MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma.

Background: In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation. Methods: In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients. Results: GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit. Conclusions: Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.

The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC.

BACKGROUND: The role of tyrosine kinase inhibitors (TKIs) in early-stage and metastatic oncogene-driven non-small cell lung cancer (NSCLC) is established, but it remains unknown how best to integrate TKIs with concurrent chemoradiotherapy (cCRT) in locally advanced disease. The phase 2 ASCENT trial assessed the efficacy and safety of afatinib and cCRT with or without surgery in locally advanced epidermal growth factor receptor (EGFR)-mutant NSCLC. PATIENTS AND METHODS: Adults ≥18 years with histologically confirmed stage III (AJCC 7th edition) NSCLC with activating EGFR mutations were enrolled at Mass General and Dana-Farber/Brigham Cancer Centers, Boston, Massachusetts. Patients received induction afatinib 40 mg daily for 2 months, then cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 IV every 3 weeks during RT (definitive or neoadjuvant dosing). Patients with resectable disease underwent surgery. All patients were offered consolidation afatinib for 2 years. The primary endpoint was the objective response rate (ORR) to induction TKI. Secondary endpoints were safety, conversion to operability, progression-free survival (PFS), and overall survival (OS). Analyses were performed on the intention-to-treat population. RESULTS: Nineteen patients (median age 56 years; 74% female) were enrolled. ORR to induction afatinib was 63%. Seventeen patients received cCRT; 2/9 previously unresectable became resectable. Ten underwent surgery; 6 had a major or complete pathological response. Thirteen received consolidation afatinib. With a median follow-up of 5.0 years, median PFS and OS were 2.6 (95% CI, 1.4-3.1) and 5.8 years (2.9-NR), respectively. Sixteen recurred or died; 6 recurrences were isolated to CNS. The median time to progression after stopping consolidation TKI was 2.9 months (95% CI, 1.1-7.2). Four developed grade 2 pneumonitis. There were no treatment-related deaths. CONCLUSION: We explored the efficacy of combining TKI with cCRT in oncogene-driven NSCLC. Induction TKI did not compromise subsequent receipt of multimodality therapy. PFS was promising, but the prevalence of CNS-only recurrences and rapid progression after TKI discontinuation speak to unmet needs in measuring and eradicating micrometastatic disease.

Predictors of prolonged hospital stay after segmentectomy.

OBJECTIVE: Segmentectomy is becoming the standard of care for small, peripheral non-small cell lung cancer. To improve perioperative management in this population, this study aims to identify factors influencing hospital length of stay after segmentectomy. METHODS: Patients who underwent segmentectomy for any indication between January 2018 and May 2023 were identified using a prospectively maintained institutional database. Multivariable logistic regression models were used to estimate associations between clinical features and prolonged (≥3 days) hospital stay. A nomogram was designed to understand better and possibly calculate the individual risk of prolonged hospital stays. RESULTS: In total, 533 cases were included; 337 (63%) were female. Median age was 66 years (interquartile range [IQR], 63-75). The median size of resected lesions was 1.6 cm (IQR, 1.3-2.1 cm). Median hospital stay was 3 days (IQR, 2-4 days). Major adverse events occurred in 31 (5.8%) cases. The 30-day readmission rate was 5.8% (n = 31). There was no 30-day mortality; 90-day mortality was <1%. Patients older than 75 years (odds ratio [OR], 2.01, 95% confidence interval [CI], 1.15-3.57, P = .02), those with forced expiratory volume in 1 second <88% predicted (OR, 1.99; 95% CI, 1.38-2.89, P < .001), or positive smoking history (OR, 1.72; 95% CI, 1.15-2.60, P = .01) were more likely to have prolonged hospital stays after segmentectomy. A nomogram accounting for age, sex, forced expiratory volume in 1 second, body mass index, smoking history, and comorbidities was created to predict the probability of prolonged hospital stay with an area under the receiver operating characteristic curve of 0.66. CONCLUSIONS: Older patients, those with reduced pulmonary function, and current and past smokers have elevated risk for prolonged hospital stays after segmentectomy. Validation of our nomogram could improve perioperative risk stratification in patients who undergo segmentectomy.

