Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes.

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Laparoscopic versus open subtotal gastrectomy for adenocarcinoma of the stomach in a Western population: peri-operative and 5-year oncological outcomes.

BACKGROUND: This study compares the peri-operative and long-term oncological outcomes for laparoscopic subtotal gastrectomy (LSG) versus open subtotal gastrectomy (OSG) for adenocarcinoma of the stomach in a Western population. METHODS: A retrospective, intention-to-treat analysis study was conducted for consecutive patients undergoing gastrectomy with curative intent for adenocarcinoma of the stomach between November 2006 and October 2016. Univariate analysis was used to compare peri-operative outcomes between LSG and OSG. Logistic regression with bootstrapping validation was used to identify independent risk factors for predicting 2-year overall survival. RESULTS: The final analysis included 79 patients. When comparing LSG (n = 30) to OSG (n = 49), there was no difference in the number of resected lymph nodes (36 (IQR 24.3-44) vs. 42 (IQR 28-59), p = 0.165), a reduction in intra-operative blood loss (150 ml (IQR 100-250) vs. 553 ml (IQR 338-1075), p < 0.001) and an increase incidence of post-operative bleeding (3 patients vs. 0, p = 0.024), respectively. Five-year overall survival for LSG (n = 22) versus OSG (n = 20) was 63.6% and 50% (p = 0.372), respectively. The number of positive lymph nodes [OR 0.64 (CI 0.47-0.88), p = 0.006] was the only significant independent risk factor for 2-year overall survival. Pre-operative ASA grading and operative approach did not influence survival outcomes at 2 years. CONCLUSION: This study suggests that LSG is comparable to OSG in Western patients with respect to oncological quality and peri-operative morbidity. Two-year overall survival is predicted by the number of positive lymph nodes and not the operative access employed for resection.

Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma.

OBJECTIVE: The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls. BACKGROUND: The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies. METHODS: A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs. RESULTS: Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal-were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ±â€Š0.01 and 0.87 ±â€Š0.03, respectively. CONCLUSIONS: Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.

Rapid evaporative ionization mass spectrometry imaging platform for direct mapping from bulk tissue and bacterial growth media.

Rapid evaporative ionization mass spectrometry (REIMS) technology allows real time intraoperative tissue classification and the characterization and identification of microorganisms. In order to create spectral libraries for training the classification models, reference data need to be acquired in large quantities as classification accuracy generally improves as a function of number of training samples. In this study, we present an automated high-throughput method for collecting REIMS data from heterogeneous organic tissue. The underlying instrumentation consists of a 2D stage with an additional high-precision z-axis actuator that is equipped with an electrosurgical diathermy-based sampling probe. The approach was validated using samples of human liver with metastases and bacterial strains, cultured on solid medium, belonging to the species P. aeruginosa, B. subtilis, and S. aureus. For both sample types, spatially resolved spectral information was obtained that resulted in clearly distinguishable multivariate clustering between the healthy/cancerous liver tissues and between the bacterial species.

Cardiopulmonary exercise testing for predicting postoperative morbidity in patients undergoing hepatic resection surgery.

OBJECTIVES: Cardiopulmonary exercise testing (CPET) may predict which patients are at risk for adverse outcomes after major abdominal surgery. The primary aim of this study was to determine whether CPET variables are predicative of morbidity. METHODS: High-risk patients undergoing elective, one-stage, open hepatic resection were preoperatively assessed using CPET. Morbidity, as defined by the Postoperative Morbidity Survey (POMS), was assessed on postoperative day 3. RESULTS: A total of 104 patients underwent preoperative CPET and were included in the analysis. Of these, 73 patients (70.2%) experienced postoperative morbidity. Oxygen consumption at anaerobic threshold (V˙O2 at AT, ml/kg/min) was the only CPET predictor of postoperative morbidity on multivariable analysis, with an area under the curve (AUC) of 0.66 [95% confidence interval (CI) 0.55-0.76]. In patients requiring a major hepatic resection (three or more segments), a V˙O2 at AT of <10.2 ml/kg/min gave an AUC of 0.79 (95% CI 0.68-0.86) with 83.9% sensitivity and 52.0% specificity, 80.6% positive predictive value and 62.5% negative predictive value. CONCLUSIONS: The application of a cut-off value for V˙O2 at AT of <10.2 ml/kg/min in patients undergoing major hepatic resection may be useful for predicting which patients will experience morbidity.

In vivo endoscopic tissue identification by rapid evaporative ionization mass spectrometry (REIMS).

Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer-related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.

A prospective cohort study of intrathecal versus epidural analgesia for patients undergoing hepatic resection.

BACKGROUND: The aim of this prospective observational study was to compare peri/post-operative outcomes of thoracic epidural analgesia (TEA) versus intrathecal morphine and fentanyl patient-controlled analgesia (ITM+fPCA) for patients undergoing a hepatic resection (HR). METHOD: Patients undergoing elective, one-stage, open HR for benign and malignant liver lesions, receiving central neuraxial block as part of the anaesthetic, in a high-volume hepato-pancreato-biliary unit, were included in the study. The primary outcome measure was post-operative length of stay (LoS). RESULTS: A total of 73 patients (36 TEA and 37 ITM+fPCA) were included in the study. The median (IQR) post-operative LoS was 13 (11-15) and 11 (9-13) days in the TEA and ITM+fPCA groups, respectively (P = 0.011). There was significantly lower median intra-operative central venous pressure (P < 0.001) and blood loss (P = 0.017) in the TEA group, and a significant reduction in the time until mobilization (P < 0.001), post-operative intra-venous fluid/vasopressor requirement (P < 0.001/P = 0.004) in the ITM+fPCA group. Pain scores were lower at a clinically significant level 12 h post-operatively in the TEA group (P < 0.001); otherwise there were no differences out to day five. There were no differences in quality of recovery or postoperative morbidity/mortality between the two groups. CONCLUSION: ITM+fPCA provides acceptable post-operative outcomes for HR, but may also increase the incidence of intra-operative blood loss in comparison to TEA.

Selected ion flow tube mass spectrometry analysis of exhaled breath for volatile organic compound profiling of esophago-gastric cancer.

Exhaled breath analysis of volatile organic compounds (VOCs) has great potential in terms of disease diagnosis and measuring physiological response to treatment. In this study, selected ion flow tube mass spectrometry (SIFT-MS) has been applied for the quantification of VOCs in the exhaled breath from 3 groups of patients, viz., those with esophago-gastric cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy upper gastrointestinal tract cohort. A total of 17 VOCs have been investigated in this study. The concentrations of 4 VOCs, hexanoic acid, phenol, methyl phenol, and ethyl phenol, were found to be significantly different between cancer and positive control groups using the Mann-Whitney U test. Receiver operating characteristics (ROC) analysis was applied for a combination of 4 VOCs (hexanoic acid, phenol, methyl phenol, and ethyl phenol) to discriminate the esophago-gastric cancer cohort from positive controls. The integrated area under the ROC curve (AUC) is 0.91. The results highlight the potential of VOC profiling as a noninvasive test to identify those with esophago-gastric cancer.

Selected ion flow tube mass spectrometry analysis of volatile metabolites in urine headspace for the profiling of gastro-esophageal cancer.

Urine is considered an ideal biofluid for clinical investigation because it is obtained noninvasively and relatively large volumes are easily acquired. In this study, selected ion flow tube mass spectrometry (SIFT-MS) has been applied for the quantification of volatile organic compounds (VOCs) in the headspace vapor of urine samples, which were retrieved from three groups of patients with gastro-esophageal cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy cohort. Eleven VOCs have been investigated in this study. The concentrations of seven VOCs-acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, methanol, and phenol-were found to be significantly different between cancer, positive control, and healthy groups using the Kruskal-Wallis test. The concentrations of acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol were increased in the cancer cohort compared with healthy controls while the concentration of phenol decreased. The differences in the concentrations of ethanol, propanol, methyl phenol, and ethyl phenol were not significant between cancer and control groups. Receiver operating characteristics (ROC) analysis was applied for a combination of six VOCs (acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol) to discriminate cancer patients from noncancer controls. The integrated area under ROC curve is 0.904. This result indicates that VOC profiling may be suitable in identifying those at high risk of gastro-esophageal cancer. Therefore, further investigations should be undertaken to assess the potential for VOC profiling as a new screening test in gastro-esophageal cancer.

Techniques to increase lymph node harvest from gastrointestinal cancer specimens: a systematic review and meta-analysis.

