Failure to Rescue After Resection of Perhilar Cholangiocarcinoma in an International Multicenter Cohort

Failure to rescue; Resection; Perhilar cholangiocarcinomaFracàs de rescat; Resecció; Colangiocarcinoma perhilarFracaso de rescate; Resección; Colangiocarcinoma perihiliarBackground Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR. Patients and Method Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals. Results In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02–1.05) years], ASA 3 or 4 [1.40 (1.01–1.95)], jaundice at presentation [1.79 (1.16–2.76)], right-sided resection [1.45 (1.06–1.98)], and annual hospital volume < 6 [1.44 (1.07–1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76–13.68). Conclusion FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR

Natural Orifice Translumenal Endoscopic Surgery in Humans: A Review

Natural orifice translumenal endoscopic surgery (NOTES) had its origins in numerous small animal studies primarily examining safety and feasibility. In human trials, safety and feasibility remain at the forefront; however, additional logistic, practical, and regulatory requirements must be addressed. The purpose of this paper is to evaluate and summarize published studies to date of NOTES in humans. The literature review was performed using PUBMED and MEDLINE databases. Articles published in human populations between 2007 and 2011 were evaluated. A review of this time period resulted in 48 studies describing procedures in 916 patients. Transcolonic and transvesicular procedures were excluded. The most common procedure was cholecystectomy (682, 75%). The most common approach was transvaginal (721, 79%). 424 procedures (46%) were pure NOTES and 491 (54%) were hybrid NOTES cases. 127 (14%) were performed in the United States of America and 789 (86%) were performed internationally. Since 2007, there has been major development in NOTES in human populations. A preponderance of published NOTES procedures were performed internationally. With further development, NOTES may make less invasive surgery available to a larger human population

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Abstract

BackgroundThe current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) -2-cm.MethodsPatients who underwent curative resection for -2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM.ResultsA total of 392 -2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P-=-.026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P-=-.019). Patients with tumors measuring 1.5-2-cm had a two-fold increase in the incidence of LNM vs patients with tumors <1.5-cm (17.9% vs 8.7%, odds ratio, 2.59; P-=-.022), as well as a higher risk of advanced tumor grade and higher Ki-67 levels (both P-<-.01). After curative resection, a total of 14 (8.0%) patients with a tumor of 1.5-2-cm and 10 (4.5%) patients with tumor <1.5-cm developed tumor recurrence.ConclusionSurgical resection with lymphadenectomy should be considered for patients with NF-pNETs -1.5-2.0-cm.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151963/1/jso25716.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151963/2/jso25716_am.pd

Abstract

BackgroundThe current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET).MethodsPatients who underwent curative resection for dNETs between 1997â 2016 were identified from 8 highâ volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cutâ off of TNLE relative to LNM was determined.ResultsAmong 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51â 68) years and median tumor size was 1.2â cm (IQR, 0.7â 2.0â cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (â ¤1â cm:52.2% vs 1â 2â cm:61.4% vs >2â cm:93.8%; Pâ 2â cm:80.0%; Pâ <â .05). TNLEâ â ¥â 8 had the highest discriminatory power relative to the incidence of LNM (area under the curveâ =â 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR]â =â 0.9; 95% confidence intervals [95%CI], 0.4â 2.3), G2/G3 tumor grade was (HRâ =â 1.5; 95%CI, 1.0â 2.1).ConclusionsWhile the incidence of LNM directly correlated with tumor size, patients with dNETsâ â ¤â 1â cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153174/1/jso25753.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153174/2/jso25753_am.pd

Survival disparities in rural versus urban patients with Pancreatic Neuroendocrine Tumor: A multi-institutional study from the US Neuroendocrine Tumor Study Group

BACKGROUND: Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA). METHODS: A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression. RESULTS: Of the 1176 PNET patients in the database, 1126 (96%) had zip code recorded. While 837 (74%) lived in UA, 289 (26%) lived in RA. RA patients had significantly shorter median OS following primary PNET resection (122 vs 149 months, p ​= ​0.01). After controlling for income, local healthcare access, distance from treatment center, ASA class, BMI, and T/N/M stage, living in a RA remained significantly associated with worse OS (HR 1.60, 95%CI 1.08-2.39, p ​= ​0.02). CONCLUSION: Rural patients have significantly shorter OS following PNET resection compared to their urban counterparts

Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi‐institutional analysis

BackgroundThe benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.MethodsPatients undergoing surgery for pNET between 1997 and 2016 were identified using a multi‐institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.ResultsAmong 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4‐16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5‐year recurrence‐free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly‐differentiated pNET (21.5), Ki‐67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1‐7: 7.5; difference of index: 11.4).ConclusionLND was mostly beneficial among patients with pNETs >2 cm, Ki‐67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151957/1/jso25689_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151957/2/jso25689.pd