (5.7 vs 5.5 days), number of lymph nodes sampled (6.2 vs 7.0), and time spent in the intensive care unit (2.1 vs 2.4 days) did not vary between both groups. The average cost per procedure did not vary significantly-$14,003.61 compared with $15,588.11 for thoracotomy and VATS, respectively. CONCLUSIONS: In our study, the VATS group was associated with no reduction in postoperative LOS and a nonsignificant reduction in the amount of time spent in the intensive care unit. Postoperative perception of pain did not vary between either group. Pain perception did, however, correlate strongly with time from operation. Cost did not vary significantly between both groups, with VATS being equivalent to thoracotomy in terms of cost at our institution. In our experience, VATS is an effective, minimally invasive, and safe approach for the resection of lung nodules.

Increased morbidity and mortality of a concomitant colectomy during a pancreaticoduodenectomy: an NSQIP propensity-score matched analysis.

BACKGROUND: Select patients with peri-ampullary cancers require concomitant colon resection (CR) during a pancreaticoduodenectomy (PD) for margin-negative resections. This study analysed the impact of concomitant CR on major morbidity (MM) and mortality. METHODS: National Surgical Quality Improvement Program (NSQIP) patients undergoing PD for peri-ampullary cancers were identified from 2005 to 2012. A 4 : 1 propensity-score matched analysis isolated the impact of CR upon PD. Risk factors for 30-day MM and mortality were analysed to determine post-operative sequelae of PD+CR. RESULTS: From 10 965 PD and 159 PD+CR patients, 624 and 156, respectively, were selected for 4 : 1 matched analysis. PD+CR resulted in a higher MM and mortality (50.0% and 9.0%) versus PD alone (28.8% and 2.9%, respectively, P < 0.001). Multivariate analysis identified risk factors for MM after PD: concomitant CR [odds ratio (OR)-3.19, P < 0.001], smoking (OR-1.92, P = 0.005), a lack of functional independence (OR-3.29, P = 0.018), cardiac disease (OR-2.39, P = 0.011), decreased albumin (per g/dl, OR-1.38, P = 0.033) and a longer operative time (versus median time, OR-1.56, P = 0.029). Independent predictors of mortality included concomitant CR (OR-3.16, P = 0.010), ventilator dependence (OR-13.87, P < 0.001) and septic shock (OR-6.02, P < 0.001). CONCLUSIONS: CR was an independent predictor of MM and mortality after a PD. Patients requiring PD+CR should be identified pre-operatively, maximally optimized and referred to experienced surgeons at expert centres.

Abdominal aortic aneurysm repair complicated by infection with Clostridium septicum.

Aortic stent-graft infection after endovascular abdominal aortic aneurysm (AAA) repair is an uncommon, but very serious complication with potentially devastating consequences.(1) Traditional open techniques of repair of AAA demonstrate an infection rate of 0.5-3%. The exact rate of infection with endovascular repair is unknown, but literature review demonstrates an overall incidence of 0.43-1.17% retrospectively.(2,3) Etiology of endovascular graft infections typically results from flora derived from the skin or gastrointestinal tract.(4)Clostridium septicum is a naturally occurring anaerobic bacterium native to the gastrointestinal tract. It is typically associated with spontaneous nontraumatic gas gangrene owing to bacteremia from the gastrointestinal tract with an incidence rate of 0.07%.(5) To our knowledge, this is the first reported case of endovascular AAA graft infection owing to Clostridium septicum species.

Isolated necrotizing aortitis presenting as incidental thoracoabdominal aortic aneurysm: a case report.

