Esophageal resection is a key component of the multidisciplinary management of esophageal cancer. Robotic-assisted minimally invasive esophagectomy is gaining widespread approval amongst few centers ...with promising early data. There is significant variability in the operative approach utilized by different centers and this review describes, step-by-step, the operative technique at a high-volume tertiary center. The cornerstone of management is individualized surgical approach, based on patient, tumor and technical factors. Although our approach is based on aforementioned factors, our preferred approach is an Ivor Lewis esophagectomy and this review focuses on that. The procedure is broken down into three key parts, starting with an abdominal exploration and creation of the gastric conduit, placement of jejunostomy tube, moving to thoracic mobilization and creation of the side-side 6 cm stapled esophagogastric anastomosis with a final abdominal portion to assure proper positioning of the conduit and reducing redundancy. This approach is fully robotic and a side to side anastomosis facilitates the creation of a widely patent anastomosis therefore minimizing the risk of anastomotic leaks and strictures. Our experience with minimally invasive esophagectomy, as has been previously published, is associated with a 5.1% of anastomotic leak and 7.6% of anastomotic stricture. The robotic platform further optimizes this technique and helps us safely accomplish a side to side stapled anastomosis. Superior instrument dexterity in a restricted thoracic space is facilitated by intracorporeal suturing and robotic stapling. Thus, it obviates the need for a larger thoracotomy incision, which is typically needed for an EEA anastomosis, and that is traditionally associated with higher stricture rate.
Tumor-associated tissue eosinophilia (TATE) has been associated with outcomes in a variety of solid tumors; however, its role in breast cancer is not well defined. We hypothesized that ...tumor-associated tissue eosinophilia is associated with a high mutation and neoantigen load, and we assessed its correlation with cancer outcomes.
The Cancer Genome Atlas was analyzed for eosinophil signatures in breast cancer specimens. Descriptive analyses were performed, including the tumor-infiltrating cell composition using CIBERSORT, cytolytic activity score, and gene set enrichment analysis. Overall survival and disease-free survival were calculated using the Kaplan-Meier method.
Out of 1069 cases analyzed, 40 (3.7%) had tissue eosinophils (the tumor-associated tissue eosinophilia group). Tumor-associated tissue eosinophilia was noted in 32.5% luminal, 5% HER2-positive, and 15% triple-negative breast cancer subtypes. The single nucleotide variant–neoantigen load was significantly higher in the tumor-associated tissue eosinophilia group (P = .005), with a higher nonsilent mutation rate (P = .01). The tumor-associated tissue eosinophilia group had lower cytolytic activity (P = .02) but had enriched MYC-targeted (P = .002), E2F-targeted (P = .04), deoxyribonucleic acid repair (P = .03), and unfolded protein response gene sets (P = .05). Tumor-associated tissue eosinophilia was associated with a trend toward improved disease-free survival (P = .06) but presented no differences in overall survival (P = .56).
Tumor-associated tissue eosinophilia was noted in 3.7% of breast cancers and was associated with a higher single nucleotide variant–neoantigen load and nonsilent mutation rate, similar to that of tumor-infiltrating lymphocytes in the triple-negative subtype. However, a lower cytolytic activity score and enriched cell proliferation–related gene sets implicate different roles for tumor-associated tissue eosinophilia than for tumor-infiltrating lymphocytes.
Purpose. To analyze the impact of botulinum toxin chemodenervation on postoperative opiate consumption through a novel intraoperative injection protocol. Methods. A retrospective review of the ...implementation of a novel intraoperative botulinum toxin injection into both rectus and oblique musculature. Patients undergoing open retrorectus release, with and without intraoperative chemodenervation with Botox, were retrospectively collected between 2015 and 2019. Demographics, comorbidities, and opioid use in morphine milligram equivalents (MMEs) were retrospectively captured. Basic descriptive statistics and linear regression analysis were performed. Results. 19 patients in the Botox and 22 in the no Botox group were analyzed. Basic demographics were similar with female preponderance in the Botox group, 58% vs 27%, P = .05. Median hernia length was 15 cm for both groups (P = .57), median hernia width was 8 vs 9 cm (P = .39), epidural catheter used in 0 vs 4 (P = .11), transverse abdominal plane blocks in 3 vs 4 (P = 1), median MME usage was 191 vs 230 (P = .37) in the inpatient setting, 225 vs 300 (P = .17) in the outpatient setting, and 405 vs 568 (P = .07) in total for Botox vs no Botox groups. Stepwise linear regression analysis identified Botox as the only predictor for MME usage, P = .048. Conclusions. Chemodenervation was the only factor associated with reduced opioid usage compared to a standard group using multimodality analgesia. The role of muscular pain in laparotomy is likely underappreciated and understudied. Intraoperative selective muscular chemodenervation may play a significant role in recovery from abdominal surgery and requires further study.