Complete anatomic segmentectomy shows improved oncologic outcomes compared to incomplete anatomic segmentectomy.

OBJECTIVES: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.

Liposomal bupivacaine intercostal block placed under direct vision reduces morphine use in thoracic surgery.

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.

Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Clinical Outcomes of Resected Pure Ground-Glass, Heterogeneous Ground-Glass, and Part-Solid Pulmonary Nodules.

BACKGROUND. Increased (but not definitively solid) attenuation within pure ground-glass nodules (pGGNs) may indicate invasive adenocarcinoma and the need for resection rather than surveillance. OBJECTIVE. The purpose of this study was to compare the clinical outcomes among resected pGGNs, heterogeneous ground-glass nodules (GGNs), and part-solid nodules (PSNs). METHODS. This retrospective study included 469 patients (335 female patients and 134 male patients; median age, 68 years [IQR, 62.5-73.5 years]) who, between January 2012 and December 2020, underwent resection of lung adenocarcinoma that appeared as a subsolid nodule on CT. Two radiologists, using lung windows, independently classified each nodule as a pGGN, a heterogeneous GGN, or a PSN, resolving discrepancies through discussion. A heterogeneous GGN was defined as a GGN with internal increased attenuation not quite as dense as that of pulmonary vessels, and a PSN was defined as having an internal solid component with the same attenuation as that of the pulmonary vessels. Outcomes included pathologic diagnosis of invasive adenocarcinoma, 5-year recurrence rates (locoregional or distant), and recurrence-free survival (RFS) and overall survival (OS) over 7 years, as analyzed by Kaplan-Meier and Cox proportional hazards regression analyses, with censoring of patients with incomplete follow-up. RESULTS. Interobserver agreement for nodule type, expressed as a kappa coefficient, was 0.69. Using consensus assessments, 59 nodules were pGGNs, 109 were heterogeneous GGNs, and 301 were PSNs. The frequency of invasive adenocarcinoma was 39.0% in pGGNs, 67.9% in heterogeneous GGNs, and 75.7% in PSNs (for pGGNs vs heterogeneous GGNs, p < .001; for pGGNs vs PSNs, p < .001; and for heterogeneous GGNs vs PSNs, p = .28). The 5-year recurrence rate was 0.0% in patients with pGGNs, 6.3% in those with heterogeneous GGNs, and 10.8% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .06; for pGGNs vs PSNs, p = .02; and for heterogeneous GGNs vs PSNs, p = .18). At 7 years, RFS was 97.7% in patients with pGGNs, 82.0% in those with heterogeneous GGNs, and 79.4% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .02; for pGGNs vs PSNs, p = .006; and for heterogeneous GGNs vs PSNs, p = .40); OS was 98.0% in patients with pGGNs, 84.6% in those with heterogeneous GGNs, and 82.9% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .04; for pGGNs vs PSNs, p = .01; and for heterogeneous GGNs vs PSNs, p = .50). CONCLUSION. Resected pGGNs had excellent clinical outcomes. Heterogeneous GGNs had relatively worse outcomes, more closely resembling outcomes for PSNs. CLINICAL IMPACT. The findings support surveillance for truly homogeneous pGGNs versus resection for GGNs showing internal increased attenuation even if not having a true solid component.

A High-Quality Blue Whale Genome, Segmental Duplications, and Historical Demography.