Noninfectious aortitis is frequently asymptomatic yet often leads to the development of ascending aortic aneurysms requiring repair. We present the case of a 64-year-old Caucasian woman who presented to our medical center with an incidentally discovered thoracoabdominal aneurysm. She had previously been in good health and had not complained of chest pain or been otherwise symptomatic. At presentation to our clinic, her ascending aorta measured 5 cm at the sinotubular junction (STJ) with dilation of her descending thoracic aorta to 6 cm. Her coronary angiogram was normal. Cross-sectional imaging was notable for thickening of the aortic wall along its length. The entity of isolated noninfectious aortitis is increasingly being recognized as an identifiable factor leading to ascending aneurysmal disease. In reviewing this case, we outline current understanding and guidelines for management and follow-up of this pathology. Operative repair of the ascending arch was conducted using an interpositional graft. The aortic valve apparatus was normal and the proximal anastomosis was created at the STJ. Intraoperatively, an inflammatory obliteration of the aortopulmonary window was noted. It was not possible to completely excise the posterior aortic wall. Our patient had an uneventful recovery and final pathology revealed necrotizing aortitis (NA). She is currently undergoing routine surveillance of her descending thoracoabdominal aneurysm. Recent case series indicate that NA is a histologically distinct process, which is associated commonly with development of ascending aneurysm, and although it is most commonly an isolated finding, it may be associated with other vascular abnormalities including stenoses of branch vessels. There is a growing body of literature suggesting that NA represents a distinct clinical entity, associated with the development of ascending aortic aneurysms. Further research is required to determine the optimal follow-up and value of medical therapies.

Consolidation Therapy in Esophageal Cancer.

Consolidation therapy describes dose intensification strategies or additional treatment performed following completion of the primary regimen. In the case of esophageal cancer, this applies to cases of potentially persistent disease after definitive multi-modality therapy, including surgery. Consolidation should also be considered for patients initially planned to undergo surgery after neoadjuvant therapy, but for any reason elected a nonoperative strategy during treatment. With the advent of targeted therapy and immunotherapy, additional options may be available for consolidation in the future.

Surgeons' Role in Local Palliation of Esophageal Cancer.

Esophageal cancer commonly presents in advanced stage, and many patients will require palliative intervention. Endoscopic stenting remains an excellent first-line therapy; however, this should be discussed in a multidisciplinary setting, considering expectations for long-term survival.

'Normal' vital signs belie occult hypoperfusion in geriatric trauma patients.

Base deficit (BD) and lactic acid (LA) are accepted markers of hypoperfusion and predictors of outcome in the trauma patient and we aim to assess the value of these markers in the triage of the elderly with "normal" vital signs. Patients older than age 65 who presented between 1997 and 2004 but who did not have isolated head injuries were included. Three patient groups were established: normal, occult hypoperfusion (OH), and shock. Outcome measures included mortality, hospital length of stay, intensive care unit length of stay, and discharge disposition. One hundred six patients were included in the analysis and had similar Injury Severity Scores. Mean systolic blood pressure was similar in the normal and OH groups. Forty-two per cent of patients had abnormal BD or LA in the emergency room indicating OH. These patients were more likely to have a longer intensive care unit length of stay (8.6 days vs. 3 days; P = 0.01) and were also more likely to be discharged to a nursing facility (P = 0.03). The trend was toward increased mortality in the OH group. OH is a common finding in elderly trauma patients. Outcomes in these patients are different and more like those presenting in shock.

Acute mesenteric and aortic thrombosis associated with antithrombin deficiency: a rare occurrence.

Antithrombin is a potent inhibitor of the coagulation cascade exerting its primary effects on activated factors X, IX and II. It is the mechanism by which heparin and low-molecular weight heparin cause anti-coagulation. Deficiency of antithrombin presents as a hypercoagulable state, and may result in unexplained deep venous thrombosis, arterial thrombosis and systemic embolization.

Thoracoscopic esophageal mobilization during minimally invasive esophagectomy: a head-to-head comparison of prone versus decubitus positions.