Abstract
Metaplastic breast cancer (MBC) constitutes a rare but unique histologic entity with poor prognosis. We hypothesized that MBC possesses unique genetic profile and tumor immune ...microenvironment. MBC cases were identified from a total of 10827 breast cancer entries in the Cancer Genome Atlas Data Set (TCGA) and the AACR-GENIE (Genomics Evidence Neoplasia Information Exchange) cohorts. Tumor infiltrated immune cells were estimated by xCell algorithm. Baseline clinical characteristics were compared, and gene set enrichment analysis (GSEA) was performed. MBC formed 0.66% of all breast cancer cohorts (13/1064 (1.2%) of TCGA and 59/9763 (0.6%) of GENIE). MBC cases were predominantly triple-negative (TNBC) (8 (61.5%) vs 151 (14.4%), p < 0.001), and high Nottingham histological grade (8 (61.5%) vs 222 (21.1%), p = 0.02) compared to non-MBC in the TCGA cohort. Node positive disease was noted in 2 (15.4%) metaplastic cases vs. 538 (51.2%) non-metaplastic cases (p = 0.01). In the tumor immune microenvironment, increased infiltration of M1 macrophages (p = 0.012), dendritic cells (p < 0.001) and eosinophils (p = 0.036) was noted in the MBC cohort however there was no difference in infiltration of CD4+ memory (p = 0.297) and CD8+ T-cells (p = 0.864) nor in cytolytic activity (p = 0.806). MBC was also significantly associated with high leucocyte fraction (p = 0.004), Transforming growth factor (TGF)-β response (p < 0.001), and macrophage regulation (p = 0.008), based on scoring by Thorsson et al, compared to non-MBC in the TCGA cohort. Tumor mutation burden was lower in the MBC compared to the non-MBC, median: 0.4 vs. 1.6/Mb in the TCGA-TNBC cohort (p = 0.67) and 3.0 vs. 4.0/Mb (p = 0.100) in the GENIE cohort. Furthermore, MBC had increased intratumor heterogeneity (p < 0.001) in the TCGA cohort. Disease-specific survival was worse in MBC (p = 0.018) compared to non-MBC. When we compared the biological function between triple-negative MBC and TNBC, angiogenesis and epithelial-to-mesenchymal transition (EMT) pathways were enriched in triple-negative MBC by GSEA (Normalized Enrichment Score (NES) = 1.81, False discovery rate (FDR) = 0.14, p = 0.004 and NES = 1.88, FDR = 0.017, p < 0.001, respectively). Our results suggest that high intratumor heterogeneity, enriched angiogenesis and EMT pathway expression represent possible mechanisms leading to worse disease-specific survival found in metaplastic breast cancer, and these factors highlight potential mechanisms rendering MBC resistant to chemotherapy and provide insight into its tumor microenvironment.
Citation Format: Masanori Oshi, Konstantinos Chouliaras, Mariko Asaoka, Rongrong Wu, Akimitsu Yamada, Thaer Khoury, Itaru Endo, Takashi Ishikawa, Kazuaki Takabe. Intratumor heterogeneity, angiogenesis and epithelial to mesenchymal transition are enhanced in metaplastic breast cancer abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-02.
Injuries after skiing and snowboarding accidents lead to an estimated 7,000 hospital admissions annually and present a significant burden to the health care system. The epidemiology, injury patterns, ...hospital resource utilization, and outcomes associated with these severe injuries need further characterization.