AIMS: This review aims to compare different histopathological techniques for lymph node harvest from ex-vivo gastrointestinal cancer specimens and to examine their influence on: (i) lymph node yield; (ii) positive lymph node detection; and (iii) cancer staging. METHOD AND RESULTS: Systematic review of the English language literature to 10 October 2011, comparing manual nodal dissection to other techniques for lymph node harvest. The methodological quality of included studies was assessed. Twenty-seven studies, examining fat clearing, methylene blue staining, fat stretching and use of a dedicated pathology assistant, were assessed. The methodological quality of the majority of included studies was poor. Meta-analysis showed that fat clearing and methylene blue staining increased mean lymph node yield by 13 and 15 nodes, respectively, when compared to manual dissection. Of the 15 studies reporting positive lymph node count, two demonstrated a significant improvement for techniques other than manual dissection. Compared to manual dissection, other techniques were not shown to influence cancer staging. CONCLUSION: This review has shown that fat clearing and methylene blue staining increases the mean lymph node yield from gastrointestinal cancer specimens. There is insufficient evidence to suggest that these techniques increase positive lymph node count or lead to upstaging.

Transverse minilaparotomy for open abdominal aortic aneurysm repair.

INTRODUCTION: Traditional open surgical repair for abdominal aortic aneurysm (AAA) is a major procedure with a relatively high risk of perioperative morbidity. This article describes the results of minimally invasive open AAA repair through a transverse left upper quadrant minilaparotomy. METHODS: Between January 2007 and June 2010, 83 consecutive patients (77 men) underwent elective or urgent repair of a nonruptured AAA through a horizontal transperitoneal left upper quadrant minilaparotomy. Postoperatively, patients were fast-tracked through a multidisciplinary recovery program. RESULTS: Repairs were urgent in 15 patients (18%), and 10 (12%) had aortoiliac aneurysms. American Society of Anesthesiologists (ASA) scores 1 to 4 were 3.6%, 44.6%, 42%, and 11%, respectively. Median (range) age was 73 (61-87) years, AAA size was 5.9 (5.1-10) cm, body mass index was 27 (19-39) kg/m(2), operation time was 150 (85-280) minutes, blood loss was 625 (200-4150) mL, critical care bed days was 1 (0-19), and hospital stay was 4 (2-88) days. Four (4.8%) patients returned to the operating theater within the same admission. No patients required conversion to full laparotomy and none had reintervention postdischarge. Two patients (2.4%) died in the hospital, and 18 (21.7%) had postoperative adverse events, ranging from urinary retention to myocardial infarction. New-onset atrial fibrillation was the commonest of these events (11, 13.3%). Respiratory tract infection incidence was low (4.8%). Incisional herniation developed in two patients (2.4%) at a median (range) follow-up of 10 (6-25) months. Correcting for age, cardiac complications were associated with increased odds of hospital stay >4 days (odds ratio [OR], 7.59; 95% confidence interval [CI], 1.12-52.42; P = .014). Correcting for ASA score, advancing age was associated with increased risk of cardiac complications (OR, 1.18; 95% CI, 1.08-1.28; P = .001), whereas AAA screening (patient identified through screening) and maintaining higher intraoperative systolic pressure were both protective (OR, 0.24; 95% CI, 0.07-0.87; P = .018) and (OR, 0.93; 95% CI, 0.89-0.98; P = .009), respectively. CONCLUSION: Left upper quadrant minilaparotomy is a feasible minimally invasive approach to open AAA repair. This technique is associated with low morbidity and mortality and short hospital stay, particularly in patients identified through AAA screening.

Fundoplication to preserve allograft function after lung transplant: Systematic review and meta-analysis.

BACKGROUND: ARS has been adopted in select patients with lung transplant for the past 2 decades in many centers. Outcomes have been reported sporadically. No pooled analysis of retrospective series has been performed. OBJECTIVE: This review and pooled analysis sought to demonstrate objective evidence of improved graft function in lung transplant patients undergoing antireflux surgery (ARS). METHODS: In accordance with Meta-analyses of Observational Studies in Epidemiology guidelines, a search of PubMed Central, Medline, Google Scholar, and Cochrane Library databases was performed. Articles documenting spirometry data pre- and post-ARS were reviewed and a random-effects model meta-analysis was performed on forced expiratory volume in 1 second (FEV1) values and the rate of change of FEV1. RESULTS: Six articles were included in the meta-analysis. Regarding FEV1 before and after ARS, we observed a small increase in FEV1 values in studies reporting raw values (2.02 ± 0.89 L/1 sec vs 2.14 ± 0.77 L/1 sec; n = 154) and % of predicted (77.1% ± 22.1% vs 81.2% ± 26.95%; n = 45), with a small pooled Cohen d effect size of 0.159 (P = .114). When considering the rate of change of FEV1 we observed a significant difference in pre-ARS compared with post-ARS (-2.12 ± 2.76 mL/day vs +0.05 ± 1.19 mL/day; n = 103). There was a pooled effect size of 1.702 (P = .013), a large effect of ARS on the rate of change of FEV1 values. CONCLUSIONS: This meta-analysis of retrospective observational studies demonstrates that ARS might benefit patients with declining FEV1, by examining the rate of change of FEV1 during the pre- and postoperative periods.