BACKGROUND: Minimally invasive esophagectomy (MIE) is being performed at an increasing number of institutions. The thoracoscopic portion is generally performed in the left lateral decubitus position. Recently there has been increasing interest in esophageal mobilization in the prone position and the potential benefits of this technique with regard to operative time, surgeon ergonomics, and operative exposure. We sought to objectively compare thoracoscopic mobilization of the esophagus in the left lateral decubitus position versus the prone position and identify potential differences between the two techniques. METHODS: A retrospective review of a prospectively maintained esophagectomy database identified 44 patients undergoing MIE during a 20-month period (June 2005-February 2007). Of these, 32 patients underwent thoracoscopic esophageal mobilization with cervical esophagogastric anastomosis. Eleven cases were performed in the left lateral decubitus position and 21 performed in the prone position. RESULTS: The patients were comparable in age, tumor stage, and fraction undergoing neoadjuvant therapy. There was no statistically significant difference between decubitus position and prone position with regard to number of lymph nodes procured (14.6 versus 15.5, p = 0.69), complications (6/11 versus 10/21, p = 1.0), length of stay (9 versus 10 days, p = 1.0), or intraoperative blood loss (85 versus 65 cc, p = 0.14). Thoracoscopic operative times were significantly shorter in the prone group than the decubitus group (86 versus 123 min, p = 0.0001). CONCLUSIONS: Prone thoracoscopic esophageal mobilization appears to be equivalent to decubitus thoracoscopic esophageal mobilization with respect to blood loss, number of lymph nodes dissected, and complications, but with a significant reduction in thoracoscopic surgical time.

Emergent Minimally Invasive Esophagogastrectomy.

Introduction. Esophageal perforation in the setting of a malignancy carries a high morbidity and mortality. We describe our management of such a patient using minimally invasive approach. Methods. An 83-year-old female presented with an iatrogenic esophageal perforation during the workup of dysphagia. She was referred for surgical evaluation immediately after the event which occurred in the endoscopy suite. Minimally invasive esophagectomy was chosen to provide definitive treatment for both her malignancy and esophageal perforation. Results. Following an uncomplicated operative course, she was eventually discharged to extended care for rehabilitation and remains alive four years after her resection. Conclusion. Although traditional open techniques are the accepted gold standard of treatment for esophageal perforation, minimally invasive esophagectomy plays an important role in experienced hands and may be offered to such patients.

National Analysis of Unplanned Readmissions After Thoracoscopic Versus Open Lung Cancer Resection.

BACKGROUND: Hospital readmissions are viewed as a mark of inferior health care quality and are penalized. Unplanned postoperative readmission reason and timing after lung resection are not well understood. We examine related, unplanned readmissions after thoracoscopic versus open anatomic lung resections to identify opportunities to improve patient care. METHODS: We analyzed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data set, 2012 to 2015, characterizing 30-day related, unplanned postoperative readmissions after anatomic lung resections for primary lung cancer. Risk-adjusted comparison of readmission after thoracoscopic and open resection was performed using propensity matching. RESULTS: Patients (n = 9,510) underwent anatomic lung resections; 4,935 (51.9%) were thoracoscopic resections and 4,575 (48.1%) were open resections. Of the thoracoscopic patients, 10.9% experienced one or more complications, versus 19.4% of patients with open resection (p < 0.0001). Of the thoracoscopic patients 5.5% experienced related, unplanned readmissions versus 7.2% of the patients with open resection (p < 0.001). 24.8% of complications after thoracoscopic approach occurred after discharge, versus 15.5% after open approach (p < 0.0001). Timing of unplanned readmission was similar for both groups. The propensity-matched odds ratio of risk of readmission after thoracoscopic versus open resection was 1.16 (95% confidence interval, 0.949 to 1.411, p = 0.15). CONCLUSIONS: Open anatomic lung resections for primary lung cancer had nearly twice the complication rate but only a slightly higher readmission rate than thoracoscopic resection. More complications occurred after discharge after thoracoscopic than open resections. Most readmissions occurred within 2 weeks after both thoracoscopic and open resections. Risk-adjusted comparison identified no statistically significant difference in risk of related, unplanned readmission after thoracoscopic versus open resections. Future studies should focus on identification of processes of care to decrease complications and unplanned readmissions after lung cancer resection.

Effects of delaying appendectomy for acute appendicitis for 12 to 24 hours.