The National Trauma Data Bank was queried for the period 2007 to 2014 for admissions with Injury Severity Score > 15 and International Classification of Diseases Codes-9th Revision codes 885.3 (fall from skis, n = 1,353) and 885.4 (fall from snowboard, n = 1,216). Demographics, emergency department data, diagnosis and procedure codes, and outcomes were abstracted from the database.
Severe (Injury Severity Score > 15) ski-associated and snowboard-associated injuries differed with respect to age distribution (median age, 38; interquartile range, 19-59 for skiers and median age, 20; interquartile range, 16-25 for snowboarders; p < 0.001) and sex (78.9% and 86.4% males, respectively, p < 0.001). Traumatic brain injury was common for both sports (56.8% of skiers vs. 46.6% of snowboarders, p < 0.001). Injuries to the spine (28.9%), chest (37.6%), and abdomen (35.0%) were also common. Eighty percent of patients used emergency medical services (50% ambulance, 30% helicopter) with a median emergency medical services transport time of 84 minutes. 50.8% of patients required interhospital transport. 43.2% of injuries required surgical intervention (21.3% orthopedic, 12.5% neurosurgical, 10.5% thoracic, 7.8% abdominal). Median hospital length of stay was 5.0 days. 60.0% of patients required intensive care unit admission with median intensive care unit length of stay 3.0 days. Overall mortality was 4.0% for skiers and 1.9% for snowboarders.
Severe injuries after ski and snowboard accidents are associated with significant morbidity and mortality. Differences in injury patterns, risk factors for severe injury, and resource utilization require further study. Increased resource allocation to alpine trauma systems is warranted.
Prognostic/epidemiologic, level III.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is ...unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival.
Methods
Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction.
Results
Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0–36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error SE 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (
p
= 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (
p
= 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (
p
= 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21.
Conclusions
The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown ...if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant.
Methods
A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease.
Results
Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years;
p
= 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years;
p
= 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI;
p
= 0.015), CC status of resection (
p
< 0.0001), and Ki67 (
p
= 0.04) as predictors of survival. Systemic chemotherapy before (
p
= 0.55) or after (
p
= 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (
p
= 0.03) and CC (
p
= 0.04) remained significant.
Conclusions
Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.
Background
Frailty is increasingly being recognized as a powerful predictor of postoperative outcomes for cancer patients. This study examined the role of the modified frailty index (MFI) in ...predicting outcomes for patients undergoing cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC).
Methods
Data from National Surgical Quality Improvement Program (NSQIP) patients who underwent CRS/HIPEC between 2005 and 2014 were reviewed. The MFI, validated for use in NSQIP, was used to determine correlation between frailty and postoperative outcomes.
Results
The analysis included 1171 patients. The patients were divided into three groups: non-frail (MFI 0), mildly frail (MFI 1 or 2), or severely frail (MFI ≥ 3). More than 90% of patients had an MFI of 0 or 1. The MFI was 0 for 716 patients (61.1%), 1 for 373 patients (31.9%), 2 for 76 patients (6.5%), 3 for 5 patients (0.4%), and 4 for 1 patient (0.1%). Overall, grade 4 Clavien morbidity was observed in 99 patients (8.5%) and mortality in 26 patients (2.2%). For non-frail, mildly frail, and severely frail patients, worsening frailty correlated respectively with increases in grade 4 Clavien morbidity (6.7% vs. 10.9% vs. 33.3%;
p
= 0.004) and mortality (1.3% vs. 3.3% vs. 33.3%;
p
< 0.001). In the multivariate analysis, which included age of 70 years or older and albumin level of 3 or lower, frailty was the only factor that correlated with postoperative mortality: non-frail:reference, mildly frail odds ratio (OR) 2.76, 95% confidence interval (CI) 1.14–6.73;
p
= 0.025, severely frail (OR 29.1, 95% CI 4–210.87;
p
= 0.01), age of 70 years or older (OR 1.16, 95% CI 0.34–3.93;
p
= 0.81), and albumin level of 3 or lower (OR 2.42, 95% CI 0.84–6.98;
p
= 0.1).
Conclusions
Frailty is a strong predictor of major grade 4 morbidity and mortality after CRS/HIPEC. Severe frailty should be a relative contraindication to CRS/HIPEC. Frailty correlates should be a selection factor in the evaluation of all candidates for CRS/HIPEC.
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