De Novo Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma.

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened glycerophospholipid chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of premalignant tissues and unveils mechanisms of phospholipidomic reprogramming. SIGNIFICANCE: These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite, as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.

A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue.

In this study, we make a direct comparison between desorption electrospray ionization-mass spectrometry (DESI-MS) and ultraperformance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) platforms for the profiling of glycerophospholipid (GPL) species in esophageal cancer tissue. In particular, we studied the similarities and differences in the range of GPLs detected and the congruency of their relative abundances as detected by each analytical platform. The main differences between mass spectra of the two modalities were found to be associated with the variance in adduct formation of common GPLs, rather than the presence of different GPL species. Phosphatidylcholines as formate adducts in UPLC-ESI-MS accounted for the majority of differences in negative ion mode and alkali metal adducts of phosphatidylcholines in DESI-MS for positive ion mode. Comparison of the relative abundance of GPLs, normalized to a common peak, revealed a correlation coefficient of 0.70 (P < 0.001). The GPL profile detected by DESI-MS is congruent to UPLC-ESI-MS, which reaffirms the role of DESI-MS for lipidomic profiling and a potential premise for quantification.

Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry.

Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intraobserver variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes (LN) and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were coregistered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within LNs. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched IHC images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign LN tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 89.5%, 100%, 100%, and 97.2%, respectively, when compared with gold-standard IHC. DESI-MSI has the potential to be a diagnostic tool for perioperative identification of LNM and compares favorably with techniques currently used by histopathology experts. Cancer Res; 76(19); 5647-56. ©2016 AACR.

Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific. RESULTS: Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly. METHODS: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples. CONCLUSIONS: We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery.

XMS: cross-platform normalization method for multimodal mass spectrometric tissue profiling.

Here we present a proof of concept cross-platform normalization approach to convert raw mass spectra acquired by distinct desorption ionization methods and/or instrumental setups to cross-platform normalized analyte profiles. The initial step of the workflow is database driven peak annotation followed by summarization of peak intensities of different ions from the same molecule. The resulting compound-intensity spectra are adjusted to a method-independent intensity scale by using predetermined, compound-specific normalization factors. The method is based on the assumption that distinct MS-based platforms capture a similar set of chemical species in a biological sample, though these species may exhibit platform-specific molecular ion intensity distribution patterns. The method was validated on two sample sets of (1) porcine tissue analyzed by laser desorption ionization (LDI), desorption electrospray ionization (DESI), and rapid evaporative ionization mass spectrometric (REIMS) in combination with Fourier transformation-based mass spectrometry; and (2) healthy/cancerous colorectal tissue analyzed by DESI and REIMS with the latter being combined with time-of-flight mass spectrometry. We demonstrate the capacity of our method to reduce MS-platform specific variation resulting in (1) high inter-platform concordance coefficients of analyte intensities; (2) clear principal component based clustering of analyte profiles according to histological tissue types, irrespective of the used desorption ionization technique or mass spectrometer; and (3) accurate "blind" classification of histologic tissue types using cross-platform normalized analyte profiles.

Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles.

Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor over a large array of nano-needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma.

Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy.

UNLABELLED: Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable esophageal adenocarcinomas, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of esophageal adenocarcinomas with the presence of heterogeneous driver mutations, parallel evolution, early genome-doubling events, and an association between high intratumor heterogeneity and poor response to NAC. Multiregion sequencing demonstrated a significant reduction in thymine to guanine mutations within a CpTpT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of cytosine to adenine mutations within a CpC context following NAC. Esophageal adenocarcinomas are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches. SIGNIFICANCE: This work illustrates dynamic mutational processes occurring during esophageal adenocarcinoma evolution and following selective pressures of platinum exposure, emphasizing the iatrogenic impact of therapy on cancer evolution. Identification of amplifications encoding targetable oncogenes maintained through NAC suggests the presence of stable vulnerabilities, unimpeded by cytotoxics, suitable for therapeutic intervention.