OBJECTIVE: To determine whether delaying appendectomy for 12 hours to avoid disturbing the operating room schedule and to minimize the number of operations during the night negatively affects the outcome of patients with acute appendicitis. DESIGN: Retrospective study. SETTING: Large teaching community hospital. PATIENTS: The medical records of 380 patients who underwent appendectomies between January 1, 2002, and December 31, 2004, were reviewed. Patients proven to have an inflamed appendix on the pathological report were divided into 2 groups. The early group comprised patients who had undergone appendectomies within 12 hours of presentation to the emergency department, including patients with generalized sepsis. The late group comprised patients who had undergone appendectomies more than 12 to 24 hours after presentation. MAIN OUTCOME MEASURES: Length of stay, operative time, and the rate of perforations and complications. INTERVENTIONS: Laparoscopic or open appendectomies. RESULTS: There were 309 patients included in our study. There were no statistically significant differences between the early and late groups in the length of stay, operative time, the percentage of advanced appendicitis, or the rate of complications. CONCLUSIONS: In selected patients, delaying appendectomies for acute appendicitis for 12 to 24 hours after presentation does not significantly increase the rate of perforations, operative time, or length of stay. It decreases the use of the nursing staff, anesthesia team, and surgical house staff during the night shifts, and it decreases the interruption of the regular operating room schedule.

Laparoscopic Robot-Assisted Diaphragm Plication.

Minimally invasive approaches to diaphragm plication for eventration include thoracoscopic and laparoscopic techniques. The elevated hemidiaphragm and ribs limit thoracoscopic techniques. We report our modification of the laparoscopic approach using robotic assistance with the da Vinci Surgical System, (Intuitive Surgical Inc, Sunnyvale, CA) to avoid single-lung ventilation, facilitate exposure, and allow more precise placement of plication sutures to achieve an even tension and maximum plication. Critical steps include creation of a small defect in the diaphragm to equalize pressures between cavities and placement of multiple, pledgeted interrupted horizontal mattresses.

Venous Thromboembolism Prophylaxis For Esophagectomy: A Survey of Practice Patterns Among Thoracic Surgeons.

BACKGROUND: Current guidelines for gastrointestinal cancer surgical intervention in high-risk patients recommend postoperative venous thromboembolism (VTE) chemical prophylaxis for 4 weeks with low-dose unfractionated heparin or low-molecular-weight heparin, but specific guidelines for esophagectomy are lacking. This survey identified the clinical patterns affecting postesophagectomy VTE chemoprophylaxis use among general thoracic surgeons. METHODS: General Thoracic Surgery Club members were invited to complete an online survey on VTE prophylaxis to analyze clinical factors affecting their choices. RESULTS: Seventy-seven surgeons (37% membership) responded; of these, 94% (72 of 77) completed fellowships, and 76% (58 of 77) worked at universities. VTE chemoprophylaxis administration varied widely in drug, dosing, and duration, with 30% using suboptimal dosing of unfractionated heparin (every 12 hours). Participants agreed that esophagectomy patients are at high VTE risk, yet 29% (22 of 76) of surgeons delay VTE chemoprophylaxis until postoperative day 1. Only 13% (10 of 77) prescribe postdischarge chemoprophylaxis. Minimally invasive surgeons (>90% of cases) were more likely to prescribe postdischarge prophylaxis (p = 0.007). Epidurals, routinely used by 65% (51 of 78), led to less compliance with recommended dosing. Only 53% (27 of 51) of pain teams allow unfractionated heparin every 8 hours, yet 73% (37 of 51) allow suboptimal dosing (every 12 h). Postoperative major complications were identified as a VTE risk factor by only 21% (15 of 72) of surgeons. Most (92% [68 of 74]) would follow esophagectomy-specific guidelines, if developed. CONCLUSIONS: Thoracic surgeons agree that VTE chemoprophylaxis is necessary for esophagectomy, yet substantial variability exists in current practice. A noteworthy proportion use suboptimal dosing, and very few choose postdischarge prophylaxis. To improve postesophagectomy morbidity and mortality outcomes, thoracic surgeons are willing to follow evidence-based guidelines for VTE chemoprophylaxis.

Impact of Residents on Surgical Outcomes in High-Complexity Procedures.

