Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett's esophagus (BE) and esophageal ...adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.
Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Histopathological confirmation is a key step in tumor diagnosis. Therefore, simplification in decision-making by ...discrimination between malignant and non-malignant cells of histological specimens can be provided by combination of new imaging technology and artificial intelligence (AI). In this work, hyperspectral imaging (HSI) data from 95 patients were used to classify three different histopathological features (squamous epithelium cells, esophageal adenocarcinoma (EAC) cells, and tumor stroma cells), based on a multi-layer perceptron with two hidden layers. We achieved an accuracy of 78% for EAC and stroma cells, and 80% for squamous epithelium. HSI combined with machine learning algorithms is a promising and innovative technique, which allows image acquisition beyond Red-Green-Blue (RGB) images. Further method validation and standardization will be necessary, before automated tumor cell identification algorithms can be used in daily clinical practice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Functional capacity is an independent indicator of morbidity in colon and rectal cancer surgery. This systematic review describes the evaluated and synthesized effects of exercise ...prehabilitation depending on the duration of interventions on functional and postoperative outcomes in colon and rectal cancer surgery.
Methods
Three electronic databases (MEDLINE Pubmed, Web of Sciences, and Cochrane Registry) were systematically searched (January 2022) for controlled trials that investigated the effects of prehabilitation prior to colo-rectal cancer resection.
Results
Twenty-three studies were included in this systematic review and 14 in our meta-analyses assessing these outcomes: the 6 min walk distance (6MWD), postoperative overall complications, and length of stay (LOS). We observed a significant improvement in preoperative functional capacity as measured with 6MWD (mean difference: 30.8 m; 95% CI 13.3, 48.3;
p
= 0.0005) due to prehabilitation. No reductions in LOS (mean difference: – 0.27 days; 95% CI – 0.93, 0.40;
p
= 0.5) or postoperative overall complications (Odds ratio: 0.84; 95% CI 0.53, 1.31;
p
= 0.44) were observed. Prehabilitation lasting more than 3 weeks tended to lower overall complications (Odds ratio: 0.66; 95% CI 0.4, 1.1;
p
= 0.11). However, the prehabilitation time periods differed between colon and rectal carcinoma resections.
Conclusion
Prehabilitation while the patient is preparing to undergo surgery for colorectal carcinoma improves functional capacity; and might reduce postoperative overall complications, but does not shorten the LOS. The studies we reviewed differ in target variables, design, and the intervention’s time period. Multicenter studies with sufficient statistical power and differentiating between colon and rectal carcinoma are needed to develop implementation strategies in the health care system.
Registration
PROSPERO CRD42022310532
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Aurora kinase A (AURKA) plays a pivotal role in regulating cell mitosis and tumor progression. However, its prognostic significance across diverse cancer types remains relatively ...unexplored.
Methods
We conducted a comprehensive analysis of AURKA expression in various cancers using data from The Cancer Genome Atlas, Genotype-Tissue Expression, and The Human Protein Atlas databases. Our investigation encompassed an exploration of the associations between AURKA expression and clinical characteristics, shedding light on potential functional roles of AURKA. Additionally, we delved into the relationship between AURKA and the tumor microenvironment. To substantiate the role of AURKA, we carried out
in vitro
experiments in esophageal adenocarcinoma (EAC), prostate cancer (PRAD), and pancreatic cancer (PAAD) cells.
Results
Our analysis revealed that AURKA is prominently overexpressed in a majority of the cancer types under investigation. Elevated AURKA expression correlated closely with poorer prognosis and advanced tumor stages. AURKA was found to be associated with key pathways involved in the cell cycle and arachidonic acid metabolism. Moreover, AURKA expression exhibited significant correlations with immunoregulatory genes and immune cell profiles. Notably,
in vitro
experiments demonstrated that silencing AURKA expression resulted in reduced cell viability in EAC, PRAD, and PAAD cells, as well as a decrease in clone formation, cell cycle elongation, diminished cell invasion and reduced spheroid size in EAC cells (OE33 and OE19).
Conclusion
Our study elucidates the oncogenic role of AURKA and underscores its prognostic value across a spectrum of cancers, including EAC. These findings suggest that AURKA holds promise as a predictive biomarker for EAC and various other tumor types.
Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations ...are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity.
Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior.
One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: - 1079; 95% CI - 2157 to - 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life.
Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed.
DRKS-ID: DRKS00020499 ; Registered 17 March 2020.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of ...alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Hyperspectral Imaging (HSI) is a reliable and safe imaging method for taking intraoperative perfusion measurements. This is the first study translating intraoperative HSI to an in vivo ...laparoscopic setting using a CE-certified HSI-system for minimally invasive surgery (HSI-MIS). We aim to compare it to an established HSI-system for open surgery (HSI-Open).
Methods
Intraoperative HSI was done using the HSI-MIS and HSI-Open at the Region of Interest (ROI). 19 patients undergoing gastrointestinal resections were analyzed in this study. The HSI-MIS-acquired images were aligned with those from the HSI-Open, and spectra and parameter images were compared pixel-wise. We calculated the Mean Absolute Error (MAE) for Tissue Oxygen Saturation (StO
2
), Near-Infrared Perfusion Index (NIR-PI), Tissue Water Index (TWI), and Organ Hemoglobin Index (OHI), as well as the Root Mean Squared Error (RMSE) over the whole spectrum. Our analysis of parameters was optimized using partial least squares (PLS) regression. Two experienced surgeons carried out an additional color-change analysis, comparing the ROI images and deciding whether they provided the same (acceptable) or different visual information (rejected).
Results
HSI and subsequent image registration was possible in 19 patients. MAE results for the original calculation were StO
2 orig.
17.2% (± 7.7%)
,
NIR-PI
orig.
16.0 (± 9.5), TWI
orig.
18.1 (± 7.9), OHI
orig.
14.4 (± 4.5). For the PLS calculation, they were StO
2 PLS
12.6% (± 5.2%), NIR-PI
PLS
10.3 (± 6.0), TWI
PLS
10.6 (± 5.1), and OHI
PLS
11.6 (± 3.0). The RMSE between both systems was 0.14 (± 0.06). In the color-change analysis; both surgeons accepted more images generated using the PLS method.
Conclusion
Intraoperative HSI-MIS is a new technology and holds great potential for future applications in surgery. Parameter deviations are attributable to technical differences and can be reduced by applying improved calculation methods. This study is an important step toward the clinical implementation of HSI for minimally invasive surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel ...treatment option for patients in stage IV of the disease.
Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered.
The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376).
Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy.
ClinicalTrials.gov Identifier: NCT03100708.
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