The blue whale, Balaenoptera musculus, is the largest animal known to have ever existed, making it an important case study in longevity and resistance to cancer. To further this and other blue whale-related research, we report a reference-quality, long-read-based genome assembly of this fascinating species. We assembled the genome from PacBio long reads and utilized Illumina/10×, optical maps, and Hi-C data for scaffolding, polishing, and manual curation. We also provided long read RNA-seq data to facilitate the annotation of the assembly by NCBI and Ensembl. Additionally, we annotated both haplotypes using TOGA and measured the genome size by flow cytometry. We then compared the blue whale genome with other cetaceans and artiodactyls, including vaquita (Phocoena sinus), the world's smallest cetacean, to investigate blue whale's unique biological traits. We found a dramatic amplification of several genes in the blue whale genome resulting from a recent burst in segmental duplications, though the possible connection between this amplification and giant body size requires further study. We also discovered sites in the insulin-like growth factor-1 gene correlated with body size in cetaceans. Finally, using our assembly to examine the heterozygosity and historical demography of Pacific and Atlantic blue whale populations, we found that the genomes of both populations are highly heterozygous and that their genetic isolation dates to the last interglacial period. Taken together, these results indicate how a high-quality, annotated blue whale genome will serve as an important resource for biology, evolution, and conservation research.

Time between imaging and surgery is not a risk factor for upstaging of clinical stage IA non-small-cell lung cancer.

OBJECTIVES: The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. METHODS: We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30-59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. RESULTS: During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30-59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P = 0.903; ground-glass, P = 0.880; part-solid, P = 0.858; solid, P = 0.959). CONCLUSIONS: This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging.

Empiric flap coverage for the pneumonectomy stump: How protective is it? A single-institution cohort study.

OBJECTIVE: To evaluate the impact of empiric tissue flaps on bronchopleural fistula (BPF) rates after pneumonectomy. METHODS: Patients who underwent pneumonectomy between January 2001 and December 2019 were included. Primary end point was development of BPF. Secondary end points were impact of flap type on BPF rates, time to BPF development, and perioperative mortality. RESULTS: During the study period, 383 pneumonectomies were performed; 93 were extrapleural pneumonectomy. Most pneumonectomy cases had empiric flap coverage, with greater use in right-sided operations (right: 97%, 154/159; left: 80%, 179/224, P < .001). Empiric flaps harvested included intercostal, latissimus dorsi, serratus anterior, omentum, pectoralis major, pericardial fat/thymus, pericardium, and pleura. BPF occurred in 10.4% of the entire cohort but decreased to 6.6% when extrapleural pneumonectomy cases were excluded; 90% (36/40) of BPFs occurred on the right side (P < .001). Median time to develop BPF was 63 days, and 90-day mortality was greater in patients with BPF (12.5% BPF vs 7.4% non-BPF, P < .0001). Intercostal muscle had the lowest rate of BPF (4.5%), even in right-sided operations (8.7%). In contrast, larger muscle flaps such as latissimus dorsi (21%) and serratus anterior (33%) had greater rates of BPF, but the sample size was small in these cohorts. CONCLUSIONS: Empiric bronchial stump coverage should be performed in all right pneumonectomy cases due to greater risk of BPF. In our series, intercostal muscle flaps had low BPF rates, even in right-sided operations. Coverage of the left pneumonectomy stump is unnecessary due to low incidence of BPF in these cases.

Technical note: hydrogel-based mimics of prostate cancer with matched relaxation, diffusion and kurtosis for validating multi-parametric MRI.