BACKGROUND: There are different views on the effects of resident involvement on surgical outcomes. We hypothesized that resident participation in surgical care does not appreciably alter outcomes. STUDY DESIGN: We analyzed an American College of Surgeons NSQIP subset of inpatients having procedures with high complexity, including 4 surgical specialties (general surgery, cardiothoracic surgery, neurosurgery, and vascular surgery) with the highest mean work relative value units. We evaluated surgical outcomes in patients having procedures performed by the attending surgeon alone, or by the attending surgeon with assistance from at least one surgical resident (PGY1 to PGY≥6). Outcomes measures included operative mortality, composite morbidity, and failure to rescue (FTR). Propensity-score matching minimized the effects of nonrandom assignment of residents to procedures. RESULTS: In 266,411 patients, unmatched comparisons showed significantly higher operative mortality and composite morbidity rates, but decreased FTR, in operations performed with resident involvement. After propensity-score matching, there were small but significant resident-related increases in composite morbidity, but significant improvement in FTR. Senior-level resident involvement translated into improved outcomes, especially in cardiothoracic surgery procedures where >63.6% of procedures had PGY≥6 resident involvement. Resident involvement attenuated the significant worsening of operative mortality and FTR associated with multiple serious complications in individual patients. Measures of resource use increased modestly with resident involvement. CONCLUSIONS: We found substantial improvement in FTR with resident involvement, both in unmatched and propensity-matched comparisons. Senior-level resident participation seemed to attenuate, and even improve, surgical outcomes, despite slightly increased resource use. These results provide some reassurance about teaching paradigms.

Nodal Upstaging During Lung Cancer Resection Is Associated With Surgical Approach.

BACKGROUND: Recent reports indicate that thoracoscopic lobectomy for lung cancer may be associated with lower rates of surgical upstaging. We queried a statewide cancer registry for differences in upstaging rates and survival by surgical approach. METHODS: The Kentucky Cancer Registry (KCR) collects data, including centralized pathology reporting, on cancer patients treated statewide. We performed a retrospective review from 2010 to 2012 to examine clinical and pathologic stage. We assessed rates of upstaging and whether the surgical approach, thoracotomy (THOR) versus minimally invasive techniques (video-assisted thoracic surgery; VATS), had an impact on final pathologic stage and survival. RESULTS: The KCR database from 2010 to 2012 contained information on 2830 lung cancer cases, 1964 having THOR procedure and 500 having VATS resections. Preoperatively, 36.4% of THOR were clinically stage 1a versus 47.4% VATS (p = 0.0002). Of these, final pathologic stage remained stage 1a in 30.5% of THOR procedures and 38.0% of VATS (p = 0.0002). The overall nodal upstaging rate for THOR was 9.9% and 4.8% for VATS (p = 0.002). Decreased nodal upstaging was found with VATS, independent of tumor size and extent of resection (odds ratio 0.6, 95% confidence interval [CI]: 0.387 to 0.985, p = 0.04). However, improved survival was found with VATS compared with THOR (hazard ratio 0.733, 95% CI: 0.592 to 0.907, p = 0.0042). CONCLUSIONS: Consistent with other reports, we report a lower upstaging rate with VATS. Nevertheless, there is a survival advantage in VATS patients. Although selection bias may play a role in these observed differences, the improved quality of life measures associated with VATS may explain survival improvement despite lower surgical upstaging.

Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator ß-glucan in a two-case ex vivo non-small-cell lung cancer study.

Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patient's target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations. In this two-case study of non-small-cell lung cancer, we performed stable isotope-resolved metabolomic (SIRM) experiments on paired CA and NC lung tissues treated with a macrophage activator ß-glucan and (13)C6-glucose, followed by ion chromatography-Fourier transform mass spectrometry (IC-FTMS) and nuclear magnetic resonance (NMR) analyses of (13)C-labeling patterns of metabolites. We demonstrated that CA lung tissue slices were metabolically more active than their NC counterparts, which recapitulated the metabolic reprogramming in CA lung tissues observed in vivo. We showed ß-glucan-enhanced glycolysis, Krebs cycle, pentose phosphate pathway, antioxidant production, and itaconate buildup in patient UK021 with chronic obstructive pulmonary disease (COPD) and an abundance of tumor-associated macrophages (TAMs) but not in UK049 with no COPD and much less macrophage infiltration. This metabolic response of UK021 tissues was accompanied by reduced mitotic index, increased necrosis, and enhaced inducible nitric oxide synthase (iNOS) expression. We surmise that the reprogrammed networks could reflect ß-glucan M1 polarization of human macrophages. This case study presents a unique opportunity for investigating metabolic responses of human macrophages to immune modulators in their native microenvironment on an individual patient basis.