BACKGROUND: Protocol standardization and optimization for clinical translation of emerging quantitative multiparametric (mp)MRI biomarkers of high-risk prostate cancer requires imaging references that mimic realistic tissue value combinations for bias assessment in derived relaxation and diffusion parameters. PURPOSE: This work aimed to develop a novel class of hydrogel-based synthetic materials with simultaneously controlled quantitative relaxation, diffusion, and kurtosis parameters that mimic in vivo prostate value combinations in the same spatial compartment and allow stable assemblies of adjacent structures. METHODS: A set of materials with tunable T2, diffusion, and kurtosis were assembled to create quantitative biomimetic (mp)MRI references. T2 was controlled with variable agarose concentration, monoexponential diffusion by polyvinylpyrrolidone (PVP), and kurtosis by addition of lamellar vesicles. The materials were mechanically stabilized by UV cross-linked polyacrylamide gels (PAG) to allow biomimetic morphologies. The reference T2 were measured on a 3T scanner using multi-echo CPMG, and diffusion kurtosis-with multi-b DWI. RESULTS: Agarose concentration controls T2 values which are nominally independent of PVP or vesicle concentration. For agarose PVP hydrogels, monoexponential diffusion values are a function of PVP concentration and independent of agarose concentration. Compared to free vesicles, for agarose-PAG combined with vesicles, diffusion was predominantly controlled by vesicles and PAG, while kurtosis was affected by agarose and vesicle concentration. Both hydrogel classes achieved image voxel parameter values (T2, Da, Ka) for relaxation (T2: 65-255 ms), apparent diffusion (Da: 0.8-1.7 µm2/ms), and kurtosis (Ka: 0.5-1.25) within the target literature ranges for normal prostate zones and cancer lesions. Relaxation and diffusion parameters remained stable for over 6 months for layered material assemblies. CONCLUSION: A stable biomimetic mpMR reference based on hydrogels has been developed with a range of multi-compartment diffusion and relaxation parameter combinations observed in cancerous and healthy prostate tissue.

Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: Interactions between tumor response and survival.

OBJECTIVES: The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. METHODS: Patients who underwent esophagectomy for EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected. RESULTS: The study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8%). Seventy-eight patients (28.1%) had TRS 1 (partial response), 97 (35%) had TRS 2 (poor response), and 36 (13%) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 (P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS. CONCLUSIONS: Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

Burn Center Patients at Risk for Upper Extremity Amputations.

Introduction Burn center patients present not only with burn injuries but also necrotizing infections, purpura fulminans, frostbite, toxic epidermal necrolysis, chronic wounds, and trauma. Burn surgeons are often faced with the need to amputate when limb salvage is no longer a viable option. The purpose of this study was to determine factors which predispose patients to extremity amputations. Methods: This retrospective registry review (2000-2019) compared patients who required upper extremity amputations with those who did not. Cases were pair-matched by age, sex, percent total body surface area (%TBSA), and type/location of injury to control for possible confounding variables. Results: There were 77 upper extremity amputee patients (APs) and 77 pair-matched non-amputees (NAPs) with the median age 45- and 43-years, %TBSA 21 and 10, respectively; second and third degree burn injuries were similar in the 2 groups. The AP group had longer hospitalizations (median 40 vs 15 days) P < .0001, with more intensive care unit days (median 28 vs 18 days). APs presented with significantly more cardiac, renal, and pulmonary comorbidities, acquired infections (61 [64%] vs 35 [36%]), escharotomies, and fasciotomies than the NAP, P < .0001. Mortality was similar (AP 14 [18.2%] vs NAP 9 [11.7%]), P = .26. Conclusions: Escharotomies, fasciotomies, sepsis, pneumonia, wound, and urinary tract infections contributed to prolonged hospitalizations and increased risk for upper extremity amputations in the AP group.

Introduction Les patients des centres de grands brûlés ne présentent pas seulement des lésions dues aux brûlures, mais aussi des infections nécrosantes, un purpura fulminans, des gelures, une épidermolyse bulleuse toxique, des plaies chroniques et des traumatismes. Les chirurgiens pour brûlés sont souvent confrontés au besoin d'amputer quand le sauvetage d'un membre n'est plus une option valable. L'objectif de cette étude était de déterminer les facteurs prédisposant les patients aux amputations de membres. Méthodes: Cette analyse rétrospective d'un registre (2000-2019) a comparé les patients ayant nécessité une amputation d'un membre supérieur à ceux pour lesquels l'amputation n'a pas été nécessaire. Les cas ont été appariés par âge, sexe, pourcentage de la surface corporelle totale (%SCT) et le type/emplacement des lésions pour contrôler les possibles variables confondantes. Résultats: Il y a eu 77 patients amputés (PA) du membre supérieur et 77 patients non amputés (PNA) appariés ayant, respectivement, un âge médian de 45 et 43 ans et un %SCT de 21% et 10%; les lésions par brûlures des 2e et 3e degrés étaient similaires dans les deux groupes. La durée d'hospitalisation pour le groupe PA a été plus longue que pour le groupe PNA (médiane : 40 jours contre 15 jours; P < .0001) avec un plus grand nombre de jours en unité de soins intensifs (médiane : 28 jours contre 18 jours). Les patients du groupe PA avaient plus de comorbidités cardiaques, rénales et pulmonaires et d'infections acquises (61 [64%] contre 35 [36%]), d'escarrotomies et d'aponévrotomies que les patients du groupe PNA (P <.0001). La mortalité a été semblable dans les deux groupes (PA: 14 [18.2%] contre PNA: 9 [11.7%], P = .26). Conclusion: Les incisions de décharge, les aponévrotomies, le sepsis, les pneumonies, les infections des plaies et des voies urinaires ont contribué à des hospitalisations prolongées et à une augmentation du risque d'amputation du membre supérieur dans le groupe PA.

The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: Staging and multidisciplinary management of patients with early-stage non-small cell lung cancer.

Novel targeted therapy and immunotherapy drugs have recently been approved for use in patients with surgically resectable lung cancer. Accurate staging, early molecular testing, and knowledge of recent trials are critical to optimize oncologic outcomes in these patients.

Analysis of recurrence in lung adenocarcinoma with spread through air spaces.

OBJECTIVES: Spread through air spaces is defined as tumor cells in air spaces away from the edge of tumor in lung carcinoma. It is associated with higher locoregional recurrence and lower survival in lung adenocarcinoma. The features of spread through air spaces portending worse outcomes are still under investigation. We reviewed our lung cancer experience to define potential factors related to spread through air spaces that influence recurrence and survival. METHODS: Between January 2010 and December 2017, we identified 968 patients who underwent resection for T1-3N0M0 lung adenocarcinoma. Of these, histologic examination was possible in 787 patients. We examined the presence of spread through air spaces, spread through air spaces characteristics (micropapillary, solid nest, or single cell), average density (number per slide), and farthest distance from tumor at which spread through air spaces was detected, or maximal spread distance. Overall survival and recurrence-free survival were estimated using Kaplan-Meier curves, and differences between spread through air spaces positive versus spread through air spaces negative groups were assessed using the log-rank test. RESULTS: Spread through air spaces was present in 389 of 787 of the reviewed cases (49.4%). Overall survival and recurrence-free survival were significantly lower in the spread through air spaces positive group over 10 years (P < .0001). The incidences of locoregional and distant recurrence were nearly doubled over 10 years in the spread through air spaces positive group compared with the spread through air spaces negative group (P = .002 and <.0001, respectively). In a multivariable Cox regression model adjusted for spread through air spaces characteristics, distance, and tumor size, lobar resection did not confer survival advantage in patients with spread through air spaces (hazard ratio of sublobar resection with respect to lobar resection, 1.44; 95% confidence interval, 0.98-2.11; P = .067). In the spread through air spaces positive group, spread through air spaces density was 2.7 ± 1.4 clusters per slide and the maximal spread distance was 2.2 ± 1.7 mm from the tumor edge. There was no observed correlation between spread through air spaces density or maximal spread distance and overall survival or recurrence. CONCLUSIONS: We show increased distant recurrence in spread through air spaces positive lung adenocarcinoma. Quantifiable measures of spread through air spaces do not appear to correlate with recurrence or survival metrics.

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). WHAT HAPPENED IN THE STUDY?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. WHAT WERE THE RESULTS?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. WHAT DO THE RESULTS OF THE STUDY MEAN?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC. Clinical Trial Registration: NCT02998528 (ClinicalTrials.gov).